Statewide Survey of Primary Care and Subspecialty Providers on Hepatocellular Carcinoma Risk-Stratification and Surveillance Practices.

BACKGROUND: Hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis is associated with improved survival. Provision of HCC surveillance is low in the US, particularly in primary care settings. AIMS: To evaluate current hepatitis C virus (HCV) and HCC surveillance practices and physician attitudes regarding HCC risk-stratification among primary care and subspecialty providers. METHODS: Using the Tailored Design Method, we delivered a 34-item online survey to 7654 North Carolina-licensed internal/family medicine or gastroenterology/hepatology physicians and advanced practice providers in 2022. We included the domains of HCV treatment, cirrhosis diagnosis, HCC surveillance practices, barriers to surveillance, and interest in risk-stratification tools. We performed descriptive analyses to summarize responses. Tabulations were weighted based on sampling weights accounting for non-response and inter-specialty comparisons were made using chi-squared or t test statistics. RESULTS: After exclusions, 266 responses were included in the final sample (response rate 3.8%). Most respondents (78%) diagnosed cirrhosis using imaging and a minority used non-invasive tests that were blood-based (~ 15%) or transient elastography (31%). Compared to primary care providers, subspecialists were more likely to perform HCC surveillance every 6-months (vs annual) (98% vs 35%, p < 0.0001). Most respondents (80%) believed there were strong data to support HCC surveillance, but primary care providers did not know which liver disease patients needed surveillance. Most providers (> 70%) expressed interest in potential solutions to improve HCC risk-stratification. CONCLUSIONS: In this statewide survey, there were great knowledge gaps in HCC surveillance among PCPs and most respondents expressed interest in strategies to increase appropriate HCC surveillance.

A retrospective cohort study of socioeconomic deprivation and post-liver transplant survival in adults.

The Area Deprivation Index is a granular measure of neighborhood socioeconomic deprivation. The relationship between neighborhood socioeconomic deprivation and recipient survival following liver transplantation (LT) is unclear. To investigate this, the authors performed a retrospective cohort study of adults who underwent LT at the University of Washington Medical Center from January 1, 2004, to December 31, 2020. The primary exposure was a degree of neighborhood socioeconomic deprivation as determined by the Area Deprivation Index score. The primary outcome was posttransplant recipient mortality. In a multivariable Cox proportional analysis, LT recipients from high-deprivation areas had a higher risk of mortality than those from low-deprivation areas (HR: 1.81; 95% CI: 1.03-3.18, p =0.04). Notably, the difference in mortality between area deprivation groups did not become statistically significant until 6 years after transplantation. In summary, LT recipients experiencing high socioeconomic deprivation tended to have worse posttransplant survival. Further research is needed to elucidate the extent to which neighborhood socioeconomic deprivation contributes to mortality risk and identify effective measures to improve survival in more socioeconomically disadvantaged LT recipients.

Hepatocellular carcinoma risk decreases as time accrues following hepatitis C virus eradication.

BACKGROUND: It is unclear whether the risk of hepatocellular carcinoma (HCC) decreases over time following hepatitis C virus (HCV) eradication. AIM: To determine if patients who have accrued longer time since sustained virologic response (SVR) have a lower risk of HCC than those with less time since SVR METHODS: We conducted a retrospective cohort study of all HCV-infected Veterans Affairs patients who achieved SVR before 1 January 2018 and remained alive without a diagnosis of HCC as of 1 January 2019 (n = 75,965). We ascertained their baseline characteristics as of 1 January 2019 (time zero), including time accrued since SVR and followed them for the subsequent 12 months for incident HCC. We used multivariable Cox proportional hazards regression to determine the association between time since SVR and HCC risk after adjusting for age, race/ethnicity, sex, diabetes, hypertension, body mass index, alcohol use, Charlson Comorbidity Index, Fibrosis-4 score, HCV genotype, hepatitis B virus co-infection and HIV co-infection. RESULTS: 96.0% were male; mean age was 64.6 years. Among those with cirrhosis (n = 19,678, 25.9%), compared to patients who had accrued only ≥1 to 2 years since SVR (HCC incidence 2.71/100 person-years), those who had accrued >2 to 4 years (2.11/100 person-years, aHR 0.80, 95% CI 0.63-1.01) and >4 to 6 years (1.65/100 person-years, aHR 0.61, 95% CI 0.41-0.90) had progressively lower HCC risk. However, HCC risk appeared to plateau for those with >6 years since SVR (1.68/100 person-years, aHR 0.70, 95% CI 0.46-1.07). Among those without cirrhosis, HCC risk was 0.23-0.27/100 person-years without a significant association between time since SVR and HCC risk. CONCLUSIONS: Among patients with cirrhosis and cured HCV infection, HCC risk declined progressively up to 6 years post-SVR-although it remained well above thresholds that warrant screening. This suggests that time since SVR can inform HCC surveillance strategies in patients with cured HCV infection and can be incorporated into HCC risk prediction models.

Extended-release Naltrexone Is Not Linked to Hepatotoxicity in Adults Experiencing Homelessness and Alcohol Use Disorder.

OBJECTIVES: The use of extended-release naltrexone (XR-NTX) as treatment for alcohol use disorder (AUD) has been limited by a prior black box warning for hepatotoxicity. We performed a secondary analysis of data from a randomized clinical trial to compare serum liver enzyme levels for those randomized to XR-NTX versus placebo. METHODS: The parent study aimed to test the efficacy of combined pharmacobehavioral harm-reduction treatment in improving alcohol and quality-of-life outcomes for adults experiencing homelessness and AUD. We compared the 2 arms that received intramuscular injections of either 380 mg XR-NTX (n = 74) or placebo (n = 77). Outcomes included ( a ) liver enzyme levels and ( b ) liver enzyme values categorized as normal (<1× upper limit of normal [ULN]), elevated (1-3× ULN), or high (>3× ULN). We performed multinomial logistic regression and negative binomial generalized estimating equations modeling to assess the effects of treatment group and the time × treatment group interaction on liver enzyme outcomes. RESULTS: The mean age was 47.9 ± 9.9 years, and the mean baseline alcohol consumption was 23.2 ± 14.0 drinks per day. There were no significant differences in the development of liver enzyme elevations 1 to 3× ULN or more than 3× ULN (all P s > 0.25) or in the change in liver enzyme values (all P s > 0.41) between the placebo and the XR-NTX groups over the treatment course. CONCLUSIONS: In our study of adults experiencing homelessness and AUD, receipt of XR-NTX was not associated with hepatotoxicity. These findings support the use of XR-NTX to treat AUD even in patients who are drinking heavily and physiologically dependent on alcohol.

Addressing racial and ethnic disparities in US liver cancer care.

HCC, the most common form of primary liver cancer, is the fastest rising cause of cancer-related death in the United States. HCC disproportionately affects racial and ethnic minorities in the United States. A practical framework is needed to organize the complex patient, provider, health system, and societal factors that drive these racial and ethnic disparities. In this narrative review, we adapted and applied the National Institute on Minority Health and Health Disparities (NIMHD) Research Framework to the HCC care continuum, as a step toward better understanding and addressing existing HCC-related disparities. We first summarize the literature on HCC-related disparities by race and ethnicity organized by the framework's 5 domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) and 4 levels (individual, interpersonal, community, and societal) of influence. We then offer strategies to guide future research initiatives toward promotion of health equity in HCC care. Clinicians and researchers may help mitigate further inequities and better address racial and ethnic disparities in HCC care by prioritizing the following in HCC research: (1) increasing racial and ethnic minority representation, (2) collecting and reporting HCC-related data by racial and ethnic subgroups, (3) assessing the patient experience of HCC care by race and ethnicity, and (4) evaluating HCC-specific social determinants of health by race and ethnicity. These 4 priorities will help inform the development of future programs and interventions that are tailored to the unique experiences of each racial and ethnic group.

Associations of Race and Ethnicity with Hepatocellular Carcinoma, Decompensation, and Mortality in US Veterans with Cirrhosis.

BACKGROUND: Among patients with cirrhosis, it remains unclear whether there are racial/ethnic differences in cirrhosis complications and mortality. We examined the associations between race/ethnicity and risk for hepatocellular carcinoma (HCC), cirrhosis decompensation, and all-cause mortality overall and by cirrhosis etiology. METHODS: US Veterans diagnosed with cirrhosis from 2001 to 2014 (n = 120,992), due to hepatitis C virus (HCV; n = 55,814), alcohol-associated liver disease (ALD; n = 36,323), hepatitis B virus (HBV; n = 1,972), nonalcoholic fatty liver disease (NAFLD; n = 17,789), or other (n = 9,094), were followed through 2020 for incident HCC (n = 10,242), cirrhosis decompensation (n = 27,887), and mortality (n = 81,441). Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Compared with non-Hispanic White patients, Hispanic patients had higher risk for HCC overall (aHR, 1.32; 95% CI, 1.24-1.41) and by cirrhosis etiology, particularly for ALD- (aHR, 1.63; 95% CI, 1.42-1.87) and NAFLD-cirrhosis (aHR, 1.76; 95% CI, 1.41-2.20), whereas non-Hispanic Black patients had lower HCC risk in ALD- (aHR, 0.79; 95% CI, 0.63-0.98) and NAFLD-cirrhosis (aHR, 0.54; 95% CI, 0.33-0.89). Asian patients had higher HCC risk (aHR, 1.70; 95% CI, 1.29-2.23), driven by HCV- and HBV-cirrhosis. Non-Hispanic Black patients had lower risk for cirrhosis decompensation overall (aHR, 0.71; 95% CI, 0.68-0.74) and by cirrhosis etiology. There was lower risk for mortality among all other racial/ethnic groups compared with non-Hispanic White patients. CONCLUSIONS: Race/ethnicity is an important predictor for risk of developing HCC, decompensation, and mortality. IMPACT: Future research should examine factors underlying these racial/ethnic differences to inform prevention, screening, and treatment for patients with cirrhosis.

Evaluating a Novel, Portable, Self-Administrable Device ("Beacon") That Measures Critical Flicker Frequency as a Test for Hepatic Encephalopathy.

INTRODUCTION: We compared critical flicker frequency (CFF) thresholds obtained using a novel portable device "Beacon" with thresholds from the commercially available Lafayette Flicker Fusion System (Lafayette-FFS) in patients with cirrhosis. METHODS: One hundred fifty-three participants with chronic liver disease underwent CFF testing using Beacon and Lafayette-FFS with a method-of-limits and/or forced-choice protocol. RESULTS: Beacon demonstrated excellent test-retest reliability (intraclass correlation 0.91-0.97) and good correlation with the Lafayette-FFS values (intraclass correlation 0.77-0.84). Forced-choice CFF were on average 4.1 Hz higher than method-of-limits descending CFFs. DISCUSSION: Beacon can be self-administered by patients with chronic liver disease and cirrhosis to measure CFF, a validated screening test for minimal hepatic encephalopathy.

Increasing Proportion of High-risk Cytomegalovirus Donor-positive/Recipient-negative Serostatus in Solid Organ Transplant Recipients.

BACKGROUND: Cytomegalovirus (CMV) donor-positive/recipient-negative (D+R-) serostatus is independently associated with worse allograft and patient survival across solid organ transplant (SOT) types. We characterized trends in CMV D+R- serostatus among adult SOT recipients performed in the United States. METHODS: Donor (D) and recipient (R) CMV serostatus and demographic factors were obtained from the Scientific Registry of Transplant Recipients for persons ≥18 y undergoing a first SOT between January 1, 2000, and December 31, 2020. The proportions of D+R- SOTs over time were assessed using Chi square for trend and modeled through 2040. Factors associated with D/R seropositivity were assessed using logistic models. RESULTS: Among 472 549 SOTs, the average proportion of D+R- SOTs increased significantly among kidney, liver, heart, and lung between 2000 to 2009 and 2010 to 2020: 18.0% to 18.3% ( P = 0.034), 19.4% to 21.8% ( P < 0.001), 22.2% to 25.5% ( P < 0.001), and 23.6% to 27.0% ( P < 0.001), respectively. The increased proportion over time resulted from a disproportionate increase in R- (34.9% to 37.0% for all organ types, P < 0.001) and a smaller corresponding change in D+ (60.8% to 60.3%, P < 0.001). CONCLUSIONS: The proportion of high-risk CMV D+R- SOTs increased significantly across all organs and is projected to continue to increase. These findings inform population-level strategies to mitigate the negative impact of CMV D+R- in SOT.

Use and outcomes of hepatitis B virus-positive grafts in orthotopic liver transplantation in the United States from 1999 to 2021.

The demand for orthotopic liver transplantation (OLT) is projected to increase, which indicates a need to expand the liver donor pool. We aimed to investigate the use of hepatitis B virus (HBV)-positive grafts and the outcomes of recipients undergoing OLT with HBV-positive grafts. We conducted a retrospective cohort study analyzing all deceased donors and OLT recipients in the Organ Procurement and Transplantation Network database from January 1999 through March 2021. Donor HBV status was positive if hepatitis B surface antigen was positive or HBV nucleic acid testing was detectable. Recipients of HBV-positive allografts were matched 1:5 to recipients of HBV-negative allografts based on recipient and donor age, transplant year, recipient sex, donation after circulatory death, recipient location, and Model for End-Stage Liver Disease score at transplant. Among the 185,212 potential donors, 422 (0.2%) were HBV positive, and 265 (63%) of the HBV-positive grafts were transplanted (14 of 265 [5.3%] in HBV-positive recipients). The overall discard rate for HBV-positive donors of 37.2% (157/422) remained significantly higher than the discard rate for HBV-negative donors of 26.5% (49,026/185,212) during the study period ( p < 0.001). Recipients of HBV-positive ( n = 209) grafts had similar mortality (log-rank, p = 0.47) and graft loss (log-rank, p = 0.72) rates to the matched recipients of HBV-negative allografts ( n = 1045). The 3-year graft survival rate was 77.9% for the HBV-positive group and 79.7% in the matched HBV-negative group. Based on this analysis, transplant recipients of HBV-positive liver allografts do not experience increased rates of mortality or graft loss. One strategy that may help expand the donor pool and lower the waitlist mortality rate is using HBV-positive allografts.

Renal Outcomes With Tenofovir Alafenamide in Liver Transplant Recipients.

Tenofovir disoproxil fumarate (TDF) is associated with a higher risk of nephrotoxicity compared with entecavir (ETV) or tenofovir alafenamide (TAF).1,2 One-fifth of transplant recipients develop chronic kidney disease (CKD) within 5 years after transplantation, contributed by the use of nephrotoxic immunosuppressive medications.3 Prior studies conducted in the nontransplant setting reported superior renal safety in TAF compared with TDF but data in liver transplant (LT) recipients have so far been limited to small case series.1,4-6 Therefore, the goals of this study were to examine changes in renal function in a large multicenter cohort of LT recipients with chronic hepatitis B who were treated with TAF, TDF, or ETV for the prevention of hepatitis B virus (HBV) reinfection or reactivation from receipt of a positive HBV core antibody graft.

Fibrosis Stage-specific Incidence of Hepatocellular Cancer After Hepatitis C Cure With Direct-acting Antivirals: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Hepatitis C virus (HCV) eradication with direct-acting antivirals reduces hepatocellular carcinoma (HCC) risk. Pooled HCC incidence rates by cirrhosis status and fibrosis stage have not been estimated using meta-analysis. METHODS: We searched PubMed, Web of Science, Embase, and Cochrane Library from January 1, 2014 to December 31, 2020 to identify studies assessing HCC incidence or outcomes by cirrhosis status, in adults with HCV who achieved sustained virologic response (SVR) after direct-acting antivirals. Pooled estimates were obtained using random-effects modeling. Subgroup, sensitivity, and meta-regression analyses were performed to evaluate heterogeneity. RESULTS: We included 31 studies involving 27,711 patients with cirrhosis (mean follow-up, 2.1 years) and 11 studies involving 32,123 patients without cirrhosis (mean follow-up, 2.6 years). HCC incidence was 2.99/100 person-years (95% confidence interval [CI], 2.52-3.54; I2 = 75%) in patients with cirrhosis, 0.47/100 person-years (95% CI, 0.32-0.70, I2 = 71%) in patients without cirrhosis, and 0.63/100 person-years (95% CI: 0.34-1.20, I2 = 0%) in stage 3 (F3) fibrosis. Among patients with cirrhosis, HCC incidence was highest in studies with <1 year of follow-up (6.17/100 person-years [95% CI, 3.73-10.19]) and progressively lower in studies with longer follow-up (1-2 years: 2.75/100 person-years [95% CI, 2.48-3.06]; 2-3 years: 2.90/100 person-years [95% CI, 1.90-4.44]; ≥3 years: 1.83/100 person-years [95% CI, 0.88-3.80]). CONCLUSION: Pooled HCC incidence after SVR in patients with cirrhosis was very high (2.99/100 person-years) but may be declining as longer time accrues after SVR. In patients without cirrhosis, including F3 fibrosis, HCC incidence was lower than thresholds associated with cost-effective HCC screening. In patients with F3 fibrosis, the lack of between-study heterogeneity provides strong evidence that HCC screening may not be warranted.

Combining FIB-4 and Liver Stiffness Into the FIB-5, a Single Model that Accurately Predicts Complications of Portal Hypertension.

INTRODUCTION: We aimed to combine the fibrosis (FIB)-4 score and fibroscan-derived liver stiffness (LS) into a single score (FIB-5) that predicts incident complications of portal hypertension (PH) in persons with compensated liver disease. METHODS: In this retrospective cohort study, we identified 5849 US veterans who underwent LS measurement from May 01, 2014 to June 30, 2019, and laboratory tests enabling FIB-4 calculation within 6 months of LS measurement. Patients were followed up from the LS measurement date until February 05, 2020, for incident complications of PH. We combined LS values and the individual components of the FIB-4 score (i.e. age, aspartate aminotransferase, alanine aminotransferase, and platelet count) using multivariable Cox proportional hazards modeling and the machine learning algorithm eXtreme gradient boosting to develop the C-FIB-5 and X-FIB-5 models, respectively. Models were internally validated using optimism-corrected measures. RESULTS: Among 5,849 patients, the mean age was 62.8 years, 95.9% were men, and the mean follow-up time was 2.14 ± 1.21 years. Within 3 years after LS measurement date, 116 (2.0%) patients developed complications of PH. The X-FIB-5 (area under the receiver operating characteristic [AUROC] 0.845) and C-FIB-5 scores (AUROC 0.868) demonstrated superior discrimination over LS (AUROC 0.688) and FIB-4 (AUROC 0.672) for predicting incident complications of PH. Both the X-FIB-5 and C-FIB-5 models demonstrated higher classification accuracy across all sensitivity cutoffs when compared with LS or FIB-4 alone. DISCUSSION: We combined LS and the individual components of the FIB-4 into a single scoring system (FIB-5, www.fib5.net ), which can help identify patients with compensated liver disease at risk of developing complications of PH.

Adult-to-adult living donor liver transplantation in acute liver failure.

BACKGROUND: Living Donor Liver Transplantation(LDLT) in acute liver failure(ALF) patients has been limited by concerns regarding donor safety, consent process and recipient outcomes. Our objective was to conduct a systematic review(SR) and meta-analysis to address the concerns about subpar LDLT outcomes in patients with ALF. METHODS: We retrieved a total of 5965 literature references in our SR. United Network for Organ Sharing (UNOS) database was queried for patients over the age of 18, who underwent LDLT for "status 1" or "status 1A" listing. RESULTS: Of 427 articles reviewed, 3 studies comprising 2574 patients (192 underwent LDLT and 2382 DDLT), were included in the meta-analysis. One, 3,5-year patient and graft survival demonstrated no difference between LDLT and DDLT group: 1-year patient survival OR1.51; 95%CI [0.58,1.90]; 1-year graft survival OR 1.19; 95%CI [0.65-2.18]; 3-year patient survival OR 0.97;95%CI [0.52-1.88]; 3-year graft survival OR 1.21 95%CI [0.67-2.16]; 5-year patient survival 0.9; 95%CI [0.37-2.20]; 5-year graft survival OR 1.30; 95%CI [0.57-2.97]. UNOS database search returned only 3 patients that underwent LDLT for ALF compared to 1562 with DDLT, precluding comparison. CONCLUSION: One, 3, and 5-year patient and graft survival following LDLT vs DDLT transplantation were not statistically significantly different; however, due to limited number of studies further studies are warranted.

Identifying Liver Transplant Candidates at Risk of Wait List Removal Due to Nonadherence Using a Quality-of-Life Survey: A Competing Risk Analysis.

OBJECTIVES: We investigated whether the Liver Disease Health-Related Quality of Life Short Form or the Area Deprivation Index could be used to help identify liver transplant candidates at risk of delisting due to nonadherence. MATERIALS AND METHODS: We conducted a retrospective study of 358 adults (≥18 years old) listed for liver transplant at the University of Washington Medical Center from September 1, 2012, to August 30, 2017, who completed the Liver Disease Health-Related Quality of Life Short Form prior to listing. Wait list removal because of substance use or lack of attendance to clinical appointments was prospectively determined by a multidisciplinary transplant committee. A competing risk analysis was used to estimate risk of delisting for nonadherence. RESULTS: Among 358 liver transplant candidates, delisting occurred in 23 patients (6.4%) for nonadherence, 205 (57.3%) for transplant, 79 (22.1%) because of death or too sick, and 51 (14.2%) for other reasons. In the multivariable competing risk analysis, Liver Disease Health-Related Quality of Life Short Form responses indicating "poor memory" (subdistribution hazard ratio: 3.53; 95% CI, 1.49-8.36; P = .004) and "poor future outlook" (subdistribution hazard ratio: 2.94; 95% CI, 1.07-8.07; P = .03) were associated with higher risk of delisting for nonadherence. Female sex (subdistribution hazard ratio: 0.31; 95% CI, 0.10-0.93; P = .04) and previous abdominal surgery (subdistribution hazard ratio: 0.36; 95% CI, 0.14-0.92; P = .03) were associated with lower risk of delisting for nonadherence. The Area Deprivation Index was not associated with wait list removal. CONCLUSIONS: Liver Disease Health-Related Quality of Life Short Form responses indicating "poor memory" and "poor future outlook" were associated with increased risk of wait list removal due to nonadherence. Proactively identifying patients at high risk of nonadherence may help transplant programs better direct resources toward helping patients improve adherence and avoid delisting.

Long-term Outcomes of Pediatric Living Versus Deceased Donor Liver Transplantation Recipients: A Systematic Review and Meta-analysis.

Living donor liver transplantation (LDLT) emerged in the 1980s as a viable alternative to scarce cadaveric organs for pediatric patients. However, pediatric waitlist mortality remains high. Long-term outcomes of living and deceased donor liver transplantation (DDLT) are inconsistently described in the literature. Our aim was to systematically review the safety and efficacy of LDLT after 1 year of transplantation among pediatric patients with all causes of liver failure. We searched the MEDLINE, Medline-in-Process, MEDLINE Epub Ahead of Print, Embase + Embase Classic (OvidSP), and Cochrane (Wiley) from February 1, 1947 to February 26, 2020, without language restrictions. The primary outcomes were patient and graft survival beyond 1 year following transplantation. A meta-analysis of unadjusted and adjusted odds and hazard ratios was performed using a random-effects model. A total of 24 studies with 3677 patients who underwent LDLT and 9098 patients who underwent DDLT were included for analysis. In patients with chronic or combined chronic liver failure and acute liver failure (ALF), 1-year (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.53-0.88), 3-year (OR, 0.73; 95% CI, 0.61-0.89), 5-year (OR, 0.71; 95% CI, 0.57-0.89), and 10-year (OR, 0.42; 95% CI, 0.18-1.00) patient and 1-year (OR, 0.50; 95% CI, 0.35-0.70), 3-year (OR, 0.55; 95% CI, 0.37-0.83), 5-year (OR, 0.5; 95% CI, 0.32-0.76), and 10-year (OR, 0.26; 95% CI, 0.14-0.49) graft survival were consistently better in LDLT recipients compared with those in DDLT recipients. In patients with ALF, no difference was seen between the 2 groups except for 5-year patient survival (OR, 0.60; 95% CI, 0.38-0.95), which favored LDLT. Sensitivity analysis by era showed improved survival in the most recent cohort of patients, consistent with the well-described learning curve for the LDLT technique. LDLT provides superior patient and graft survival outcomes relative to DDLT in pediatric patients with chronic liver failure and ALF. More resources may be needed to develop infrastructures and health care systems to support living liver donation.

Associations Between Alcohol Use and Liver-Related Outcomes in a Large National Cohort of Patients With Cirrhosis.

Alcohol use can cause hepatic necroinflammation and worsening portal hypertension in patients with cirrhosis. We aimed to evaluate the associations between degree of alcohol use and clinical liver-related outcomes according to etiology of cirrhosis. In this retrospective cohort analysis, 44,349 U.S. veterans with cirrhosis from alcohol-associated liver disease (ALD), chronic hepatitis C virus (HCV) infection, or nonalcoholic fatty liver disease were identified who completed the Alcohol Use Disorders Identification Test Consumption questionnaire in 2012. Based on this score, level of alcohol use was categorized as none, low level, or unhealthy. Multivariable Cox proportional hazards regression was used to assess for associations between alcohol use and mortality, cirrhosis decompensation (new ascites, encephalopathy, or variceal bleeding), and hepatocellular carcinoma (HCC). At baseline, 36.4% of patients endorsed alcohol use and 17.1% had unhealthy alcohol use. During a mean 4.9 years of follow-up, 25,806 (57.9%) patients died, 9,409 (21.4%) developed a new decompensation, and 4,733 (11.1%) developed HCC. In patients with ALD-cirrhosis and HCV-cirrhosis, unhealthy alcohol use, compared with no alcohol use, was associated with higher risks of mortality (adjusted hazard ratio [aHR] = 1.13, 95% confidence interval [CI] = 1.07-1.19 and aHR = 1.14, 95% CI = 1.08-1.20, respectively) and decompensation (aHR = 1.18, 95% CI = 1.07-1.30 and aHR = 1.08, 95% CI = 1.00-1.16, respectively). Alcohol use was not associated with HCC, regardless of cirrhosis etiology. Conclusion: Unhealthy alcohol use was common in patients with cirrhosis and was associated with higher risks of mortality and cirrhosis decompensation in patients with HCV-cirrhosis and ALD-cirrhosis. Therefore, health care providers should make every effort to help patients achieve abstinence. The lack of association between alcohol use and HCC merits further investigation.