The Lower Survival in Patients With Alcoholism and Hepatitis C Continues in the DAA Era.

BACKGROUND: Alcohol liver disease (ALD) may coexist with hepatitis C (HCV) in many transplant recipients (alcoholic cirrhosis with hepatitis C [AHC]). Our objective was to determine whether there were differences in postliver transplantation outcomes of patients with AHC when compared with those with alcoholic cirrhosis (AC) and/or alcoholic hepatitis (AH). METHODS: Using UNOS explant data sets (2016-2020), the survival probabilities of AC, AH, and AHC were compared by Kaplan-Meier survival analysis. Cox proportional-hazard regression analysis was used to determine outcomes after adjusting for disease confounders. The outcomes were also compared with predirect antiviral agent (DAA) period. RESULTS: During study period, 8369 biopsy-proven ALD liver transplant recipients were identified. Of those, 647 had AHC (HCV + alcohol), 353 had AH, and 7369 had AC. MELD-Na score (28.7 ± 9.5 versus 23.8 ± 10.7; P < 0.001) and presence of ACLF-3 (19% versus 11%; P < 0.001) were higher in AC + AH as compared with AHC. AHC and AC+AH has similar adjusted mortality at 1-y, but 3-y (hazard ratios, 1.76; 95% confidence intervals, 1.32-2.35; P < 0.0001) and 5-y (hazard ratios, 1.64; 95% confidence intervals, 1.24-2.15; P = 0.0004) mortality rates were higher in AHC. Survival improved in the DAA era (2016-2020) compared with 2009 to 2013 in AHC, but remained worse in AHC group versus AC and/or AH. Malignancy-related mortality was higher in AHC (15% versus 9.3% in AC) in the DAA era. CONCLUSIONS: AHC was associated with lower 3- and 5-y post-LT survival as compared with ALD without HCV and the worse outcomes in AHC group continued in the DAA era.

Cirrosis hepática alcohólica: actualización epidemiológica de la tasa de mortalidad entre los años 2017-2021 en Chile / Alcoholic liver cirrhosis: epidemiological update of mortality rates between 2017-2021 in Chile

Introducción: La cirrosis hepática alcohólica (CHA) es una etapa final de la enfermedad hepática por alcohol. Dada la falta de análisis epidemiológicos recientes en Chile, el objetivo de este estudio es comparar descriptivamente la tasa de mortalidad (TM) por CHA entre los años 2017-2021 en Chile. Metodología: Estudio observacional y transversal, sobre defunciones por CHA en Chile durante 2017-2021 según sexo y edad (n=2.551). Datos obtenidos del Departamento de Estadística e Información en Salud. Se utilizó estadística descriptiva y cálculo de TM. No requirió aprobación del comité de ética. Resultados: Se obtuvo una TM para el período estudiado de 3,98/100.000 habitantes. El sexo masculino presenta la mayor TM con 7,05. El grupo etario de 65-79 años presenta la mayor TM con 9,08/100.000 habitantes. Para TM por región, lidera Los Lagos con 39,84/100.000 habitantes, la menor es Coquimbo con 10,03/100.000 habitantes. Discusión: La mayor TM por CHA se encuentra en hombres, lo cual puede deberse a un mayor consumo social. El grupo etario de 65-79 años presentó la mayor TM, coincidiendo con estadísticas internacionales. El porcentaje de ruralidad pudiera afectar el consumo de alcohol, aumentando la TM por CHA en aquellas más rurales. La prevención es vital para evitar el desarrollo de CHA, siendo crucial establecer programas de salud pública para evitar el consumo de alcohol en Chile. Se identificó una falta de datos epidemiológicos en Chile, por lo que se invita a la actualización de estos.

Introduction: Alcoholic liver cirrhosis (ALC) is one of the final stages of alcoholic-related liver disease (ARLD). Due to the lack of recent epidemiological research in Chile, the main objective of this study is to descriptively compare the mortality rate (MR) due to ALC between the years 2017-2021 in Chile. Methodology: Observational and cross-sectional study, on the number of deaths owing to ALC in Chile during 20172021 according to sex and age (n=2,551). Data obtained from the department of statistics and health information. Descriptive statistics and MR calculation were used. Ethics committee approval was not required. Results: A MR was obtained for the studied period of 3.98/100,000 inhabitants. The male sex submitted the highest MR with 7.05. The age group of 65-79 years presents the highest MR with 9,08/100,000 inhabitants. The region with the highest MR is Los Lagos with 39,84/100.000 inhabitants and the one with the lowest is Coquimbo with 10,03/100.000 inhabitants. Discussion: The highest MR is found in men, which may be due the fact that, socially, men consume more alcohol than women. The age group of 65-79 years presented the highest MR, which coincides with the international statistics. The percentage of rurality impacts the alcohol consumption increasing the MR due to ALD in the most rural areas. Prevention is vital to avoid its development, so it's crucial to establish public health programs to avoid alcohol consumption in Chile. A lack of updated epidemiological information has been identified in our country, therefore it is invited to update the epidemiological data.

A scoring system for predicting hepatocellular carcinoma risk in alcoholic cirrhosis.

The role of hepatocellular carcinoma (HCC) surveillance is being questioned in alcoholic cirrhosis because of the relative low HCC risk. This study aimed to assess the risk and predictors of HCC in Korean patients with alcoholic cirrhosis by using competing risk analysis. A total of 745 patients with alcoholic cirrhosis were recruited at a university-affiliated hospital in Korea and randomly assigned to either the derivation (n = 507) and validation (n = 238) cohort. Subdistribution hazards model of Fine and Gray was used with deaths and liver transplantation treated as competing risks. Death records were confirmed from Korean government databases. A nomogram was developed to calculate the Alcohol-associated Liver Cancer Estimation (ALICE) score. The cumulative incidence of HCC was 15.3 and 13.3% at 10 years for derivation and validation cohort, respectively. Age, alpha-fetoprotein level, and albumin level were identified as independent predictors of HCC and incorporated in the ALICE score, which discriminated low, intermediate, and high risk for HCC in alcoholic cirrhosis at the cut-off of 60 and 100. The risk of HCC can be stratified by using a combination of readily available clinical parameters (age, AFP level, and albumin level) in patients with alcoholic cirrhosis.

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.

Role of Bacterial Infection in the Development of Acute Liver Failure in Patients with Decompensated Alcoholic Liver Cirrhosis.

We examined 74 patients with acute decompensation of alcoholic liver cirrhosis: 34 (45.9%) with bacterial infection (group 1) and 40 (54.1%) without bacterial infection (group 2). The degree and index of acute-on-chronic liver failure (ACLF) were determined using an on-line CLIF-C ACLF Calculator and the levels of cytokeratin-18 fragments, TNFα, IL-1ß, IL-4, IL-6, and IL-8. In group 1, AST, cytokeratin-18, TNFα, IL-1ß, IL-6, degree and score of ACLF were significantly higher than in group 2. ACLF developed in 18 (52.9%) patients in group 1 and in 11 (27.5%) (p<0.05) patients in group 2. Within 1 month, 10 (29.4%) patients of group 1 and 2 (5%) patients of group 2 died (p<0.05). Patients with bacterial infection showed a more severe course of alcoholic liver cirrhosis and ACLF than those without bacterial infection.

Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis.

In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.

Abstinence from alcohol and alcohol rehabilitation therapy in alcoholic liver disease: a population-based study.

Objective: Abstinence from alcohol is recommended in patients diagnosed with alcoholic hepatitis (AH) and alcoholic cirrhosis (AC). We aimed to determine the impact of alcohol abstinence on prognosis of patients with AC and AH.Methods: All incident AC and AH patients in Iceland 2001-2016 were identified. Cirrhosis was confirmed clinically, biochemically, with imaging and histologically. Abstinence, alcohol rehabilitation and survival were analyzed.Results: Overall, 169 patients with AC and/or AH were identified. Eleven died during index hospitalization, leaving 158 patients for final analysis, median (IQR) age 56 years (48-65), 72% males. Over all 61 patients (39%) had AC, 40 (25%) AH and 57 (36%) features of both. Thirty-nine percent of patients remained abstinent during follow-up and 63% underwent alcohol rehabilitation. Moderate to severe ascites at diagnosis (odds ratio (OR): 3.05, 95% confidence interval (CI): 1.37-7.02) and lack of alcoholic rehabilitation (OR: 5.28, 95% CI: 2.24- 14.11) were independent predictors of abstinence. Abstinence at one year of follow-up was not related to increased survival. Patients surviving one year, abstinence during follow-up was related to increased survival for both groups.Conclusion: Abstinence from alcohol following AC/AH diagnosis was achieved in 39% of patients. Abstinence was not related to increased survival for alcoholic liver disease patients at one-year, which might partly indicate that this might be a marker that some patients were 'too sick to drink'. AC and AH patients who survived one year and remained abstinent had a favorable long-term prognosis.

Trends in the Burden of Chronic Liver Disease Among Hospitalized US Adults.

Importance: One factor associated with the rapidly increasing clinical and economic burden of chronic liver disease (CLD) is inpatient health care utilization. Objective: To understand trends in the hospitalization burden of CLD in the US. Design, Setting, and Participants: This cross-sectional study of hospitalized adults in the US used data from the National Inpatient Sample from 2012 to 2016 on adult CLD-related hospitalizations. Data were analyzed from June to October 2019. Main Outcomes and Measures: Hospitalizations identified using a comprehensive review of CLD-specific International Classification of Diseases, Ninth Revision, Clinical Modification and International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes. Survey-weighted annual trends in national estimates of CLD-related hospitalizations, in-hospital mortality, and hospitalization costs, stratified by demographic and clinical characteristics. Results: This study included 1 016 743 CLD-related hospitalizations (mean [SD] patient age, 57.4 [14.4] years; 582 197 [57.3%] male; 633 082 [62.3%] white). From 2012 to 2016, the rate of CLD-related hospitalizations per 100 000 hospitalizations increased from 3056 (95% CI, 3042-3069) to 3757 (95% CI, 3742-3772), and total inpatient hospitalization costs increased from $14.9 billion (95% CI, $13.9 billion to $15.9 billion) to $18.8 billion (95% CI, $17.6 billion to $20.0 billion). Mean (SD) patient age increased (56.8 [14.2] years in 2012 to 57.8 [14.6] years in 2016) and, subsequently, the proportion with Medicare also increased (41.7% [95% CI, 41.1%-42.2%] to 43.6% [95% CI, 43.1%-44.1%]) (P for trend < .001 for both). The proportion of hospitalizations of patients with hepatitis C virus was similar throughout the period of study (31.6% [95% CI, 31.3%-31.9%]), and the proportion with alcoholic cirrhosis and nonalcoholic fatty liver disease showed increases. The mortality rate was higher among hospitalizations with alcoholic cirrhosis (11.9% [95% CI, 11.7%-12.0%]) compared with other etiologies. Presence of hepatocellular carcinoma was also associated with a high mortality rate (9.8% [95% CI, 9.5%-10.1%]). Cost burden increased across all etiologies, with a higher total cost burden among hospitalizations with alcoholic cirrhosis ($22.7 billion [95% CI, $22.1 billion to $23.2 billion]) or hepatitis C virus ($22.6 billion [95% CI, $22.1 billion to $23.2 billion]). Presence of cirrhosis, complications of cirrhosis, and comorbidities added to the CLD burden. Conclusions and Relevance: Over the study period, the total estimated national hospitalization costs in patients with CLD reached $81.1 billion. The inpatient CLD burden in the US is likely increasing because of an aging CLD population with increases in concomitant comorbid conditions.

Long-term outcomes in patients with decompensated alcohol-related liver disease, steatohepatitis and Maddrey's discriminant function <32.

BACKGROUND & AIMS: Patients with alcoholic hepatitis and a modified Maddrey's discriminant function (mDF) <32 have a low risk of short-term mortality. However, few data exist concerning long-term outcomes. The aims of this study were to evaluate 5-year survival rates and to identify predictive factors for long-term prognosis in this patient population. METHODS: We studied patients from 2 centers who were admitted for hepatic decompensation (ascites, hepatic encephalopathy, or jaundice) and who had histological findings of steatohepatitis and an mDF <32. Clinical and biological parameters were recorded at the time of liver biopsy and alcohol consumption was recorded during follow-up. We performed Cox proportional hazard survival analysis to identify factors associated with 5-year survival. RESULTS: One hundred and twenty-one patients were included (male: 64%, mean age: 51.5 ± 10.3 years, presence of cirrhosis: 84%). The median model for end-stage liver disease and mDF scores were 14 (IQR 11.7-16.1) and 19 (IQR 11.1-24), respectively. During follow-up, 30% of the patients remained abstinent. Survival rates at 1, 6, 12, 24, and 60 months were 96.7 ± 1.6%, 90.1 ± 2.7%, 80.8 ± 3.6%, 69.9 ± 4.3%, and 50.7 ± 4.9%, respectively. The majority of deaths (80%) were liver related. In multivariable analysis, encephalopathy at baseline and alcohol abstinence were predictive of 5-year survival. The 5-year survival rates of patients without and with encephalopathy at baseline were 60.5 ± 5.8% and 29.7 ± 8.0%, respectively, and the 5-year survival rates of abstinent and non-abstinent patients were 74.0 ± 8.0% and 40.9 ± 5.8%, respectively. CONCLUSIONS: The mortality rate of patients with alcoholic hepatitis and an mDF <32 is around 50% at 5 years. Hepatic encephalopathy at baseline and lack of alcohol abstinence impair long-term prognosis. New treatment strategies, including measures to ensure abstinence, are required. LAY SUMMARY: Patients with alcoholic hepatitis that is of intermediate severity have a low risk of short-term mortality but not much is known regarding long-term outcomes for these patients. This study clearly indicates that patients with intermediate disease characteristics have poor long-term outcomes. The presence of hepatic encephalopathy at the time of diagnosis and the absence of alcohol abstinence during follow-up are factors that predict poor long-term mortality.

Trends in Characteristics, Mortality, and Other Outcomes of Patients With Newly Diagnosed Cirrhosis.

Importance: Changes in the characteristics of patients with cirrhosis are likely to affect future outcomes and are important to understand in planning for the care of this population. Objective: To identify changes in demographic and clinical characteristics and outcomes in patients with newly diagnosed cirrhosis. Design, Setting, and Participants: A retrospective cohort study of patients with a new diagnosis of cirrhosis was conducted using the Indiana Network for Patient Care, a large statewide regional health information exchange, between 2004 and 2014. Patients with at least 1 year of continuous follow-up before the cirrhosis diagnosis were followed up through August 1, 2015. The analysis was conducted from December 2018 to January 2019. Exposures: Age, cause of cirrhosis, and year of diagnosis. Main Outcomes and Measures: Overall rates for mortality, liver transplant, hepatocellular carcinoma, and hepatic decompensation (composite of ascites, hepatic encephalopathy, or variceal bleeding). Results: A total of 9261 patients with newly diagnosed cirrhosis were identified (mean [SD] age, 57.9 [12.6] years; 5109 [55.2%] male). A 69% increase in new diagnoses occurred over the course of the study period (620 in 2004 vs 1045 in 2014). The proportion of those younger than 40 years increased by 0.20% per year (95% CI, 0.04% to 0.36%; P for trend = .02), and the proportion of those aged 65 years and older increased by 0.81% per year (95% CI, 0.51% to 1.11%; P for trend < .001). The proportion of patients with alcoholic cirrhosis increased by 0.80% per year (95% CI, 0.49% to 1.12%), and the proportion with nonalcoholic steatohepatitis increased by 0.59% per year (95% CI, 0.30% to 0.87%), whereas the proportion with viral hepatitis decreased by 1.36% per year (95% CI, -1.68% to -1.03%) (P < .001 for all). In patients younger than 40 years, 40 to 64 years, and 65 years and older, mortality rates were 6.4 (95% CI, 5.4 to 7.6), 9.9 (95% CI, 9.5 to 10.4), and 16.2 (95% CI, 15.2 to 17.2) per 100 person-years, respectively (P < .001). Mortality rates decreased during the study period (11.9 [95% CI, 10.7-13.1] per 100 person-years in 2004 vs 10.0 [95% CI, 8.1-12.2] per 100 person-years in 2014; annual adjusted hazard ratio, 0.87 [95% CI, 0.86 to 0.88]) and were lower in those with alcoholic cirrhosis compared with patients with viral hepatitis (adjusted hazard ratio, 0.89 [95% CI, 0.80 to 0.98]). Rates of hepatocellular carcinoma were low in patients younger than 40 years (0.5 [95% CI, 0.2 to 0.9] per 100 person-years). Liver transplant rates were low throughout the study period (0.3 [95% CI, 0.3-0.4] per 100 person-years). In patients with compensated cirrhosis, rates of hepatic decompensation were lower in patients younger than 40 years (adjusted subhazard ratio 0.78; 95% CI, 0.62 to 0.99) and in patients with nonalcoholic steatohepatitis (adjusted subhazard ratio, 0.51; 95% CI, 0.43 to 0.60). Conclusions and Relevance: The population of patients with newly diagnosed cirrhosis in Indiana has experienced changes in the age distribution and cause of cirrhosis, with decreasing mortality rates. These findings support investment in the prevention and treatment of alcoholic liver disease and nonalcoholic steatohepatitis, particularly in younger and older patients. Additional study is needed to identify the reasons for decreasing mortality rates.

Natural history of histologically proven alcohol-related liver disease: A systematic review.

BACKGROUND & AIMS: To date, studies into the natural history of alcohol-related liver disease (ALD) have lacked long-term follow-up, large numbers of participants, or both. We performed a systematic review to summarise studies that describe the natural history of histologically proven ALD. METHODS: PubMed and Medline were searched for relevant studies according to pre-specified criteria. Data were extracted to describe the prevalence of ALD, histological progression of disease and mortality. Single-proportion meta-analysis was used to combine data from studies regarding rates of progression or mortality. RESULTS: Thirty-seven studies were included, reporting data from 7,528 participants. Amongst cohorts of hazardous drinkers, on average 15% had normal histological appearance, 27% had hepatic steatosis, 24% had steatohepatitis and 26% had cirrhosis. The annualised rates of progression of pre-cirrhotic disease to cirrhosis were 1% (0-8%) for patients with normal histology, 3% (2-4%) for hepatic steatosis, 10% (6-17%) for steatohepatitis and 8% (3-19%) for fibrosis. Annualised mortality was 6% (4-7%) in patients with steatosis and 8% (5-13%) in cirrhosis. In patients with steatohepatitis on biopsy a marked difference was seen between inpatient cohorts (annual mortality 15%, 8-26%) and mixed cohorts of inpatients and outpatients (annual mortality 5%, 2-10%). Only in steatosis did non-liver-related mortality exceed liver-specific causes of mortality (5% per year vs. 1% per year). CONCLUSIONS: These data confirm the observation that alcohol-related hepatic steatohepatitis requiring admission to hospital is the most dangerous subtype of ALD. Alcohol-related steatosis is not a benign condition as it is associated with significant risk of mortality. LAY SUMMARY: Knowledge of the natural history of a disease allows clinicians and patients to understand the risks that are associated with a medical condition. In this study we systematically gathered all the published data regarding the natural history of alcohol-related liver disease in people who had a liver biopsy. We used this data to define the prevalence of the disease, the annual risk of progression to cirrhosis and the annual risk of death at each stage of the disease.

Meta-analysis of patient survival and rate of alcohol relapse in liver-transplanted patients for acute alcoholic hepatitis.

PURPOSE: This review investigated survival and alcoholic relapse following liver transplantation (LT) in patients with severe acute alcoholic hepatitis (AH) without 6 months of alcohol abstinence. METHODS: All studies comparing acute AH patients undergoing LT with a control group were included. CENTRAL, MEDLINE, and Web of Science databases were searched. Survival benefits or odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using a random effects model. The study was registered in PROSPERO (CRD42017057971). According to the search results, two separate meta-analyses were performed: meta-analysis A compared early LT with medical therapy alone in patients with severe AH that were not responding to medical therapy and meta-analysis B compared LT outcome in patients with AH and chronic alcoholic cirrhosis (AC). RESULTS: The search yielded 2232 articles. Eight studies were included in the two meta-analyses-two studies in meta-analysis A and six studies in meta-analysis B. The two studies (n = 70) included in meta-analysis A revealed that 1-year patient survival was significantly higher in the LT group compared with the medical therapy-alone group (survival benefit, 15.88; 95% CI, 3.98-63.35; p < 0.0001). The six studies in meta-analysis B (including 1091 patients) showed that 1-year (survival benefit, 1.65; 95% CI, 0.95-2.89; p = 0.08), 3-year (survival benefit, 1.31; 95% CI, 0.79-2.18; p = 0.30), and 5-year survival (survival benefit, 1.54; 95% CI, 0.92-2.56; p = 0.10) were not significantly different between AH and AC groups. There was no significant difference in the rate of alcohol relapse between the groups (OR, 1.26; 95% CI, 0.53-2.96; p = 0.60). CONCLUSIONS: Early LT is a life-saving treatment for AH patients that do not respond to medical therapy. The chance of alcohol relapse after LT is not increased in selected patients.

Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis.

BACKGROUND & AIMS: More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC. METHODS: Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS). RESULTS: From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients' inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5-95.4), 80.3% (95% CI 76.9-83.9), and 3.2% (95% CI 1.6-4.8) respectively. CONCLUSION: This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%. LAY SUMMARY: Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening.

Alcohol Relapse After Liver Transplantation for Alcoholic Cirrhosis-Impact on Liver Graft and Patient Survival: A Meta-analysis.

AIM: We performed meta-analysis to determine effect of alcohol relapse after liver transplantation (LT) for alcoholic cirrhosis on graft histology and survival. METHODS: Studies were selected using following criteria: (a) LT for alcoholic cirrhosis, (b) reporting data on liver histology and/or patient survival among relapsers and abstainers, (c) minimum follow-up of 3 years. Random effects model was used to pool data to compare relapsers and abstainers on liver histology and patient survival. RESULTS: On analysis of seven studies, pooled prevalence of self-reported alcohol relapse was 26.3% (18.0-36.7%) over median (range) follow-up of 6.0 (3.7-8.3) years, with annual alcohol relapse rate of 4.7% (3.0-6.4%) for any alcohol use and 2.9% (0.5-5.3%) for heavy alcohol use. Relapsers compared to abstainers had higher odds for graft steatosis [4.1 (2.4-6.9)], steatohepatitis [4.5 (1.4-14.2)], alcoholic hepatitis [9.3 (1.01-85)], advanced fibrosis or cirrhosis [8.4 (3.5-20)]. Relapsers were over 3-fold more likely to die at 10 years of follow-up: [3.67 (1.42-9.50)] without differences in overall or 5-year survival. Recurrent alcoholic cirrhosis occurring in 9% of biopsied patients and 2% of all transplants was responsible for about 20% of all deaths on follow-up after LT. Extra-hepatic malignancy, and cardiovascular events were common causes for patient mortality. CONCLUSION: Alcohol relapse after LT for alcoholic cirrhosis negatively impacts the graft and long-term patient survival. Studies are needed to develop strategies to reduce alcohol relapse after LT for alcoholic cirrhosis. SHORT SUMMARY: Alcohol relapse in liver transplant recipients can negatively affect graft histology and patient survival. Strategies to reduce alcohol relapse are needed to preserve graft function?

Liver Transplantation in Patients with Alcoholic Liver Disease: A Retrospective Study.

AIM: Alcoholic liver disease (ALD) is the most common liver disease in the Western World. Liver transplantation (LT) is the treatment for end-stage ALD. However, many transplant centers are still reluctant to transplant these patients because of the risk of alcohol relapse, recurrence of the primary liver disease and associated post-transplant complications. We examined survival rate, prevalence of primary liver disease recurrence, re-transplantation and post-transplant complications among transplanted patients for alcoholic cirrhosis compared with those transplanted for viral cirrhosis. METHODS: data about patients transplanted for alcoholic and viral cirrhosis at the Gemelli Hospital from January 1995 to April 2016 were retrospectively collected. Survival rate was evaluated according to the Kaplan-Meier method. Recurrence was defined as histological evidence of primary liver disease. Data on the onset of complication, causes of death and graft failure after liver transplant were analyzed. RESULTS: There was no statistically significant difference regarding survival rate between the two groups. Only patients transplanted for viral cirrhosis presented with primary liver disease recurrence. There was a higher rate of cancer development in patients transplanted for alcoholic cirrhosis. Cancer was the major cause of death in this population. Risk factors associated with the onset of cancer were a high MELD score at the transplant time and smoking after transplantation. CONCLUSION: ALD is a good indication for LT. Patients transplanted for alcoholic cirrhosis should receive regular cancer screening and should be advised against smoking. SHORT SUMMARY: No difference was found between patients transplanted for alcoholic cirrhosis and viral cirrhosis in term of survival rate. Only patients transplanted for viral cirrhosis presented primary liver disease recurrence. A higher rate of cancer development was found in patients transplanted for alcoholic cirrohosis. This complication was associated with post-trasplant smoking.

Liver Transplantation in Cryptogenic Cirrhosis: Outcome Comparisons Between NASH, Alcoholic, and AIH Cirrhosis.

BACKGROUND: The outcomes of liver transplantation (LT) in patients with cryptogenic cirrhosis (CC) have not been adequately examined except for small case series. We believe that patients currently listed as CC have truly cryptogenic liver disease and may have different post-LT outcomes compared with nonalcoholic steatohepatitis (NASH). METHODS: We compared the post-LT outcomes of adults with CC (n = 3241) and compared them with cirrhosis from NASH (n = 4089), alcoholic cirrhosis (AC) (n = 7837), and autoimmune hepatitis (AIH) (n = 1435) using the United Network for Organ Sharing database from 2002 to 2016. We excluded those who had multiorgan transplantation and hepatocellular carcinoma. In addition to the well-known predictors of liver transplant outcomes, we analyzed the impact of Karnofsky Performance Status score at LT on immediate and late outcomes. RESULTS: There were significant differences in clinical characteristics between the groups. Despite these differences in clinical characteristics and risk factors, CC had similar graft and patient survival to NASH, AC, and AIH when assessed by Kaplan-Meier survival. Multivariate Cox regression analysis showed that graft and patient survival was similar in all 4 groups after adjusting for other confounders. Hispanics had a 24% lower risk of death (hazard ratio, 0.76) compared with whites in these combined cohorts after adjusting for all risk factors. In addition to other known risk factors, Karnofsky Performance Status score of 30% or less was associated with a 33% increase in risk of death (hazard ratio, 1.33) on multivariate analysis. CONCLUSION: Patients with CC had similar graft and patient survival when compared with NASH, AC, and AIH cirrhosis.

Neighborhood Inequalities in Hepatitis C Mortality: Spatial and Temporal Patterns and Associated Factors.

Deaths attributable to hepatitis C (HCV) infection are increasing in the USA even as highly effective treatments become available. Neighborhood-level inequalities create barriers to care and treatment for many vulnerable populations. We seek to characterize citywide trends in HCV mortality rates over time and identify and describe neighborhoods in New York City (NYC) with disproportionately high rates and associated factors. We used a multiple cause of death (MCOD) definition for HCV mortality. Cases identified between January 1, 2006, and December 31, 2014, were geocoded to NYC census tracts (CT). We calculated age-adjusted HCV mortality rates and identified spatial clustering using a local Moran's I test. Temporal trends were analyzed using joinpoint regression. A multistep global and local Poisson modeling approach was used to test for neighborhood associations with sociodemographic indicators. During the study period, 3697 HCV-related deaths occurred in NYC, with an average annual percent increase of 2.6% (p = 0.02). The HCV mortality rates ranged from 0 to 373.6 per 100,000 by CT, and cluster analysis identified significant clustering of HCV mortality (I = 0.23). Regression identified positive associations between HCV mortality and the proportion of non-Hispanic black or Hispanic residents, neighborhood poverty, education, and non-English-speaking households. Local regression estimates identified spatially varying patterns in these associations. The rates of HCV mortality in NYC are increasing and vary by neighborhood. HCV mortality is associated with many indicators of geographic inequality. Results identified neighborhoods in greatest need for place-based interventions to address social determinants that may perpetuate inequalities in HCV mortality.

Survival Outcomes in Liver Transplantation With Elderly Donors: Analysis of Andalusian Transplant Register.

Recently, there has been a large discrepancy between the number of patients on the waiting list for a liver transplant and the availability of deceased donors, with an increase in annual wait list mortality rates. Elderly donor livers are thought to be marginal grafts; however, in recent years, their utilization has constantly increased. The aim of this study is to evaluate the utilization of elderly donors in Andalusia and post-transplant outcomes. This retrospective observational study of 2408 liver transplants, performed in Andalusia between 2000 and 2014, analyzes the outcomes from donors aged 70 plus (n = 423) in terms of survival rates of the graft and the recipient, the type of transplant, donor age, and D-MELD score (product of donor age and preoperative Model for End-stage Liver Disease score). The most frequent indications for transplant were alcoholic cirrhosis (49.2%), hepatitis C cirrhosis (13%), and hepatocellular carcinoma (12.5%). The overall survival at 5 years was 64%, with a significant fall in survival for recipients with a D-MELD greater than 1500 (57%; P = .045). In the 70-year-old-plus donor group, the overall patient survival was 58.4%. The retransplant rate increased proportionately with donor age. In the alcoholic cirrhosis recipient subgroup, the overall survival at 5 years was 67.6% (P < .05) compared with 33.5% in patients with hepatitis C. Use of elderly donors is a safe strategy to reduce the scarcity of donors, provided that a D-MELD score below 1500 is obtained. Retransplant rates increase progressively with donor age. It is necessary to carefully screen recipients of older organs, taking into account that the best results are obtained for alcoholic cirrhosis, negative viral load hepatitis C, and a D-MELD score below 1500.

Incidence, survival and cause-specific mortality in alcoholic liver disease: a population-based cohort study.

OBJECTIVE: We studied the incidence of severe ALD requiring hospitalization in Finland, and survival and causes of death among the ALD patients. METHODS: A cohort of 11,873 persons (8796 men and 3077 women) with diagnosis of ALD during the years 1996-2012 was identified from Finnish national Inpatient Register. The annual incidence of alcoholic hepatitis (AH) and alcoholic liver cirrhosis was calculated. The cohort was combined with the data from national Cause of Death Register of Statistics Finland. RESULTS: The incidence of alcoholic liver cirrhosis increased from 8.8/100,000 in year 2001 to 14.6/100,000 in year 2012 among men and from 2.4 to 4.2/100,000 among women. The incidence of AH increased from 3.7 to 6.5/100,000 among men and from 1.3 to 2.7/100,000 among women. The relative 5-year survival ratios of patients with alcoholic liver cirrhosis and AH were 29 and 50% among men and 38 and 52% among women, respectively. Out of 8440 deaths, 65% were due to alcoholic-related causes. The risk of death among ALD patients was increased in malignancies (SMR 6.82; 95% CI: 6.35-7.29), cardiovascular diseases (6.13; 5.74-6.52), respiratory diseases (7.86; 6.70-9.10), dementia (3.31; 2.41-4.44) and accidents and violence (11.12; 10.13-12.15). CONCLUSIONS: The incidence of AH and alcoholic liver cirrhosis is increasing. The survival is poor. Most deaths are alcohol-related and other common causes of excess deaths are cancers especially in the upper aerodigestive tract and cardiovascular, digestive and respiratory diseases as well as violence and accidents.

Decreasing Mortality Among Danish Alcoholic Cirrhosis Patients: A Nationwide Cohort Study.

OBJECTIVES: Clinical management of certain cirrhosis complications has improved over the last two decades. In this study we aimed to examine whether mortality among Danish alcoholic cirrhosis patients has decreased during this period. METHODS: In this historical cohort study we used nationwide hospital data to identify Danish alcoholic cirrhosis patients diagnosed in 1996-1998, 1999-2001, 2002-2004, 2005-2007, 2008-2010, and 2011-2013. We used Cox regression to examine time trends in mortality after cirrhosis diagnosis, adjusting for confounding by age, gender, and prevalence of variceal bleeding, ascites, hepatorenal syndrome, alcoholic hepatitis, infection, hepatocellular carcinoma, comorbidity, and in-patient status at the time of cirrhosis diagnosis. RESULTS: We included 22,734 patients (69% men). The adjusted mortality hazard ratio (HR) for patients diagnosed in each period compared with those diagnosed in 1996-1998 was 0.99 (95% confidence interval (CI): 0.92-1.06) in 1999-2001, 1.00 (95% CI: 0.94-1.08) in 2002-2004, 0.97 (95% CI: 0.90-1.04) in 2005-2007, 0.94 (95% CI: 0.88-1.01) in 2008-2010, and finally 0.84 (95% CI: 0.79-0.90) in 2011-2013. CONCLUSIONS: In recent years, mortality among Danish alcoholic cirrhosis patients has decreased.