Hepatitis C and Alcohol
The alcoholic patient is no less subject to the spectrum of
hepatobiliary disorders that may afflict the nonalcoholic patient
and, in some cases, may be predisposed to liver injury because of
specific socioeconomic, epidemiologic, or metabolic risk
Prevalence of Anti-HCV Markers
Multiple studies have clearly demonstrated a high prevalence of
anti-HCV among alcoholic patients with liver disease. (1-5) Testing
with supplemental assays (e.g., recombinant immunoblot assay
[RIBA]) confirmed that 8~5 percent of alcoholic patients with liver
disease have anti-HCV (RIBA+). The prevalence of anti-HCV is
sevenfold higher among alcoholics than in the population at large
(10 percent vs. 1.4 percent), but is even higher in those with
liver disease (30 percent). Most of those with liver disease have
detectable HCV RNA which may also be present in some
anti-HCV(-)patients. Anti-HCV(+)(RIBA+) patients are likely to have
HCV RNA detected, which is indicative of active viral infection,
usually associated with some degree of necroinflammatory changes,
with or without fibrosis, regardless of alanine aminotransferase
HCV Correlation With Severity of Liver Injury
The prevalence of anti-HCV(RIBA+) correlates with the severity
of liver injury seen in alcoholic patients. Anti-HCV positivity
(RIBA+) correlated positively and significantly with cirrhosis,
cellular unrest, periportal inflammation, and piecemeal necrosis,
in contrast to anti-HBc, which did not correlate with any of these
histologic features, in a large Veterans Administration (VA) study.
(6) In a study of 144 alcoholic patients, a prevalence of 20
percent anti-HCV positivity in alcoholic fibrosteatosis, 21.4
percent in alcoholic hepatitis, and 42.6 percent in alcoholic
cirrhosis, as compared to 2.2 percent in alcoholic patients without
liver disease, was noted. (7) Histologic features, with the
exception of sinusoidal cellularity, were comparable in alcoholic
patients with and without anti-HCV. Nishiguchi et al. performed
both immunoblot and HCV RNA determinations among 80 alcoholic
patients with liver disease. (8) Patients with cirrhosis and HCV
RNA had higher ALT activity than comparable patients without HCV
RNA. The HCV RNA(+) patients had higher histologic activity indices
(Knodell) than those without detectable HCV RNA. The presence of
HCV RNA conferred a more severe degree of periportal and bridging
necrosis, intralobular de~eneration, focal necrosis. and Dortal
Effect of Abstinence on Alcoholic Patients with Histologic
Evidence of Chronic Hepatitis
In HCV RNA(+) alcoholic patients with histologic evidence of
chronic hepatitis, abstinence was not followed by resolution of
aminotransferase elevation, which has been observed in both
anti-HCV(+) HCV RNA(-) and anti-HCV(-), HBsAg(-) alcoholic patients
with similar histologic features. (9) This suggests that chronic
hepatitis C infection perpetuates the liver damage in these
alcoholic patients who have abstained. Nevertheless, serum HCV RNA
levels will decrease with abstinence. (10)
Epidemiology of Hepatitis C Among Alcoholic Patients
The epidemiology of hepatitis C among alcoholic patients with
bonafide viral C infection has not been definitively characterized.
Intravenous drug abuse (IVDA) is the most common risk factor. Yet
there has not been a good explanation for the disproportionately
high prevalence of HCV among alcoholic patients with liver disease
without a history of IVDA. (11) Caldwell et al. found the
prevalence of anti-HCV similar among patients with alcoholic liver
disease who had high risk factors as compared to those without
identifiable modes of parenteral transmission. (12)
Effect of Alcohol on HCV Replication
A critical question is whether or not alcohol and hepatitis C
infection are synergistic in a combined liver injury. In some
patients, there are both histologic features of alcoholic liver
injury and chronic viral hepatitis, but in most studies the
predominant pattern is chronic hepatitis. (13) Alcohol may enhance
the replication of hepatitis C and produce a more severe injury
independent of the direct alcohol-induced toxic injury. There is a
correlation between HCV RNA levels and amount of alcohol consumed.
(14) Alcoholic patients with HCV infection have higher hepatic iron
concentrations, which may be germane to increased HCV replication.
(15) Clinical evidence of hepatic activity and viral levels is
significantly greater in those consuming greater than 10g of
alcohol per day. (16)
Effect of Alcohol on Progression of Chronic Viral C Hepatitis
to Cirrhosis and Hepatocellular Carcinoma
There is a more rapid development of cirrhosis and
hepatocellular carcinoma in the alcoholic with chronic HCV
infection. (17,18) The period from transfusion to the diagnosis of
cirrhosis is shorter in the heavy drinker. The risk for the
development of hepatocellular carcinoma in alcoholic cirrhotics is
8.3 times higher in the HCV(+) patients than HCV(-) patients, and
the prevalence of anti-HCV among alcoholics with HCC is 50-70
percent. (20,21) Therefore, alcohol may modify the replication of
HCV as well as the oncogenicity of HCV in hepatocellular
Interferon Therapy in Alcoholic Patients with Chronic
Among alcoholic patients with chronic hepatitis C who remained
abstinent during therapy with interferon, there was a significantly
lower rate of HCV RNA clearance in those who consumed more than
70g/day of ethanol as compared to lass than 70g/day drinkers or
nondrinkers. (22) A similar experience noted zero HCV RNA clearance
in those consuming >70g/day up to the time of interferon
The most common type of nonalcoholic liver disease seen in
alcoholic patients is chronic viral hepatitis C. Evidence
accumulated thus far supports the concept that superimposed
hepatitis C infection confers a more severe liver injury in
alcoholic patients, possibly by enhancing viral replication. The
progression of the liver disease is more rapid and the risk for the
development of hepatocellular carcinoma, once cirrhosis has
developed, is high. It remains to be proven whether or not
successful antiviral therapy will change the natural history and
improve the prognosis in such patients who abstain. Regardless,
part of the mystery of why some alcoholics develop liver disease
while most do not can be explained by the presence of chronic viral
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and the association with alcoholic liver disease. Semin Liver Dis
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Caballeria L, Castillo R, Rodes J. Hepatitis C virus antibodies in
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8. Nishiguchi S, Kuroki T, Yabusako T, Seki S, Kobayashi K, Monna
T, Otani S, et al. Detection of hepatitis C virus antibodies and
hepatitis C virus RNA in patients with alcoholic liver disease.
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hepatitis in alcoholic patients: does chronic hepatitis induced by
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R, Mizokami M, Lau JYN, Tanikawa K. Hepatitis C virus infection in
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CS. Alcoholism is associated with hepatitis C but not hepatitis B
in an urban population. Am J Gastroenterol 1996;91(3):498-505.
12. Caldwell SH, Jeffers LJ, Ditomaso A, Millar A, Clark RM,
Rabassa A, Reddy KR, deMedina M, Schiff ER. Antibody to hepatitis C
is common among patients with alcoholic liver disease with and
without risk factors. Am J Gastroenterol 1991;86(9):1219-23.
13. Uchimura Y, Sata M, Kage M, Abe H, Tanikawa K. A
histopathological study of alcoholics with chronic HCV infection:
comparison with chronic hepatitis C and alcoholic liver disease.
14. Oshito M, Takei Y, Kawano S, Hijioka T, Masuda E, Goto M,
Nishimuro Y, Nagui H, Ito S, Tsuji S, Fusamoto H, Kamada T.
Endogenous nitric oxide attenuates ethanol-induced perturbation of
hepatic circulation in the isolated perfused rat liver. Hepatology
15. Izumi N, Enomoto N, Uchihara M, Murakami T, Ono K, Noguchi 0,
Miyake S, Nouchi T, Fujisawa K, Marumo F, Sato C. Hepatic iron
contents and response to interferon-a in patients with chronic
hepatitis C. Dig Dis Sci 1996;41(5):989-94.
16. Cromie SL, Jenkins PJ, Bowden DS, Dudley FJ. Chronic hepatitis
C: effect of alcohol on hepatic activity and viral titre. J Hepatol
17. Takase S, Tsutsumi M, Kawahara H, et al. The alcohol-altered
liver membrane antibody and hepatitis C virus infection in the
progression of alcoholic liver disease. Hepatology
18. Noda K, Yoshihara H, Suzuki K, Yamada Y, Kasahara A, Hayashi N,
Fusamoto H, Kamada T. Progression of type C chronic hepatitis to
liver cirrhosis and hepatocellular carcinoma-its relationship to
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19. Sato Y, Okabe K. Studies on the incidence of hepatocellular
carcinoma in heavy drinkers with liver cirrhosis [abstract].
Alcohol Alcohol 1993;(1B Suppl): 109-14.
20. Nalpas B, Feitelsol M, Brechot C, Rubin E. Alcohol,
hepatotropic viruses, and hepatocellular carcinoma [editorial].
Alcohol Clin Exp Res 1995;19(5);1089-95.
21. Miyakawa H, Sato C, Izumi N, Tazawa J, Ebata A, Hattori K,
Sakai H, Ikeda T, Hirata R, Sakai Y, et al. Hepatitis C virus
infection in alcoholic liver cirrhosis in Japan: its contribution
to the development of hepatocelluar carcinoma. Alcohol Alcohol
22. Okazaki T, Yoshihara H, Suzuki K, Yamada Y, Tsujimura T, Kawano
K, Yamada Y, Abe H. Efficacy of interferon therapy in patients with
chronic hepatitis C. Comparison between non-drinkers and drinkers.
Scand J Gastroenterol 1994;29(11):1039-43 .
23. Ohnishi K, Matsuo S, Matsutani K, Itahashi M, Kakihara K,
Suzuki K, Ito S, Fujiwara K. Interferon therapy for chronic
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SOURCE: From the NIH Consensus Development Conference on
Management of Hepatitis C
Title: Hepatitis C and Alcohol;Author: Eugene R. Schiff,
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