Advertisement

Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort

Published:November 21, 2022DOI:https://doi.org/10.1016/j.jhep.2022.11.013

      Highlights

      • -
        Alcohol recurrence occurs in more than 30% of cases after a diagnosis of cirrhosis
      • -
        A history of drug abuse and a recent alcohol withdrawal are drivers of recurrence
      • -
        Even a moderate recurrence influences outcome of patients with cirrhosis
      • -
        Cirrhotic patients should be advised to completely stop alcohol, even at low levels

      Abstract

      Background and aims

      The harmful impact of heavy alcohol recurrence has been confirmed in patients with alcohol-related cirrhosis although this is based on old studies. The drivers of long-term outcome still need to be clearly investigated.

      Method

      All patients with biopsy-proven compensated alcohol-related cirrhosis included in the CIRRAL cohort (22 centers) were prospectively studied. Prognostic variables of survival and liver event-free survival were assessed using multivariable Cox models with stepwise selection. The prognostic impact of alcohol recurrence during follow-up (computed in glasses-years in the same way as pack-years for tobacco) was assessed using a time-dependent covariable.

      Results

      From 2010 to 2016, 650 patients were included. The median age at baseline was 58.4 years old, 67.4% were men and the median BMI was 27.8 kg/m2, 63.8% had a history of liver decompensation, and 70.2% had discontinued alcohol. At 5 years, 30.9% of abstinent patients developed recurrence and this risk was higher in patients with a history of drug abuse and in those with shorter alcohol discontinuation times. Median survival was 97 months. Age, alcohol consumption at baseline, platelet count and Child-Pugh score >5 were associated with overall and liver event-free survival on multivariate analysis. Alcohol consumption during follow-up of more than 25 glasses-year was independently associated with lower survival and with a trend toward significant liver event-free survival, but the risk increased from 1 glass-year, though not significantly. Simon & Makuch plots confirm the benefit of no alcohol consumption (<1 glass/week) on both outcomes and the dose-dependent impact of alcohol over time.

      Conclusion

      This prospective study in patients with compensated alcohol-related cirrhosis identifies factors of alcohol recurrence during the follow-up and shows that moderate alcohol consumption during follow-up negatively impacts outcomes. Patients with alcohol-related cirrhosis should be advised to stop alcohol completely.

      Impact and implications

      In patients with alcohol-related cirrhosis, data are lacking about the impact of the amount of alcohol consumed on both survival and liver events. The present study based on the CIRRAL cohort demonstrates that alcohol recurrence occurs in more than 30% of patients with compensated cirrhosis and even a moderate recurrence strongly influences outcome. Patients with compensated alcohol-related cirrhosis should be advised to completely discontinue alcohol intake, even small amounts because, from the present study, no alcohol consumption can be regarded as safe when cirrhosis has developed.

      Graphical abstract

      Keywords

      Abbreviations:

      AFP (alfa-fetoprotein), BMI (Body Mass Index), HBV (hepatitis B virus), HCV (hepatitis C virus), HCC (hepatocellular carcinoma), HR (hazard ratio), IQR (interquartile range), US (abdominal ultrasonography examination)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hepatology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Pimpin L.
        • Cortez-Pinto H.
        • Negro F.
        • Corbould E.
        • Lazarus J.V.
        • Webber L.
        • et al.
        Burden of liver disease in Europe: Epidemiology and analysis of risk factors to identify prevention policies.
        J Hepatol. 2018; 69: 718-735
        • Corrao G.
        • Bagnardi V.
        • Zambon A.
        • La Vecchia C.
        A meta-analysis of alcohol consumption and the risk of 15 diseases.
        Prev Med. 2004; 38: 613-619
        • Rehm J.
        • Taylor B.
        • Mohapatra S.
        • Irving H.
        • Baliunas D.
        • Patra J.
        • et al.
        Alcohol as a risk factor for liver cirrhosis: a systematic review and meta-analysis.
        Drug Alcohol Rev. 2010; 29: 437-445
        • Roerecke M.
        • Vafaei A.
        • Hasan O.S.M.
        • Chrystoja B.R.
        • Cruz M.
        • Lee R.
        • et al.
        Alcohol Consumption and Risk of Liver Cirrhosis: A Systematic Review and Meta-Analysis.
        Am J Gastroenterol. 2019; 114: 1574-1586
        • European Association for the Study of the Liver
        European Association for the Study of the L. EASL Clinical Practice Guidelines: Management of alcohol-related liver disease.
        J Hepatol. 2018; 69 (Electronic address eee): 154-181
        • Hart C.L.
        • Morrison D.S.
        • Batty G.D.
        • Mitchell R.J.
        • Davey Smith G.
        Effect of body mass index and alcohol consumption on liver disease: analysis of data from two prospective cohort studies.
        BMJ. 2010; 340: c1240
        • Bell H.
        • Jahnsen J.
        • Kittang E.
        • Raknerud N.
        • Sandvik L.
        Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow-up study of 100 Norwegian patients admitted to one unit.
        Scand J Gastroenterol. 2004; 39: 858-863
        • Borowsky S.A.
        • Strome S.
        • Lott E.
        Continued heavy drinking and survival in alcoholic cirrhotics.
        Gastroenterology. 1981; 80: 1405-1409
        • Bouchier I.A.
        • Hislop W.S.
        • Prescott R.J.
        A prospective study of alcoholic liver disease and mortality.
        J Hepatol. 1992; 16: 290-297
        • Brunt P.W.
        • Kew M.C.
        • Scheuer P.J.
        • Sherlock S.
        Studies in alcoholic liver disease in Britain. I. Clinical and pathological patterns related to natural history.
        Gut. 1974; 15: 52-58
        • Lucey M.R.
        • Connor J.T.
        • Boyer T.D.
        • Henderson J.M.
        • Rikkers L.F.
        • Group D.S.
        Alcohol consumption by cirrhotic subjects: patterns of use and effects on liver function.
        Am J Gastroenterol. 2008; 103: 1698-1706
        • Orholm M.
        • Sorensen T.I.
        • Bentsen K.
        • Hoybye G.
        • Eghoje K.
        • Christoffersen P.
        Mortality of alcohol abusing men prospectively assessed in relation to history of abuse and degree of liver injury.
        Liver. 1985; 5: 253-260
        • Pande N.V.
        • Resnick R.H.
        • Yee W.
        • Eckardt V.F.
        • Shurberg J.L.
        Cirrhotic portal hypertension: morbidity of continued alcoholism.
        Gastroenterology. 1978; 74: 64-69
        • Pessione F.
        • Ramond M.J.
        • Peters L.
        • Pham B.N.
        • Batel P.
        • Rueff B.
        • et al.
        Five-year survival predictive factors in patients with excessive alcohol intake and cirrhosis. Effect of alcoholic hepatitis, smoking and abstinence.
        Liver Int. 2003; 23: 45-53
        • Veldt B.J.
        • Laine F.
        • Guillygomarc'h A.
        • Lauvin L.
        • Boudjema K.
        • Messner M.
        • et al.
        Indication of liver transplantation in severe alcoholic liver cirrhosis: quantitative evaluation and optimal timing.
        J Hepatol. 2002; 36: 93-98
        • Naveau S.
        • Gaude G.
        • Asnacios A.
        • Agostini H.
        • Abella A.
        • Barri-Ova N.
        • et al.
        Diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with alcoholic liver disease.
        Hepatology. 2009; 49: 97-105
        • Nguyen-Khac E.
        • Thiele M.
        • Voican C.
        • Nahon P.
        • Moreno C.
        • Boursier J.
        • et al.
        Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis.
        Lancet Gastroenterol Hepatol. 2018; 3: 614-625
        • Hagstrom H.
        • Thiele M.
        • Roelstraete B.
        • Soderling J.
        • Ludvigsson J.F.
        Mortality in biopsy-proven alcohol-related liver disease: a population-based nationwide cohort study of 3453 patients.
        Gut. 2021; 70: 170-179
        • Louvet A.
        • Trabut J.B.
        • Moreno C.
        • Moirand R.
        • Aubin H.J.
        • Ntandja Wandji L.C.
        • et al.
        Management of alcohol-related liver disease: the French Association for the Study of the Liver and the French Alcohol Society clinical guidelines.
        Liver Int. 2022; 42: 1330-1343
        • Ganne-Carrie N.
        • Chaffaut C.
        • Bourcier V.
        • Archambeaud I.
        • Perarnau J.M.
        • Oberti F.
        • et al.
        Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis.
        J Hepatol. 2018; 69: 1274-1283
        • Alberti K.G.
        • Eckel R.H.
        • Grundy S.M.
        • Zimmet P.Z.
        • Cleeman J.I.
        • Donato K.A.
        • et al.
        Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.
        Circulation. 2009; 120: 1640-1645
      1. Institute NC

        • Swihart B.J.
        • Caffo B.
        • James B.D.
        • Strand M.
        • Schwartz B.S.
        • Punjabi N.M.
        Lasagna plots: a saucy alternative to spaghetti plots.
        Epidemiology. 2010; 21: 621-625
        • Simon R.
        • Makuch R.W.
        A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias.
        Stat Med. 1984; 3: 35-44
        • Louvet A.
        • Labreuche J.
        • Moreno C.
        • Vanlemmens C.
        • Moirand R.
        • Feray C.
        • et al.
        Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study.
        Lancet Gastroenterol Hepatol. 2022;
        • Mathurin P.
        • Moreno C.
        • Samuel D.
        • Dumortier J.
        • Salleron J.
        • Durand F.
        • et al.
        Early liver transplantation for severe alcoholic hepatitis.
        N Engl J Med. 2011; 365: 1790-1800
        • Tandon P.
        • Goodman K.J.
        • Ma M.M.
        • Wong W.W.
        • Mason A.L.
        • Meeberg G.
        • et al.
        A shorter duration of pre-transplant abstinence predicts problem drinking after liver transplantation.
        Am J Gastroenterol. 2009; 104: 1700-1706
        • Addolorato G.
        • Mirijello A.
        • Leggio L.
        • Ferrulli A.
        • D'Angelo C.
        • Vassallo G.
        • et al.
        Liver transplantation in alcoholic patients: impact of an alcohol addiction unit within a liver transplant center.
        Alcohol Clin Exp Res. 2013; 37: 1601-1608
        • DiMartini A.
        • Day N.
        • Dew M.A.
        • Lane T.
        • Fitzgerald M.G.
        • Magill J.
        • et al.
        Alcohol use following liver transplantation: a comparison of follow-up methods.
        Psychosomatics. 2001; 42: 55-62
        • Donnadieu-Rigole H.
        • Jaubert L.
        • Ursic-Bedoya J.
        • Hanslik B.
        • Mura T.
        • Gamon L.
        • et al.
        Integration of an Addiction Team in a Liver Transplantation Center.
        Liver Transpl. 2019; 25: 1611-1619
        • Carr R.M.
        • Correnti J.
        Insulin resistance in clinical and experimental alcoholic liver disease.
        Ann N Y Acad Sci. 2015; 1353: 1-20
        • Kennedy O.J.
        • Roderick P.
        • Buchanan R.
        • Fallowfield J.A.
        • Hayes P.C.
        • Parkes J.
        Systematic review with meta-analysis: coffee consumption and the risk of cirrhosis.
        Aliment Pharmacol Ther. 2016; 43: 562-574
        • Klatsky A.L.
        • Morton C.
        • Udaltsova N.
        • Friedman G.D.
        Coffee, cirrhosis, and transaminase enzymes.
        Arch Intern Med. 2006; 166: 1190-1195
        • Inoue M.
        • Yoshimi I.
        • Sobue T.
        • Tsugane S.
        • Group J.S.
        Influence of coffee drinking on subsequent risk of hepatocellular carcinoma: a prospective study in Japan.
        J Natl Cancer Inst. 2005; 97: 293-300