Even low levels of alcohol consumption increase the risk of liver cancer for people with HCV infection with compensated cirrhosis

Low-to-moderate alcohol consumption is associated with an increased risk of liver cancer for people with hepatitis C virus (HCV) infection with compensated cirrhosis, investigators from Belgium report in the Journal of Hepatology. Five-year incidence of hepatocellular carcinoma (HCC) was twice as high among people who reported alcohol consumption compared to individuals who did not drink alcohol. Levels of daily alcohol consumption among people who developed liver cancer were low, the investigators stressing, “drinking alcohol, not the amount of alcohol intake, was associated with an increased risk of HCC.” They therefore caution, “there is no safe threshold for alcohol” for people with HCV infection with cirrhosis.

Patients who drank alcohol and who did not eradicate their HCV infection during follow-up had especially poor outcomes, including an increased risk of decompensated liver disease and death.

Heavy alcohol consumption is a well-established risk factor for cirrhosis, decompensated liver disease, HCC and death in people with chronic HCV infection. Whether light-to-moderate alcohol consumption is similarly associated with poorer outcomes after cirrhosis has developed is unclear. The interaction between alcohol use and eradication of HCV with antiviral treatment on outcomes in people with compensated cirrhosis is also unknown.

Investigators in Belgium therefore designed a prospective study involving people with compensated HCV-related cirrhosis. Data on alcohol consumption and viral eradication were collected prospectively at intervals of at most six months. Study participants were asked to report their typical quantity, frequency and duration of alcohol consumption. Each alcoholic drink was assumed to contain 10g of pure ethanol. HCV therapy was provided according to Belgium national guidelines and after 2011 included direct-acting agents. The study outcomes were development of HCC, decompensated cirrhosis and death.

Recruitment took place between January 2009 and December 2010. Of the 192 people eligible for inclusion, 61% were abstinent from alcohol. Median daily alcohol consumption among the 39% of individuals who reported drinking was 15g/day – approximately 1.5 units. During follow-up, 86% of people underwent antiviral treatment and 41% had a sustained virological response.

During the course of the study, 17% of people developed HCC, including 14% of people who abstained from alcohol and 23% of those who reported alcohol consumption (p = 0.009).

Analysis of study participants who reported drinking alcohol showed that median daily intake of alcohol was 10g for those who developed HCC and 20g for individuals who did not progress to liver cancer. Therefore, it was alcohol consumption per se, and not the level of drinking, that was associated with the development of HCC.

The rate of HCC was significantly lower among people who achieved viral eradication compared to those with persistent viraemia (10% vs. 20%).

The proportion of people developing decompensated cirrhosis did not differ according to alcohol use. The rate of this outcome was lower among people with viral eradication compared to those without viral eradication (15% vs. 35%).

A fifth of study participants died. Mortality rates did not differ according to alcohol consumption (20% for both groups). Only 3% of people with viral eradication died compared to 30% of people without viral eradication.

The cumulative five-year incidence of HCC was 11% among alcohol abstainers and 24% among those who reported alcohol consumption (p = 0.087). Annual incidence rates among abstainers and consumers were 2% and 6%, respectively.

The cumulative five-year incidence of HCC was 2% in people with viral eradication and 22% in those with persistent viraemia; annual rates were 0.4% and 5%, respectively.

In multivariate analysis, lack of viral eradication (p = 0.04) and alcohol consumption (p = 0.04) were both associated with an increased risk of HCC.

The lowest risk of HCC was seen in people who abstained from alcohol and who had viral eradication (0%), followed by people with alcohol consumption and viral eradication (6%), people without alcohol consumption but persistent viraemia (16%) and people with alcohol consumption and no viral eradication (29%).

There was no evidence that alcohol consumption had a significant association with the risk of decompensated cirrhosis (18% five-year incidence for abstainers vs. 22% for consumers). However, incidence was significantly lower among people with viral eradication compared to those without eradication (4% vs. 27%, p = 0.001). Individuals without alcohol consumption and with viral eradication had the lowest risk of decompensation (3%; p = 0.012 compared to other groups).

Mortality risk did not differ according to alcohol use. Five-year incidence of all-cause mortality and liver-related mortality were similar for people who abstained and consumed alcohol (20% vs. 18%; 14% vs. 14%). Individuals without alcohol consumption and viral eradication had the lowest risk of death (0%) and liver-related death (0%).

“Alcohol consumption was associated with an increased risk of HCC,” comment the authors. “As the median amount of alcohol intake was low in consumers, we can conclude that light-to-moderate alcohol intake increases the risk of HCC.”

They recommend, “patients with HCV-related cirrhosis should be strongly advised against any alcohol intake. Patient care should include measures to ensure abstinence.”