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Patients are prioritized for liver transplantation (LT) under an "urgency-based" system using the Model for End-Stage Liver Disease score. This system focuses solely on waitlist mortality, without considerations of posttransplant morbidity, mortality, and health care use. We sought to develop and internally validate a continuous posttransplant risk score during 5-year and 10-year time horizons. This retrospective cohort study used national registry data of adult deceased donor LT (DDLT) recipients with ≥90 days of pretransplant waiting time from February 27, 2002 to December 31, 2018. We fit Cox regression models at 5 and 10 years to estimate beta coefficients for a risk score using manual variable selection and calculated the absolute predicted survival time. Among 21,103 adult DDLT recipients, 11 variables were selected for the final model. The area under the curves at 5 and 10 years were 0.63 (95% confidence interval [CI], 0.60-0.66) and 0.67 (95% CI, 0.64-0.70), respectively. The group with the highest ("best") scores had 5-year and 10-year survivals of 89.4% and 85.4%, respectively, compared with 45.9% and 22.2% for those with the lowest ("worst") scores. Our score was significantly better at predicting long-term survival compared with the existing scores. We developed and validated a risk score using nearly 17 years of data to prioritize patients with end-stage liver disease based on projected posttransplant survival. This score can serve as the building block by which the transplant field can change the entire approach to prioritizing patients to an approach that is based on considerations of maximizing benefits (ie, survival benefit-based allocation) rather than simply waitlist mortality.

Background Periodic surveillance of the hepatitis C virus (HCV) care cascade is important for tracking progress toward HCV elimination goals, identifying gaps in care, and prioritizing resource allocation. In the pre-direct-acting antiviral (DAA) era, it was estimated that 50% of HCV-infected individuals were diagnosed and that 16% had been prescribed interferon-based therapy. Since then, few studies utilizing nationally representative data from the DAA era have been conducted in the United States. Methods We performed a cross-sectional study to describe the HCV care cascade in the United States using the Optum de-identified Clinformatics® Data Mart Database to identify a nationally representative sample of commercially insured beneficiaries between January 1, 2014 and December 31, 2019. We estimated the number of HCV-viremic individuals in Optum based on national HCV prevalence estimates and determined the proportion who had: (1) recorded diagnosis of HCV infection, (2) recorded HCV diagnosis and underwent HCV RNA testing, (3) DAA treatment dispensed, and (4) assessment for cure. Results Among 120,311 individuals estimated to have HCV viremia in Optum during the study period, 109,233 (90.8%; 95% CI, 90.6%–91.0%) had a recorded diagnosis of HCV infection, 75,549 (62.8%; 95% CI, 62.5%–63.1%) had a recorded diagnosis of HCV infection and underwent HCV RNA testing, 41,102 (34.2%; 95% CI, 33.9%–34.4%) were dispensed DAA treatment, and 25,760 (21.4%; 95% CI, 21.2%–21.6%) were assessed for cure. Conclusions Gaps remain between the delivery of HCV-related care and national treatment goals among commercially insured adults. Efforts are needed to increase HCV treatment among people diagnosed with chronic HCV infection to achieve national elimination goals.

Colorectal cancer (CRC) screening is underused in the US. Tailored message interventions have shown benefit for increasing screening uptake of mammography and Papanicolaou testing, but their role in CRC screening is less clear.To evaluate the effectiveness of a tailored message telephone intervention prior to scheduling of a screening or surveillance colonoscopy and its effect on CRC screening completion rates.This randomized clinical trial was conducted from July 2017 through August 2018 at the University of Pennsylvania Health System (UPHS), an urban academic medical center. Participants were asymptomatic patients aged 50 to 75 years who were eligible for CRC screening or surveillance, had been referred for colonoscopy, and did not have a scheduled colonoscopy appointment. Data analysis was conducted from January to September 2019.Patients underwent block randomization in a 1:1:1 ratio to 1 of 3 study arms. Participants in the usual care group were contacted via a mailed letter and instructed to call to schedule a colonoscopy. In the generic message group, participants were contacted by telephone, completed an assessment, and received a uniform, nontailored message encouraging colonoscopy scheduling. Participants in the tailored message group were contacted by telephone, completed an assessment, and received a tailored message encouraging colonoscopy scheduling based on their identified assessment cohort.The primary outcome was colonoscopy completion rate within 120 days of enrollment. The secondary outcome was colonoscopy scheduling rate appointment within 120 days of enrollment.A total of 600 participants (median [IQR] age, 56 [51-63] years; 373 women [62.2%]) were enrolled, including 200 participants randomized to usual care, 200 participants randomized to the generic message, and 200 participants randomized to the tailored message. The total sample included 12 Asian participants (2.0%), 324 Black participants (54.0%), and 227 White participants (37.8%), and 9 participants (1.5%) were of Latino or Hispanic ethnicity. Colonoscopy completion was significantly higher for both the tailored message group (69 participants [34.5%]) and the generic message group (64 participants [32.0%]) compared with the usual care group (37 participants [18.5%]) (P .001 and P = .002, respectively). Scheduling rates were also significantly higher in both groups, with 106 participants (53.0%) in the tailored message group and 105 participants (52.5%) in the generic message group scheduling appointments, compared with 54 participants (27.0%) in the usual care arm (P .001 for both).In this randomized clinical trial among individuals whose CRC screening was not up to date, both a tailored message intervention and a generic message intervention were significantly more effective at increasing colonoscopy scheduling and completion rates compared with usual care. These findings suggest that individualized health communications can increase individual motivation to obtain CRC screening.ClinicalTrials.gov Identifier: NCT03310892.

Background and Aims: Portopulmonary hypertension (POPH) was previously associated with a single-nucleotide polymorphism (SNP) rs7175922 in aromatase (cytochrome P450 family 19 subfamily A member 1 [CYP19A1]). We sought to determine whether genetic variants and metabolites in the estrogen signaling pathway are associated with POPH. Approach and Results: We performed a multicenter case-control study. POPH patients had mean pulmonary artery pressure >25 mm Hg, pulmonary vascular resistance >240 dyn-sec/cm −5, and pulmonary artery wedge pressure ≤15 mm Hg without another cause of pulmonary hypertension. Controls had advanced liver disease, right ventricular (RV) systolic pressure

BackgroundHepatopulmonary syndrome affects 10–30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation.MethodsThe Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar–arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography and absence of lung disease.ResultsWe included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-Stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median (interquartile range) 15 (12–19) versus 14 (10–17), p=0.006). Hepatopulmonary syndrome patients had significantly lower 6-min walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin 2, Tie2, tenascin C, tyrosine protein kinase Kit (c-Kit), vascular cell adhesion molecule 1 and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80, 95% CI 1.03–3.16, p=0.04), which persisted despite adjustment for covariates (hazard ratio 1.79, 95% CI 1.02–3.15, p=0.04). This association did not vary based on levels of oxygenation, reflecting the severity of hepatopulmonary syndrome.ConclusionHepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

Rationale & Objective Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. Study Design Retrospective cohort study. Setting & Participants Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. Exposure HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. Outcomes Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. Analytical Approach After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. Results Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. Limitations No data for HCV viral load or liver biopsy. Conclusions HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

Aim of the study Autoimmune hepatitis (AIH) may result in liver fibrosis and cirrhosis. While the gold standard for staging fibrosis is biopsy, transient elastography (TE) represents a non-invasive alternative. TE has been validated in several chronic liver diseases, but no data exist to establish an association between histologic fibrosis on biopsy and TE liver stiffness measurements among a United States cohort of AIH patients. Material and methods We conducted a retrospective cohort study of 53 AIH patients who received TE assessment and liver biopsy. Histologic fibrosis was classified as advanced (F3-F4) or mild/moderate (F0-F2). Liver stiffness by TE was measured in kilopascals (kPa). We performed a score test for trend to test the association between histologic fibrosis stage and increasing TE kPa categories. Analyses incorporated probe type (medium or extra-large) and body mass index (BMI). Linear regression was used to generate predicted associations between median kPa and histologic fibrosis score with the medium probe. Results The cohort was primarily female (83%) with median age 56.3 years. Increasing kPa category was associated with worsening fibrosis stage when using the medium probe (p = 0.04), but not the extra-large probe (p = 0.40). BMI, however, differed between these groups (median 25.8 vs. 33.1, respectively, p < 0.001). In adjusted linear regression, increasing median kPa corresponded well to worsening fibrosis stage (p = 0.003). Conclusions In a United States AIH cohort, increasing TE kPa measurements are associated with worsening histologic fibrosis staging. While medium probe performance was superior to the extra-large probe, significant variation in BMI between groups may explain this difference.

INTRODUCTION: Post-transplant diabetes mellitus (PTDM), an increasingly recognized complication of solid organ transplantation, is associated with increased morbidity and mortality following liver transplantation. Hepatitis C virus (HCV) infection is a consistent and modifiable risk factor for PTDM. Prior studies have demonstrated improvement in glucose metabolism following sustained virologic response (SVR). However, the effect of SVR on the incidence of PTDM has not been previously investigated in a large cohort of liver transplant (LT) recipients. METHODS: We performed a single center retrospective cohort study of LT recipients with HCV from 1/1/2010 to 6/30/2015 to compare the risk of sustained PTDM (s-PTDM) prior to and following SVR. SVR was treated as a discrete time varying exposure. s-PTDM was defined as de novo diabetes mellitus following LT of greater than 6-months duration. Univariable and multivariable Cox proportional hazards model were used to compare crude and adjusted time to s-PTDM, prior to and following SVR. RESULTS: 256 eligible LT recipients were analyzed. Median follow up was 41.2 months. Overall, 31 (12.1%) and 178 (69.5%) patients achieved SVR prior to LT and following LT respectively. During follow up, 71 (27.7%) patients developed s-PTDM. The incidence of s-PTDM was greatest in the first year after LT. After adjustment for potential confounders, SVR was associated with a significantly reduced risk of s-PTDM (HR 0.40, p=0.048). CONCLUSIONS: Eradication of HCV is independently associated with a reduced incidence of s-PTDM. This benefit appears to be most influenced by pre-LT SVR and persists throughout the post-LT period. Given the association between PTDM and post-transplant morbidity and mortality, these data provide another motivator for pre- or early post-LT treatment of HCV.

Disconnected pancreatic duct syndrome (DPDS) is a recognized complication of necrotizing pancreatitis (NP). Manifestations include recurrent peripancreatic fluid collections (R-PFC) and pancreatocutaneous fistulae (PC-Fistulae). Pancreatitis of the disconnected pancreatic segment (DPDS-P) and its relationship to new-onset diabetes after pancreatitis (NODAP) are not well characterized.We performed a retrospective cohort study of consecutive patients with NP admitted to University of California, San Francisco from January 2011 to June 2019. A diagnosis of a disconnected pancreatic duct (PD) was confirmed using computed tomography and magnetic resonance cholangiopancreatography/endoscopic retrograde cholangiopancreatography. DPDS was defined as a disconnected PD presenting with R-PFC, PC-Fistulae, or DPDS-P. The primary outcome was NODAP, defined as diabetes mellitus (DM) occurring3 months after NP. Cox proportional hazards regression was used to evaluate the relationship between DPDS and NODAP.Of 171 patients with NP in this study, the mean clinical follow-up was 46 ± 18 months and the imaging follow-up was 38 ± 20 months. Twenty-seven patients (16%) developed DPDS-P at a median of 28 months. New-onset DM occurred in 54 of the 148 patients (36%), with 22% developing DM within 3 months of NP and 14% developing NODAP at a median of 31 months after AP. DPDS-P was associated with NODAP when compared with non-DPDS patients (adjusted hazard ratio 5.63 95% confidence interval: 1.69-18.74, P = 0.005) while R-PFCs and PC-Fistulae were not.DPDS and NODAP occurred in 28% and 14% of the patients, respectively. Pancreatitis of the disconnected pancreas occurred in 16% of the patients and was associated with higher rates of NODAP when compared with patients with other manifestations of DPDS and patients without DPDS.

Most patients with hepatitis C virus (HCV) infection perceive some degree of disease-related stigma. Misunderstandings about diseases may contribute to disease-related stigma. The objective of this study was to evaluate patient-level knowledge about HCV infection transmission and natural history and its association with HCV-related stigma among HCV-infected patients. We conducted a cross-sectional survey study among 265 patients with HCV in Philadelphia using the HCV Stigma Scale and the National Health and Nutrition Examination Survey (NHANES) Hepatitis C Follow-up Survey (2001–2008). The association between HCV knowledge and HCV-related stigma was evaluated via linear regression. Overall knowledge about HCV transmission and natural history was high, with >80% of participants answering ≥9 of 11 items correctly (median number of correct responses, 9 [82%]), HCV-related knowledge was similar between HIV/HCV-coinfected and HCV-monoinfected participants (p = 0.30). A higher level of HCV-related knowledge was associated with greater perceived HCV-related stigma (β, 2.34 ([95% CI, 0.51–4.17]; p = 0.013). Results were similar after adjusting for age, race, ethnicity, HIV status, education level, stage of HCV management, time since diagnosis, and history of injection drug use. In this study, increased HCV-related knowledge was associated with greater perceptions of HCV stigma. Clinicians may consider allotting time to address common misconceptions about HCV when educating patients about HCV infection, which may counterbalance the stigmatizing impact of greater HCV-related knowledge.

PURPOSE To compare patients treated with large-volume paracentesis (LVP), transjugular intrahepatic portosystemic shunt (TIPS), and peritoneovenous shunt (PVS) for ascites. MATERIALS AND METHODS A retrospective study of 192 patients treated with LVP (94), TIPS (75), or PVS (23) was performed. Records were reviewed for patient characteristics and outcomes. The patients' age differed (LVP, 59.5 years; TIPS, 58.8 years; and PVS, 65.6 years; P = .003). Nonalcoholic steatohepatitis was the most common etiology in the PVS cohort (11/23, 47%), and hepatitis C in the TIPS (27/75, 36%), and LVP cohorts (43/94, 46%) (P = .032). The model for end-stage liver disease score was significantly different (LVP, 14; TIPS, 13; and PVS, 8; P = .035). Hepatocellular carcinoma was higher in the PVS cohort (6/23 patients, 25%) than in the TIPS (4/75, 5%), and LVP (12/94, 12%) cohorts (P = .03). RESULTS Emergency department visits and hospital readmissions were the highest in the LVP cohort (40%, ≥2 readmissions, P < .001). Patients required fewer LVPs after TIPS (1.5 to 0.14, P < .001) or PVS (2.1 to 0.5, P = .019). In an unadjusted Cox model, patients in the TIPS cohort were found to have a 58% reduction in the risk of death compared with patients in the LVP cohort (P = .003). Transplant-free survival (PVS, 44 days; TIPS, 155 days; and LVP, 213 days) differed (log rank = 0.001). CONCLUSIONS The survival in the PVS and TIPS cohorts was similar, with less healthcare utilization than the LVP cohort. PVS is a satisfactory alternative to LVP.

PURPOSE OF REVIEW: Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) are both pulmonary vascular complications of advanced liver disease; however, these syndromes have distinct pathophysiology, clinical implications, and management. RECENT FINDINGS: While both conditions are associated with portal hypertension, HPS results from diffuse pulmonary capillary vasodilation and PoPH results from vasoconstriction and vascular remodeling of pulmonary arteries. In HPS, no medical therapies clearly improve outcomes; however, patients have excellent post-LT outcomes with near uniform reversal of hypoxemia. In PoPH, several medical therapies used in idiopathic pulmonary hypertension have been shown improve pulmonary hemodynamics, symptoms, and potentially LT outcomes; however, further study is needed to determine best treatment regimens, long-term outcomes on medical therapy, and role of LT. SUMMARY: While HPS results in severe hypoxemia that is usually reversible by LT, PoPH patients develop progressive pulmonary hypertension that may improve with medical therapy.

Importance Differences in local organ supply and demand have introduced geographic inequities in the Model for End-stage Liver Disease (MELD) score–based liver allocation system, prompting national debate and patient-initiated lawsuits. No study to our knowledge has quantified the sex disparities in allocation associated with clinical vs geographic characteristics. Objective To estimate the proportion of sex disparity in wait list mortality and deceased donor liver transplant (DDLT) associated with clinical and geographic characteristics. Design, Setting, and Participants This retrospective cohort study used adult (age ≥18 years) liver-only transplant listings reported to the Organ Procurement and Transplantation Network from June 18, 2013, through March 1, 2018. Exposure Liver transplant waiting list. Main Outcomes and Measures Primary outcomes included wait list mortality and DDLT. Multivariate Cox proportional hazards regression models were constructed, and inverse odds ratio weighting was used to estimate the proportion of disparity across geographic location, MELD score, and candidate anthropometric and liver measurements. Results Among 81 357 adults wait-listed for liver transplant only, 36.1% were women (mean [SD] age, 54.7 [11.3] years; interquartile range, 49.0-63.0 years) and 63.9% were men (mean [SD] age, 55.7 [10.1] years; interquartile range, 51.0-63.0 years). Compared with men, women were 8.6% more likely to die while on the waiting list (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.04-1.18) and were 14.4% less likely to receive a DDLT (aHR, 0.86; 95% CI, 0.84-0.88). In the geographic domain, organ procurement organization was the only variable that was significantly associated with increased disparity between female sex and wait list mortality (22.1% increase; aHR, 1.22; 95% CI, 1.09-1.30); no measure of the geographic domain was associated with DDLT. Laboratory and allocation MELD scores were associated with increases in disparities in wait list mortality: 1.14 (95% CI, 1.09-1.19; 50.1% increase among women) and DDLT: 0.87 (95% CI, 0.86-0.88; 10.3% increase among women). Candidate anthropometric and liver measurements had the strongest association with disparities between men and women in wait list mortality (125.8% increase among women) and DDLT (49.0% increase among women). Conclusions and Relevance Our findings suggest that addressing geographic disparities alone may not mitigate sex-based disparities, which were associated with the inability of the MELD score to accurately estimate disease severity in women and to account for candidate anthropometric and liver measurements in this study.

Background: Patients with cirrhosis and coronary artery disease (CAD) are at high risk for morbidity during surgical revascularization so they are often referred for complex percutaneous coronary intervention (PCI). Percutaneous coronary intervention in the cirrhotic population also has inherent risks; however, quantifiable data on long-term outcomes are lacking. Methods: Patients with angiographically significant CAD and cirrhosis were identified from the catheterization lab databases of the University of Pennsylvania Health System between 2007 and 2015. Outcomes were obtained from the medical record and telephonic contact with patients/families. Results: Percutaneous coronary intervention was successfully performed in 42 patients (51 PCIs). Twenty-nine patients with significant CAD were managed medically (36 angiograms). The primary outcome (a composite of mortality, subsequent revascularization, and myocardial infarction) was not significantly different between the 2 groups during a follow-up period at 1 year (PCI: 50%, Control: 40%, P = .383). In the PCI group, a composite adverse outcome rate that included acute kidney injury (AKI), severe bleed, and peri-procedural stroke was elevated (40%), with severe bleeding occurring after 23% of PCI events and post-procedural AKI occurring after 26% of events. The medical management group had significantly fewer total matched adverse outcomes (17% vs 40% in the PCI group, P = .03), with severe bleeding occurring after 11% of events and AKI occurring after 6% of events. Increased risk of adverse events following PCI was associated with severity of liver disease by Child-Pugh class. Conclusions: Percutaneous coronary intervention in patients with cirrhosis is associated with an elevated risk of adverse events, including severe bleeding and AKI.

We investigated the prevalence of spirometric restriction in liver transplantation (LT) candidates and the clinical impacts of restriction. We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease 2 (PVCLD2) study, a multicenter prospective cohort study of patients being evaluated for LT. Patients with obstructive lung disease or missing spirometry or chest imaging were excluded. Patients with and without restriction, defined as a forced vital capacity (FVC)

Individuals with HIV infection are at elevated risk of developing end-stage renal disease. However, their outcomes after starting chronic dialysis in the contemporary era of widespread antiretroviral therapy are not well described. Using detailed data from a national dialysis provider, we determined HIV status by administrative codes and antiretroviral medication prescriptions, with hepatitis C virus (HCV) co-infection status provided by routinely measured serology. The survival on dialysis among 5348 individuals in the HIV + group and 1863 HIV + /HCV + individuals to a HIV - /HCV - reference cohort was compared. Race significantly modified the effect of HIV and HIV/HCV infection on mortality. In a multivariable model, HIV infection was not associated with an increased risk of death among Caucasians (hazard ratio 1.03, 95% confidence interval 0.91-1.16) but HIV/HCV co-infection (1.48, 1.18-1.87) was. In the same model for non-Caucasians, both HIV infection (1.44, 1.37-1.52) and HIV/HCV co-infection (1.71, 1.60-1.84) were significantly associated with higher mortality. A secondary analysis using propensity scores yielded similar results. Median follow-up for the reference group was 645 days (interquartile range 230-1323), 772 days (276-1623) for the HIV + group and 777 days (334-1665) for the co-infected group. Thus, in the contemporary era of widespread antiretroviral use, HIV infection remains associated with a significant reduction in dialysis survival for non-Caucasians while HIV/HCV co-infection is associated with impaired survival regardless of race or ethnicity. Hence, interventions to improve the care for these vulnerable populations are needed.

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.

Chronic infection with hepatitis B affects more than 240 million persons worldwide and is a major public health concern. Despite national and global initiatives to promote hepatitis B elimination, including newborn vaccination, catch-up vaccination in adolescents and high-risk adults, screening of the blood supply, and treatment of those in need, both new infections and a reservoir of chronic infections continue to result in morbidity and mortality. As with many chronic diseases, racial and ethnic disparities are seen in hepatitis B virus infection. The goal of this review is to synthesize the data concerning the burden of hepatitis B infection in African Americans and Hispanics, two racial/ethnic groups in the United States who encounter barriers in access to care, low engagement in care, and low utilization of diagnostic and treatment services. Recent data, though sparse in certain areas, continue to suggest differences in rates of incidence and prevalence of hepatitis B virus infection in African Americans, and differences in screening, specialty referral and initiation of therapy for African Americans and Hispanics. Data are lacking about differences in liver disease progression and manifestations in both African Americans and Hispanics. Disparities in hepatitis B diagnosis, disease management, treatment, and prevention remain for African Americans and Hispanics. These disparities require a commitment from governmental and public health organizations. The efforts should include increasing vaccination in those most susceptible to infection, screening those at highest risk for infection, initiating antiviral therapy in those who require it, and monitoring for liver-related complications, such as decompensated cirrhosis and hepatocellular carcinoma in the chronically infected. This multipronged approach is necessary to realize hepatitis B elimination.

Background & Aims Biliary complications occur in up to 25% of patient following liver transplantation and are often managed by endoscopic retrograde cholangiopancreatography (ERCP). Pancreatitis is the most common adverse event after ERCP (PEP). Tacrolimus and rectal indomethacin have each been reported to reduce risk of PEP. We investigated the incidence of PEP in patients who have undergone ERCP after liver transplantation and the effectiveness of tacrolimus and/or indomethacin in reducing risk of PEP. Methods We performed a retrospective study of 337 patients who underwent ERCP (n = 937 procedures) for biliary complications after liver transplantation from June 1, 2007 through December 1, 2015. After June 1, 2012, rectal indomethacin (100 mg) was routinely administered at the conclusion of the ERCP unless patients had contraindications. Indomethacin was given after 286 ERCP procedures. After excluding patients with acute/chronic rejection, 323 patients were maintained on a stable dose of tacrolimus prior to ERCP (901 procedures). We collected data on demographic and clinical variables, pre-procedural tacrolimus trough levels, and development of PEP. We calculated adjusted odds ratios (ORs) for the association between tacrolimus and indomethacin use and risk of PEP using mixed-effects multivariable logistic regression. The primary outcome was development of PEP; secondary outcomes included the development moderate-to-severe PEP, cholangitis and bleeding. Results PEP occurred after 2.2% of ERCP procedures. A trough level of tacrolimus above 2.5 ng/mL was associated with 79% lower odds of PEP (OR, 0.21; 95% CI, 0.06–0.72; P = .01). Indomethacin was associated with a 91% reduction in risk of PEP (OR, 0.09; 95% CI, 0.01–0.85; P = .03). Indomethacin use did not affect rates of bleeding or cholangitis or decrease in glomerular filtration rate. In patients with trough levels of tacrolimus above 2.5 ng/mL, addition of indomethacin reduced the odds of PEP by 93% compared with patients who were unexposed to indomethacin. (OR, 0.07; 95% CI, 0.01–0.90; P = .04). Conclusions In a retrospective study of patients who underwent ERCP for biliary complications after liver transplantation, we found trough levels of tacrolimus above 2.5 ng/mL to significantly reduce risk for PEP. Rectal administration of indomethacin after ERCP significantly decreased rates of pancreatitis, and reduced risk further in patients given tacrolimus. Administration of both drugs prevented patients from developing moderate or severe pancreatitis. Indomethacin did not worsen renal function in patients with chronic kidney disease.

Screening for hepatopulmonary syndrome (HPS) using pulse oximetry is recommended in liver transplant (LT) candidates because mortality is increased, independently of the severity of the oxygenation defect. LT exception points may be afforded to those with HPS and severe hypoxemia. We assessed the screening characteristics of pulse oximetry for HPS. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study of adults undergoing their first LT evaluation. Patients underwent protocolized assessment of oxygen saturation by pulse oximetry (SpO2 ), arterial blood gas, spirometry, and contrast-enhanced echocardiography (CE). HPS was defined as an alveolar-arterial gradient ≥15 mm Hg (≥20 mm Hg if age >64 years), intrapulmonary vascular dilatation on CE, and absence of lung disease. The study sample included 363 patients. Of these, 75 (20.7%; 95% confidence interval [CI], 16.6%-25.2%) met the criteria for HPS. The area under the receiver operating characteristic curve (or c-statistic) for SpO2 in discriminating HPS was 0.59 (95% CI, 0.51-0.66). An SpO2

Objective Low muscle mass is associated with reduced survival in HIV, possibly mediated by systemic inflammation. Viral hepatitis coinfection can induce additional inflammation and hepatic dysfunction that may exacerbate low muscle mass. We determined the prevalence of and risk factors for low muscle mass in HIV/viral hepatitis coinfection. Design and methods A cross-sectional study of participants in the Multicenter AIDS Cohort Study and Women's Interagency HIV Study with anthropometry performed after 1 January 2000. Viral hepatitis defined by positive hepatitis B virus surface antigen and/or hepatitis C virus RNA. Low muscle mass defined as less than 10th percentile of age-matched and sex-matched reference values for mid-upper arm circumference. Using multivariable logistic regression, we determined adjusted odds ratios with 95% confidence intervals (CIs) of the association of HIV/viral hepatitis coinfection with low muscle mass and factors associated with low muscle mass in coinfected persons. Analyses adjusted for age, race, BMI, alcohol use, and IDU (also, nadir CD4 cell count and HIV RNA where appropriate). Results Among 3518 participants (164 HIV/viral hepatitis, 223 viral hepatitis alone, 1070 HIV alone, and 2061 uninfected), HIV/viral hepatitis-coinfected persons had a 3.50-fold (95% CI, 1.51-8.09), 1.93-fold (1.17-3.20), and 2.65-fold (1.62-4.35) higher odds of low muscle mass than viral hepatitis-monoinfected, HIV-monoinfected, and uninfected persons, respectively. Lack of HIV RNA suppression [odds ratio, 2.26 (95% CI, 1.10-4.63)] was the only factor associated with low muscle mass in coinfected persons. Conclusion HIV/viral hepatitis-coinfected persons have a higher likelihood of low muscle mass than those with viral hepatitis monoinfection, HIV monoinfection, or neither infection. HIV viremia is an important risk factor for low muscle mass among coinfected persons.

The direct-acting antivirals (DAAs) constitute an emerging group of small molecule inhibitors that effectively treat hepatitis C virus (HCV) infection, a common comorbidity in end-stage renal disease patients. To date, there are no data to guide use of these agents in kidney transplant patients. The authors collected data from 20 consecutive kidney recipients treated with interferon-free treatment regimens for HCV at their center: 88% were infected with genotype 1; 50% had biopsy-proved advanced hepatic fibrosis on their most recent liver biopsy preceding treatment (Metavir stage 3 fibrosis [F3] or F4); and 60% had failed treatment pretransplantation with interferon-based therapy. DAA treatment was initiated a median of 888 days after renal transplantation. All patients cleared the virus while on therapy, and 100% have achieved a sustained virologic response at 12 weeks after completion of DAA therapy. The most commonly used regimen was sofosbuvir 400 mg daily in combination with simeprevir 150 mg daily. However, four different treatment approaches were used, with comparable results. The DAAs were well tolerated, and less than half of patients required calcineurin inhibitor dose adjustment during treatment. Eradication of HCV infection with DAAs is feasible after kidney transplantation with few treatment-related side effects.

Use of deceased diabetic donor kidneys has increased over recent decades. However, scarce patient and allograft survival data are available taking into account recipient diabetes status. Here we performed a retrospective cohort study using data from the United Network of Organ Sharing in patients transplanted from 1994 to 2014. Multivariable Cox regression assessed recipient outcomes of 9074 diabetic vs. 152,555 non-diabetic donor kidneys. Recipients of diabetic donor kidneys had elevated rates of all-cause allograft failure (hazard ratio 1.21, 95% confidence interval 1.16-1.26) and death (1.19, 1.13-1.24) compared to recipients of kidneys from non-diabetic donors. Younger recipients of diabetic donor kidneys had worse allograft survival than older recipients of non-diabetic donor kidneys. There was significant interaction between donor and recipient diabetes status. To minimize the effect of unmeasured confounders, we used paired analyses of recipients of mate-kidneys from the same donor, with one diabetic recipient and the other non-diabetic. Among discordant recipient pairs of diabetic donor kidneys, diabetic recipients had significantly higher risk of allograft failure (1.27, 1.05-1.53) and death (1.53, 1.22-1.93) than non-diabetic recipients. After stratifying by Kidney Donor Profile Index risk category, diabetic recipients of diabetic donor kidneys continued to have worse allograft survival compared to all other patients. Thus, risks are associated with the use of diabetic donor kidneys. Understanding these risks will enable clinicians to better educate potential recipients.Kidney International advance online publication, 21 October 2015; doi:10.1038/ki.2015.325.

Background & Aims Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy's Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. Methods We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Results Hy's Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76–0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71–0.99) and a specificity value of 0.76 (95% CI, 0.75–0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52–1.00) in the validation analysis. Conclusions Hy's Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity.

Background Stigma is an important and understudied barrier to hepatitis C virus (HCV) infection treatment and elimination. Education to dispel disease-based myths and misinformation has been identified as a key intervention point to reduce disease-related stigma; however, the association between knowledge about HCV infection and perceptions of stigma among HCV-infected patients remains unknown. Methods To address this gap and evaluate the association between patient-level HCV knowledge and HCV-related stigma, we conducted a cross-sectional study among 270 HCV-infected patients (147 [56%] HIV-coinfected) from 5 clinics across Philadelphia. HCV-related stigma was measured using the validated 33-item HCV Stigma Scale (range, 33-132). HCV-related knowledge was measured via the National Health and Nutrition Examination Survey (NHANES) Hepatitis C Follow-up Survey (2003-2008), an eleven item True/False survey (range, 0 to 11) comprising statements about HCV-related health effects and transmission. The association between HCV knowledge and HCV-related stigma was evaluated via linear regression by HIV status. Self-reported demographic, behavioral, and clinical covariates were evaluated in adjusted analyses. Results The median overall HCV knowledge score was high at 9 out of 11 points (IQR, 9-10). Median knowledge scores did not significantly differ between HIV/HCV-coinfected and HCV-monoinfected participants (10 versus 9; p=0.29). However, higher HCV knowledge scores were associated with higher HCV-related stigma score among HCV-monoinfected participants (p=0.03) but not among HCV/HIV-coinfected participants (p=0.12). Differences by HIV status were also observed when adjusting for demographic, behavioral, and clinical covariates. Conclusion Regardless of HIV status, the majority of both HIV/HCV-coinfected and HCV-monoinfected participants in this study answered questions about HCV knowledge correctly. Surprisingly, greater HCV knowledge was associated with increased HCV-related stigma among HCV-monoinfected participants, but this association was not observed among coinfected participants. Additional studies are needed to understand why this association was observed only among monoinfected persons. Disclosures M. Elle Saine, PhD, MA, Leonard Davis Institute of Health Economics Research (Grant/Research Support)

Background Despite a survival benefit from transplantation and acceptable outcomes, patients with human immunodeficiency virus (HIV+) face barriers to kidney transplantation. Little is known about the acceptance or decline of organ offers on their behalf because waitlist registry data do not include HIV serostatus. Methods We performed a retrospective cohort study using match run data from the Organ Procurement and Transplantation Network, including every kidney offer from May 1, 2007, to July 3, 2013. HIV and hepatitis C virus (HCV) serostatus were obtained by merging the match run with clinical data from a large dialysis provider. We used Cox proportional hazards modeling to evaluate differences in time to the first organ offer and to transplantation. A total of 35 646 uninfected, 2213 HCV+, 418 HIV+, and 71 HIV+/HCV+ candidates received organ offers during the study period. Results Compared to uninfected candidates, HIV+ candidates had a significantly lower likelihood of receiving a first offer (adjusted hazard ratio [aHR] 0.88, 95% confidence interval [CI] 0.79-0.99) and undergoing transplantation (aHR 0.82, 95% CI: 0.68-0.98) after receiving a first offer; HCV+ candidates had a similar likelihood of receiving a first offer (aHR 0.98, 95% CI: 0.92-1.03) and greater likelihood of transplantation after receiving a first offer (aHR 1.23, 95% CI: 1.12-1.36). Conclusions HIV+ candidates had a significantly longer wait until their first organ offer and to transplantation. Efforts to increase their access to transplantation are needed.

Cirrhosis is associated with hormonal dysregulation, as evidenced by secondary amenorrhoea in reproductive-aged women, and feminization of cirrhotic men. Whether hormone levels vary by severity of cirrhosis in women is not known. If identified, such changes may have important clinical relevance, particularly, as low sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) are known to promote metabolic and cardiovascular disease in women. In a cohort of post-menopausal women with chronic hepatitis C virus (HCV) infection, we compared comprehensive sex hormone levels by presence of cirrhosis, as well as across Child-Turcotte-Pugh (CTP) class. Results: There were n=18 cirrhotic and n=21 noncirrhotic women with a median age of 57years (interquartile range [IQR] 53-62). Compared to noncirrhotics, cirrhotic women had higher oestradiol (11.0 vs 6.0pg/mL, P=0.05) and oestrone levels (32.0 vs 8.0ng/mL, P&nbsp

Continuous-flow left ventricular assist devices (LVADs) for advanced heart failure have been associated with gastrointestinal bleeding (GIB). We examined the association between time of GIB after LVAD implantation and bleeding location (determined by endoscopy), etiology, and patient outcomes.We performed a retrospective study of consecutive patients who underwent implantation of continuous-flow LVADs from 2008 through 2015. We analyzed data on anatomic location of GIB, etiology, length of hospital stay, transfusion requirement, time to endoscopy, and readmission to the hospital within 30 days (30-day readmission).GIB developed in 59 of the 271 patients (22%). Higher proportions of patients with GIB during their index hospitalization for LVAD implantation had upper or lower GIB (86.7%) than patients with GIB during a subsequent hospitalization (50.0%; P = .013). Patients with GIB during their index hospitalization also had lower rates of middle GIB (0 vs 20.5%; P = .052), higher rates of overt GIB (100% vs 63.6%; P = .006), longer hospital stays (24 days vs 11 days; P .001), and more transfusions before endoscopy (7 units vs 4 units; P = .021) than patients with GIB during a subsequent hospitalization. There were no significant differences between groups in time to endoscopy (2 days vs 2.5 days) or 30-day readmission (6.7% vs 9.3%). Angiodysplasias were identified in 100% of patients with middle GIB compared to 48.5% of patients with upper or lower GIB (P.001) in whom a bleeding lesion was identified.In a retrospective study of patients who underwent implantation of continuous-flow LVADs, we found that timing of GIB associates with the location and severity of bleeding. Although patients with LVADs have an overall increase in risk of middle GIB, patients with GIB during their index LVAD hospitalization should undergo initial evaluation by upper endoscopy and colonoscopy, due to insufficient time for development of small bowel angiodysplasias. Patients who later develop GIB should be evaluated early for middle GI bleeding.

Summary Objectives In cystic fibrosis (CF) patients, elevations in 1 hr plasma glucose (PG1) during a 75 g oral glucose tolerance test are common, but of unclear long-term clinical relevance. Thus, we examined associations of PG1 with percent-predicted forced expiratory volume in 1 sec (FEV1% predicted), CF exacerbations, and CF related diabetes (CFRD) development. Study Design We conducted a retrospective cohort study of 80 pediatric patients with CF (43 males) followed over 5 years in a single CF center. We considered the association between elevated versus normal PG1 (greater vs. no greater than 160 mg/dl) and linear changes in FEV1% predicted over time for males and female, as well as the odds of a CF exacerbation and the odds of developing CFRD. Results No significant difference in FEV1% predicted between normal versus elevated PG1 was found at baseline, or over time in males or females. However, males with elevated PG1 tended to have worse FEV1% predicted over time than those with normal PG1 (reduction of 0.9 FEV1% predicted/year, 95%CI: −2.5, 0.6). Subjects with PG1 > 160 mg/dl were more likely to develop CFRD (OR 4.5, 95%CI: 1.7, 18.7, P = 0.04) but CF exacerbation risk was similar in both groups. Conclusion The risk of CFRD increases with PG1 > 160 mg/dl. No statistically significant evidence of an association between elevated PG1 and pulmonary function was found, yet our results do not exclude the possibility that in males, elevated PG1 may signal adverse changes in FEV1% predicted over time. This possibility requires further study with a larger sample size. Pediatr Pulmonol. Pediatr Pulmonol. 2015; 50:963–969. © 2015 Wiley Periodicals, Inc.

Purpose Identification of acute liver failure (ALF) is important for post-marketing surveillance of medications, but the validity of using ICD-9 diagnoses and laboratory data to identify these events within electronic health records is unknown. We examined positive predictive values (PPVs) of hospital ICD-9 diagnoses and laboratory tests of liver dysfunction for identifying ALF within a large, community-based integrated care organization.

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney–pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40–393 days), and persistent BK viremia was defined as lasting ≥140 days. Kaplan–Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.

Background Intrapulmonary vascular dilatations (IPVD) frequently are detected in patients with liver disease by the delayed appearance of microbubbles at contrast-enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome (HPS); however, the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease. Methods We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease 2 Study, a multicenter, prospective cohort study of patients being evaluated for liver transplant. We excluded patients with obstructive or restrictive lung disease, HPS, or intracardiac shunting. We compared patients with and those without IPVD. Results Forty-six patients with IPVD and 81 patients without IPVD were included. Patients with IPVD were more likely to have autoimmune hepatitis and less likely to have cryptogenic cirrhosis and hepatocellular carcinoma. Patients with IPVD had higher Child-Pugh scores (6 [interquartile range (IQR), 5-7] vs 5 [IQR, 4-7]; P = .04), possibly higher Model for End-Stage Liver Disease scores (14.5 [IQR, 11.6-15.8] vs 12.2 [IQR, 9.4-15.5]; P = .06), higher PaO2 levels (97.9 [IQR, 92.0-103.0] vs 89.0 [IQR, 82.0-96.9] mm Hg; P Conclusions Autoimmune hepatitis and increased liver disease severity were associated with the presence of IPVD, which was characterized by higher PaO2 levels. Future studies to better characterize IPVD pathogenesis and the relationship of IPVD to HPS are warranted.

Although tacrolimus is the basis of most maintenance immunosuppression regimens for kidney transplantation, concerns about toxicity have made alternative agents, such as belatacept, attractive to clinicians. However, limited data exist to directly compare outcomes with belatacept-based regimens to tacrolimus.We performed a propensity score matched cohort study of adult kidney transplant recipients transplanted between May 1, 2001, and December 31, 2015, using national transplant registry data to compare patient and allograft survival in patients discharged from their index hospitalization on belatacept-based versus tacrolimus-based regimens.In the primary analysis, we found that belatacept was not associated with a statistically significant difference in risk of patient death (hazard ratio, 0.84; 95% confidence interval [CI], 0.61-1.15, P = 0.28) or allograft loss (hazard ratio, 0.83; 95% CI, 0.62-1.11; P = 0.20) despite an increased risk of acute rejection in the first year posttransplant (odds ratio, 3.12; 95% CI, 2.13-4.57; P0.001). These findings were confirmed in additional sensitivity analyses that accounted for use of belatacept in combination with tacrolimus, transplant center effects, and differing approaches to matching.Belatacept appears to have similar longitudinal risk of mortality and allograft failure compared with tacrolimus-based regimens. These data are encouraging but require confirmation in prospective randomized controlled trials.

Author(s): 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; Lo Re, Vincent | 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 g200 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 g200 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.

Use of diabetic donor kidneys has been a necessary response to the donor organ shortage. Recipients of diabetic donor kidneys have higher mortality risk compared with recipients of nondiabetic donor kidneys. However, the survival benefit of transplantation with diabetic donor kidneys over remaining on the waitlist has not been previously evaluated.We performed an observational cohort study of 437,619 kidney transplant candidates from the Organ Procurement and Transplantation Network database, including 8101 recipients of diabetic donor kidneys and 126,560 recipients of nondiabetic donor kidneys. We used time-varying Cox proportional hazards modeling to assess the mortality risk of accepting a diabetic donor kidney compared with remaining on the waitlist or receiving a nondiabetic donor kidney.Among transplant recipients, median follow-up was 8.9 years and mortality rate was 35 deaths per 1000 person-years. Recipients of diabetic donor kidneys had 9% lower mortality compared with remaining on the waitlist or transplantation with a nondiabetic donor kidney (adjusted hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.98). Although recipients of nondiabetic donor kidneys with a Kidney Donor Profile Index score85% had lower mortality risk (adjusted hazard ratio, 0.86; 95% confidence interval, 0.81 to 0.91), recipients of diabetic donor kidneys with an index score85% did not show any difference (adjusted hazard ratio, 1.09; 95% confidence interval, 0.97 to 1.22). Patients aged40 years attained no survival benefit from transplantation with diabetic donor kidneys; diabetic patients at centers with long waitlist times attained the greatest survival benefit.Diabetic donor kidneys appear associated with higher mortality risk compared with nondiabetic donor kidneys, but offer greater survival benefit compared with remaining on the waitlist for many candidates. Patients with high risk of mortality on the waitlist at centers with long wait times appear to benefit most from transplantation with diabetic donor kidneys.

The landscape of therapeutic options for HCV infection has dramatically changed with the approval of all-oral direct-acting antiviral (DAA) regimens. DAAs target important steps in the HCV viral life cycle, resulting in higher response rates and fewer adverse events than were afforded with interferon and ribavirin, the prior standard of care. The achievement of sustained virologic response (SVR) rates in excess of 90% with use of DAA regimens has not only translated into HCV eradication for the hundreds of thousands treated but is also anticipated to decrease the incidence of major complications associated with chronic HCV infection. Additionally, the favorable side effect profile of DAAs has made HCV therapy feasible in difficult-to-treat populations, including those with previous exposure to interferon and ribavirin, cirrhosis, decompensated liver disease, HIV and HCV co-infection, and severe renal dysfunction/end stage renal disease. Given this tremendous progress, all patients infected with HCV infection should be treated.