A prospective study of alcoholic liver disease and mortality

doi:10.1016/S0168-8278(05)80659-2

Journal of Hepatology

Volume 16, Issue 3, 1992, Pages 290-297

https://doi.org/10.1016/S0168-8278(05)80659-2 Get rights and content

Abstract

We report the 10-year survival of 510 patients with a histological diagnosis of alcoholic liver disease. Eight centres in Scotland and North England contributed to this study. Information was available on 92% of the initial cohort. Age was important, with each decade increasing mortality by 55%. A highly significant interaction between sex and histology was observed with a marked survival benefit for males with non-cirrhotic alcoholic liver disease, while in cirrhotic subjects the pattern was reversed. Patients with decompensated liver disease had a relative increase in mortality in excess of 86% while the increase in mortality for alcoholic hepatitis, ‘active’ cirrhosis and ‘inactive’ cirrhosis were 52%, 57% and 91% relative to fatty liver. Alcohol intake at the time of diagnosis did not influence outcome. This study emphasises yet again the increased mortality rate of individuals abusing alcohol compared with the general population.

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Cited by (55)

Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort
2023, Journal of Hepatology
The harmful impact of heavy alcohol consumption and recurrence in patients with alcohol-related cirrhosis is long-established, although this is based on old studies. However, the drivers of long-term outcome still need to be clearly investigated.
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 glass-years in the same way as pack-years for tobacco) was assessed using a time-dependent covariable.
From 2010 to 2016, 650 patients were included. The median age at baseline was 58.4 years, 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, recurrence occurred in 30.9% of abstinent patients 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 of more than 25 glass-years during follow-up was independently associated with lower survival and with a trend toward lower liver event-free survival, with the risk increasing 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.
This prospective study in patients with compensated alcohol-related cirrhosis identifies factors predictive of alcohol recurrence during follow-up and shows that moderate alcohol consumption during follow-up negatively impacts outcomes. Patients with alcohol-related cirrhosis should be advised to completely stop drinking alcohol.
CIRRAL (NCT01213927) cohort was registered at ClinicalTrials.gov and the full protocol is available at the following link: https://clinicaltrials.gov/ct2/show/NCT01213927.
In patients with alcohol-related cirrhosis, data are lacking about the impact of the amount of alcohol consumed on both survival and liver-related events. The present study based on the CIRRAL cohort demonstrates that alcohol recurrence occurs in more than 30% of patients with compensated cirrhosis and that even a moderate recurrence strongly influences outcomes. Patients with compensated alcohol-related cirrhosis should be advised to completely discontinue alcohol consumption, even in small amounts, as the present study shows that no alcohol consumption can be regarded as safe when cirrhosis has developed.
Natural history of histologically proven alcohol-related liver disease: A systematic review
2019, Journal of Hepatology
Citation Excerpt :
Twenty-three studies described mortality outcomes.7,9,15,17,18,22,25,33,35,38–49 In the 8 studies (including 1,091 participants) that reported mortality in alcohol-related steatosis7,9,18,25,43,45,46,49 overall annual mortality was 6.0% (95% CI 4.0–7.0%), annual non-liver mortality was 4.0% (95% CI 3.0–6.0%) and annual liver-related mortality was 1.0% (95% CI 1.0–2.0%) (Fig. 3, Table S4). In the 7 studies (including 732 participants) that reported mortality in alcohol-related steatohepatitis,9,18,25,35,42,44,45 overall annual mortality was 11% (95% CI 6.0–19.0%), annual non-liver mortality was 4.0% (95% CI 2.0–9.0%) and annual liver-related mortality was 7.0% (95% CI 3.0–14.0%) (Fig. 4, Table S4).
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.
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.
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).
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.
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.
Histological parameters and alcohol abstinence determine long-term prognosis in patients with alcoholic liver disease
2017, Journal of Hepatology
Citation Excerpt :
Ideally, such models should be based on non-invasive clinical and/or biochemical parameters to avoid liver biopsy. Although some prognostic histological factors have been defined for long-term prognosis [23–28], it is not known if histological parameters would confer any additional prognostic utility over non-invasive factors. Since the clinical presentation and management of ALD patients is determined by the degree of liver dysfunction, our study was designed to (i) define histological, clinical and biochemical prognostic parameters and (ii) compare their utility for prediction of long-term outcome in patients with early vs. advanced stages of ALD in whom other causes of liver disease have been carefully excluded on clinical as well as histological grounds.
Few data exist on predictors of long-term prognosis in patients with alcoholic liver disease (ALD). Most studies have only assessed short-term prognosis in patients with advanced ALD. We aimed to assess the prognostic impact of clinical, biochemical and histological parameters on long-term prognosis in patients with early/compensated and decompensated ALD.
Consecutive patients (n = 192) with biopsy-proven liver disease due to alcohol abuse were analyzed retrospectively. Prognostic factors were evaluated in patients with early/compensated ALD (n = 60) and in patients with decompensated ALD (clinical decompensation and/or bilirubin >3 mg/dl at entry) (n = 132). Factors that predict long-term survival were identified using Cox regression models.
Liver-related mortality at 5 years was 13% in early/compensated and 43% in decompensated ALD. In early/compensated ALD patients, long-term prognosis was determined by fibrosis stage, but not by clinical or biochemical variables. Severe fibrosis (F3/4) was present in 52% and had a major impact on 10-year mortality (F3/4: 45% vs. F0-2: 0%, p <0.001). In contrast, in decompensated patients, a combination of clinical features (sex), biochemical markers of liver failure (bilirubin, international normalized ratio [INR]), and histological features (pericellular fibrosis) predicted long-term survival. During follow-up, abstinence from alcohol was an important predictor of survival in both early/compensated and decompensated ALD.
Fibrosis stage is the main predictor of long-term survival in patients with early/compensated ALD, while clinical, biochemical and histological parameters predict survival in patients with decompensated disease. Promoting abstinence may improve survival in patients with both early and advanced ALD.
In this study, we evaluated long-term outcome in 192 patients with alcoholic liver disease who underwent liver biopsy: 60 patients with early disease (no symptoms) and 132 patients with advanced disease (jaundice, complications of cirrhosis). Importantly, half of the patients with ‘early’ disease already had severe fibrosis or cirrhosis on liver histology and dismal outcome (45% mortality at 10 years). Abstinence from alcohol improved the prognosis in both early and advanced stages of the disease.
EASL clinical practical guidelines: Management of alcoholic liver disease
2012, Journal of Hepatology
Fatty liver disease. Alcoholic and non-alcoholic
2012, MacSween's Pathology of the Liver
Fatty Liver Disease: Alcoholic and Non-Alcoholic
2011, MacSween's Pathology of the Liver: Expert Consult: Online and Print

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Regular PaperA prospective study of alcoholic liver disease and mortality

Abstract

Gastroenterology

Am J Med

Gastroenterology

Lancet

Gastroenterology

Lancet

Alcoholic liver disease in Scotland and Northeastern England: presenting features in 510 patients

Q J Med

Alcoholic liver disease: morphological manifestations

Lancet

The liver in obesity

Arch Intern Med

Pericellular hepatic fibrosis and intracellular hyalin in diabetes mellitus

Gastroenterology

Obesity, small bowel bypass and liver disease

N Engl J Med

Alcohol and cancer

Hepatology

Alcoholic liver disease: evaluation of natural history and prognostic factors

Hepatology

Studies in alcoholic liver disease in Britain

Gut

A 20-year prospective study of cirrhosis

Br Med J

The natural history of Laennec's cirrhosis of the liver: an analysis of 386 cases

Medicine

Regular Paper
A prospective study of alcoholic liver disease and mortality