This review will focus on the prevalence of hepatitis c virus (HCV) infection in alcoholics with and without liver disease. Evidence will be presented to demonstrate that ethanol and chronic HCV infection synergistically accelerate liver injury. Some of the major postulated mechanisms responsible for disease progression include high rates of apoptosis, lipid peroxidation, and generation of free radicals and reactive oxygen species with reduced antioxidant capacity of the liver. Acquisition and persistence of HCV infection may be due to the adverse effects of ethanol on humoral and cellular immune responses to HCV. Dendritic cells (DC) appear to be one of the major targets for ethanol's action and DC dysfunction impairs the ability of the host to generate viral specific cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune responses. There is a relationship between increased alcohol intake and decreased response to interferon (IFN) therapy, which may be reversed by abstinence. Clinical studies are needed to optimize treatment responses in alcoholic patients with chronic HCV infection. KeywordsHepatic C virus; cellular immune response; liver disease Chronic hepatitis C virus (HCV) infection is a major cause of liver disease, cirrhosis, and hepatocellular carcinoma (HCC) in alcoholics. 1 Since chronic ethanol abuse in the setting of persistent HCV infection accelerates the progression of liver disease, we will focus on several pathogenic mechanisms of how acute and chronic liver injury is produced by both alcohol and HCV infection. The critical role of the host cellular immune response will be addressed including clinical and pre-clinical studies that document alcohol suppressive effects on generation of viral specific cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) immune responses required for HCV elimination from the liver. It appears that dendritic cells (DCs) are a critical cellular target of alcohol, and acute and chronic exposure substantially inhibits the ability of these cells to function as antigen-presenting cells. Because alcohol has effects on interferon-(IFN-) generated signal transduction pathways that modulate immune responses, patients suffering from alcoholism may have suboptimal therapeutic responses to antiviral agents. Reduced efficacy of treatment may also be related to HCV RNA titers, extent of liver fibrosis, increased hepatic fat deposition, and decreased cellular immunity. EPIDEMIOLOGYStudies on the prevalence of HCV were made possible in 1989 by discovery of the virus and subsequent generation of anti-HCV markers. 2 The first generation enzyme-linked Address for correspondence and reprint requests: Jack R. Wands, M.D., Director, Division of Gastroenterology and The Liver Research Center, Warren Alpert Medical School of Brown University, 55 Claverick Street, 4th Floor, Providence, RI 02903 (jack_wands_md@brown.edu). NIH Public Access Author ManuscriptSemin Liver Dis. Author manuscript; available in PMC 2010 June 28. NIH-PA A...

Spontaneous resolution of chronic hepatitis C virus (HCV) infection is exceedingly rare and poorly understood. As HCV and human immunodeficiency virus (HIV) have shared routes of transmission, HCV coinfection is estimated to affect 15%-30% of the HIV-positive population. We report 2 patients with HCV-HIV coinfection who underwent orthotopic liver transplantation at our center and had spontaneous clearance of their chronic HCV infection after transplantation without any anti-HCV treatment. Both patients showed no evidence of HCV recurrence for more than 3 years despite long-term immunosuppressant therapy. Spontaneous clearance of chronic HCV infection can occur in HIV-HCV-coinfected patients after liver transplantation. The mechanism of this phenomenon remains unclear. Liver Transpl 14:92-95, 2008.

United States guidelines endorse one-time HCV antibody screening at HIV diagnosis. Rescreening HCVseronegative patients on a regular basis is still not policy, although HIV-infected persons have reasonably substantial HCV incidence. We evaluated routine risk factor-independent HCV antibody re-testing in a Rhode Island HIV clinic. We instituted annual HCV antibody testing for HCV-seronegative patients who had not been rescreened in a year or more. Testing based on clinical suspicion continued. We conducted a chart review of new antibody-positive cases in the first year of rescreening, July 2006 to June 2007. Of 245 rescreened patients, 11 (4.5%) seroconverted. Five (45%) were female. Median time between last negative and first positive result was 32 months (range 8-98 months). Six (55%) had documented risk factors and 6 (55%) elevated ALT ( > 45 IU/L) between antibody tests; none prompted re-testing. One seroconverter died of hepatocellular carcinoma 3.7 years after HCV diagnosis. A twelfth was rescreened for suspected acute HCV based on ALT of 515 IU/L. He had newly detectable HCV RNA then seroconversion, and achieved SVR following 6 months of treatment in the acute phase for genotype 1 infection. Incident HCV is not uncommon among HIV-infected patients in care. Rescreening identified undiagnosed HCV in this population. HCV RNA should be checked promptly in HCV-seronegative persons with ALT elevation. We observed consequences of late diagnosis (hepatocellular carcinoma) and benefits of early diagnosis (cure with treatment of acute HCV). Adding annual rescreening to the Ryan White Program would facilitate earlier identification of undiagnosed HCV and create an instant widespread surveillance system, providing HCV incidence data.

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