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[Background and Aims] Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver‐related complications in patients with NASH cirrhosis., [Approach and Results] Patients with compensated cirrhosis due to NASH were enrolled in two placebo‐controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha‐smooth muscle actin (α‐SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis‐4 index [FIB‐4]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver‐related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow‐up of 16.6 months, 71 (6.3%) had a liver‐related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α‐SMA expression, ML‐based fibrosis parameters, LS, ELF, NFS, and FIB‐4. Cirrhosis regression observed in 16% (176/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2/176] vs. 7.2% [69/957]; HR, 0.16; 95% CI, 0.04, 0.65 [p = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α‐SMA, ML‐based fibrosis parameters, NFS, and LS were associated with an increased risk of events., [Conclusions] In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver‐related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis., This analysis was supported by Gilead Sciences, Inc., Foster City, CA, USA.

To summarize recommendations and common practices for long-term surveillance after hepatitis C cure. Patients with advanced fibrosis and cirrhosis have continued risk of the complications of portal hypertension and hepatocellular carcinoma after hepatitis C cure. While improvement in fibrosis has been noted, the clinical implications are not fully understood. Guidelines recommend no alteration in surveillance strategies based upon fibrosis measurements after hepatitis C cure. Liver wellness approaches and strategies to avoid reinfection are recommended for all patients after hepatitis C cure. Patients with early stage fibrosis after hepatitis C cure can be discharged from specialty care unless a co-existing liver disease is present, including nonalcoholic fatty liver disease. Patients with advanced fibrosis or cirrhosis are recommended to have indefinite surveillance for the complications of portal hypertension and hepatocellular carcinoma. Further investigation is needed to understand fibrosis regression and thresholds when surveillance can be discontinued.

Background Non-alcoholic fatty liver disease (NAFLD) has high morbidity and mortality related to cardiovascular disease (CVD), but statins have been historically underutilised in these patients due to concern for hepatotoxicity. Aims To characterise trends in statin use among individuals with NAFLD and to determine predictors of statin utilisation in this population. Methods Individuals with NAFLD were identified from 2005 to 2018 continuous National Health and Nutrition Examination Survey. Trends in statin use over time were assessed, and predictors of statin under-utilisation for primary prevention were identified. The roles of a known diagnosis of liver disease and disease severity were examined. Results We included 14 113 individuals; 34.6% had NAFLD, of whom 5.4% reported a liver disease diagnosis. There was a significant increase in statin use for primary prevention between 2005 and 2018 (18.1%-25.0%; P = 0.03), but guideline-indicated use for this purpose was low (54.5% between 2005 and 2012; 48.6% between 2013 and 2018). A known NAFLD diagnosis was a negative predictor of statin use during the earlier time period but not more recently. Utilisation did not decrease with increasing liver disease severity. Conclusions In a nationally representative population with NAFLD, statin use for primary prevention has increased over time, but guideline-concordant use remains low. A known liver disease diagnosis was associated with lack of statin use in the earlier time period but not more recently, suggesting a changing perspective of underlying liver disease impacting statin utilisation. Further work to improve guideline-indicated statin use in this high-risk population is needed.

The authors describe a family’s adaptive challenges and adaptive work during a family member’s treatment for Chronic Hepatitis C. We audiorecorded index and final clinical visits and interviewed participants (patients and providers) following the visits. We interviewed by telephone and reviewed medical records over the course of treatment. Transcripts were analyzed using directed content analysis. Three themes were identified: family adaptive challenges, patient-described aspects of family members’ adaptive challenges, and family adaptive work. There were four subthemes related to family adaptive work. The adaptive leadership framework for chronic illness provided direction for future family intervention.

Purpose Proton pump inhibitor (PPI) use is a potential risk factor for hepatic encephalopathy (HE), but few studies have examined the effect on post-TIPS HE. The purpose of this study was to determine whether PPIs are associated with increased rates of post-TIPS HE in an independent patient cohort. Materials and methods This single-institution retrospective study analyzed 86 patients (54 male, mean age 58.2) following TIPS from 1/1/2017 to 12/31/2019. Dates of PPI usage and episodes of new or worsening HE were recorded. Poisson regression with generalized estimating equations was used to test for association between PPI use and post-TIPS HE and to test for dose dependence. Post-TIPS HE was also analyzed using the Andersen-Gill survival model for recurrent events. Results There were 1.88 episodes of new or worsening post-TIPS HE per person-year among 35 patients on uninterrupted PPIs therapy, 1.95 on PPIs and 0.94 off PPIs among 35 patients on intermittent therapy, and 0.47 among 16 patients never on PPIs. PPI use was significantly associated with post-TIPS HE in both univariable (incidence rate ratio (IRR) = 2.62; CI = 1.41–4.84; p = 0.002) and multivariable (IRR = 2.31; CI = 1.37–3.89; p = 0.002) regression. Analysis of only those patients on PPIs showed increased rates of HE with higher doses (IRR = 1.17 per 10 mg omeprazole equivalent; CI = 1.04–1.33; p = 0.011). Recurrent events survival analysis supported the association between PPI use and HE in univariable (hazard ratio (HR) = 2.17; CI = 1.19–3.95; p = 0.011) and multivariable (HR = 1.87; CI = 1.12–3.13; p = 0.017) analysis. Conclusion In an independent patient cohort PPI use was associated with increased rates of new or worsening post-TIPS HE.

Serum alkaline phosphatase (ALP) and the enhanced liver fibrosis (ELF) score are used as endpoints in trials of patients with primary sclerosing cholangitis (PSC). We aimed to quantify inter- and intra-individual variation in levels of ALP and the ELF score over time, and evaluated their association with fibrosis progression.We analyzed data from 234 patients with large-duct PSC enrolled in a 2-year, phase 2b placebo-controlled trial of simtuzumab. Participants were assessed by laboratory tests every 4 weeks, and liver biopsies collected at time of screening, week 48, and week 96.Serum levels of ALP and ELF scores did not differ significantly between simtuzumab and placebo groups, so the data were pooled. Median per-patient variations in ALP between clinic visits were approximately 12% over 12 weeks, 20% over 48 weeks, and 20% over 96 weeks. Reductions, unrelated to study intervention, of more than 40% in ALP were observed in 10.9% of patients with baseline activity greater than 2-fold the upper limit of normal (ULN) and 12.5% of patients with more than 3-fold the ULN at 1 year. At 2 years, reductions of more than 40% in ALP were observed in 15.8% of patients with baseline activity greater than 2-fold the ULN and 17.9% of patients with more than 3-fold the ULN. Among the 209 patients with Ishak fibrosis stage 0-4 at baseline, serum ALP activity did not associate with development of cirrhosis or with a 2-point increase in fibrosis stage at 2 years. In contrast, the median per-patient variation in ELF scores between clinic visits was approximately 3% over 12 weeks, 4% over 48 weeks, and 4% over 96 weeks. Elevated ELF scores at baseline and at weeks 12, 24 and 48, each associated with development of cirrhosis at 2 years (odds ratio2.75; P.01 for all timepoints). ELF scores at baseline and weeks 12, 24 and 48, also associated with a 2-point increase in fibrosis stage at 2 years (odds ratios all greater than 2; P.01 for all timepoints).In an analysis of data from patients with large-duct PSC enrolled in a prospective trial, we found large interindividual and intraindividual variations in serum ALP activity. Serum ALP activity did not associate with disease progression over a 2-year period. Variations in ELF score were smaller, and scores determined at multiple timepoints associated with fibrosis progression and development of cirrhosis.

Alcohol consumption in the setting of chronic HCV is associated with accelerated progression towards cirrhosis, increased risk of hepatocellular carcinoma and higher mortality. This analysis contextualizes how sociodemographic factors, chronic pain and depression relate to the motivations of individuals with chronic HCV to consume alcohol. We conducted a secondary analysis of baseline data from the Hep ART trial of behavioural interventions on alcohol use among patients with HCV. Alcohol consumption was measured using the Drinking Motives Questionnaire and a novel 6-item measure of pain-related drinking motives. Statistical analyses performed included ANOVA for bivariate analyses and multivariable ordinary least-squares linear regression. At study baseline, 181 participants had an average age of 55 years; the majority (66.7%) reported beyond-minor pain; and a third (37%) met criteria for depression; drinking motives were higher for individuals with beyond-minor pain (means 9.9 vs. 4.6, p < .001) and who met criteria for depression (means 10.9 vs. 6.4, p < .001) when using the pain-related drinking motives items. Average pain(coef = 1.0410067141 < .001) was significantly associated with increased motives to drink to relieve pain in the full baseline model specification controlling for all covariates using ordinary at least squares; depression (coef = 7.06; 95% CI 1.32, 12.81; p = .016) was significantly associated with increased non-pain-related motives to drink. From baseline to 3-month follow-up, compared to participants who had mean average pain scores among the sample, motives to drink to relieve pain decreased in participants who had higher average pain scores (coef = −0.30; 95% CI −0.59, −0.01; p = .40). Physical pain and depression are associated with increased motives to consume alcohol. Patients with chronic liver disease should be screened for chronic pain and depression and, if present, referred to pain specialists or co-managed in partnership with pain specialists in hepatology clinics.

Few studies exist on the change over time in positive and negative emotions during treatment for alcoholism disorders. We aimed to evaluate relationship between alcohol reduction and change in positive and negative emotions. Chronic HCV patients (n=174) with alcohol use received brief alcohol counseling. Participants completed the PANAS-Short Form, MHC-Short Form, and the Alcohol Timeline Follow back at baseline and 3, 6, and 12 months. Decreases in alcohol use were related to decreased negative emotions from baseline to 3 months, baseline to 6 months and baseline to 12 months. Decreases in alcohol use were associated with increased positive emotions from baseline to 12 months but not sooner.

Background Patients with nonalcoholic steatohepatitis (NASH) are waitlisted at older ages than individuals with other liver diseases, but the effect of age on liver transplantation (LT) outcomes in this population and whether it differs from other etiologies is not known. We aimed to evaluate the impact of age on LT outcomes in NASH. Methods The United Network for Organ Sharing database was used to identify adults with NASH, hepatitis C virus (HCV) infection, and alcohol-related liver disease (ALD) listed for LT during 2004-2017. Patients were split into age groups (18-49, 50-54, 55-59, 60-64, 65-69, ≥70), and their outcomes were compared. Results From 2004 to 2017, 14 197 adults with NASH were waitlisted, and the proportion ≥65 increased from 15.8% to 28.9%. NASH patients ages 65-69 had an increased risk of waitlist and posttransplant mortality compared to younger groups, whereas the outcomes in ages 60-64 and 55-59 were similar. The outcomes of individuals with NASH were similar to patients of the same age group with ALD or HCV. Functional status and dialysis were predictors of posttransplant mortality in individuals ≥65 with NASH, and cardiovascular disease was the leading cause of death. Conclusions Older NASH patients (≥65) have an increased risk of waitlist and posttransplant mortality compared to younger individuals, although outcomes were similar to patients with ALD or HCV of corresponding age. These individuals should be carefully evaluated prior to LT, considering their functional status, renal function, and cardiovascular risk. Further studies are needed to optimize outcomes in this growing population of transplant candidates.

Hepatitis C virus (HCV) infection is common in the United States and leads to significant morbidity, mortality, and economic costs. Simplified screening recommendations and highly effective direct-acting antivirals for HCV present an opportunity to eliminate HCV. The objective of this study was to increase testing, linkage to care, treatment, and cure of HCV. This was an observational, prospective, population-based intervention program carried out between September 2014 and September 2018 and performed in three community health centers, three large multiclinic health care systems, and an HCV patient education and advocacy group in King County, WA. There were 232,214 patients included based on criteria of documented HCV-related diagnosis code, positive HCV laboratory test or prescription of HCV medication, and seen at least once at a participating clinical site in the prior year. Electronic health record (EHR) prompts and reports were created. Case management linked patients to care. Primary care providers received training through classroom didactics, an online curriculum, specialty clinic shadowing, and a telemedicine program. The proportion of baby boomer patients with documentation of HCV testing increased from 18% to 54% during the project period. Of 77,577 baby boomer patients screened at 87 partner clinics, 2,401 (3%) were newly identified HCV antibody positive. The number of patients staged for treatment increased by 391%, and those treated increased by 1,263%. Among the 79% of patients tested after treatment, 95% achieved sustained virologic response.

GOAL: The goal of this study was to determine the accuracy of Model of End-stage Liver Disease-Sodium (MELD-Na) in predicting 6-month mortality for patients listed for liver transplantation on the United Network of Organ Sharing (UNOS) waitlist. BACKGROUND: End-stage liver disease patients underutilize hospice services despite significant morbidity and mortality associated with advanced liver disease. A well-known barrier to hospice referral is clinician uncertainty in identifying patients with an expected survival of

Background and aims Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. Approach and results We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12. Conclusions This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.

Progression of nonalcoholic steatohepatitis (NASH) is incompletely characterized. We analyzed data on longitudinal changes in liver histology, hepatic venous pressure gradient (HVPG), and serum markers of fibrosis in 475 patients with NASH with bridging fibrosis (F3) or compensated cirrhosis (F4) enrolled in two phase 2b, placebo-controlled trials of simtuzumab. The trials were terminated after 96 weeks because of lack of efficacy, so data from treatment groups were combined. Liver biopsies and HVPG measurements (only for patients with F4 fibrosis) were collected at screening and at weeks 48 and 96. Patients were assessed for Ishak fibrosis stage, hepatic collagen content and alpha-smooth muscle actin (by morphometry), NAFLD Activity Score (NAS), and serum markers of fibrosis. Associations with progression to cirrhosis (in patients with F3 fibrosis) and liver-related clinical events (in patients with F4 fibrosis) were determined. Progression to cirrhosis occurred in 22% (48/217) of F3 patients, and liver-related clinical events occurred in 19% (50/258) of patients with cirrhosis. Factors significantly associated with progression to cirrhosis included higher baseline values of and greater increases in hepatic collagen content, level of alpha-smooth muscle actin, and Enhanced Liver Fibrosis score. Similar factors, plus lack of fibrosis stage improvement (hazard ratio, 9.30; 95% confidence interval, 1.28-67.37), higher HVPG at baseline, and greater increase in HVPG over time, were associated with an increased risk of liver-related clinical events in patients with cirrhosis. Disease progression was not associated with the NAS at baseline or changes in NAS during treatment after adjustment for fibrosis stage. Conclusion: In patients with advanced fibrosis due to NASH, the primary determinant of clinical disease progression is fibrosis and its change over time.

Healthcare workers are a vulnerable population for exposure to a variety of bloodborne pathogens including hepatitis C (HCV). With the development of novel efficacious treatments for chronic HCV, the role of post-exposure prophylaxis (PEP) has been suggested instead of the current approach to monitor for the development of infection. The lack of robust studies that HCV PEP lowers transmission risk as well as the significant financial cost limits enthusiasm for routine use of HCV PEP at this time. We support stringent monitoring protocols with prompt referral for evaluation and treatment when infection is detected. However, it is important to consider providing HCV PEP for clinicians engaged in invasive procedures who may be displaced from work for extended periods of time due to the nature of their work where they have a higher risk for transmission to additional patients.

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double-blind, placebo-controlled study, we tested the safety and efficacy of cilofexor (formerly GS-9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large-duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20), or placebo (n = 10) orally once daily for 12 weeks. All patients had serum alkaline phosphatase (ALP) > 1.67 × upper limit of normal and total bilirubin ≤ 2 mg/dL at baseline. Safety, tolerability, pharmacodynamic effects of cilofexor (serum C4 [7α-hydroxy-4-cholesten-3-one] and bile acids), and changes in liver biochemistry and serum fibrosis markers were evaluated. Overall, 52 patients were randomized (median age 43 years, 58% male, 60% with inflammatory bowel disease, 46% on ursodeoxycholic acid). Baseline median serum ALP and bilirubin were 348 U/L (interquartile range 288-439) and 0.7 mg/dL (0.5-1.0), respectively. Dose-dependent reductions in liver biochemistry were observed. At week 12, cilofexor 100 mg led to significant reductions in serum ALP (median reduction -21%; P = 0.029 versus placebo), gamma-glutamyl transferase (-30%; P < 0.001), alanine aminotransferase (ALT) (-49%; P = 0.009), and aspartate aminotransferase (-42%; P = 0.019). Cilofexor reduced serum C4 compared with placebo; reductions in bile acids were greatest with 100 mg. Relative reductions in ALP were similar between ursodeoxycholic acid-treated and untreated patients. At week 12, cilofexor-treated patients with a 25% or more relative reduction in ALP had greater reductions in serum alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, tissue inhibitor of metalloproteinase 1, C-reactive protein, and bile acids than nonresponders. Adverse events were similar between cilofexor and placebo-treated patients. Rates of grade 2 or 3 pruritus were 14% with 100 mg, 20% with 30 mg, and 40% with placebo. Conclusion: In this 12-week, randomized, placebo-controlled study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.

Although patients with cryptogenic cirrhosis have historically been considered as having "burnt-out" non-alcoholic steatohepatitis (NASH), some controversy remains. The aim of this study was to compare outcomes of patients with cryptogenic cirrhosis and NASH-related cirrhosis from a cohort with longitudinal follow-up data.Patients with cryptogenic cirrhosis or NASH cirrhosis were screened for a clinical trial. Patients with5% hepatic steatosis regardless of other histologic features were considered to have cryptogenic cirrhosis. Clinico-laboratory data and adjudicated liver-related events (e.g. decompensation, qualification for transplantation, death) were available.A total of 247 patients with cirrhosis (55.3 ± 7.4 years, 37% male) were included; 144 had NASH cirrhosis and 103 had cryptogenic cirrhosis. During a median follow-up of 29 (IQR 21-33) months (max 45 months), 20.6% of patients had liver-related clinical events. Patients with NASH cirrhosis and cryptogenic cirrhosis were of a similar age and gender, as well as having a similar body mass index, PNPLA3 rs738409 genotype, and prevalence of diabetes (p 0.05). However, patients with cryptogenic cirrhosis had higher serum fibrosis markers and greater collagen content and α-smooth muscle actin expression on liver biopsy. Compared to cirrhotic patients with NASH, patients with cryptogenic cirrhosis experienced significantly shorter mean time to liver-related clinical events (12.0 vs. 19.4 months; p = 0.001) with a hazard ratio of 1.76 (95% CI 1.02-3.06).Populations with NASH and cryptogenic cirrhosis have similar demographics, but patients with cryptogenic cirrhosis have evidence of more active fibrosis and a higher risk of liver-related clinical events. Thus, we believe these patients belong to the same spectrum of disease, with cryptogenic cirrhosis representing a more advanced stage of fibrosis.Significant liver damage and cirrhosis of the liver may develop without a known cause - a liver disease referred to as cryptogenic cirrhosis. In this work we found that, in the presence of metabolic abnormalities, cryptogenic cirrhosis may actually be a part of the non-alcoholic fatty liver disease spectrum. Yet, it appears to be more progressive than typical non-alcoholic fatty liver disease, leading to advanced liver disease at a faster rate.

Background and aimsPrimary sclerosing cholangitis (PSC) is a heterogeneous cholangiopathy characterized by progressive biliary fibrosis. RNA sequencing of liver tissue from patients with PSC (n=74) enrolled in a 96-week clinical trial was performed to identify associations between biological pathways that were independent of fibrosis and clinical events.Approach and resultsThe effect of fibrosis was subtracted from gene expression using a computational approach. The fibrosis-adjusted gene expression patterns were associated with time to first PSC-related clinical event (e.g., cholangitis, hepatic decompensation), and differential expression based on risk groups and Ingenuity Pathway Analysis were performed. Baseline demographic data were representative of PSC: median age 48years, 71% male, 49% with inflammatory bowel disease, and 44% with bridging fibrosis or cirrhosis. The first principle component (PC1) of RNA-sequencing data accounted for 18% of variance and correlated with fibrosis stage (ρ=-0.80; P0.05). The top pathways identified by Ingenuity Pathway Analysis were eukaryotic translation inhibition factor 2 (eIF2) signaling and regulation of eIF4/p70S6K signaling. Genes involved in the unfolded protein response, activating transcription factor 6 (ATF6) and eIF2, were differentially expressed between the PSC clusters (down-regulated in the high-risk group by log-fold changes of -0.18 [P=0.02] and -0.16 [P=0.02], respectively). Clinical events were enriched in the high-risk versus low-risk group (38% [12/32] vs. 2.4% [1/42], P&nbsp

The coronavirus disease 2019 (COVID-19) pandemic resulted in a rapid expansion of telehealth services in hepatology. However, known racial and socioeconomic disparities in internet access potentially translate into barriers for the use of telehealth, particularly video technology. The specific aim of this study was to determine if disparities in race or socioeconomic status exist among patients utilizing telehealth visits during COVID-19. We performed a retrospective cohort study of all adult patients evaluated in hepatology clinics at Duke University Health System. Visit attempts from a pre-COVID baseline period (January 1, 2020 through February 29, 2020; n = 3328) were compared to COVID period (April 1, 2020 through May 30, 2020; n = 3771). On multinomial regression modeling, increasing age was associated with higher odds of a phone or incomplete visit (canceled, no-show, or rescheduled after May 30,2020), and non-Hispanic Black race was associated with nearly twice the odds of completing a phone visit instead of video visit, compared to non-Hispanic White patients. Compared to private insurance, Medicaid and Medicare were associated with increased odds of completing a telephone visit, and Medicaid was associated with increased odds of incomplete visits. Being single or previously married (separated, divorced, widowed) was associated with increased odds of completing a phone compared to video visit compared to being married. Though liver telehealth has expanded during the COVID-19 pandemic, disparities in overall use and suboptimal use (phone versus video) remain for vulnerable populations including those that are older, non-Hispanic Black, or have Medicare/Medicaid health insurance.

The opioid epidemic has resulted in an increase in organ donors with hepatitis C virus (HCV) infection in the United States. With the development of direct-acting antiviral regimens that offer high sustained virologic response rates even in the setting of immunosuppression after transplantation, these HCV-viremic organs are now being offered to transplant candidates with or without preexisting HCV infection. Strategies for HCV treatment with HCV-viremic organs have included delayed and preemptive approaches. This review will discuss key studies in the different solid organ transplants, recent reports of adverse events, and ethical and regulatory considerations. The efficacy of current HCV therapies has created this important opportunity to improve survival for patients with end-organ failure through greater access to organ transplantation and decreased waitlist mortality rate.

Achieving sustained virologic response (SVR) among patients with hepatitis C virus (HCV) leads to patient reported outcome (PRO) improvement. We aimed to assess the long-term post-SVR PRO trends in HCV patients with cirrhosis.Patients with HCV and cirrhosis treated in clinical trials with direct acting antiviral agents (DAAs) who achieved SVR-12 were prospectively enrolled in a long-term registry (clinicaltrials.gov #NCT02292706). PROs were collected every 24 weeks using the Short Form-36v2 (SF-36), CLDQ-HCV, and WPAI-HCV.Pre-treatment baseline data were available for 854 cirrhotic patients who achieved SVR after DAAs. Of these, 730 had compensated (CC) and 124 had decompensated cirrhosis (DCC) before treatment- patients with DCC reported severe impairment in their PROs in comparison to CC patients (by mean -5% to -16% of a PRO range size; p.05 for 16 out of 20 studied PROs]. After achieving SVR and registry enrollment, significant PRO improvements were noted from pre-treatment levels in 11/20 domains for those with DCC (+4% to +21%) and 19/20 PRO domains in patients with CC (+3% to +17%). Patients with baseline DCC had higher rates of hepatocellular carcinoma and mortality (P.05). In patients with CC, the PRO gains persisted up to 168 weeks (3.5 years) of registry follow-up. In patients with DCC, the improvements lasted for at least 96 weeks but a declining trend after year 2.Patients with HCV cirrhosis experience severe PRO impairment at baseline with sustainable improvement after SVR. Though those with DCC experience improvement, there is a decline after 2 years.

PURPOSE To determine whether socioeconomic status (SES) is associated with hepatic encephalopathy (HE) risk after transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIALS AND METHODS This single-institution retrospective study included 368 patients (mean age = 56.7 years; n = 229 males) from 5 states who underwent TIPS creation. SES was estimated using the Agency for Healthcare Research and Quality SES index, a metric based on neighborhood housing, education, and income statistics. Episodes of new or worsening HE after TIPS creation, defined as hospitalization for HE or escalation in outpatient medical therapy, were identified from medical records. Multivariable ordinal regression, negative binomial regression, and competing risks survival analysis were used to identify factors associated with SES quartile, the number of episodes of new or worsening HE per unit time after TIPS creation, and mortality after TIPS creation, respectively. RESULTS There were 83, 113, 99, and 73 patients in the lowest, second, third, and highest SES quartiles, respectively. In multivariable regression, only older age (β = 0.04, confidence interval [CI] = 0.02-0.05; P < .001) and white, non-Hispanic ethnicity (β = 0.64, CI = 0.07-1.21; P = .03) were associated with higher SES quartile. In multivariable regression, lower SES quartile (incidence rate ratio [IRR] = 0.80, CI = 0.68-0.94; P = .004), along with older age, male sex, higher model for end-stage liver disease score, nonalcoholic steatohepatitis, and proton pump inhibitor use were associated with higher rates of HE after TIPS creation. Ethnicity was not associated with the rate of HE after TIPS creation (IRR = 0.77, CI = 0.46-1.29; P = .28). In multivariable survival analysis, neither SES quartile nor ethnicity predicted mortality after creation of a TIPS. CONCLUSION Lower SES is associated with higher rates of new or worsening HE after TIPS creation.

BACKGROUND: Patients with chronic hepatitis C and risky/harmful alcohol use experience poor outcomes. Granular data evaluating whether alcohol counseling during hepatitis C treatment impacts longitudinal alcohol consumption are lacking. AIMS: To evaluate whether provider-delivered counseling in the context of direct-acting antiviral hepatitis C treatment associates with decreased longitudinal alcohol consumption. METHODS: We performed secondary data analysis from the Hep ART study including adults with hepatitis C who underwent provider-delivered counseling during direct-acting antiviral treatment between October 2014 and September 2017. Demographics and disease characteristics were summarized. Alcohol consumption, abstinence, and heavy drinking were evaluated in periods before, during, and after direct-acting antiviral treatment. Multivariate regression analyses were performed to evaluate the association of alcohol consumption with each 12-week time period for all patients and a subsample with cirrhosis. RESULTS: One hundred twenty-three patients were included; 41 had cirrhosis. Most patients were male (74.0%) and Black (58.5%). Alcohol consumption improved during direct-acting antiviral treatment and was notably sustained (< 12 weeks before treatment 32.5 g/day; during treatment 20.0 g/day; and 12–24 weeks after treatment 23.7 g/day). Multivariable analyses showed significantly improved alcohol consumption metrics during and after antiviral treatment compared to < 12 weeks before treatment (during treatment 13.04 g/day less, p = 0.0001; > 24 weeks after treatment 15.29 g/day less, p = 0.0001). The subsample with cirrhosis showed similar results (during treatment 13.21 g/day less, p = 0.0001; > 24 weeks after treatment 7.69 g/day less, p = 0.0001). CONCLUSIONS: Patients with chronic HCV and risky/harmful alcohol use given provider-delivered alcohol-related counseling during HCV treatment sustain decreased alcohol consumption patterns during and after treatment.

BACKGROUND & AIMS: The direct-acting antiviral combination glecaprevir/pibrentasvir has been approved by the Food and Drug Administration for 8 weeks of treatment in treatment-naïve patients with hepatitis C virus (HCV) infection without cirrhosis or with compensated cirrhosis. We performed an integrated analysis of data from trials to evaluate the overall efficacy and safety of 8 weeks of glecaprevir/pibrentasvir in treatment-naïve patients without cirrhosis or with compensated cirrhosis. METHODS: We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir. RESULTS: Of 1248 patients, 343 (27%) had cirrhosis. Most patients were white (80%) and had HCV genotype 1 infection (47%) or genotype 3 infection (22%); the median age was 54 years. Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations. When we excluded patients with genotype 3 infections with compensated cirrhosis (consistent with the European label), rates of sustained virologic response at post-treatment week 12 were 97.6% in the ITT and 99.4% in the modified ITT populations. Eight virologic failures (7 in patients without cirrhosis and 1 in a patient with cirrhosis) occurred in the ITT population. Virologic failure was not associated with markers of advanced liver disease or populations of interest (current alcohol use, opioid substitution therapy, history of injection-drug use, and severe renal impairment). Treatment-emergent adverse events (AEs) occurred in 58% of patients. The most frequent AEs (>10%) were headache (12%) and fatigue (12%). Serious AEs and AEs that led to glecaprevir/pibrentasvir discontinuation were reported in 2% and less than 1% of patients, respectively. CONCLUSIONS: In a pooled analysis of data from 8 trials, we found that 8 weeks of treatment with glecaprevir/pibrentasvir is efficacious and well tolerated in treatment-naïve patients with HCV genotype 1 to 6 infections, with or without cirrhosis. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:18 issue:11 pages:2544-+ ispartof: location:United States status: published

The aim of this study is to validate a proposed definition of sarcopenia in predicting wait-list mortality. We retrospectively evaluated 355 adults (age ≥18 years) with cirrhosis listed for first-time LT from January 1, 2010, to April 1, 2018 from our center. Demographic, laboratory, and outcome data were collected in conjunction with computed tomography scans performed within 3 months of listing. Using imaging analysis software, the skeletal muscle index (SMI), which is a marker for sarcopenia-related mortality, was calculated. A survival analysis was performed to evaluate the association of the proposed sarcopenia definition of SMI

The prevalence of Hepatitis C virus (HCV) in the US incarcerated population is disproportionately high, and when inmates with infection are released back into the general population, they play a substantial role in the spread of disease. This review provides support for targeting the jail/prison population to eliminate HCV in the general population. It will also summarize various screening/treatment models to curtail the burden of disease behind and beyond bars. Transitioning from risk-based testing to opt-out testing in prisons/jails would be cost-effective through greater identification of cases and treatment to prevent complications from cirrhosis. Other innovative strategies, such as the nominal pricing mechanism or the “Netflix” DAA subscription model, have the potential to be cost-effective and to increase access to treatment. Addressing HCV in the incarcerated population is a strategy to bring the US closer to successfully eradicating the epidemic. Such findings should incentivize policymakers to implement care models that target this population.

Background & Aims Direct-acting antiviral (DAA) therapy for HCV has high efficacy and limited toxicity. We hypothesised that the efficacy of glecaprevir-pibrentasvir for chronic HCV with a simplified treatment monitoring schedule would be non-inferior to a standard treatment monitoring schedule. Methods In this open-label multicentre phase IIIb trial, treatment-naive adults with chronic HCV without cirrhosis were randomly assigned (2:1) to receive glecaprevir-pibrentasvir 300 mg–120 mg daily for 8 weeks administered with a simplified or standard monitoring strategy. Clinic visits occurred at baseline and post-treatment week 12 in the simplified arm, and at baseline, week 4, week 8, and post-treatment week 12 in the standard arm. Study nurse phone contact occurred at week 4 and week 8 in both arms. Participants requiring adherence support were not eligible, including those reporting recent injecting drug use. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12), with a non-inferiority margin of 6%. Results Overall, 380 participants (60% male, 47% genotype 1, 32% genotype 3) with chronic HCV were randomised and treated with glecaprevir-pibrentasvir in the simplified (n = 253) and standard (n = 127) arms. In the intention-to-treat population, SVR12 was 92% (95% CI 89%–95%) in the simplified and 95% (95% CI 92%–99%) in the standard arm (difference between arms −3.2%; 95% CI −8.2% to 1.8%) and did not reach non-inferiority. In the per-protocol population, SVR12 was 97% (95% CI 96%–99%) in the simplified and 98% (95% CI 96%–100%) in the standard arm. No treatment-related serious adverse events were reported. Conclusions In patients with chronic HCV infection without cirrhosis, treatment with glecaprevir-pibrentasvir was safe and effective. In comparison to standard monitoring, a simplified monitoring schedule did not achieve non-inferiority. Trial Registration: clinicaltrials.gov Identifier: NCT03117569. Lay summary Direct-acting antiviral (DAA) therapy for hepatitis C is highly effective and well tolerated. The SMART-C randomised trial evaluated an 8-week regimen of glecaprevir-pibrentasvir for hepatitis C treatment, using a simplified monitoring schedule that included no pathology tests or clinic visits during treatment. This simplified strategy produced a high cure rate (92%), but this was not equivalent to the standard monitoring schedule cure rate (95%).

Background & Aims Lysyl oxidase-like 2 contributes to fibrogenesis by catalyzing cross-linkage of collagen. We evaluated the safety and efficacy of simtuzumab, a monoclonal antibody against lysyl oxidase-like 2, in two phase 2b trials of patients with advanced fibrosis caused by nonalcoholic steatohepatitis. Methods We performed a double-blind study of 219 patients with bridging fibrosis caused by nonalcoholic steatohepatitis who were randomly assigned (1:1:1) to groups given weekly subcutaneous injections of simtuzumab (75 or 125 mg) or placebo for a planned duration of 240 weeks. We performed a separate study of 258 patients with compensated cirrhosis randomly assigned (1:1:1) to groups given intravenous infusions of simtuzumab (200 or 700 mg) or placebo every other week. The studies were performed from January 2013 through July 2014 at 80 sites in North America and Europe. Biopsy specimens were collected and analyzed at screening and at weeks 48 and 96; clinical information and serum levels of fibrosis biomarkers were collected throughout the study. The primary end point was change from baseline to week 96 in hepatic collagen content, measured by morphometry of liver specimens, in patients with bridging fibrosis; for patients with cirrhosis, the primary end point was change in hepatic venous pressure gradient from baseline to week 96. Results The 2 studies were stopped after week 96 because of lack of efficacy. All 3 groups of patients with bridging fibrosis—including those given placebo—had significant decreases in hepatic collagen content, but there was no statistically significant difference in decrease between patients receiving simtuzumab 75 mg and those receiving placebo (−0.2%, 95% confidence interval [CI] −1.3 to 1.0, P = .77) or between patients receiving simtuzumab 125 mg and those receiving placebo (−0.4%, 95% CI −1.5 to 0.8, P = .52). In patients with cirrhosis, the mean difference in hepatic venous pressure gradient between the 2 simtuzumab groups and the placebo group was 0.1 mm Hg (95% CI −1.2 to 1.5, P = .84 for 200 mg; 95% CI −1.2 to 1.4, P = .88 for 700 mg). Simtuzumab did not significantly decrease fibrosis stage, progression to cirrhosis in patients with bridging fibrosis, or liver-related clinical events in patients with cirrhosis. Rates of adverse events were similar among groups. Conclusion In two phase 2b trials of patients with bridging fibrosis or compensated cirrhosis associated with nonalcoholic steatohepatitis, simtuzumab was ineffective in decreasing hepatic collagen content or hepatic venous pressure gradient, respectively. Clinicaltrials.gov NCT01672866 and NCT01672879.

Patients with primary biliary cholangitis (PBC) who had an inadequate response to ursodiol have few treatment options. Alkaline phosphatase (ALP) and bilirubin levels correlate with the risk of liver transplant or death in PBC patients. Fibroblast growth factor (FGF) 19 is a hormone that acts directly in the liver to regulate bile acid synthesis. We evaluated NGM282, an engineered analogue of FGF19, for the treatment of PBC. In this 28-day, double-blind, placebo-controlled phase 2 trial, 45 PBC patients who had an inadequate response to ursodiol were randomly assigned 1:1:1 to receive subcutaneous daily doses of either NGM282 at 0.3 mg (n = 14), 3 mg (n = 16), or placebo (n = 15). The primary endpoint was a change in ALP from baseline after 28 days of treatment. At day 28, ALP was significantly reduced with NGM282 treatment at both 0.3 mg (least-squares mean -51.0 IU/L [standard error (SE) 15.4]) and 3 mg (-66.0 IU/L [SE 16.0]) versus placebo (3.3 IU/L [SE 14.8]), with least-squares mean differences of -54.3 IU/L (95% confidence interval -104.2 to -4.5; P = 0.0149) and -69.3 IU/L (95% confidence interval -120.5 to -18.3; P = 0.0030), respectively. Fifty percent (7 of 14) of patients receiving NGM282 0.3 mg and 46% (6 of 13) of those receiving NGM282 3mg achieved 15% or greater reduction in ALP levels from baseline, compared with 7% (1 of 15) of patients receiving placebo. NGM282 also significantly reduced serum concentrations of transaminases and immunoglobulins. Most adverse events were grade 1 (mild) to grade 2 (moderate) in severity, with gastrointestinal disorders more frequent in the NGM282 treatment groups. No worsening of pruritus was observed with NGM282 treatment. Conclusion: NGM282 administered for 28 days resulted in significant improvements in ALP and transaminase levels compared with placebo, with an acceptable safety profile in patients with PBC. (Hepatology Communications 2018; 00:000-000).

Background Direct-acting anti-virals (DAA) are highly effective for hepatitis C virus (HCV) treatment, but perceived risks of medication non-adherence may restrict access to care. Digital medicine programme (DMP) has improved adherence and outcomes for some conditions. Aims To conduct a prospective, single-arm, open-label study across the United States to assess the impact of DMP on adherence and efficacy in adults with chronic HCV infection at high risk for non-adherence. Methods Eligible participants were placed on the DMP to evaluate real-time adherence; primary outcome was sustained virological response (SVR) at ≥10 weeks post-treatment. Results Between August 2017 and April 2019, 288 participants (Medicaid, 64.9%; psychiatric disorders, 61.1%; homeless, 9.4%) received DAAs for 8-12 weeks (sofosbuvir/velpatasvir or ledipasvir, 45%; glecaprevir/pibrentasvir, 55%). SVR was achieved in 99.1% of 218 participants who had HCV RNA assessed at ≥10 weeks post-treatment; of the 70 participants who did not have SVR assessed, 17 had SVR4 with HCV RNA assessed at a median (IQR; interquartile range) 5.6 weeks (4.1, 7.9) post-treatment; one completed treatment but did not have HCV RNA assessed, and 52 discontinued treatment early without assessment. Overall, the primary analysed participants (n = 218) actively used the DMP for median (range) 92.9% (12.5%, 100%) of their prescribed treatment time, and overall pill-taking adherence was 95.0% (57.1%, 100%). Participants reported the programme was useful and easy to use through satisfaction surveys. Conclusions HCV treatment with DMP was accepted by patients and clinicians and may support HCV treatment outcomes among patients at high risk for treatment non-adherence (Clinical trials.gov NCT03164902).

Direct acting antivirals (DAA's) have revolutionized the treatment of hepatitis C (HCV). However, questions persist concerning their efficacy in minority populations.In this review, the authors review outcomes for treatment of HCV by race and ethnicity among the clinical trials that have led to the current recommended treatments for HCV. The authors highlight the efficacy and safety differences by race and ethnicity. They also highlight deficiencies within the literature including small populations of racial/ethnic minorities within HCV clinical trials. DAA's can achieve cure rates for HCV over 95% with the use of once daily medications that have minimal side effects and few significant drug-drug interactions. Regimens with high pan-genotypic efficacy have further simplified treatment paradigms. The purpose of this review is to describe the data on DAA's in treating HCV in racial/ethnic populations.While the overall data in racial/ethnic minority populations is sparse, DAA's appear to have high efficacy in curing HCV in diverse racial/ethnic populations. Although achieving high sustained virologic response (SVR) rates, there are also data that suggests that some disparities in SVR persist, especially when considering shorter regimens for HCV treatment in racial/ethnic populations.

Introduction A deficiency of glycogen debrancher enzyme in patients with glycogen storage disease type III (GSD III) manifests with hepatic, cardiac, and muscle involvement in the most common subtype (type a), or with only hepatic involvement in patients with GSD IIIb. Objective and methods To describe longitudinal biochemical, radiological, muscle strength and ambulation, liver histopathological findings, and clinical outcomes in adults (≥18 years) with glycogen storage disease type III, by a retrospective review of medical records. Results Twenty-one adults with GSD IIIa (14 F & 7 M) and four with GSD IIIb (1 F & 3 M) were included in this natural history study. At the most recent visit, the median (range) age and follow-up time were 36 (19–68) and 16 years (0–41), respectively. For the entire cohort: 40% had documented hypoglycemic episodes in adulthood; hepatomegaly and cirrhosis were the most common radiological findings; and 28% developed decompensated liver disease and portal hypertension, the latter being more prevalent in older patients. In the GSD IIIa group, muscle weakness was a major feature, noted in 89% of the GSD IIIa cohort, a third of whom depended on a wheelchair or an assistive walking device. Older individuals tended to show more severe muscle weakness and mobility limitations, compared with younger adults. Asymptomatic left ventricular hypertrophy (LVH) was the most common cardiac manifestation, present in 43%. Symptomatic cardiomyopathy and reduced ejection fraction was evident in 10%. Finally, a urinary biomarker of glycogen storage (Glc4) was significantly associated with AST, ALT and CK. Conclusion GSD III is a multisystem disorder in which a multidisciplinary approach with regular clinical, biochemical, radiological and functional (physical therapy assessment) follow-up is required. Despite dietary modification, hepatic and myopathic disease progression is evident in adults, with muscle weakness as the major cause of morbidity. Consequently, definitive therapies that address the underlying cause of the disease to correct both liver and muscle are needed.

With the recent introduction of direct acting antiviral agents for hepatitis C treatment, many patients are receiving these highly effective therapies. Patients with advanced fibrosis or cirrhosis prior to antiviral treatment will have decreased but persistent risk of hepatocellular carcinoma following cure of hepatitis C. This review will discuss this risk and review current surveillance recommendations.

There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. To characterize phenotypic variations and liver transplantation outcomes by age group in adults with PSC. The United Network for Organ Sharing database was used to identify waitlist registrations for primary liver transplantation in adults with PSC. Patients were split into three age groups: 18–39 (young), 40–59 (middle-aged), and ≥60 (older). Their clinical characteristics and outcomes on the waitlist and post-transplant were compared. Overall, 8272 adults with PSC were listed for liver transplantation during the study period, of which 28.9% were young, 52.0% were middle-aged, and 19.1% were older. The young age group had the greatest male predominance (70.0 vs. 66.2 vs. 65.1%, p = 0.001), the highest proportion of black individuals (20.0 vs. 11.0 vs. 5.5%, p

We tested an uncertainty self-management telephone intervention (SMI) with patients awaiting liver transplant and their caregivers.Participants were recruited from four transplant centers and completed questionnaires at baseline, 10, and 12 weeks from baseline (generally two and four weeks after intervention delivery, respectively). Dyads were randomized to either SMI (n=56) or liver disease education (LDE; n=59), both of which involved six weekly telephone sessions. SMI participants were taught coping skills and uncertainty management strategies while LDE participants learned about liver function and how to stay healthy. Outcomes included illness uncertainty, uncertainty management, depression, anxiety, self-efficacy, and quality of life. General linear models were used to test for group differences.No differences were found between the SMI and LDE groups for study outcomes.This trial offers insight regarding design for future interventions that may allow greater flexibility in length of delivery beyond our study's 12-week timeframe.Our study was designed for the time constraints of today's clinical practice setting. This trial is a beginning point to address the unmet needs of these patients and their caregivers as they wait for transplants that could save their lives.

Purpose To identify demographic and imaging features in magnetic resonance imaging (MRI) that are associated with upgrade of Liver Imaging Reporting and Data System (LI-RADS) category 4 (LR-4) observations to category 5 (LR-5), and to assess their effects on risk of upgrade and time to upgrade. Materials and Methods Institutional Review Board approval was obtained for this retrospective, dual-institution Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Radiologists reviewed 1.5T and 3T MRI examinations for 181 LR-4 observations in 139 patients, as well as follow-up computed tomography (CT) and MRI examinations and treatment. A stepwise multivariate Cox proportional hazards model analysis was performed to identify predictive risk factors for upgrade to LR-5, including patient demographics and LI-RADS imaging features. Overall cumulative risk of upgrade was calculated by using the Kaplan–Meier method. The cumulative risks were compared in the presence/absence of significant predictive risk factors using the log-rank test. Results The independent significant predictive risk factors in the 56 LR-4 observations that upgraded to LR-5 were mild–moderate T2 hyperintensity (P

Prisoners in the United States are disproportionately affected by hepatitis C. Addressing the disease behind bars is crucial for curtailing the epidemic in the greater population. Effective strategies for testing and treatment are elucidated here. Recommendations for changes in hepatitis C health care policy in North Carolina prisons are also described.

http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-4-reading-kapila a video presentation of this article.

Malnutrition is common in patients with cirrhosis and is associated with poor outcomes after hepatic resection and liver transplantation. Transjugular intrahepatic portosystemic shunt (TIPS) is performed for complications of cirrhosis. To assess the impact of malnutrition on TIPS outcomes. A retrospective analysis was performed using the Healthcare Cost and Utilization Project: National Inpatient Sample database for TIPS procedures from 2005 to 2014. The primary end point was in-hospital mortality. The association of specific malnutrition diagnostic codes and race–ethnicity on mortality was evaluated with survey-weighted logistic regression adjusted for age, gender, admission type, insurance payer, hospital region, comorbidities, and length of stay (LOS). From 2005 to 2014, an estimated 53,207 (95% CI 49,330–57,085) admissions with TIPS occurred. A diagnosis of malnutrition was present in 11%. In-hospital death post-TIPS occurred in 15.0% versus 10.7% (p value

Although there is substantial evidence suggesting poor health-related quality of life (HRQL) in patients with chronic hepatitis C (CHC), similar data in nonalcoholic steatohepatitis (NASH) have not been fully assessed. The aim is to compare HRQL scores in patients with CHC to those with NASH.Matched patients with advanced fibrosis (bridging fibrosis and compensated cirrhosis) due to CHC and NASH completed Short Form-36 (SF-36) questionnaire, Chronic Liver Disease Questionnaire (CLDQ), and Work Productivity and Activity Instrument questionnaire.We included 1,338 patients with NASH with advanced fibrosis (mean age 57.2 years, 47% men, 55% cirrhosis) and 1,338 matched patients with CHC. Patients with CHC and NASH had similar rates of employment and psychiatric disorders (P0.05). As expected, patients with NASH had higher body mass index (mean 33.7 vs 27.6) and more type 2 diabetes (74% vs 16%) (all P0.01). Patients with NASH had significantly lower HRQL scores related to physical health: Physical Functioning, Bodily Pain, General Health, Vitality, Physical Summary of SF-36, and Fatigue of CLDQ (P0.02). By contrast, patients with CHC had a lower Mental Health score of SF-36 and Emotional score of CLDQ and reported greater impairment in daily activities as measured by the Work Productivity and Activity Instrument questionnaire (P0.002). In multivariate analysis, after adjustment for demographic parameters, cirrhosis, and history of psychiatric disorders, having NASH was associated with lower physical HRQL scores and higher mental health-related scores (P0.05).Patients with NASH and advanced fibrosis have more impairment of their physical health-related scores than patients with CHC with advanced fibrosis. These data should dispel the misconception that NASH is an asymptomatic disease with little negative impact on patients' well-being.

N-acetylcysteine (NAC) has been well studied in the treatment of acetaminophen-induced and select non-acetaminophen-induced liver failure. However, its role in the management of sickle cell hepatic crisis resulting in acute liver failure (ALF) is unknown. We describe and discuss the novel and beneficial use of NAC in a 25-year-old man with ALF due to sickle cell hepatic crisis. We further review ALF in sickle cell disease and NAC in the treatment of non-acetaminophen-induced liver failure. Our case highlights the promising role of NAC in sickle cell-related liver injury.

Background and aims Hepatitis C virus (HCV) and alcohol use are patient risk factors for accelerated fibrosis progression, yet few randomized controlled trials have tested clinic-based alcohol interventions. Approach and results A total of 181 patients with HCV and qualifying alcohol screener scores at three liver center settings were randomly assigned to the following: (1) medical provider-delivered Screening, Brief Intervention, and Referral to Treatment (SBIRT), including motivational interviewing counseling and referral out for alcohol treatment (SBIRT-only), or (2) SBIRT plus 6 months of integrated colocated alcohol therapy (SBIRT + Alcohol Treatment). The timeline followback method was used to assess alcohol use at baseline and 3, 6, and 12 months. Coprimary outcomes were alcohol abstinence at 6 months and heavy drinking days between 6 and 12 months. Secondary outcomes included grams of alcohol consumed per week at 6 months. Mean therapy hours across 6 months were 8.8 for SBIRT-only and 10.1 for SBIRT + Alcohol Treatment participants. The proportion of participants exhibiting full alcohol abstinence increased from baseline to 3, 6, and 12 months in both treatment arms, but no significant differences were found between arms (baseline to 6 months, 7.1% to 20.5% for SBIRT-only; 4.2% to 23.3% for SBIRT + Alcohol Treatment; P = 0.70). Proportions of participants with any heavy drinking days decreased in both groups at 6 months but did not significantly differ between the SBIRT-only (87.5% to 26.7%) and SBIRT + Alcohol Treatment (85.7% to 42.1%) arms (P = 0.30). Although both arms reduced average grams of alcohol consumed per week from baseline to 6 and 12 months, between-treatment effects were not significant. Conclusions Patients with current or prior HCV infection will engage in alcohol treatment when encouraged by liver medical providers. Liver clinics should consider implementing provider-delivered SBIRT and tailored alcohol treatment referrals as part of the standard of care.

Background: Diabetes is a risk factor for advanced fibrosis due to NASH, but the effect of diabetes on disease progression is not well-characterized. Here, we describe clinical outcomes for patients with and without diabetes in two negative, randomized, placebo-controlled trials of simtuzumab. Methods: 217 patients with bridging fibrosis (F3) and 258 subjects with compensated cirrhosis (F4) were enrolled. Liver biopsies were reviewed by a central pathologist at screening and weeks 48 and 96. Patients were stratified based on the presence or absence of diabetes. Adjudicated clinical outcomes included: esophageal varices, variceal bleeding, ascites, hepatic encephalopathy, ≥2 point increase in Child-Pugh-Turcotte score, MELD >15, or death. Results: 145 (67%) of patients with F3 and 179 (69%) of patients with F4 had diabetes at baseline. Median age was 56 years. By week 96, 25% (31/129) of F3 patients with diabetes had progressed to cirrhosis, compared to 18% (11/67) of patients without diabetes [p=0.27]. Cirrhotic (F4) patients with diabetes had a higher rate of clinical events (Figure). Conclusion: Diabetes is common in patients with advanced fibrosis due to NASH and associated with numerically higher rates of progression. Larger studies are needed to confirm these findings. Patients with diabetes have a high unmet need for therapies that target advanced fibrosis due to NASH. Disclosure A.J. Sanyal: Consultant; Self; Ardelyx, Boehringer Ingelheim Pharmaceuticals, Inc., Exhalenz, Gilead Sciences, Inc., Hemoshear, Intercept Pharmaceuticals, Inc., Lilly, Mallinckrodt Pharmaceuticals, Nimbus Therapeutics, Nitto Denko, Novartis Pharmaceuticals Corporation, Pfizer Inc. Employee; Self; Sanyal Bio. Research Support; Self; Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Echosens, Galectin Therapeutics Inc., Immuron Ltd, Merck & Co., Inc., Salix Pharmaceuticals, Sequanna. Stock/Shareholder; Self; Akarna Therapeutics, GENFIT, Natural Shield, NewCo LLC, Tiziana. Other Relationship; Self; Elsevier, UpToDate. M.F. Abdelmalek: Advisory Panel; Self; Allergan, Bristol-Myers Squibb Company, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Prometic Life Sciences Inc. Consultant; Self; TaiwanJ Pharmaceuticals Co., Ltd. Research Support; Self; Akcea Therapeutics, Allergan, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Galectin Therapeutics Inc., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Prometheus, Shire, TaiwanJ Pharmaceuticals Co., Ltd. Speaker's Bureau; Self; Alexion Pharmaceuticals, Inc. S. Caldwell: Research Support; Self; Conatus Pharmaceuticals Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Halyard, Mallinckrodt Pharmaceuticals, TARGET PharmaSolutions, Vital Therapy, Zydus Pharmaceuticals, Inc. Other Relationship; Self; Dova. M.L. Shiffman: Advisory Panel; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. Research Support; Self; Allergan, Conatus, Enanta Pharmaceuticals, Inc., Exhalenz, GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Novartis AG, Shire. Speaker's Bureau; Self; Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc. R. Ghalib: None. E. Lawitz: Research Support; Self; birdrock bio, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Conatus Pharmaceuticals Inc., Durect Corporation, Enanta Pharmaceuticals, Inc., Galmed Pharmaceuticals Ltd., GENFIT, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., madrigal, Novartis AG, octeta, Zydus Cadila. D. Jiang: Employee; Self; Gilead Sciences, Inc. R.E. Aguilar Schall: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. B.J. McColgan: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. R. Myers: Employee; Self; Gilead Sciences, Inc. Stock/Shareholder; Self; Gilead Sciences, Inc. S. Djedjos: Employee; Self; Gilead Sciences, Inc. A. Muir: Advisory Panel; Self; AbbVie Inc., Gilead Sciences, Inc. Research Support; Self; AbbVie Inc., Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., NGM Biopharmaceuticals. V. Ratziu: Other Relationship; Self; Gilead Sciences, Inc. N. Afdhal: Advisory Panel; Self; Gilead Sciences, Inc., Ligand Pharmaceuticals, Inc. Consultant; Self; Echosens. Employee; Self; Spring bank Pharmaceuticals. Z. Goodman: None. J. Bosch: Advisory Panel; Self; Actelion Pharmaceuticals US, Inc., Conatus Pharmaceuticals Inc., Exhalenz. S.A. Harrison: Advisory Panel; Self; Gilead Sciences, Inc. Funding Gilead Sciences, Inc.

The causative relationship between the clearance of infections and long-term, health-related quality-of-life (HRQL) improvements in patients with hepatitis C virus (HCV) has been generally accepted. The aim of this study was to assess long-term HRQL trends in HCV patients who did not achieve sustained virologic responses (SVRs) after treatment with direct-acting antivirals.HCV patients who completed treatment in clinical trials and did not achieve SVRs were enrolled in a long-term registry (#NCT01457768). HRQL scores were prospectively collected using the short form-36 instrument (8 HRQL domains and 2 summary scores).There were 242 patients included: they had a median age of 54 years (standard deviation ± 8 years), 85% were male, and 38% had cirrhosis. Before treatment, patients' HRQL scores were similar to the general population norms (all 1-sided P0.05), but were followed by significant decreases by the end of treatment (-3.4 to -6.2 points; P.05 for 5/8 HRQL domains and mental summary). By the time subjects entered the registry, all but 1 of the mean HRQL scores had returned to their pretreatment levels (P.05). During subsequent periods in the registry, patients experienced further HRQL decrements: up to -9.2 points (P.05 for all HRQL domains) at Week 24 and up to -8.3 points (P.05 for 5/8 HRQL domains) at Week 48. Although these HRQL decrements were observed regardless of cirrhosis status, they were more pronounced in patients with cirrhosis (P.05 for 3/8 HRQL domains).Patients who did not achieve an SVR after treatment experienced worsening HRQL scores in long-term follow-ups. Retreatment of these patients will be important not only to improve their clinical outcomes, but also their quality of life.

Chronic hepatitis C virus (HCV) infection is burdensome in patients with chronic kidney disease and contributes to substantial liver-related and all-cause morbidity and mortality. HCV infection itself may cause kidney dysfunction, as exemplified through mixed cryoglobulinemic vasculitis. HCV is more prevalent in patients with significant kidney disease compared to the general population, and recent reports have shown inadvertent HCV transmission in U.S. hemodialysis centers. Further, HCV has been demonstrated to accelerate kidney dysfunction and is associated with worse clinical outcomes in patients with kidney disease. As such, the HCV-infected population with concurrent kidney disease is an important patient subgroup that warrants focused medical care and attention. With the advent of direct-acting antivirals (DAAs), the successful treatment of HCV is now a medical reality for many patients. Nuances in regimen selection and timing need to be considered when treating those with kidney dysfunction, particularly for those considering kidney transplantation.