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Severe acute alcohol-associated hepatitis that is nonresponsive to medical therapy has an extremely high mortality. Liver transplantation is a feasible treatment option and available at certain transplant centers globally. Selection criteria for liver transplantation are not, uniform but there are important key criteria shared across protocols. Of equal importance to the management of liver disease is the treatment of alcohol use disorder. A thorough assessment of candidates involves input from an addiction specialist and psychiatrist. With careful selection practices, graft and patient survival among transplant recipients with severe alcohol-associated hepatitis is similar to other etiologies of chronic liver disease.

Persistent serum alanine aminotransferase (ALT) elevation in nucleotide/nucleoside analogue (NA)-treated patients with chronic hepatitis B (CHB) has been associated with unfavorable long-term outcomes.1 It has been consistently shown that a higher proportion of patients receiving tenofovir alafenamide (TAF) achieve normal ALT in comparison with recipients of tenofovir disoproxil fumarate,2-5 the mechanism for which remains unknown.2.

The accuracy of liver biopsy to stage fibrosis due to Fontan-associated liver disease (FALD) remains unclear. We compared the results of biopsy pre-combined heart and liver transplantation (CHLT) to the results of whole liver explant. Liver biopsy and explants from 15 Fontan patients (ages 16-49, median 28 years) were retrospectively reviewed. Staging was as follows: stage 0: no fibrosis, stage 1: pericellular fibrosis, stage 2: bridging fibrosis, and stage 3: regenerative nodules. There is no stage 4. Clinical characteristics including Model of End-stage Liver Disease eXcluding INR and Varices, Ascites, Splenomegaly, and Thrombocytopenia (VAST) scores were collected, and descriptive statistics and Mann-Whitney U tests were used to analyze the data. All patients had biopsies with at least bridging fibrosis, and all had nodularity on explant; transjugular biopsy never overestimated fibrosis. Explant showed higher-grade fibrosis (stage 3) than pre-CHLT biopsy (stage 2) in 6 of 15 patients and equal grade of fibrosis (stage 3) in 9 of 15 patients. Though clinical characteristics varied significantly, VAST score was ≥2 in all but two patients. Transjugular liver biopsy does not overestimate and can underestimate fibrosis in Fontan patients undergoing CHLT, likely due to the patchy nature of fibrosis in FALD.

Liver transplantation (LT) is definitive treatment for end‐stage liver disease. This study evaluated factors predicting successful evaluation in patients transferred for urgent inpatient LT evaluation. Eighty‐two patients with cirrhosis were transferred for urgent LT evaluation from January 2016 to December 2018. Alcohol‐associated liver disease was the common etiology of liver disease (42/82). Of these 82 patients, 35 (43%) were declined for LT, 27 (33%) were wait‐listed for LT, 5 (6%) improved, and 15 (18%) died. Psychosocial factors were the most common reasons for being declined for LT (49%). Predictors for listing and receiving LT on multivariate analysis included Hispanic race (odds ratio [OR], 1.89; P = 0.003), Asian race (OR, 1.52; P = 0.02), non‐Hispanic ethnicity (OR, 1.49; P = 0.04), hyponatremia (OR, 1.38; P = 0.04), serum albumin (OR, 1.13; P = 0.01), and Model for End‐Stage Liver Disease (MELD)‐Na (OR, 1.02; P = 0.003). Public insurance (i.e., Medicaid) was a predictor of not being listed for LT on multivariate analysis (OR, 0.77; P = 0.02). Excluding patients declined for psychosocial reasons, predictors of being declined for LT on multivariate analysis included Chronic Liver Failure Consortium (CLIF‐C) score >51.5 (OR, 1.26; P = 0.03), acute‐on‐chronic liver failure (ACLF) grade 3 (OR, 1.41; P = 0.01), hepatorenal syndrome (HRS) (OR, 1.38; P = 0.01), and respiratory failure (OR, 1.51; P = 0.01). Predictors of 3‐month mortality included CLIF‐C score >51.5 (hazard ratio [HR], 2.52; P = 0.04) and intensive care unit (HR, 8.25; P

Patients with failing Fontan physiology and liver cirrhosis are being considered for combined heart and liver transplantation. We performed a retrospective review of our experience with en bloc combined heart and liver transplantation in Fontan patients > 10 years old from 2006 to 18 per Institutional Review Board approval. Six females and 3 males (median age 20.7, range 14.2-41.3 years) underwent en bloc combined heart and liver transplantation. Indications for heart transplant included ventricular dysfunction, atrioventricular valve regurgitation, arrhythmia, and/or lymphatic abnormalities. Indication for liver transplant included portal hypertension and cirrhosis. Median Fontan/single ventricular end-diastolic pressure was 18/12 mm Hg, respectively. Median Model for End-Stage Liver Disease excluding International Normalized Ratio score was 10 (7-26), eight patients had a varices, ascites, splenomegaly, thrombocytopenia score of ≥ 2, and all patients had cirrhosis. Median cardiopulmonary bypass and donor ischemic times were 262 (178-307) and 287 (227-396) minutes, respectively. Median intensive care and hospital stay were 19 (5-96) and 29 (13-197) days, respectively. Survival was 100%, and rejection was 0% at 30 days and 1 year post-transplant. En bloc combined heart and liver transplantation is an acceptable treatment in the failing Fontan patient with liver cirrhosis.

Goals We aimed to determine the incidence and predictors of recurrent hepatocellular carcinoma (HCC) after partial hepatectomy. Background Liver transplantation is the preferred treatment for selected patients with HCC, but access to donor organs is limited. Partial hepatectomy is another accepted treatment option; however, postoperative recurrence is frequently observed. Methods This is a retrospective cohort study of 107 consecutive patients who underwent partial hepatectomy for HCC between January 1993 and February 2011 at a US University Medical Center. Study endpoints were recurrent HCC, death, loss to follow-up, or last visit without HCC. Results The study cohort was 78% male with a median age of 61 years and 59% Asians. A total of 50 patients developed recurrent HCC (46.7%) after a median follow-up of 12 (1 to 69) months postresection. Recurrent HCC was significantly higher in patients with left-sided resection (41% at year 1, 54% at year 2, 62% at year 3, 81% at year 4, and 90% at year 5) compared with right-sided resection (18% at year 1, 34% at year 2, 36% at year 3, 44% at year 4, and 72% at year 5). In multivariate Cox proportional hazards model also inclusive of anatomic resection and TNM stage 3/4, left-sided resection was significantly associated with increased HCC recurrence (hazard ratio, 2.13; P=0.02; 95% confidence interval, 1.08-4.2) compared with right-sided resection. Conclusions HCC recurrence rate is higher among those undergoing left-sided resection: 54% at year 2 and 81% at year 4. Liver transplantation should be considered in patients who are at high risk for recurrence.

We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

The incidence of hepatocellular carcinoma (HCC) is higher in Asian Americans than in other ethnicities. While hepatitis B virus (HBV) is common, hepatitis C virus (HCV) is more prevalent in some subgroups. Our goal was to determine the etiology of liver disease associated with HCC in subgroups of Asian Americans. This was an analysis of 510 Asian HCC patients at a US medical center. Patients were identified using ICD9 diagnosis. Multivariate logistic regression was used to study predictors of HCV as the cause of HCC. Patients were Southeast Asian, Chinese, and Korean, with similar gender, age, and foreign-born status. Southeast Asians had a similar proportion of HBV- and HCV-related HCC, while Chinese and Korean patients had a higher proportion of HBV-related HCC. HCC was usually associated with HBV in Chinese and Korean patients, but both HCV and HBV were important associations in Southeast Asians.

Real-life data on interferon (IFN)-free direct acting antiviral (DAA) therapies for chronic hepatitis C (CHC) is limited for Asian Americans. To evaluate sustained virologic response (SVR) and adverse events (AE) in Asian Americans treated with sofosbuvir (SOF)-based, IFN-free DAA therapies. This is a retrospective study of 110 consecutive Asian Americans with HCV genotypes 1 to 3 or 6 treated with IFN-free SOF-based regimens for 8 to 24 weeks between February 2014 and March 2016 at a university center in Northern California. Mean age was 63 ± 12 years, mean BMI was 25 ± 6 (kg/m2), and about half (52%) were male. Most patients were infected with HCV genotype 1 (HCV-1, 64%), followed by HCV-2 (14%), HCV-6 (13%), and HCV-3 (8%). Half had cirrhosis, and the majority of these (67%) had decompensation. Overall SVR12 was 93% (102/110), and highest among patients without cirrhosis, liver transplant, or HCC (100%, 37/37). SVR12 was lower among patients with HCC (82%, 14/17), decompensated cirrhosis (84%, 31/37), or liver transplant (89%, 17/19), regardless of treatment and genotype. Most common AEs were anemia (25%), fatigue (20%), and headache (12%). Anemia was highest in patients receiving SOF/RBV (67%). There was 1 treatment-unrelated serious adverse effect (SAE). There were 7 dose reductions due to anemia or fatigue from RBV and 2 treatment discontinuations due to fatigue or loss of insurance authorization. This real-life cohort of Asian American CHC patients treated with IFN-free SOF-based therapies showed high overall treatment response and good tolerability, despite very high rates of advanced disease and prior treatment failure.

Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysis-dependent form a unique group, in which safety, tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation. Methods: We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy. We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience. Results: Sustained virological response (defined as undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15 (86.7%) treatment courses. Seven (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential toxicity. In 13 out of 15 treatment courses, patients completed the designated treatment duration. One patient was treated twice and developed SVR-12 with the retreatment. One patient was lost to follow-up and counted as a non-responder. Premature discontinuations were not due to DAA-related adverse effects. There were no reports of severe adverse effects or drug interactions. Conclusion: We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.

SummaryBackground Hepatitis C virus genotype 1a (HCV-1a), prior treatment, cirrhosis and post-transplant status are historically associated with poor treatment responses. The new oral direct-acting agents appear to be effective and safe in these patients. Aims To evaluate the effectiveness and tolerability of simeprevir and sofosbuvir in a diverse real-life cohort of patients, including difficult-to-treat patients. Methods We conducted a retrospective cohort study in 198 consecutive patients with hepatitis C genotype 1 (148 nontransplant, 50 post transplant), who were treated with simeprevir and sofosbuvir for 12 weeks between December 2013 and December 2014. Primary outcome was sustained virological response with undetectable HCV RNA 12 weeks after completion of therapy (SVR12). Risk factors evaluated for lack of SVR12 included HCV 1a (vs. 1b), prior treatment (vs. none), and cirrhosis (vs. no cirrhosis). Results SVR12 rates were similar in non- and post-transplant settings, 82% and 88%, respectively. There were no significant differences in adverse events in patients regardless of cirrhosis or transplant status. On multivariate analysis also inclusive of gender and liver transplant status, negative predictors of SVR12 were having at least 2 or 3 risk factors (OR 0.30, 95% CI 0.10–0.87, P = 0.027 or 0.29, 95% CI 0.09–0.85, P = 0.025, respectively). Conclusion Simeprevir and sofosbuvir combination is a safe and effective regimen for the treatment of non- and post-transplant patients with traditional risk factors for poor treatment response, unless more than 2 difficult-to-treat risk factors are present.

The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case–control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one’s lifetime. Diabetes mellitus (DM) was defined by random glucose level of ≥200 mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR = 8.5 [2.6–28.3]), male gender (OR = 3.5 [2.2–5.8]), presence of cirrhosis (OR = 2.8 [1.6–4.9]), Asian ethnicity (OR = 2.8 [1.8–4.6]), AFP > 50 (OR = 4.2 [2.6–6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR = 1.7 [1.0–2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.

Summary. Commonly known risk factors for infection with hepatitis C virus (HCV) include blood transfusion, injection drug use, intranasal cocaine use, and body tattoos. We hypothesized that Asian Americans infected with HCV may not identify with these established risk factors present in Caucasians and Hispanics, and our aim was to conduct a survey of risk factors in HCV-infected patients in these ethnic groups. In this prospective study, 494 patients infected with HCV completed a detailed risk assessment questionnaire at a liver centre in Northern California from 2001 to 2008. Among subjects participating in this study, 55% identified themselves as Caucasian, 20% as Hispanic, and 25% as Asian. Asian Americans were older, less likely to smoke or consume alcohol, and have a family history of cancer compared with Caucasians and Hispanics. The laboratory profiles were similar, and genotype 1 was the most common infection in all groups (74–75%). The great majority of Caucasians (94%) and Hispanics (86%) identified with commonly known risk factors, which was in contrast to 67% of Asians (P

A 47-year-old handyman presented to the emergency department with worsening exertional dyspnea and persistent lassitude at rest for 2 weeks. He had experienced moderate unremitting epigastric pain over the preceding months requiring narcotics, as well as intermittent jaundice and low-grade fever. His epigastric pain frequently worsened after meals, resulting in anorexia and weight loss, but also was present at rest and radiated through to his back. He denied epistaxis, hemoptysis, and gingival or gastrointestinal bleeding. Although he admitted binge drinking of alcohol in the past, without obvious social or medical complications, he had been sober for several years. He continued to chew tobacco daily. His mother reportedly had alcoholic liver disease, and his two children were healthy. Physical examination revealed a slender man with a fever of 102 F but in no obvious distress. His conjunctivae were anicteric, and his oropharynx did not reveal any lesions or bleeding. His breath sounds were normal. Cardiac examination revealed tachycardia, a 3/6 systolic ejection murmur best heard over the apex, and jugular venous distention. His abdomen was soft and not distended, but tender over the epigastrium, where a loud bruit was also present. The liver and spleen were both enlarged. No jaundice, palmar erythema, or rashes were present. The patient was fully alert and oriented, without asterixis. Comprehensive laboratory studies were significant for a normocytic anemia with a hematocrit of 35%, mild thrombocytopenia with a platelet count of 142,000/mm, and abnormal liver tests with a total bilirubin of 3.7 mg/dl, aspartate aminotransferase (AST) 43 U/l, alanine aminotransferase (ALT) 55 U/l, and alkaline phosphatase of 579 U/l. His international normalized ratio for prothrombin time (INR) was normal at 1.1. B-type natriuretic peptide was elevated at 1,067 pg/ml. Blood cultures grew Streptococcus anginosus (a member of the Streptococcus milleri family). Echocardiogram revealed moderate left ventricular enlargement with normal left ventricular systolic function, and mild right ventricular enlargement with mildly decreased right ventricular systolic function. There was trace aortic regurgitation and mild mitral regurgitation, with increased aortic flow velocity with a mean gradient of 19 mmHg. There was also mild tricuspid regurgitation with an estimated right ventricular systolic pressure of 51 mmHg. No other valvular lesions or vegetations were found. Abdominal computed tomography (CT) revealed diffuse angiomatous tissue within the liver, early opacification of all hepatic veins, and low-attenuation tissue in segment 7 of the liver likely representing biliary necrosis (Fig. 1). Abdominal magnetic resonance imaging (MRI) confirmed the diffuse heterogeneous enhancement of the liver and presence of multiple arteriovenous malformations (Fig. 2). Angiography was performed, and the initial aortogram revealed a hugely dilated celiac artery and replaced left hepatic and common hepatic arteries (Fig. 3). The proper M. Lee (&) T. J. Daugherty Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 300 Pasteur Drive, Alway Building, M211, Stanford, CA 94305-5187, USA e-mail: maxlee@stanford.edu

Orthotopic liver transplantation (OLT) for acute liver failure (ALF) during pregnancy is an uncommon occurrence with variable outcomes. In pregnancy-related liver failure, prompt diagnosis and immediate delivery are essential for a reversal of the underlying process and for maternal and fetal survival. In rare cases, the reason for ALF during pregnancy is either unknown or irreversible, and thus OLT may be necessary. This case demonstrates the development of cryptogenic ALF during the 26th week of pregnancy in a woman with sickle cell disease. She underwent successful cesarean delivery of a healthy male fetus at 27 weeks with concurrent OLT. This report provides a literature review of OLT in pregnancy and examines the common causes of ALF in the pregnant patient. On the basis of the management and outcome of our case and the literature review, we present an algorithm for the suggested management of ALF in pregnancy.

Hepatitis C is found in approximately a third of patients infected with HIV. Therapy of hepatitis C in HIV patients is very important from several view points. First, hepatitis C in the setting of immunosuppression may progress faster, although recent data show that mortality from liver disease was decreased in highly active antiretroviral therapy. HIV/hepatitis C coinfection is associated with more frequent elevation in liver tests (drug-induced liver injury) during highly active antiretroviral therapy, and in some studies, hepatitis C has been associated with lower CD4+ recoveries. The therapeutic standard of care is a combination of peginterferon and ribavirin at a fixed dose, 800 mg/day, although higher ribavirin doses may further improve virologic outcomes. In patients that do not respond virologically, maintenance therapy with peginterferon monotherapy is a potential avenue to stem the advance of liver fibrosis, although controlled data in coinfected patients are needed to issue formal recommendations.

The pathologic liver changes in chronic heart failure have been characterized mostly based on autopsy series and include sinusoidal dilation and congestion progressing to pericellular fibrosis, bridging fibrosis, and ultimately to cardiac cirrhosis or sclerosis. Liver biopsies are commonly obtained as part of the work up before heart transplantation in patients with longstanding right heart failure, particularly if ascites, abnormal liver function tests or abnormal abdominal imaging are noted as part of the pre-transplant evaluation. In these cases, the liver biopsy findings may be used to further risk stratify patients for isolated heart or combined heart and liver transplantation. Thus, it is important to be able to correlate the histologic changes with post-transplant outcomes. We report the pathologic and clinical findings in liver explants from six patients who underwent combined heart-liver transplantation. We also report preoperative liver biopsy findings from 21 patients who underwent heart transplantation without simultaneous liver transplantation. We staged the changes related to chronic passive congestion as follows: stage 0-no fibrosis; stage I-pericellular fibrosis; stage II-bridging fibrosis; and stage III-regenerative nodules. Nineteen biopsies showed fibrosis with bridging fibrosis in 13 and regenerative nodules in 6. Fifteen patients were alive at 1 year post transplant. Only three patients had a post-operative course that was characterized by signs and symptoms of chronic liver disease. Pre-transplant liver biopsies from these patients all showed at least stage II fibrosis. These patients survived for 3, 6, and 10 months after cardiac transplant. The presence of bridging fibrosis was not significantly associated with post-operative survival (P=0.336) or post-operative liver failure (P=0.257). We conclude that patients with bridging fibrosis may still be considered viable candidates for isolated heart transplantation. Because the pattern of fibrosis due to passive congestion is highly variable throughout the liver, a diagnosis of cirrhosis, which implies fibrosis and regenerative nodules throughout the liver, should be made with great caution on biopsy.

Hepatocellular carcinoma (HCC) is a leading cause of mortality worldwide. Existing studies comparing outcomes after liver transplantation (LT) versus surgical resection among transplant-eligible patients are conflicting. The purpose of this study was to compare long-term survival between consecutive transplant-eligible HCC patients treated with resection versus LT. The present retrospective matched case cohort study compares long-term survival outcomes between consecutive transplant-eligible HCC patients treated with resection versus LT using intention-to-treat (ITT) and as-treated models. Resection patients were matched to LT patients by age, sex, and etiology of HCC in a 1:2 ratio. The study included 171 patients (57 resection and 114 LT). Resection patients had greater post-treatment tumor recurrence (43.9 vs. 12.9 %, p

Summary Background Prior studies have shown that precore mutations abolish and basal core promoter (BCP) mutations down-regulate hepatitis B e antigen (HBeAg) production. Thus, the presence of precore and BCP mutations in HBeAg-positive patients indicates an infection with a mixed viral population of wild-type and precore and/or BCP mutant hepatitis B virus (HBV). To date, there has been limited study of the prevalence and clinical significance of precore and BCP mutations in patients with HBeAg-positive chronic hepatitis B. Aim To determine the prevalence, predictors and clinical characteristics of mixed wild-type and precore/BCP HBV infection, through a cross-sectional study, in a US cohort of patients with chronic hepatitis B. Methods We conducted a retrospective study of 828 chronic hepatitis B patients with HBV genotype and mutation panel testing seen at three US gastroenterology and liver clinics from June 2005 to September 2009. Results A majority of our patients (92.3%) were either Vietnamese or Chinese American. In the HBeAg-positive cohort, 17% of patients had precore mutations only, 28% had BCP mutations only and 5% had both BCP and precore mutations. On multivariate analyses, HBV genotype C, increasing age, lower HBV DNA level and an ALT quotient >2 were independent predictors for the presence of precore and/or BCP mutations. Conclusions The current distinction and management recommendations for HBeAg-positive vs. HBeAg-negative patients with chronic hepatitis B should be reassessed. Additional biomarkers and treatment endpoints should be studied for their usefulness in predicting continued viral suppression after treatment discontinuation.

Background & Aims We aimed to identify risk factors for hepatocellular carcinoma (HCC) in patients with cirrhosis in the United States. We performed a prospective study to identify associations between etiologies of cirrhosis and ethnicity with HCC incidence. Methods We used convenience sampling to select a cohort of 379 patients with cirrhosis who visited the liver clinic at the Stanford University Medical Center from 2001 to 2009 (65% male, 75% white or Hispanic, and 20% Asian). Study end points were HCC diagnosis by histology or noninvasive criteria, liver transplantation, or last screening without HCC. Patients were followed up, with ultrasound or computed tomographic imaging analyses and measurements of serum levels of α-fetoprotein, approximately every 6 months, for a median time of 34 months (range, 6–99 mo). Results The etiologies of cirrhosis in the cohort were 68% hepatitis C, 7% hepatitis B, and 25% nonviral. Forty-four patients (12%) were diagnosed with HCC during the follow-up period. Patients with cirrhosis related to viral hepatitis had a statistically significantly higher incidence of HCC than those with nonviral diseases in Kaplan–Meier analysis ( P = .04). There was no statistically significant difference in HCC incidence between Asian and non-Asian patients. In a multivariate Cox proportional hazards model that included age, sex, ethnicity, etiology, and Child–Pugh–Turcotte score, viral cirrhosis was associated significantly with HCC, compared with nonviral cirrhosis (hazard ratio, 3.6; 95% confidence interval, 1.3–10.1; P = .02) but Asian ethnicity was not. Conclusions In a diverse cohort of patients in the United States with cirrhosis, a viral etiology of cirrhosis was associated with increased incidence of HCC, but Asian ethnicity was not. These findings indicate the importance of cirrhosis etiology in determining risk for HCC.

Background: The interferon-free antiviral regimen, Sofosbuvir (SOF) and Simeprevir (SMV), is well tolerated and achieves high sustained virologic response (SVR) rates when treating patients with compensated hepatitis C genotype 1 (HCV GT1) infection. However, the safety and efficacy of a Simeprevir containing regimen in decompensated cirrhosis is unclear. Aim & Methods: We aim to report the safety, tolerability and efficacy of SOF+SMV to treat decompensated HCV GT1 cirrhosis in a single center cohort study. Results: 31 patients with decompensated HCV GT1 cirrhosis met criteria to be considered for treatment. 22 patients have received SOF+SMV to date: 55% male, 50% subtype 1a, 41% with HCV RNA >800,000 IU/mL, 68% who previously failed or did not tolerate interferon-based treatments. Additionally 82% were classified as Child-Pugh score (CPS) B cirrhosis and 18% as CPS C cirrhosis. Median MELD score was 11 (range 6 19). Complications prior to treatment include ascites (60%), hepatic encephalopathy (60%) and hepatic hydrothorax (9%). All patients had estimated GFR >30 mL/min. Patients have been followed for a median of 12 weeks (range 2 48 weeks). Of the 17 patients who completed 4 weeks of treatment, 14 (82%) achieved HCV RNA levels below the limit of quantification; and of the 14 patients who completed treatment, 12 (86%) achieved HCV RNA levels below the limit of detection (table). One patient with CPS C10 cirrhosis never achieved undetectable HCV RNA, and one patient with CPS C10 cirrhosis had treatment stopped due to severe adverse events of worsening ascites, encephalopathy and spontaneous bacterial peritonitis. To date, HCV RNA data is available post-treatment in 6 patients, of which one patient relapsed. 5 of 14 patients by end of treatment (36%) developed signs of worsening portal hypertension including: worsening ascites (2/14), worsening hepatic encephalopathy (1/14), worsening hepatic hydrothorax (1/14) and variceal bleed (1/14). Two of these patients required hospital admission. Conclusions: The interferon-free antiviral regimen SOF+SMV combination achieves virological response rate at end of treatment. However, during treatment, patients may be at risk for complications of worsening portal hypertension. Complete SVR12 data will be reported at the meeting. Virological Response Rates

comparison, a trend was found favoring SVR12 for patients with mild fibrosis over advanced fibrosis (OR 2.66, CI 0.816-8.650; p-value=0.105). Data was insufficient to allow evaluation of serious adverse events or subanalysis for outcomes of SMV+SOF with and without RBV or treatment naive and experienced patients. Conclusions: Pooled rate of SVR12 was approximately 83% in SIM+SOF±RBV based on cohort studies from real-world settings which include a large proportion of patients with advanced fibrosis and/or prior treatment failure and slightly lower than reported rated from clinical trial, suggesting the importance of examining treatment effectiveness in diverse real-world patients in addition to treatment efficacy seen in highly selected clinical trial patients. Characteristics of studies included in meta-analysis