ReviewHepatocellular carcinoma in the setting of alcohol-related liver disease
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.
References (100)
- et al.
Primary liver cancer: worldwide incidence and trends
Gastroenterology
(2004) - et al.
Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies
J Hepatol
(2018) - et al.
Hepatocellular carcinoma
Lancet
(2018) - et al.
Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus
Hepatology
(2002) - et al.
Liver cancer and alcohol
Clin Liver Dis
(2012) - et al.
Geographical variations in incidence, management and survival of hepatocellular carcinoma in a Western country
J Hepatol
(2017) - et al.
Annual incidence of hepatocellular carcinoma among patients with alcoholic cirrhosis and identification of risk groups
Clin Gastroenterol Hepatol
(2013) - et al.
Estimate of hepatocellular carcinoma's incidence in patients with alcoholic cirrhosis
J Hepatol
(2018) - et al.
Risk factors for hepatocellular carcinoma in patients with alcoholic or viral C cirrhosis
Clin Gastroenterol Hepatol
(2006) - et al.
Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis
J Hepatol
(2012)
Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family
Biochem Pharmacol
Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer
Lancet Oncol
Mitochondrial free radical generation, oxidative stress, and aging
Free Radic Biol Med
An Alu element in the myeloperoxidase promoter contains a composite SP1-thyroid hormone-retinoic acid response element
J Biol Chem
The manganese superoxide dismutase Ala16Val dimorphism modulates iron accumulation in human hepatoma cells
Free Radic Biol Med
Liver iron, HFE gene mutations, and hepatocellular carcinoma occurrence in patients with cirrhosis
Gastroenterology
Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol liver disease
J Hepatol
Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression
Cell
Signalling pathways in alcohol-induced liver inflammation
J Hepatol
Inflammation-associated cancer development in digestive organs: mechanisms and roles for genetic and epigenetic modulation
Gastroenterology
Mitotic responsiveness of cultured adult human hepatocytes to epidermal growth factor, transforming growth factor alpha, and human serum
Gastroenterology
Association between functional polymorphism in EGF gene and malignant melanoma
Lancet
Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes
Am J Hum Genet
A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis
J Biol Chem
Common polymorphism in the PNPLA3/adiponutrin gene confers higher risk of cirrhosis and liver damage in alcoholic liver disease
J Hepatol
PNPLA3 rs738409, hepatocellular carcinoma occurrence and risk model prediction in patients with cirrhosis
J Hepatol
A common polymorphism in the NCAN gene is associated with hepatocellular carcinoma in alcoholic liver disease
J Hepatol
A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010
Lancet
Update on biomarkers of hepatocellular carcinoma
Clin Gastroenterol Hepatol
Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine
J Hepatol
Hepatocellular carcinoma: clinical frontiers and perspectives
Gut
Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
Lancet
The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015
JAMA Oncol
How the risk of liver cancer changes after alcohol cessation: a review and meta-analysis of the current literature
BMC Cancer
EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma
J Hepatol
EASL Clinical Practice Guidelines: Management of alcohol-related liver disease
J Hepatol
Compliance with hepatocellular carcinoma surveillance guidelines associated with increased lead-time adjusted survival of patients with compensated viral cirrhosis: a multi-center cohort study
Gastroenterology
Risk for hepatocellular carcinoma in patients with alcoholic cirrhosis: a Danish nationwide cohort study
Ann Intern Med
Risk of hepatocellular carcinoma among individuals with different aetiologies of cirrhosis: a population-based cohort study
Aliment Pharmacol Ther
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
Hepatic and extrahepatic malignancies in cirrhosis caused by nonalcoholic steatohepatitis and alcoholic liver disease
Alcohol Clin Exp Res
Diabetes mellitus increases the risk of hepatocarcinogenesis in patients with alcoholic cirrhosis: a preliminary report
Hepatol Res
Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates
Clin Gastroenterol Hepatol
Alcoholic liver disease
Nat Rev Dis Primers
Molecular mechanisms of alcohol-mediated carcinogenesis
Nat Rev Cancer
Early alcoholic liver injury: formation of protein adducts with acetaldehyde and lipid peroxidation products, and expression of CYP2E1 and CYP3A
Alcohol Clin Exp Res
Alcohol dehydrogenase 1C*1 allele is a genetic marker for alcohol-associated cancer in heavy drinkers
Int J Cancer
Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma
J Cancer Res Clin Oncol
Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population
Int J Cancer
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