People with hepatitis C have a much greater risk of liver-related hospitalisation or death if they have an alcohol use disorder or another serious comorbidity such as HIV infection, chronic kidney disease or cancer, according to an analysis of everyone hospitalised in France between 2008 and 2012. In the absence of these problems, people with hepatitis C did not have an increased risk of death compared to the general population.
The findings were presented by Michael Schwarzinger of the Translational Health Economics Network, Paris, at the International Liver Congress in Vienna, Austria, on Saturday.
Previous research in smaller cohorts has shown that alcohol use greatly increases the risk of liver-related death in people with hepatitis C, but the French study is the largest study of the effects of alcohol on liver-related clinical disease and death ever reported.
The study was designed to assess the contribution of various confounding factors to the prognosis of people with hepatitis C infection. In particular, the study sought to determine the extent to which alcohol might contribute to the poor prognosis of hepatitis C infection – and whether people without high levels of alcohol consumption have a poor prognosis if infected with hepatitis C.
The study could assess alcohol use only by physician report of an 'alcohol use disorder', and the hospitals database does not contain any information about average consumption, the definition of alcohol misuse or the duration of heavy drinking. The diagnosis of alcohol use disorder covers a spectrum of problematic drinking, ranging from regular over-indulgence to severe physical dependence, and is classified as mild, moderate or severe. The appearance of 'alcohol use disorder' on a medical record is therefore a red flag that someone has a history of high alcohol consumption, but can provide no information that can be used to calculate less harmful levels of consumption or how many years of heavy drinking might negatively affect the prognosis of people with hepatitis C.
The study also looked at the contribution of serious comorbidities to the need for hospitalisation for liver-related events.
During the period 2008-2012, 28,953,755 people in France were admitted to hospital and 1,506,453 people died in hospital. Chronic infection with hepatitis C virus (HCV) was present in 112,146 (0.39%) of hospitalised patients, alcohol use disorder in 705,259 (2.44%), and both chronic HCV infection and alcohol use disorder in 23,351 (i.e., 20.8% alcohol use disorder recorded in hepatitis C patients).
The analysis found that people with hepatitis C were six times more likely to have an alcohol use disorder than other hospital patients, and 2.4 times more likely to have at least one serious comorbidity.
Forty-six per cent of all liver-related events in people with hepatitis C occurred in those with alcohol use disorders, approximately one-third in people with at least one serious comorbidity, and only 14% in people with hepatitis C who had neither a comorbidity or an alcohol use disorder. Among people with hepatitis C, one-third of all deaths in hospital, of whatever cause, occurred in people with alcohol use disorders, and 57% in people with other serious co-morbidities.
The study also found that people in the general population had a much worse prognosis than others if they had an alcohol use disorder. They were three times more likely to die in hospital than people who did not drink alcohol.
The poor prognosis of people with hepatitis C is largely explained by alcohol misuse and by severe comorbidities, Schwarzinger told a press conference. The findings call into question the cost-effectiveness of direct-acting antiviral treatment for hepatitis C for people without alcohol use disorders, he went on, because rates of progression and consequent medical costs averted by immediate treatment may be much lower than current models suggest.
“These results show that alcohol use disorders are a much more accurate indicator of mortality in chronic HCV infection, and highlight the need to encourage alcohol withdrawal and abstinence in all patients,” said Professor Tom Hemming Karlsen, Scientific Committee Member, European Association for the Study of the Liver (EASL).
People who had stopped drinking or who had remained abstinent had a one-third reduction in the risk of death compared to people who drank any alcohol, while in the general population abstinence or withdrawal reduced the risk of death by one quarter.
Schwarzinger said that the effect of alcohol abstinence and withdrawal should be investigated more closely in people with hepatitis C. For example, the better prognosis of people with genotype 4 hepatitis C may be a consequence of its epidemiology – genotype 4 is prevalent in Muslim countries in North Africa and the Middle East where alcohol consumption is culturally unacceptable – rather than any feature of the genotype, Schwarzinger argued.
SchwarzingerM et al. The confounding role of severe comorbidities and alcohol use disorders on prognosis in chronic hepatitis C virus infection: an analysis of the 2008-2012 French national hospital discharge database. Abstract G16, 50th International Liver Congress, 2015.