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.