Elsevier

Journal of Hepatology

Volume 70, Issue 2, February 2019, Pages 284-293
Journal of Hepatology

Review
Hepatocellular carcinoma in the setting of alcohol-related liver disease

https://doi.org/10.1016/j.jhep.2018.10.008Get rights and content

Summary

Alcohol-related liver disease is the most prevalent type of chronic liver disease worldwide, accounting for 30% of hepatocellular carcinoma (HCC) cases and HCC-specific deaths. Alcohol has been associated with an increased risk of several malignancies, this risk starting at doses as low as 10 g/1 unit/day. The carcinogenic process includes direct acetaldehyde toxicity through the formation of protein and DNA adducts, an increased production of reactive oxygen species, changes to lipid peroxidation and metabolism, inflammation and an impaired immune response and modifications to DNA methylation. A high annual incidence of HCC has been observed in large European cohorts of patients with alcoholic cirrhosis, reaching 2.9%, with numerous host factors modulating this risk (age, gender, liver failure, genetic polymorphisms affecting oncogenic pathways). Because of impaired surveillance and poor patient compliance, HCC is often detected late in patients with chronic liver disease of alcoholic aetiology. This delay in detection, which is frequently made in the context of advanced liver cirrhosis rather than in surveillance programmes, results in more advanced HCC that is less amenable to curative treatment. Consequently, patients with alcohol-related HCC generally have a worse prognosis than those with non-alcoholic HCC.

Introduction

Worldwide, alcohol accounts for around one-third of global incident cases of primary liver cancer with marked variations between countries and regions.[1], [2], [3] Alcohol is a recognised carcinogen. The risk of liver cancer-mortality rises with increasing levels of consumption and the level of consumption that minimises health loss is zero.[4], [5] As well as epidemiological data, this paper will focus on the mechanisms underlying alcohol-induced liver carcinogenesis and the characteristics of primary liver cancer that develop in the context of alcohol-related liver disease (ALD).

Section snippets

Epidemiology

Primary liver cancer is one of the leading causes of cancer and cancer-related deaths and its incidence has risen markedly in recent decades. Hepatocellular carcinoma (HCC) accounts for the vast majority of primary liver cancers, followed by cholangiocarcinoma and more rarely malignant stromal tumours (sarcoma, haemangioendothelioma, etc.). Almost 90% of cases of HCC develop in a context of underlying chronic liver disease, usually advanced and accompanied by severe liver fibrosis and

Pathogenesis and genetics of alcohol-induced liver carcinogenesis

Chronic alcohol intake alters the architecture and compromises the functional capacity of the liver by triggering steatosis, steatohepatitis and cirrhosis.24 These pathological events are subsequently sustained and participate in the carcinogenetic process. As well as the development of cirrhosis, which can be considered a precancerous condition, a number of pathophysiological factors are specific to hepatic alcohol-mediated carcinogenesis, including: i) the formation of acetaldehyde and its

HCC screening, tumour characteristics, access to curative treatment and survival in patients with HCC that has developed in the setting of ALD

Several publications have reported a positive impact of HCC screening on diagnosis at an early-stage, eligibility for curative treatment and overall survival. However, despite international guidelines on HCC screening in patients with cirrhosis, periodic surveillance is not optimal in clinical practice. In the USA and Europe, fewer than 30% of HCC cases are diagnosed by surveillance and surveillance is indicated but missed in more than one-third of patients. Moreover, in eligible patients under

Conclusion/perspectives

Alcohol is a recognised carcinogen for several malignancies, with the risk starting at low doses (10 g/1 unit/day). The contribution of an alcoholic aetiology to global incident cases of HCC – estimated at around 30% in 2015 – is expected to increase in the years to come, concurrent with both the decline in virally induced HCC because of more effective viral eradication94 and control,95 and the rising alcohol consumption observed in developing countries.96 Because of impaired surveillance and

Conflict of interest

Prof Ganne-Carrié has received honoraria from Abbvie, Bayer, Bristol-Myers Squibb, and Gilead. Prof Nahon has received honoraria from Abbvie, Bayer, Bristol-Myers Squibb, Gilead and Ipsen.

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