477 results on '"Lim, Joseph K."'
Search Results
2. AGA Clinical Practice Update on Diagnosis and Management of Acute Hepatic Porphyrias: Expert Review
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Wang, Bruce, Bonkovsky, Herbert L, Lim, Joseph K, and Balwani, Manisha
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Rare Diseases ,Liver Disease ,Clinical Trials and Supportive Activities ,Pain Research ,Patient Safety ,Digestive Diseases ,Detection ,screening and diagnosis ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,4.2 Evaluation of markers and technologies ,Renal and urogenital ,Oral and gastrointestinal ,Humans ,Female ,United States ,Middle Aged ,Porphyria ,Acute Intermittent ,Porphobilinogen Synthase ,Porphobilinogen ,Hemin ,Aminolevulinic Acid ,Carcinoma ,Hepatocellular ,Antiemetics ,Creatinine ,Quality of Life ,Porphyrias ,Hepatic ,Heme ,Hypertension ,Liver Neoplasms ,Renal Insufficiency ,Chronic ,Abdominal Pain ,5-Aminolevulinic Acid ,5-Aminolevulinic Acid Synthase ,Porphyria ,Porphyrins ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
DescriptionThe acute hepatic porphyrias (AHP) are rare, inborn errors of heme-metabolism and include acute intermittent porphyria, hereditary coproporphyria, variegate porphyria, and porphyria due to severe deficiency of 5-aminolevulinic acid dehydratase. Acute intermittent porphyria is the most common type of AHP, with an estimated prevalence of patients with symptoms of approximately 1 in 100,000. The major clinical presentation involves attacks of severe pain, usually abdominal and generalized, without peritoneal signs or abnormalities on cross-sectional imaging. Acute attacks occur mainly in women in their childbearing years. AHP should be considered in the evaluation of all patients, and especially women aged 15-50 years with recurrent severe abdominal pain not ascribable to common causes. The screening tests of choice include random urine porphobilinogen and δ-aminolevulinic acid corrected to creatinine. All patients with elevations in urinary porphobilinogen and/or δ-aminolevulinic acid should initially be presumed to have AHP. The cornerstones of management include discontinuation of porphyrinogenic drugs and chemicals, administration of oral or intravenous dextrose and intravenous hemin, and use of analgesics and antiemetics. Diagnosis of AHP type can be confirmed after initial treatment by genetic testing for pathogenic variants in HMBS, CPOX, PPOX, and ALAD genes. AHP is also associated with chronic symptoms and long-term risk of systemic arterial hypertension, chronic renal and liver disease, and hepatocellular carcinoma. Patients who have recurrent acute attacks (4 or more per year) should be considered for prophylactic therapy with intravenous hemin or subcutaneous givosiran. Liver transplantation is curative and reserved for patients with intractable symptoms who have failed other treatment options.MethodsThis expert review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Women aged 15-50 years with unexplained, recurrent severe abdominal pain without a clear etiology after an initial workup should be considered for screening for an AHP. BEST PRACTICE ADVICE 2: Initial diagnosis of AHP should be made by biochemical testing measuring δ-aminolevulinic acid, porphobilinogen, and creatinine on a random urine sample. BEST PRACTICE ADVICE 3: Genetic testing should be used to confirm the diagnosis of AHP in patients with positive biochemical testing. BEST PRACTICE ADVICE 4: Acute attacks of AHP that are severe enough to require hospital admission should be treated with intravenous hemin, given daily, preferably into a high-flow central vein. BEST PRACTICE ADVICE 5: In addition to intravenous hemin, management of acute attacks of AHP should include pain control, antiemetics, management of systemic arterial hypertension, tachycardia, and hyponatremia, and hypomagnesemia, if present. BEST PRACTICE ADVICE 6: Patients should be counseled to avoid identifiable triggers that may precipitate acute attacks, such as alcohol and porphyrinogenic medications. BEST PRACTICE ADVICE 7: Prophylactic heme therapy or givosiran, administered in an outpatient setting, should be considered in patients with recurrent attacks (4 or more per year). BEST PRACTICE ADVICE 8: Liver transplantation for AHP should be limited to patients with intractable symptoms and significantly decreased quality of life who are refractory to pharmacotherapy. BEST PRACTICE ADVICE 9: Patients with AHP should be monitored annually for liver disease. BEST PRACTICE ADVICE 10: Patients with AHP, regardless of the severity of symptoms, should undergo surveillance for hepatocellular carcinoma, beginning at age 50 years, with liver ultrasound every 6 months. BEST PRACTICE ADVICE 11: Patients with AHP on treatment should undergo surveillance for chronic kidney disease annually with serum creatinine and estimated glomerular filtration rate. BEST PRACTICE ADVICE 12: Patients should be counseled on the chronic and long-term complications of AHP, including neuropathy, chronic kidney disease, hypertension, and hepatocellular carcinoma, and need for long-term monitoring.
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- 2023
3. Hepatitis B care cascade among people with HIV/HBV coinfection in the North American AIDS Cohort Collaboration on Research and Design, 2012–2016
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Kim, Jessica, Newcomb, Craig W, Carbonari, Dena M, Torgersen, Jessie, Althoff, Keri N, Kitahata, Mari M, Klein, Marina B, Moore, Richard D, Reddy, K Rajender, Silverberg, Michael J, Mayor, Angel M, Horberg, Michael A, Cachay, Edward R, Lim, Joseph K, Gill, M John, Chew, Kara, Sterling, Timothy R, Hull, Mark, Seaberg, Eric C, Kirk, Gregory D, Coburn, Sally B, Lang, Raynell, McGinnis, Kathleen A, Gebo, Kelly A, Napravnik, Sonia, Kim, H Nina, Re, Vincent Lo, and Research and Design of IeDEA, for the North American AIDS Cohort Collaboration on
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Hepatitis ,Infectious Diseases ,Digestive Diseases ,Hepatitis - B ,HIV/AIDS ,Sexually Transmitted Infections ,Liver Disease ,Infection ,Good Health and Well Being ,Female ,Humans ,Middle Aged ,Male ,Hepatitis B virus ,HIV Infections ,Acquired Immunodeficiency Syndrome ,Coinfection ,Cross-Sectional Studies ,DNA ,Viral ,Canada ,Hepatitis B ,Tenofovir ,North American AIDS Cohort Collaboration on Research and Design of IeDEA ,General Science & Technology - Abstract
A care cascade is a critical tool for evaluating delivery of care for chronic infections across sequential stages, starting with diagnosis and ending with viral suppression. However, there have been few data describing the hepatitis B virus (HBV) care cascade among people living with HIV infection who have HBV coinfection. We conducted a cross-sectional study among people living with HIV and HBV coinfection receiving care between January 1, 2012 and December 31, 2016 within 13 United States and Canadian clinical cohorts contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). We evaluated each of the steps in this cascade, including: 1) laboratory-confirmed HBV infection, 2) tenofovir-based or entecavir-based HBV therapy prescribed, 3) HBV DNA measured during treatment, and 4) viral suppression achieved via undetectable HBV DNA. Among 3,953 persons with laboratory-confirmed HBV (median age, 50 years; 6.5% female; 43.8% were Black; 7.1% were Hispanic), 3,592 (90.9%; 95% confidence interval, 90.0-91.8%) were prescribed tenofovir-based antiretroviral therapy or entecavir along with their antiretroviral therapy regimen, 2,281 (57.7%; 95% confidence interval, 56.2-59.2%) had HBV DNA measured while on therapy, and 1,624 (41.1%; 95% confidence interval, 39.5-42.6) achieved an undetectable HBV DNA during HBV treatment. Our study identified significant gaps in measurement of HBV DNA and suppression of HBV viremia among people living with HIV and HBV coinfection in the United States and Canada. Periodic evaluation of the HBV care cascade among persons with HIV/HBV will be critical to monitoring success in completion of each step.
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- 2023
4. Brief Report: Accuracy of FIB-4 for Cirrhosis in People Living With HIV and Hepatocellular Carcinoma.
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Torgersen, Jessie, Kallan, Michael J, Carbonari, Dena M, Park, Lesley S, Mehta, Rajni L, D'Addeo, Kathryn, Tate, Janet P, Lim, Joseph K, Goetz, Matthew Bidwell, Rodriguez-Barradas, Maria C, Bräu, Norbert, Brown, Sheldon T, Taddei, Tamar H, Justice, Amy C, and Lo Re, Vincent
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Liver Cancer ,HIV/AIDS ,Rare Diseases ,Chronic Liver Disease and Cirrhosis ,Prevention ,Cancer ,Liver Disease ,Digestive Diseases ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Age Factors ,Alanine Transaminase ,Aspartate Aminotransferases ,Carcinoma ,Hepatocellular ,Clinical Decision Rules ,Cross-Sectional Studies ,Female ,HIV Infections ,Humans ,Liver Cirrhosis ,Liver Neoplasms ,Male ,Middle Aged ,Platelet Count ,Registries ,Virginia ,FIB-4 ,cirrhosis ,HIV ,hepatocellular carcinoma ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundHepatocellular carcinoma (HCC) may develop in the absence of cirrhosis in HIV, and determining how often this occurs can provide insights into mechanisms of carcinogenesis. Studies evaluating the prevalence of cirrhosis in the setting of HCC among people living with HIV (PLWH) often rely on noninvasive markers, such as the Fibrosis-4 Index for Hepatic Fibrosis (FIB-4). However, the accuracy of FIB-4 for cirrhosis in the setting of HCC has not been determined among PLWH.MethodsWe conducted a cross-sectional study among PLWH in the Veterans Aging Cohort Study with VA cancer registry-confirmed HCC diagnosed between 1999 and 2015. FIB-4 was calculated using the age, alanine aminotransferase, aspartate aminotransferase, and platelet count obtained closest to, but within 1 year before, HCC diagnosis. Medical records were reviewed within 1 year before HCC diagnosis to determine the cirrhosis status. We evaluated the area under the receiver-operating characteristic curve and performance characteristics of FIB-4 for confirmed cirrhosis.ResultsIncident HCC was diagnosed in 302 PLWH. After medical record review, 203 (67.2%, 95% confidence interval: 61.6% to 72.5%) had evidence of cirrhosis. FIB-4 identified patients with cirrhosis with an area under the receiver-operating characteristic curve of 0.67 (95% confidence interval: 0.60 to 0.73). FIB-4 scores >5.0 had a positive predictive value >80% and specificity of >77%, negative predictive value of
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- 2020
5. HIV RNA, CD4+ Percentage, and Risk of Hepatocellular Carcinoma by Cirrhosis Status.
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Torgersen, Jessie, Kallan, Michael J, Carbonari, Dena M, Park, Lesley S, Mehta, Rajni L, D’Addeo, Kathryn, Tate, Janet P, Lim, Joseph K, Goetz, Matthew Bidwell, Rodriguez-Barradas, Maria C, Gibert, Cynthia L, Bräu, Norbert, Brown, Sheldon T, Roy, Jason A, Taddei, Tamar H, Justice, Amy C, and Lo Re, Vincent
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Digestive Diseases ,Cancer ,Prevention ,Hepatitis ,Infectious Diseases ,Rare Diseases ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,HIV/AIDS ,Liver Disease ,Liver Cancer ,Infection ,Good Health and Well Being ,Adult ,CD4-Positive T-Lymphocytes ,CD8-Positive T-Lymphocytes ,Carcinoma ,Hepatocellular ,Cohort Studies ,Female ,HIV ,HIV Infections ,Humans ,Liver Cirrhosis ,Liver Neoplasms ,Male ,Middle Aged ,RNA ,Viral ,Retrospective Studies ,United States ,United States Department of Veterans Affairs ,Veterans ,Viremia ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundDespite increasing incidence of hepatocellular carcinoma (HCC) among HIV-infected patients, it remains unclear if HIV-related factors contribute to development of HCC. We examined if higher or prolonged HIV viremia and lower CD4+ cell percentage were associated with HCC.MethodsWe conducted a cohort study of HIV-infected individuals who had HIV RNA, CD4+, and CD8+ cell counts and percentages assessed in the Veterans Aging Cohort Study (1999-2015). HCC was ascertained using Veterans Health Administration cancer registries and electronic records. Cox regression was used to determine hazard ratios (HR, 95% confidence interval [CI]) of HCC associated with higher current HIV RNA, longer duration of detectable HIV viremia (≥500 copies/mL), and current CD4+ cell percentage less than 14%, adjusting for traditional HCC risk factors. Analyses were stratified by previously validated diagnoses of cirrhosis prior to start of follow-up.ResultsAmong 35 659 HIV-infected patients, 302 (0.8%) developed HCC over 281 441 person-years (incidence rate = 107.3 per 100 000 person-years). Among patients without baseline cirrhosis, higher HIV RNA (HR = 1.25, 95% CI = 1.12 to 1.40, per 1.0 log10 copies/mL) and 12 or more months of detectable HIV (HR = 1.47, 95% CI = 1.02 to 2.11) were independently associated with higher risk of HCC. CD4+ percentage less than 14% was not associated with HCC in any model. Hepatitis C coinfection was a statistically significant predictor of HCC regardless of baseline cirrhosis status.ConclusionAmong HIV-infected patients without baseline cirrhosis, higher HIV RNA and longer duration of HIV viremia increased risk of HCC, independent of traditional HCC risk factors. This is the strongest evidence to date that HIV viremia contributes to risk of HCC in this group.
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- 2020
6. AGA Clinical Practice Update on Screening and Surveillance for Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: Expert Review
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Loomba, Rohit, Lim, Joseph K, Patton, Heather, and El-Serag, Hashem B
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Liver Cancer ,Cancer ,Hepatitis ,Prevention ,Digestive Diseases ,Clinical Research ,4.1 Discovery and preclinical testing of markers and technologies ,Good Health and Well Being ,Carcinoma ,Hepatocellular ,Disease Progression ,Early Detection of Cancer ,Gastroenterology ,Humans ,Incidence ,Liver Neoplasms ,Mass Screening ,Non-alcoholic Fatty Liver Disease ,Practice Guidelines as Topic ,Risk Factors ,Societies ,Medical ,United States ,Watchful Waiting ,Cirrhosis ,Fibrosis ,HCC ,NASH ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Nonalcoholic fatty liver disease (NAFLD) is a leading etiology for chronic liver disease with an immense public health impact and affects >25% of the US and global population. Up to 1 in 4 NAFLD patients may have nonalcoholic steatohepatitis (NASH). NASH is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Recent data confirm that HCC represents the fifth most common cancer and is the second leading cause of cancer-related death worldwide, and NAFLD has been identified as a rapidly emerging risk factor for this malignancy. NAFLD-associated liver complications are projected to become the leading indication for liver transplantation in the next decade. Despite evidence that NAFLD-associated HCC may arise in the absence of cirrhosis, is often diagnosed at advanced stages, and is associated with lower receipt of curative therapy and with poorer survival, current society guidelines provide limited guidance/recommendations addressing HCC surveillance in patients with NAFLD outside the context of established cirrhosis. Limited data are presently available to guide clinicians with respect to which patients with NAFLD should undergo HCC surveillance, optimal screening tools, frequency of monitoring, and the influence of coexisting host- and disease-related risk factors. Herein we present an evidence-based review addressing HCC risk in patients with NAFLD and provide Best Practice Advice statements to address key issues in clinical management.
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- 2020
7. FIB-4 stage of liver fibrosis is associated with incident heart failure with preserved, but not reduced, ejection fraction among people with and without HIV or hepatitis C.
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So-Armah, Kaku A, Lim, Joseph K, Lo Re, Vincent, Tate, Janet P, Chang, Chung-Chou H, Butt, Adeel A, Gibert, Cynthia L, Rimland, David, Marconi, Vincent C, Goetz, Matthew Bidwell, Ramachandran, Vasan, Brittain, Evan, Long, Michelle, Nguyen, Kim-Lien, Rodriguez-Barradas, Maria C, Budoff, Matthew J, Tindle, Hilary A, Samet, Jeffrey H, Justice, Amy C, Freiberg, Matthew S, and VACS Project Team
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VACS Project Team ,Humans ,Hepatitis C ,HIV Infections ,Liver Cirrhosis ,Anti-HIV Agents ,Stroke Volume ,Prognosis ,Viral Load ,Severity of Illness Index ,Incidence ,Risk Assessment ,Risk Factors ,Health Status ,Ventricular Function ,Left ,Time Factors ,Adult ,Middle Aged ,HIV Long-Term Survivors ,United States ,Female ,Male ,Heart Failure ,Veterans Health ,Cohort ,Ejection fraction ,HIV ,Heart failure ,Hepatitis ,Liver fibrosis ,Clinical Research ,Heart Disease ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Cardiovascular ,Digestive Diseases ,Cardiovascular System & Hematology ,Cardiorespiratory Medicine and Haematology - Abstract
BackgroundLiver fibrosis, is independently associated with incident heart failure (HF). Investigating the association between liver fibrosis and type of HF, specifically HF with reduced ejection fraction (EF; HFrEF) or HF with preserved ejection fraction (HFpEF), may provide mechanistic insight into this association. We sought to determine the association between liver fibrosis score (FIB-4) and type of HF, and to assess whether HIV or hepatitis C status modified this association.MethodsWe included patients alive on or after 4/1/2003 from the Veterans Aging Cohort Study. We followed patients without prevalent cardiovascular disease until their first HF event, death, last clinic visit, or 9/30/2015. We defined liver fibrosis as: likely advanced fibrosis (FIB-4 > 3.25), indeterminate (FIB-4 range 1.45-3.25), unlikely advanced fibrosis (FIB-4
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- 2020
8. Comparison of the prevalence, severity, and risk factors for hepatic steatosis in HIV-infected and uninfected people
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Torgersen, Jessie, So-Armah, Kaku, Freiberg, Matthew S, Goetz, Matthew B, Budoff, Matthew J, Lim, Joseph K, Taddei, Tamar, Butt, Adeel A, Rodriguez-Barradas, Maria C, Justice, Amy C, Kostman, Jay R, and Lo Re, Vincent
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Clinical Research ,HIV/AIDS ,Infectious Diseases ,Digestive Diseases ,Cardiovascular ,Chronic Liver Disease and Cirrhosis ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Comorbidity ,Cross-Sectional Studies ,Fatty Liver ,Female ,HIV Infections ,Humans ,Male ,Middle Aged ,Prevalence ,Prospective Studies ,Risk Factors ,Severity of Illness Index ,Tomography ,X-Ray Computed ,United States ,Hepatic steatosis ,HIV ,Liver fibrosis ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
BackgroundHepatic steatosis is prevalent in Western countries, but few studies have evaluated whether the frequency and severity of steatosis are greater in the setting of HIV infection. We compared the prevalence and severity of hepatic steatosis between HIV-infected (HIV+) and uninfected persons and identified factors associated with greater steatosis severity within both groups.MethodsWe performed a cross-sectional study among participants without cardiovascular disease who participated in a substudy of the Veterans Aging Cohort Study. Hepatic steatosis was defined by noncontrast computed tomography (CT) liver-to-spleen (L/S) attenuation ratio
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- 2019
9. Patient-reported symptoms during and after direct-acting antiviral therapies for chronic hepatitis C: The PROP UP study
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Evon, Donna M, Sarkar, Souvik, Amador, Jipcy, Lok, Anna S, Sterling, Richard K, Stewart, Paul W, Reeve, Bryce B, Serper, Marina, Reau, Nancy, Reddy, K Rajender, Di Bisceglie, Adrian M, Nelson, David R, Golin, Carol E, Lim, Joseph K, and Fried, Michael W
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Behavioral and Social Science ,Infectious Diseases ,Emerging Infectious Diseases ,Clinical Research ,Brain Disorders ,Hepatitis - C ,Hepatitis ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Digestive Diseases ,Mental Health ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,2-Naphthylamine ,Adult ,Aged ,Aged ,80 and over ,Amides ,Anilides ,Antiviral Agents ,Benzimidazoles ,Benzofurans ,Carbamates ,Cyclopropanes ,Drug Therapy ,Combination ,Female ,Fluorenes ,Hepacivirus ,Hepatitis C ,Chronic ,Heterocyclic Compounds ,4 or More Rings ,Humans ,Imidazoles ,Lactams ,Macrocyclic ,Macrocyclic Compounds ,Male ,Middle Aged ,Patient Reported Outcome Measures ,Proline ,Prospective Studies ,Quinoxalines ,Ritonavir ,Sofosbuvir ,Sulfonamides ,Sustained Virologic Response ,Uracil ,Valine ,Young Adult ,HCV ,Liver ,PRO ,Patient-reported outcome ,Quality of life ,Treatment ,Sleep ,Pain ,Functioning ,Symptom ,Clinical Sciences ,Public Health and Health Services ,Gastroenterology & Hepatology - Abstract
Background & aimsA comprehensive analysis of changes in symptoms and functioning during and after direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection has not been conducted for patients treated in real-world clinical settings. Therefore, we evaluated patient-reported outcomes (PROs) in a diverse cohort of patients with HCV treated with commonly prescribed DAAs.MethodsPROP UP is a US multicenter observational study of 1,601 patients with HCV treated with DAAs in 2016-2017. PRO data were collected at baseline (T1), early on-treatment (T2), late on-treatment (T3) and 3-months post-treatment (T4). PRO mean change scores were calculated from baseline and a minimally important change (MIC) threshold was set at 5%. Regression analyses investigated patient and treatment characteristics independently associated with PRO changes on-treatment and post-treatment.ResultsOf 1,564 patients, 55% were male, 39% non-white, 47% had cirrhosis. Sofosbuvir/ledipasvir was prescribed to 63%, sofosbuvir/velpatasvir to 21%, grazoprevir/elbasvir to 11%, and paritaprevir/ombitasvir/ritonavir + dasabuvir to 5%. During DAA therapy, mean PRO scores improved slightly in the overall cohort, but did not reach the 5% MIC threshold. Between 21-53% of patients experienced >5% improved PROs while 23-36% experienced >5% worse symptoms. Of 1,410 patients with evaluable sustained virologic response (SVR) data, 95% achieved SVR. Among those with SVR, all mean PRO scores improved, with the 5% MIC threshold met for fatigue, sleep disturbance, and functioning well-being. Regression analyses identified subgroups, defined by age 35-55, baseline mental health issues and a higher number of health comorbidities as predictors of PRO improvements.ConclusionsIn real-world clinical practices, we observed heterogeneous patient experiences during and after DAA treatment. Symptom improvements were more pronounced in younger patients, those with baseline mental health issues and multiple comorbidities.Lay summaryPatients who received direct-acting antiviral medications for hepatitis C at several liver centers in the US did not generally experience significant changes in baseline symptoms during treatment. We observed a full range of patient experiences with some patients experiencing substantial symptom improvements, yet others experiencing less improvements and some even experiencing a worsening of symptoms. The 1,346 patients who were cured of hepatitis C experienced improvements in fatigue, sleep disturbance, and functional well-being, and trends for improved pain and depression; whereas the 64 who were not cured experienced minimal improvements. Clinicaltrial.gov: NCT02601820.
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- 2019
10. Determinants of Liver Complications Among HIV/Hepatitis B Virus-Coinfected Patients.
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Lo Re, Vincent, Newcomb, Craig W, Carbonari, Dena M, Roy, Jason A, Althoff, Keri N, Kitahata, Mari M, Reddy, K Rajender, Lim, Joseph K, Silverberg, Michael J, Mayor, Angel M, Horberg, Michael A, Cachay, Edward R, Kirk, Gregory D, Hull, Mark, Gill, John, Sterling, Timothy R, Kostman, Jay R, Peters, Marion G, Moore, Richard D, Klein, Marina B, and Kim, H Nina
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Public Health ,Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Hepatitis ,Clinical Research ,Digestive Diseases ,HIV/AIDS ,Infectious Diseases ,Alcoholism ,Alcohol Use and Health ,Chronic Liver Disease and Cirrhosis ,Substance Misuse ,Hepatitis - B ,Rare Diseases ,Sexually Transmitted Infections ,Liver Disease ,Liver Cancer ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Adult ,CD4 Lymphocyte Count ,Canada ,Carcinoma ,Hepatocellular ,End Stage Liver Disease ,Esophageal and Gastric Varices ,Female ,Gastrointestinal Hemorrhage ,HIV Infections ,Hepatitis B ,Humans ,Liver ,Liver Cirrhosis ,Liver Neoplasms ,Male ,Middle Aged ,Retrospective Studies ,Risk Factors ,United States ,hepatitis B ,HIV ,end-stage liver disease ,hepatocellular carcinoma ,coinfection ,North American AIDS Cohort Collaboration on Research and Design of IeDEA ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundHepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown.SettingNorth American AIDS Cohort Collaboration on Research and Design.MethodsWe performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL).ResultsAmong 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-4
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- 2019
11. Safety and Effectiveness of Ledipasvir and Sofosbuvir, With or Without Ribavirin, in Treatment-Experienced Patients With Genotype 1 Hepatitis C Virus Infection and Cirrhosis
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Lim, Joseph K, Liapakis, Ann Marie, Shiffman, Mitchell L, Lok, Anna S, Zeuzem, Stefan, Terrault, Norah A, Park, James S, Landis, Charles S, Hassan, Mohamed, Gallant, Joel, Kuo, Alexander, Pockros, Paul J, Vainorius, Monika, Akushevich, Lucy, Michael, Larry, Fried, Michael W, Nelson, David R, Ben-Ari, Ziv, and Group, HCV-TARGET Study
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Trials and Supportive Activities ,Chronic Liver Disease and Cirrhosis ,Hepatitis ,Emerging Infectious Diseases ,Hepatitis - C ,Digestive Diseases ,Clinical Research ,Infectious Diseases ,Liver Disease ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Antiviral Agents ,Benzimidazoles ,Drug Therapy ,Combination ,Drug-Related Side Effects and Adverse Reactions ,Europe ,Female ,Fluorenes ,Genotype ,Hepacivirus ,Hepatitis C ,Chronic ,Humans ,Liver Cirrhosis ,Longitudinal Studies ,Male ,Middle Aged ,North America ,Prospective Studies ,Ribavirin ,Sofosbuvir ,Sustained Virologic Response ,Treatment Outcome ,Young Adult ,Real World ,Viral Hepatitis ,Therapy ,HCV-TARGET ,HCV-TARGET Study Group ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
BACKGROUND & AIMS:We aimed to evaluate the safety and effectiveness of 12 or 24 weeks treatment with ledipasvir and sofosbuvir, with or without ribavirin, in treatment-experienced patients with hepatitis C virus (HCV) genotype 1 infection and cirrhosis in routine clinical practice. Patients were followed in a multi-center, prospective, observational cohort study (HCV-TARGET). METHODS:We collected data from 667 treatment-experienced adults with chronic genotype 1 HCV infection who began treatment with ledipasvir and sofosbuvir, with or without ribavirin, from 2011 through September 15, 2016, according to the regional standards of care, at academic (n = 39) and community (n = 18) centers in the United States, Canada, Germany, and Israel. Information was collected from medical records and abstracted into a unique centralized data core. Independent monitors systematically reviewed data entries for completeness and accuracy. Demographic, clinical, adverse event, and virologic data were collected every 12 weeks during treatment and during the follow-up period. The primary efficacy endpoint was sustained virologic response, defined as a level of HCV RNA below the lower limit of quantification or undetectable at a minimum 64 days after the end of treatment (SVR12). The per-protocol population (n = 610) was restricted to patients who completed 12 or 24 weeks of treatment (±2 weeks) and had final virologic outcomes available. RESULTS:The per-protocol analysis revealed that 579 patients (93.8%) achieved an SVR12, including 50/51 patients who received ledipasvir and sofosbuvir for 12 weeks (98%), 384/408 patients who received ledipasvir and sofosbuvir for 24 weeks (94.1%), 68/70 patients who received ledipasvir and sofosbuvir with ribavirin for 12 weeks (97.1%), and 57/60 patients who received ledipasvir and sofosbuvir with ribavirin for 24 weeks (95%). On multivariate analysis, neither treatment duration nor the addition of ribavirin was associated with SVR12. Compensated cirrhosis (odds ratio [OR] compared to decompensated cirrhosis, 2.41; 95% CI, 1.16-5.02), albumin ≥ 3.5 g/dL (OR, 3.15; 95% CI 1.46-6.80), or total bilirubin ≤ 1.2 mg/dL (OR 3.34; 95% CI, 1.59-7.00) were associated with SVR12. CONCLUSIONS:In an analysis of safety and effectiveness data from the HCV-TARGET study, we found treatment with ledipasvir and sofosbuvir, with or without ribavirin, to be effective and well tolerated by treatment-experienced patients with genotype 1 HCV infection and compensated cirrhosis. There were no significant differences in rate of SVR12 among patients treated with ledipasvir and sofosbuvir for 12 or 24 weeks, with or without ribavirin. Patients with decompensated cirrhosis appear to benefit from the addition of ribavirin or extension of ledipasvir and sofosbuvir treatment to 24 weeks. ClinicalTrials.gov no: NCT10474811.
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- 2018
12. Identification of hepatic steatosis among persons with and without HIV using natural language processing.
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Torgersen, Jessie, Skanderson, Melissa, Kidwai-Khan, Farah, Carbonari, Dena M., Tate, Janet P., Park, Lesley S., Bhattacharya, Debika, Lim, Joseph K., Taddei, Tamar H., Justice, Amy C., and Re III, Vincent Lo
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- 2024
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13. Bilirubin Is Inversely Associated With Cardiovascular Disease Among HIV‐Positive and HIV‐Negative Individuals in VACS (Veterans Aging Cohort Study)
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Marconi, Vincent C, Duncan, Meredith S, So‐Armah, Kaku, Re, Vincent Lo, Lim, Joseph K, Butt, Adeel A, Goetz, Matthew Bidwell, Rodriguez‐Barradas, Maria C, Alcorn, Charles W, Lennox, Jeffrey, Beckman, Joshua A, Justice, Amy, and Freiberg, Matthew
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Heart Disease - Coronary Heart Disease ,Clinical Research ,Cardiovascular ,Prevention ,Heart Disease ,Aging ,Good Health and Well Being ,Adult ,Age Factors ,Bilirubin ,Biomarkers ,Cardiovascular Diseases ,Female ,HIV Infections ,Humans ,Incidence ,Male ,Middle Aged ,Prognosis ,Prospective Studies ,Protective Factors ,Risk Assessment ,Risk Factors ,Time Factors ,United States ,Up-Regulation ,Veterans Health ,cardiovascular disease ,bilirubin ,HIV ,stroke ,myocardial infarction ,heart failure ,HIV ,Cardiorespiratory Medicine and Haematology - Abstract
Bilirubin may protect against cardiovascular disease (CVD) by reducing oxidative stress. Whether elevated bilirubin reduces the risk of CVD events among HIV+ individuals and if this differs from uninfected individuals remain unclear. We assessed whether bilirubin independently predicted the risk of CVD events among HIV+ and uninfected participants in VACS (Veterans Aging Cohort Study). We conducted a prospective cohort study using VACS participants free of baseline CVD. Total bilirubin was categorized by quartiles. CVD as well as acute myocardial infarction, heart failure, and ischemic stroke events were assessed. Cox regression was used to evaluate hazard ratios of outcomes associated with quartiles of total bilirubin in HIV+ and uninfected people after adjusting for multiple risk factors. There were 96 381 participants (30 427 HIV+); mean age was 48 years, 48% were black, and 97% were men. There were 6603 total incident CVD events over a mean of 5.7 years. In adjusted models, increasing quartiles of baseline total bilirubin were associated with decreased hazards of all outcomes (hazard ratio, 0.86; 95% confidence interval, 0.80-0.91). Among HIV+ participants, results persisted for heart failure, ischemic stroke, and total CVD, but nonsignificant associations were observed for acute myocardial infarction. VACS participants (regardless of HIV status) with elevated bilirubin levels had a lower risk of incident total CVD, acute myocardial infarction, heart failure, and ischemic stroke events after adjusting for known risk factors. Future studies should investigate how this apparently protective effect of elevated bilirubin could be harnessed to reduce CVD risk or improve risk estimation among HIV+ individuals.
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- 2018
14. Prevalence and impact of baseline resistance-associated substitutions on the efficacy of ledipasvir/sofosbuvir or simeprevir/sofosbuvir against GT1 HCV infection.
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Wang, Gary P, Terrault, Norah, Reeves, Jacqueline D, Liu, Lin, Li, Eric, Zhao, Lisa, Lim, Joseph K, Morelli, Giuseppe, Kuo, Alexander, Levitsky, Josh, Sherman, Kenneth E, Frazier, Lynn M, Ramani, Ananthakrishnan, Peter, Joy, Akuskevich, Lucy, Fried, Michael W, and Nelson, David R
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Humans ,Hepacivirus ,Hepatitis C ,Chronic ,Benzimidazoles ,Fluorenes ,Antiviral Agents ,Prevalence ,Drug Resistance ,Viral ,Genotype ,Aged ,Middle Aged ,Female ,Male ,Clinical Trials as Topic ,Simeprevir ,Sofosbuvir ,Clinical Research ,Cancer ,Liver Disease ,Emerging Infectious Diseases ,Digestive Diseases ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Hepatitis C ,Chronic ,Drug Resistance ,Viral ,Biochemistry and Cell Biology ,Other Physical Sciences - Abstract
Baseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or more drug classes. Baseline LDV RASs in GT1a, TE, and cirrhosis LDV/SOF subgroup was associated with 2-4% lower SVR12 rates. SMV RASs was associated with lower SVR12 rates in GT1a, treatment-experienced, cirrhotics SMV/SOF subgroup. Pooled analysis of all patients with baseline RASs revealed that SVR12 was 100% (19/19) in patients treated for longer than 98 days but was 87% (81/93) in patients treated for shorter than 98 days. These results demonstrate that RASs prevalence and their impact in real world practice are in general agreement with registration trials, and suggest that longer treatment duration may overcome the negative impact of baseline RASs on SVR12 rates in clinical practice.
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- 2018
15. A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: Results from a large US multi-center observational study
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Evon, Donna M, Stewart, Paul W, Amador, Jipcy, Serper, Marina, Lok, Anna S, Sterling, Richard K, Sarkar, Souvik, Golin, Carol E, Reeve, Bryce B, Nelson, David R, Reau, Nancy, Lim, Joseph K, Reddy, K Rajender, Di Bisceglie, Adrian M, and Fried, Michael W
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Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Digestive Diseases ,Pain Research ,Hepatitis ,Infectious Diseases ,Chronic Liver Disease and Cirrhosis ,Hepatitis - C ,Patient Safety ,Emerging Infectious Diseases ,Chronic Pain ,Clinical Research ,Clinical Trials and Supportive Activities ,Liver Disease ,Substance Misuse ,Good Health and Well Being ,Adult ,Aged ,Aged ,80 and over ,Antiviral Agents ,Cohort Studies ,Comorbidity ,Female ,Hepatitis C ,Chronic ,Humans ,Insurance ,Major Medical ,International Normalized Ratio ,Liver ,Liver Cirrhosis ,Male ,Mental Disorders ,Middle Aged ,Patient Reported Outcome Measures ,RNA ,Viral ,United States ,Young Adult ,General Science & Technology - Abstract
BackgroundSymptom burden, medical comorbidities, and functional well-being of patients with chronic hepatitis C virus (HCV) initiating direct acting antiviral (DAA) therapy in real-world clinical settings are not known. We characterized these patient-reported outcomes (PROs) among HCV-infected patients and explored associations with sociodemographic, liver disease, and psychiatric/substance abuse variables.Methods and findingsPROP UP is a large US multicenter observational study that enrolled 1,600 patients with chronic HCV in 2016-2017. Data collected prior to initiating DAA therapy assessed the following PROs: number of medical comorbidities; neuropsychiatric, somatic, gastrointestinal symptoms (PROMIS surveys); overall symptom burden (Memorial Symptom Assessment Scale); and functional well-being (HCV-PRO). Candidate predictors included liver disease markers and patient-reported sociodemographic, psychiatric, and alcohol/drug use features. Predictive models were explored using a random selection of 700 participants; models were then validated with data from the remaining 900 participants. The cohort was 55% male, 39% non-white, 48% had cirrhosis (12% with advanced cirrhosis); 52% were disabled or unemployed; 63% were on public health insurance or uninsured; and over 40% had markers of psychiatric illness. The median number of medical comorbidities was 4 (range: 0-15), with sleep disorders, chronic pain, diabetes, joint pain and muscle aches being present in 20-50%. Fatigue, sleep disturbance, pain and neuropsychiatric symptoms were present in over 60% and gastrointestinal symptoms in 40-50%. In multivariable validation models, the strongest and most frequent predictors of worse PROs were disability, unemployment, and use of psychiatric medications, while liver markers generally were not.ConclusionsThis large multi-center cohort study provides a comprehensive and contemporary assessment of the symptom burden and comorbid medical conditions in patients with HCV treated in real world settings. Pain, fatigue, and sleep disturbance were common and often severe. Sociodemographic and psychiatric markers were the most robust predictors of PROs. Future research that includes a rapidly changing population of HCV-infected individuals needs to evaluate how DAA therapy affects PROs and elucidate which symptoms resolve with viral eradication.Trial registration(Clinicaltrial.gov: NCT02601820).
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- 2018
16. Risk of Acute Liver Injury After Statin Initiation by Human Immunodeficiency Virus and Chronic Hepatitis C Virus Infection Status.
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Byrne, Dana D, Tate, Janet P, Forde, Kimberly A, Lim, Joseph K, Goetz, Matthew Bidwell, Rimland, David, Rodriguez-Barradas, Maria C, Butt, Adeel A, Gibert, Cynthia L, Brown, Sheldon T, Bedimo, Roger, Freiberg, Matthew S, Justice, Amy C, Kostman, Jay R, Roy, Jason A, and Lo Re, Vincent
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Emerging Infectious Diseases ,Rare Diseases ,Genetics ,Hepatitis - C ,Infectious Diseases ,Hepatitis ,Clinical Research ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,HIV/AIDS ,Infection ,Good Health and Well Being ,Chemical and Drug Induced Liver Injury ,Female ,HIV Infections ,Hepatitis C ,Chronic ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Incidence ,Male ,Middle Aged ,Retrospective Studies ,Risk Factors ,statins ,HIV ,hepatitis C ,hepatotoxicity ,acute liver injury ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundPatients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status.MethodsWe conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases >200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups.ResultsAmong HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels >200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons.ConclusionsRegardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.
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- 2017
17. Risk of liver decompensation with cumulative use of mitochondrial toxic nucleoside analogues in HIV/hepatitis C virus coinfection
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Re, Vincent Lo, Zeldow, Bret, Kallan, Michael J, Tate, Janet P, Carbonari, Dena M, Hennessy, Sean, Kostman, Jay R, Lim, Joseph K, Goetz, Matthew Bidwell, Gross, Robert, Justice, Amy C, and Roy, Jason A
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Medical Microbiology ,Biomedical and Clinical Sciences ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Digestive Diseases ,HIV/AIDS ,Emerging Infectious Diseases ,Clinical Research ,Hepatitis ,Prevention ,Infectious Diseases ,Clinical Trials and Supportive Activities ,Hepatitis - C ,Infection ,Good Health and Well Being ,Chemical and Drug Induced Liver Injury ,Chronic ,Coinfection ,Female ,HIV Infections ,Hepatitis C ,Chronic ,Humans ,Incidence ,Liver ,Liver Cirrhosis ,Liver Failure ,Male ,Middle Aged ,Mitochondria ,Proportional Hazards Models ,Retrospective Studies ,Reverse Transcriptase Inhibitors ,drug-induced liver injury ,hepatic decompensation ,hepatitis C ,hepatotoxicity ,HIV ,mitochondrial toxicity ,pharmacoepidemiology ,Pharmacology and Pharmaceutical Sciences ,Public Health and Health Services ,Pharmacology & Pharmacy ,Pharmacology and pharmaceutical sciences ,Epidemiology - Abstract
PurposeAmong patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death.MethodsWe conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs.ResultsOver 7033 person-years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person-years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person-years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1-11 mo: HR, 1.79 [95% confidence interval (CI), 0.74-4.31]; 12-35 mo: HR, 1.39 [95% CI, 0.68-2.87]; 36-71 mo: HR, 2.27 [95% CI, 0.92-5.60]; >71 mo: HR, 4.66 [95% CI, 1.04-20.83]; P = .045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1-11 mo: HR, 2.24 [95% CI, 1.04-4.81]; 12-35 mo: HR, 2.05 [95% CI, 0.68-6.20]; 36-71 mo: HR, 3.04 [95% CI, 1.12-8.26]; >71 mo: HR, 3.93 [95% CI, 0.75-20.50]; P = .030).ConclusionsThese findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients.
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- 2017
18. Risk of liver decompensation with cumulative use of mitochondrial toxic nucleoside analogues in HIV/hepatitis C virus coinfection.
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Lo Re, Vincent, Zeldow, Bret, Kallan, Michael J, Tate, Janet P, Carbonari, Dena M, Hennessy, Sean, Kostman, Jay R, Lim, Joseph K, Goetz, Matthew Bidwell, Gross, Robert, Justice, Amy C, and Roy, Jason A
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Liver ,Mitochondria ,Humans ,Hepatitis C ,Chronic ,HIV Infections ,Liver Failure ,Liver Cirrhosis ,Reverse Transcriptase Inhibitors ,Incidence ,Proportional Hazards Models ,Retrospective Studies ,Middle Aged ,Female ,Male ,Coinfection ,Chemical and Drug Induced Liver Injury ,Chronic ,HIV ,drug-induced liver injury ,hepatic decompensation ,hepatitis C ,hepatotoxicity ,mitochondrial toxicity ,pharmacoepidemiology ,Hepatitis C ,Chronic ,Chemical and Drug Induced Liver Injury ,Pharmacology & Pharmacy ,Pharmacology and Pharmaceutical Sciences ,Public Health and Health Services - Abstract
PurposeAmong patients dually infected with human immunodeficiency virus (HIV) and chronic hepatitis C virus (HCV), use of antiretroviral therapy (ART) containing mitochondrial toxic nucleoside reverse transcriptase inhibitors (mtNRTIs) might induce chronic hepatic injury, which could accelerate HCV-associated liver fibrosis and increase the risk of hepatic decompensation and death.MethodsWe conducted a cohort study among 1747 HIV/HCV patients initiating NRTI-containing ART within the Veterans Aging Cohort Study (2002-2009) to determine if cumulative mtNRTI use increased the risk of hepatic decompensation and death among HIV-/HCV-coinfected patients. Separate marginal structural models were used to estimate hazard ratios (HRs) of each outcome associated with cumulative exposure to ART regimens that contain mtNRTIs versus regimens that contain other NRTIs.ResultsOver 7033 person-years, we observed 97 (5.6%) decompensation events (incidence rate, 13.8/1000 person-years) and 125 (7.2%) deaths (incidence rate, 17.8 events/1000 person-years). The risk of hepatic decompensation increased with cumulative mtNRTI use (1-11 mo: HR, 1.79 [95% confidence interval (CI), 0.74-4.31]; 12-35 mo: HR, 1.39 [95% CI, 0.68-2.87]; 36-71 mo: HR, 2.27 [95% CI, 0.92-5.60]; >71 mo: HR, 4.66 [95% CI, 1.04-20.83]; P = .045) versus nonuse. Cumulative mtNRTI use also increased risk of death (1-11 mo: HR, 2.24 [95% CI, 1.04-4.81]; 12-35 mo: HR, 2.05 [95% CI, 0.68-6.20]; 36-71 mo: HR, 3.04 [95% CI, 1.12-8.26]; >71 mo: HR, 3.93 [95% CI, 0.75-20.50]; P = .030).ConclusionsThese findings suggest that cumulative mtNRTI use may increase the risk of hepatic decompensation and death in HIV/HCV coinfection. These drugs should be avoided when alternatives exist for HIV/HCV patients.
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- 2017
19. FIB-4 stage of liver fibrosis predicts incident heart failure among HIV-infected and uninfected patients.
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So-Armah, Kaku A, Lim, Joseph K, Lo Re, Vincent, Tate, Janet P, Chang, Chung-Chou H, Butt, Adeel A, Gibert, Cynthia L, Rimland, David, Marconi, Vincent C, Goetz, Matthew B, Rodriguez-Barradas, Maria C, Budoff, Matthew J, Tindle, Hilary A, Samet, Jeffrey H, Justice, Amy C, Freiberg, Matthew S, and Veterans Aging Cohort Study Project Team
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Veterans Aging Cohort Study Project Team ,Humans ,HIV Infections ,Liver Cirrhosis ,Severity of Illness Index ,Case-Control Studies ,Cohort Studies ,Adult ,Middle Aged ,Female ,Male ,Heart Failure ,Heart Disease ,Infectious Diseases ,Hepatitis - C ,Digestive Diseases ,HIV/AIDS ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Aging ,Hepatitis ,Clinical Research ,Cardiovascular ,Emerging Infectious Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology - Abstract
Liver fibrosis is common, particularly in individuals who are infected with human immunodeficiency virus (HIV). HIV-infected individuals have excess congestive heart failure (CHF) risk compared with uninfected people. It remains unknown whether liver fibrosis stage influences the CHF risk or if HIV or hepatitis C virus (HCV) infection modifies this association. Our objectives were to assess whether 1) stage of liver fibrosis is independently associated with incident CHF and 2) the association between stage of liver fibrosis and incident CHF is modified by HIV/HCV status. Participants alive on or after April 1, 2003, in the Veterans Aging Cohort Study were included. Those without prevalent cardiovascular disease were followed until their first CHF event, death, last follow-up date, or December 31, 2011. Liver fibrosis was measured using the fibrosis 4 index (FIB-4), which is calculated using age, aminotransferases, and platelets. Cox proportional hazards regression models were adjusted for cardiovascular disease risk factors. Among 96,373 participants over 6.9 years, 3844 incident CHF events occurred. FIB-4 between 1.45 and 3.25 (moderate fibrosis) and FIB-4 > 3.25 (advanced fibrosis/cirrhosis) were associated with CHF (hazard ratio [95% confidence interval], 1.17 [1.07-1.27] and 1.65 [1.43-1.92], respectively). The association of advanced fibrosis/cirrhosis and incident CHF persisted regardless of HIV/HCV status.ConclusionModerate and advanced liver fibrosis/cirrhosis are associated with an increased risk of CHF. The association for advanced fibrosis/cirrhosis persists even among participants without hepatitis C and/or HIV infection. Assessing liver health may be important for reducing the risk of future CHF events, particularly among HIV and hepatitis C infected people among whom cardiovascular disease risk is elevated and liver disease is common. (Hepatology 2017;66:1286-1295).
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- 2017
20. Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B: A comprehensive review of phases II and III therapeutic agents
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Lam, Robert, primary and Lim, Joseph K, additional
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- 2024
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21. Management of HBV reactivation: Challenges and opportunities
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Mezzacappa, Catherine, primary and Lim, Joseph K., additional
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- 2024
- Full Text
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22. Clinical Liver Disease: Legacy of innovation in hepatology education
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Lim, Joseph K., primary
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- 2024
- Full Text
- View/download PDF
23. AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review
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Dougan, Michael, Wang, Yinghong, Rubio-Tapia, Alberto, and Lim, Joseph K.
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- 2021
- Full Text
- View/download PDF
24. Patient engagement and study design of PROP UP: A multi-site patient-centered prospective observational study of patients undergoing hepatitis C treatment
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Evon, Donna M, Golin, Carol E, Stewart, Paul, Fried, Michael W, Alston, Shani, Reeve, Bryce, Lok, Anna S, Sterling, Richard K, Lim, Joseph K, Reau, Nancy, Sarkar, Souvik, Nelson, David R, Reddy, KR, and Di Bisceglie, Adrian M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Hepatitis ,Clinical Trials and Supportive Activities ,Substance Misuse ,Liver Disease ,Hepatitis - C ,Infectious Diseases ,Chronic Liver Disease and Cirrhosis ,Behavioral and Social Science ,Comparative Effectiveness Research ,Drug Abuse (NIDA only) ,Clinical Research ,Emerging Infectious Diseases ,Good Health and Well Being ,Adult ,Antiviral Agents ,Benzimidazoles ,Benzofurans ,Carbamates ,Drug Combinations ,Female ,Fluorenes ,Hepatitis C ,Chronic ,Heterocyclic Compounds ,4 or More Rings ,Humans ,Imidazoles ,Macrocyclic Compounds ,Male ,Patient Participation ,Patient-Centered Care ,Prospective Studies ,Pyrrolidines ,Quinoxalines ,Ritonavir ,Sofosbuvir ,Sulfonamides ,Treatment Outcome ,Uracil ,Uridine Monophosphate ,Valine ,Liver ,Patient-reported outcomes ,Patient-centered outcomes research ,Direct acting antiviral ,Medical and Health Sciences ,General Clinical Medicine ,Public Health ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundNew highly efficacious direct-acting antiviral (DAA) therapies are available to treat chronic hepatitis C viral (HCV) infection. Real-world, patient-centered data on harms and benefits associated with these therapies are needed.MethodsPROP UP is a multi-center prospective observational study that plans to enroll 1600 patients starting treatment with recently-approved DAA regimens. Informed by extensive input from a HCV patient engagement group who prioritized outcomes most important to them, patient-reported outcomes will be characterized using surveys at five time points: Baseline (T1), treatment week 4 (T2), end of treatment (T3), 12weeks post-treatment (T4), 12months post-treatment (T5).Outcomes(1) Changes in side effects, functioning, pre-existing conditions, and out-of-pocket costs during therapy (T1 vs T2/T3); (2) Medication adherence in relation to a history of mental health/substance abuse, treatment regimens, pill burden, reasons for missed doses, and cure rates; (3) Short term impact of cure on functioning and amelioration of symptoms (T1 vs T4); (4) Long-term treatment harms or benefits of cure on symptoms, side effects, pre-existing conditions, and functioning (T1 vs T5). Similarities between regimens will be examined where comparisons are appropriate and meaningful.ConclusionPROP UP complements previous clinical trials by focusing on patient-reported outcomes in a representative sample of patients treated in clinical practice, by collaborating with a patient engagement group, by characterizing the experiences of vulnerable subgroups, and by investigating long-term harms and benefits of treatments. PROP UP is designed to provide novel and detailed information to support informed decision-making for patients and providers contemplating HCV treatment (PCORI CER-1408-20,660; NCT02601820).
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- 2017
25. Risk of Acute Liver Injury With Antiretroviral Therapy by Viral Hepatitis Status
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Gowda, Charitha, Newcomb, Craig W, Liu, Qing, Carbonari, Dena M, Lewis, James D, Forde, Kimberly A, Goldberg, David S, Reddy, K Rajender, Roy, Jason A, Marks, Amy R, Schneider, Jennifer L, Kostman, Jay R, Tate, Janet P, Lim, Joseph K, Justice, Amy C, Goetz, Matthew Bidwell, Corley, Douglas A, and Re, Vincent Lo
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Liver Disease ,HIV/AIDS ,Rare Diseases ,Prevention ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Emerging Infectious Diseases ,Clinical Research ,Hepatitis ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Infection ,Good Health and Well Being ,antiretroviral ,drug-induced liver injury ,hepatotoxicity ,HIV ,HIV. ,Clinical sciences ,Medical microbiology - Abstract
BackgroundThe risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status.MethodsWe followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Within the first year of ART, we determined occurrence of (1) liver aminotransferases >200 U/L and (2) severe ALI (coagulopathy with hyperbilirubinemia). We used Cox regression to determine hazard ratios (HRs) with 95% confidence intervals (CIs) of endpoints among initiators of nucleos(t)ide analogue combinations, antiretroviral classes, and ART regimens, all stratified by viral hepatitis status.ResultsLiver aminotransferases >200 U/L developed in 206 (2%) persons and occurred more frequently among HIV/viral hepatitis-coinfected than HIV-monoinfected persons (116.1 vs 20.7 events/1000 person-years; P < .001). No evidence of differential risk was found between initiators of abacavir/lamivudine versus tenofovir/emtricitabine among coinfected (HR, 0.68; 95% CI, .29-1.57) or HIV-monoinfected (HR, 1.19; 95% CI, .47-2.97) groups. Coinfected patients had a higher risk of aminotransferases >200 U/L after initiation with a protease inhibitor than nonnucleoside reverse-transcriptase inhibitor (HR, 2.01; 95% CI, 1.36-2.96). Severe ALI (30 events; 0.3%) occurred more frequently in coinfected persons (15.9 vs 3.1 events/1000 person-years; P < .001) but was too uncommon to evaluate in adjusted analyses.ConclusionsWithin the year after ART initiation, aminotransferase elevations were infrequently observed and rarely led to severe ALI. Protease inhibitor use was associated with a higher risk of aminotransferase elevations among viral hepatitis-coinfected patients.
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- 2017
26. Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response
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Terrault, Norah A, Zeuzem, Stefan, Di Bisceglie, Adrian M, Lim, Joseph K, Pockros, Paul J, Frazier, Lynn M, Kuo, Alexander, Lok, Anna S, Shiffman, Mitchell L, Ari, Ziv Ben, Akushevich, Lucy, Vainorius, Monika, Sulkowski, Mark S, Fried, Michael W, Nelson, David R, and Group, HCV-TARGET Study
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Biomedical and Clinical Sciences ,Clinical Sciences ,Emerging Infectious Diseases ,Digestive Diseases ,Hepatitis ,Clinical Trials and Supportive Activities ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Liver Disease ,Infectious Diseases ,Hepatitis - C ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Antiviral Agents ,Benzimidazoles ,Bilirubin ,Drug Therapy ,Combination ,Female ,Fluorenes ,Genotype ,Hepacivirus ,Hepatitis C ,Chronic ,Humans ,Liver Cirrhosis ,Longitudinal Studies ,Male ,Middle Aged ,Prospective Studies ,Proton Pump Inhibitors ,Ribavirin ,Risk Factors ,Serum Albumin ,Sofosbuvir ,Sustained Virologic Response ,Time Factors ,Treatment Failure ,Uridine Monophosphate ,Young Adult ,DAA ,NS5A Inhibitor ,NS5B Inhibitor ,Antiviral ,HCV-TARGET Study Group ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsThe combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA
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- 2016
27. Disparities in hepatitis C testing in U.S. veterans born 1945–1965
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Sarkar, Souvik, Esserman, Denise A, Skanderson, Melissa, Levin, Forrest L, Justice, Amy C, and Lim, Joseph K
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Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Hepatitis ,Emerging Infectious Diseases ,Hepatitis - C ,Infectious Diseases ,Clinical Research ,Health Services ,Chronic Liver Disease and Cirrhosis ,Genetics ,Hepatitis - B ,Prevention ,Digestive Diseases ,Infection ,Good Health and Well Being ,Hepacivirus ,Hepatitis C ,Hepatitis C Antibodies ,Humans ,Male ,Risk Factors ,United States ,Veterans ,HCV ,Hepatitis C virus ,Epidemiology ,Variances ,Testing ,U.S ,U.S. ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsUniversal one-time antibody testing for hepatitis C virus (HCV) infection has been recommended by the centers for disease control (CDC) and the United States preventative services task force (USPSTF) for Americans born 1945-1965 (birth cohort). Limited data exists addressing national HCV testing practices. We studied patterns and predictors of HCV testing across the U.S. within the birth cohort utilizing data from the national corporate data warehouse of the U.S. Veterans Administration (VA) health system.MethodsTesting was defined as any HCV test including antibody, RNA or genotype performed during 2000-2013.ResultsOf 6,669,388 birth cohort veterans, 4,221,135 (63%) received care within the VA from 2000-2013 with two or more visits. Of this group, 2,139,935 (51%) had HCV testing with 8.1% HCV antibody and 5.4% RNA positive. Significant variation in testing was observed across centers (range: 7-83%). Older, male, African-Americans, with established risk factors and receiving care from urban centers of excellence were more likely to be tested. Among veterans free of other established risk factors (HIV negative, HBV negative, ALT ⩽40U/L, FIB-4 ⩽1.45, or APRI 3.25) with >30-43% having positive HCV RNA but >16-20% yet to undergo testing for HCV.ConclusionsSignificant disparities are observed in HCV testing within the United States VA health system. Examination of the predictors of testing and HCV positivity may help inform national screening policies.Lay summaryAnalysis of United States Veterans Administration data show significant disparities in hepatitis C virus testing of veterans born 1945-1965 (birth cohort). A fifth of those not tested had evidence of advanced liver fibrosis. Our data suggests some predictors for this disparity and will potentially help inform future policy measures in the era of universal birth cohort testing for HCV.
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- 2016
28. Safety and efficacy of sofosbuvir‐containing regimens in hepatitis C‐infected patients with impaired renal function
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Saxena, Varun, Koraishy, Farrukh M, Sise, Meghan E, Lim, Joseph K, Schmidt, Monica, Chung, Raymond T, Liapakis, Annmarie, Nelson, David R, Fried, Michael W, Terrault, Norah A, and HCV‐TARGET
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Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Liver Disease ,Kidney Disease ,Hepatitis ,Clinical Research ,Digestive Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Renal and urogenital ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Antiviral Agents ,Databases ,Factual ,Drug Therapy ,Combination ,Europe ,Female ,Glomerular Filtration Rate ,Hepacivirus ,Hepatitis C ,Chronic ,Humans ,Liver Cirrhosis ,Longitudinal Studies ,Male ,Middle Aged ,Multivariate Analysis ,North America ,Regression Analysis ,Renal Dialysis ,Renal Insufficiency ,Chronic ,Simeprevir ,Sofosbuvir ,Sustained Virologic Response ,Young Adult ,decompensated cirrhosis ,haemodialysis ,liver transplantation ,sustained virologic response ,HCV-TARGET ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsRenal clearance is the major elimination pathway for sofosbuvir (SOF). We assessed the safety and efficacy of SOF-containing regimens in patients with varying baseline estimated glomerular filtration rate (eGFR).MethodsHCV-TARGET database is a multicentre, longitudinal 'real-world' treatment cohort.ResultsA total of 1789 patients [genotypes 1 (72%), 2 (17%) 3 (9%), 4-6 (2%)] had baseline eGFR determination: 73 with eGFR≤45 (18 with eGFR≤30, 5 on dialysis) were compared to 1716 with eGFR>45 ml/min/1.73 m(2) . Patients with baseline eGFR≤45 vs. >45 differed in being female (55% vs. 36%), age ≥65 years (24% vs. 16%), Black race (22% vs. 12%), having cirrhosis with decompensation (73% vs. 24%) and being post-transplant (49% vs. 10%), all P < 0.05. All patients with eGFR≤45 were treated with SOF 400 mg/day (including those on haemodialysis) and had median starting ribavirin (RBV) dose of 800 mg (IQR: 400-1200). Sustained virologic response (SVR) frequencies were similar across eGFR groups, ranging from 82-83%. Patients with eGFR ≤45 more frequently experienced anaemia, worsening renal function and serious AEs (all P < 0.05), and these associations persisted when limiting analysis to RBV-free regimens. Patients with baseline eGFR≤30 and eGFR 31-45 had similar frequencies of efficacy and safety outcomes.ConclusionsSustained viral clearance was achieved in 83% of patients with renal impairment (eGFR ≤45 ml/min/1.73 m(2) ) treated with SOF-containing regimens. However, these patients had higher rates of anaemia, worsening renal dysfunction and serious adverse events regardless of use of RBV. Patient with renal impairment require close monitoring and should be treated by providers extensively experienced with SOF-containing regimens.
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- 2016
29. Isolated Hepatitis B Core Antibody is Associated With Advanced Hepatic Fibrosis in HIV/HCV Infection But Not in HIV Infection Alone
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Bhattacharya, Debika, Tseng, Chi-hong, Tate, Janet P, Re, Vincent Lo, Gibert, Cynthia L, Butt, Adeel A, Brown, Sheldon T, Lim, Joseph K, Rodriguez-Barradas, Maria C, Rimland, David, Kaufman, Erica, Justice, Amy C, and Goetz, Matthew Bidwell
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Good Health and Well Being ,Adult ,Aspartate Aminotransferases ,CD4 Lymphocyte Count ,Coinfection ,Cross-Sectional Studies ,Female ,HIV Infections ,Hepatitis B Antibodies ,Hepatitis B Core Antigens ,Hepatitis B Surface Antigens ,Hepatitis B virus ,Hepatitis C ,Humans ,Liver Cirrhosis ,Male ,Middle Aged ,Platelet Count ,Veterans ,Viremia ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
HIV+/HCV+ persons with isolated HBcAb have a higher prevalence of advanced fibrosis than persons who are non-immune to HBV, who have resolved HBV, or who are HbsAb+ only.
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- 2016
30. Colitis Following Initiation of Sofosbuvir and Simeprevir for Genotype 1 Hepatitis C
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Sarkar, Souvik, Mitchell, Kisha A, Lim, Joseph K, Oikonomou, Ioannis, and Jakab, Simona
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Biomedical and Clinical Sciences ,Clinical Sciences ,Emerging Infectious Diseases ,Prevention ,Hepatitis ,Chronic Liver Disease and Cirrhosis ,Infectious Diseases ,Digestive Diseases ,Hepatitis - C ,Liver Disease ,Autoimmune Disease ,Inflammatory Bowel Disease ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Oral and gastrointestinal ,Good Health and Well Being - Abstract
Sofosbuvir and simeprevir are used for the treatment of chronic hepatitis C (HCV) genotype 1. Both drugs have been well-tolerated, with diarrhea noted in 6% cases with sofosbuvir, 16% with sofosbuvir plus simeprevir, and 0% with simeprevir. No prior reports exist of colitis secondary to either drug or their combination. We report a patient with no prior history of inflammatory bowel disease who developed significant bloody diarrhea within 2 weeks of sofosbuvir/simeprevir initiation. Colonoscopy and biopsy confirmed pancolitis, which responded to mesalamine and completion of sofosbuvir/simeprevir.
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- 2016
31. 1026. Hepatitis B Reactivation in Persons with HIV with Positive Hepatitis B Core Antibody after Switching to Antiretroviral Therapy without Hepatitis B Activity
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Denyer, Rachel V, primary, Tate, Janet P, additional, Benator, Debra A, additional, Lim, Joseph K, additional, and Weintrob, Amy, additional
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- 2023
- Full Text
- View/download PDF
32. Precipitous changes in nomenclature and definitions—NAFLD becomes SLD: Implications for and expectations of AASLD journals
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Malhi, Harmeet, primary, Brown, Robert S., additional, Lim, Joseph K., additional, Reau, Nancy, additional, Tapper, Elliot B., additional, Wong, Carmen Chak-Lui, additional, and Gores, Gregory J., additional
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- 2023
- Full Text
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33. Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention
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Lim, Joseph K, primary and Njei, Basile, additional
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- 2023
- Full Text
- View/download PDF
34. Colitis Following Initiation of Sofosbuvir and Simeprevir for Genotype 1 Hepatitis C.
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Sarkar, Souvik, Mitchell, Kisha A, Lim, Joseph K, Oikonomou, Ioannis, and Jakab, Simona
- Abstract
Sofosbuvir and simeprevir are used for the treatment of chronic hepatitis C (HCV) genotype 1. Both drugs have been well-tolerated, with diarrhea noted in 6% cases with sofosbuvir, 16% with sofosbuvir plus simeprevir, and 0% with simeprevir. No prior reports exist of colitis secondary to either drug or their combination. We report a patient with no prior history of inflammatory bowel disease who developed significant bloody diarrhea within 2 weeks of sofosbuvir/simeprevir initiation. Colonoscopy and biopsy confirmed pancolitis, which responded to mesalamine and completion of sofosbuvir/simeprevir.
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- 2015
35. AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review
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Bowlus, Christopher L., Lim, Joseph K., and Lindor, Keith D.
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- 2019
- Full Text
- View/download PDF
36. Excess Weight Gain After Cure of Hepatitis C Infection with Direct-Acting Antivirals
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Do, Albert, Esserman, Denise A., Krishnan, Supriya, Lim, Joseph K., Taddei, Tamar H., Hauser, III, Ronald G., Tate, Janet P., Re, III, Vincent Lo, and Justice, Amy C.
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- 2020
- Full Text
- View/download PDF
37. Medication Non-adherence in a Prospective, Multi-center Cohort Treated with Hepatitis C Direct-Acting Antivirals
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Serper, Marina, Evon, Donna M., Stewart, Paul W., Lok, Anna S., Amador, Jipcy, Reeve, Bryce B., Golin, Carol E., Fried, Michael W., Reddy, K. Rajender, Sterling, Richard K., Sarkar, Souvik, Di Bisceglie, Adrian M., Lim, Joseph K., Nelson, David R., and Reau, Nancy
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- 2020
- Full Text
- View/download PDF
38. Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients
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Re, Vincent Lo, Kallan, Michael J, Tate, Janet P, Lim, Joseph K, Goetz, Matthew Bidwell, Klein, Marina B, Rimland, David, Rodriguez-Barradas, Maria C, Butt, Adeel A, Gibert, Cynthia L, Brown, Sheldon T, Park, Lesley S, Dubrow, Robert, Reddy, K Rajender, Kostman, Jay R, Justice, Amy C, and Localio, A Russell
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,HIV/AIDS ,Infectious Diseases ,Liver Disease ,Clinical Research ,Hepatitis ,Hepatitis - C ,Chronic Liver Disease and Cirrhosis ,Emerging Infectious Diseases ,Digestive Diseases ,Infection ,Good Health and Well Being ,end-stage liver disease ,hepatic decompensation ,HIV ,hepatitis C ,HIV/HCV coinfection ,Clinical sciences ,Medical microbiology - Abstract
Background. End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.
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- 2015
39. Predicting Risk of End-Stage Liver Disease in Antiretroviral-Treated Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients.
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Lo Re, Vincent, Kallan, Michael J, Tate, Janet P, Lim, Joseph K, Goetz, Matthew Bidwell, Klein, Marina B, Rimland, David, Rodriguez-Barradas, Maria C, Butt, Adeel A, Gibert, Cynthia L, Brown, Sheldon T, Park, Lesley S, Dubrow, Robert, Reddy, K Rajender, Kostman, Jay R, Justice, Amy C, and Localio, A Russell
- Subjects
HIV ,HIV/HCV coinfection ,end-stage liver disease ,hepatic decompensation ,hepatitis C ,Liver Disease ,HIV/AIDS ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Hepatitis - C ,Emerging Infectious Diseases ,Clinical Research ,Hepatitis ,Infectious Diseases ,Infection - Abstract
Background. End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Quantifying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.
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- 2015
40. Status of Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection and Remaining Challenges
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Baumert, Thomas F., Berg, Thomas, Lim, Joseph K., and Nelson, David R.
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- 2019
- Full Text
- View/download PDF
41. Relationship Between Alcohol Use Categories and Noninvasive Markers of Advanced Hepatic Fibrosis in HIV-Infected, Chronic Hepatitis C Virus–Infected, and Uninfected Patients
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Lim, Joseph K, Tate, Janet P, Fultz, Shawn L, Goulet, Joseph L, Conigliaro, Joseph, Bryant, Kendall J, Gordon, Adam J, Gibert, Cynthia, Rimland, David, Goetz, Matthew Bidwell, Klein, Marina B, Fiellin, David A, Justice, Amy C, and Re, Vincent Lo
- Subjects
Liver Disease ,Alcoholism ,Alcohol Use and Health ,Hepatitis - C ,Hepatitis ,Infectious Diseases ,Pediatric ,Emerging Infectious Diseases ,Underage Drinking ,Substance Misuse ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,HIV/AIDS ,Clinical Research ,Infection ,Oral and gastrointestinal ,Good Health and Well Being ,Adult ,Alcohol Drinking ,Alcoholism ,Biomarkers ,Cohort Studies ,Coinfection ,Cross-Sectional Studies ,Female ,HIV Infections ,Hepatitis C ,Chronic ,Humans ,Liver Cirrhosis ,Liver Cirrhosis ,Alcoholic ,Male ,Middle Aged ,Prevalence ,alcohol ,liver fibrosis ,HIV ,hepatitis C ,FIB-4 ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
BackgroundIt is unclear if the risk of liver disease associated with different levels of alcohol consumption is higher for patients infected with human immunodeficiency virus (HIV) or chronic hepatitis C virus (HCV). We evaluated associations between alcohol use categories and advanced hepatic fibrosis, by HIV and chronic HCV status.MethodsWe performed a cross-sectional study among participants in the Veterans Aging Cohort Study who reported alcohol consumption at enrollment (701 HIV/HCV-coinfected; 1410 HIV-monoinfected; 296 HCV-monoinfected; 1158 HIV/HCV-uninfected). Alcohol use category was determined by the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire and alcohol-related diagnoses and was classified as nonhazardous drinking, hazardous/binge drinking, or alcohol-related diagnosis. Advanced hepatic fibrosis was defined by FIB-4 index >3.25.ResultsWithin each HIV/HCV group, the prevalence of advanced hepatic fibrosis increased as alcohol use category increased. For each alcohol use category, advanced hepatic fibrosis was more common among HIV-infected than uninfected (nonhazardous: 6.7% vs 1.4%; hazardous/binge: 9.5% vs 3.0%; alcohol-related diagnosis: 19.0% vs 8.6%; P < .01) and chronic HCV-infected than uninfected (nonhazardous: 13.6% vs 2.5%; hazardous/binge: 18.2% vs 3.1%; alcohol-related diagnosis: 22.1% vs 6.5%; P < .01) participants. Strong associations with advanced hepatic fibrosis (adjusted odds ratio [95% confidence interval]) were observed among HIV/HCV-coinfected patients with nonhazardous drinking (14.2 [5.91-34.0]), hazardous/binge drinking (18.9 [7.98-44.8]), and alcohol-related diagnoses (25.2 [10.6-59.7]) compared with uninfected nonhazardous drinkers.ConclusionsAdvanced hepatic fibrosis was present at low levels of alcohol consumption, increased with higher alcohol use categories, and was more prevalent among HIV-infected and chronic HCV-infected patients than uninfected individuals. All alcohol use categories were strongly associated with advanced hepatic fibrosis in HIV/HCV-coinfected patients.
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- 2014
42. Hepatic decompensation in antiretroviral-treated patients co-infected with HIV and hepatitis C virus compared with hepatitis C virus-monoinfected patients: a cohort study.
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Lo Re, Vincent, Kallan, Michael J, Tate, Janet P, Localio, A Russell, Lim, Joseph K, Goetz, Matthew Bidwell, Klein, Marina B, Rimland, David, Rodriguez-Barradas, Maria C, Butt, Adeel A, Gibert, Cynthia L, Brown, Sheldon T, Park, Lesley, Dubrow, Robert, Reddy, K Rajender, Kostman, Jay R, Strom, Brian L, and Justice, Amy C
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Hepatitis - C ,Digestive Diseases ,Clinical Research ,Chronic Liver Disease and Cirrhosis ,HIV/AIDS ,Emerging Infectious Diseases ,Infectious Diseases ,Liver Disease ,Hepatitis ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Anti-Retroviral Agents ,Ascites ,Bacterial Infections ,Carcinoma ,Hepatocellular ,Coinfection ,Esophageal and Gastric Varices ,Female ,Gastrointestinal Hemorrhage ,HIV ,HIV Infections ,Hepatitis C ,Chronic ,Humans ,Incidence ,Liver Neoplasms ,Male ,Medication Adherence ,Middle Aged ,Peritonitis ,RNA ,Viral ,Retrospective Studies ,Treatment Outcome ,Viral Load ,Clinical Sciences ,Public Health and Health Services - Abstract
BackgroundThe incidence and determinants of hepatic decompensation have been incompletely examined among patients co-infected with HIV and hepatitis C virus (HCV) in the antiretroviral therapy (ART) era, and few studies have compared outcome rates with those of patients with chronic HCV alone.ObjectiveTo compare the incidence of hepatic decompensation between antiretroviral-treated patients co-infected with HIV and HCV and HCV-monoinfected patients and to evaluate factors associated with decompensation among co-infected patients receiving ART.DesignRetrospective cohort study.SettingVeterans Health Administration.Patients4280 co-infected patients who initiated ART and 6079 HCV-monoinfected patients receiving care between 1997 and 2010. All patients had detectable HCV RNA and were HCV treatment-naive.MeasurementsIncident hepatic decompensation, determined by diagnoses of ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage.ResultsThe incidence of hepatic decompensation was greater among co-infected than monoinfected patients (7.4% vs. 4.8% at 10 years; P < 0.001). Compared with HCV-monoinfected patients, co-infected patients had a higher rate of hepatic decompensation (hazard ratio [HR] accounting for competing risks, 1.56 [95% CI, 1.31 to 1.86]). Co-infected patients who maintained HIV RNA levels less than 1000 copies/mL still had higher rates of decompensation than HCV-monoinfected patients (HR, 1.44 [CI, 1.05 to 1.99]). Baseline advanced hepatic fibrosis (FIB-4 score >3.25) (HR, 5.45 [CI, 3.79 to 7.84]), baseline hemoglobin level less than 100 g/L (HR, 2.24 [CI, 1.20 to 4.20]), diabetes mellitus (HR, 1.88 [CI, 1.38 to 2.56]), and nonblack race (HR, 2.12 [CI, 1.65 to 2.72]) were each associated with higher rates of decompensation among co-infected patients.LimitationObservational study of predominantly male patients.ConclusionDespite receiving ART, patients co-infected with HIV and HCV had higher rates of hepatic decompensation than HCV-monoinfected patients. Rates of decompensation were higher for co-infected patients with advanced liver fibrosis, severe anemia, diabetes, and nonblack race.Primary funding sourceNational Institutes of Health.
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- 2014
43. Antiretroviral Therapy Reduces the Rate of Hepatic Decompensation Among HIV- and Hepatitis C Virus–Coinfected Veterans
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Anderson, Jeffrey P, Tchetgen, Eric J Tchetgen, Re, Vincent Lo, Tate, Janet P, Williams, Paige L, Seage, George R, Horsburgh, C Robert, Lim, Joseph K, Goetz, Matthew Bidwell, Rimland, David, Rodriguez-Barradas, Maria C, Butt, Adeel A, Klein, Marina B, and Justice, Amy C
- Subjects
Emerging Infectious Diseases ,HIV/AIDS ,Clinical Research ,Digestive Diseases ,Hepatitis ,Chronic Liver Disease and Cirrhosis ,Hepatitis - C ,Liver Disease ,Infectious Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Aged ,Aged ,80 and over ,Antiretroviral Therapy ,Highly Active ,Cohort Studies ,Coinfection ,HIV Infections ,Hepatitis C ,Humans ,Liver Failure ,Male ,Middle Aged ,Veterans ,Young Adult ,HIV ,hepatitis C ,coinfection ,hepatic decompensation ,marginal structural model ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
Background Human immunodeficiency virus (HIV) coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure.Methods We evaluated 10 090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying ART regimen of ≥3 drugs from ≥2 classes. Hepatic decompensation was defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HRs) of hepatic decompensation, comparing initiation of ART to noninitiation.Results We observed 645 hepatic decompensation events in 46 444 person-years of follow-up (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to noninitiators (HR = 0.72; 95% confidence interval [CI], .54-.94). When we removed individuals with HIV RNA ≤400 copies/mL at baseline from the analysis (assuming that they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR = 0.59; 95% CI, .43-.82).Conclusions Initiation of ART significantly reduced the rate of hepatic decompensation by 28%-41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease.
- Published
- 2014
44. Exercise Does Not Independently Improve Histological Outcomes in Biopsy-Proven Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
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Chen, George, primary, Banini, Bubu A., additional, Do, Albert, additional, Gunderson, Craig, additional, Zaman, Saif, additional, and Lim, Joseph K., additional
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- 2023
- Full Text
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45. HIV- and HCV-specific markers and echocardiographic pulmonary artery systolic pressure among United States veterans
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Zola, Courtney E., Duncan, Meredith S., So-Armah, Kaku, Crothers, Kristina A., Butt, Adeel A., Gibert, Cynthia L., Kim, Joon Woo W., Lim, Joseph K., Re, III, Vincent Lo, Tindle, Hilary A., Freiberg, Matthew S., and Brittain, Evan L.
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- 2020
- Full Text
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46. Liver fibrosis and accelerated immune dysfunction (immunosenescence) among HIV-infected Russians with heavy alcohol consumption - an observational cross-sectional study
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So-Armah, Kaku, Freiberg, Matthew, Cheng, Debbie, Lim, Joseph K., Gnatienko, Natalia, Patts, Gregory, Doyle, Margaret, Fuster, Daniel, Lioznov, Dmitry, Krupitsky, Evgeny, and Samet, Jeffrey
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- 2019
- Full Text
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47. Impact of Direct Acting Antivirals on Survival in Patients with Chronic Hepatitis C and Hepatocellular Carcinoma
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Kamp, William M., Sellers, Cortlandt M., Stein, Stacey, Lim, Joseph K., and Kim, Hyun S.
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- 2019
- Full Text
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48. Reply
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Long, Michelle T., primary, Noureddin, Mazen, additional, and Lim, Joseph K., additional
- Published
- 2023
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49. The independent effect of exercise on biopsy-proven non-alcoholic fatty liver disease: A systematic review
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Chen, George, primary, Banini, Bubu, additional, Do, Albert, additional, and Lim, Joseph K., additional
- Published
- 2023
- Full Text
- View/download PDF
50. Tailoring stepwise treatment for Budd-Chiari syndrome: insights from the Asian Pacific Association for the Study of the Liver (APASL) consensus guidance
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Haque, Lamia Y., primary and Lim, Joseph K., additional
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- 2023
- Full Text
- View/download PDF
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