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Background/aims: The prevalence of hepatitis C virus infection in the USA is higher among African-Americans than among Caucasians. Despite this, little information is available on the course of hepatitis C virus infection in Blacks and in other minority groups. The aim of this retrospective case-control study was to determine the response rate to high dose interferon-alpha treatment in two racial groups with chronic hepatitis C virus infection., Methodology: Thirty-one African-Americans and 62 Caucasians with chronic hepatitis C were considered in the study. The subjects were matched for gender, age, presence/absence of cirrhosis, histologic score, and viral genotype. All were treated with interferon-alpha (5 mU/day for 12 months). Three end-points (on-therapy, after 6 months of interferon-alpha, end-of-therapy, at the end of the 12 months of treatment, and off-therapy, 6 months after treatment) were chosen to describe the response to interferon-alpha treatment., Results: African-Americans had a significantly reduced response to interferon-alpha as compared to Caucasians at all end-points. At the on-therapy end-point, 26% of African-Americans were HCV-RNA negative and had normal transaminases level as compared to 60% of the Caucasians (P < 0.01); at the end-of-therapy end-point the rates were, respectively, 10% and 53% (P < 0.0001). No differences were detected in terms of pretreatment serum ALT, HCV-RNA, iron and ferritin levels or hepatic iron contents between the two groups., Conclusions: African-Americans have a reduced response to high-dose interferon-alpha treatment as compared to Caucasians. Both environmental and genetic factors may be implicated in this impaired ability to clear hepatitis C virus infection.

Objective: Individuals with chronic hepatitis C who are anti-HBc positive may carry an occult hepatitis B virus (HBV) infection that can affect their response to antiviral therapy., Methods: In this study the prevalence of anti-HBc and HBV-DNA positivity was assessed in the serum and liver of 285 HCV-RNA-positive subjects treated with interferon-alpha at 5 mU/day for 12 months. The response to interferon (normal ALT and undetectable serum HCV-RNA) was evaluated at three different endpoints: 1) after 6 months; 2) at the end of treatment; and 3) 6 months after interferon discontinuation., Results: Ninety individuals were anti-HBc positive (32%), 2 of these were HBV-DNA positive in serum and 7 in liver (8%). None of the anti-HBc-negative individuals was HBV-DNA positive in serum or liver. The prevalence of cirrhosis was greater in the anti-HBc-positive group than in the anti-HBc-negative group (p < 0.05), whereas HCV-RNA levels were lower. Anti-HBc-positive individuals had a lower response rate to interferon at 6 months and at the end of treatment as compared to anti-HBc-negative subjects (respectively 42% vs 66%, p < 0.01; and 32% vs 57%, p < 0.01). No difference between the two groups in terms of sustained response was detected 6 months after interferon discontinuation., Conclusions: The prevalence of anti-HBc is high among HCV-positive individuals. HCV-positive individuals who are anti-HBc positive have: 1) a higher prevalence of cirrhosis; 2) lower HCV-RNA levels; and 3) an impaired ability to respond to interferon treatment.

Background: Oxidative stress contributes to the development of liver injury after chronic alcohol intake. Women exhibit greater sensitivity to alcohol-induced liver disease than do men. The aim of the study was to determine the relationship between the sex hormone status of male and female rats and the degree of alcohol-induced oxidative stress in the liver., Methods: Male and female rats were pair-fed a liquid diet that contained 36% of their total daily calories as ethanol (EtOH group) or maltose (control group). Blood and liver samples were collected at the end of 8 weeks of diet., Results: Male EtOH rats experienced a reduction in plasma testosterone (T) and an increase in estradiol (E2) levels, with an increase in their calculated E2/T ratio with respect to their controls. Malonaldehyde (MDA) levels, an index of lipid peroxidation, and protein carbonyl content, an index of protein oxidation, in the liver were greater among the EtOH groups in females than in males. In males, an inverse correlation was found between hepatic MDA and circulating T levels, and a direct correlation was disclosed between MDA and estradiol levels. In addition, the hepatic histopathological score correlated inversely with the plasma T levels and directly with the calculated E2/T ratio, an index of feminization., Conclusions: Alcohol-induced oxidative injury, which contributes to hepatic injury in both male and female rats, is enhanced in females compared with males. A role for plasma T levels in protecting male rat liver from ethanol-induced oxidative injury can be hypothesized.

Nuclear factor kappaB (NF-kappaB) is activated during viral infection and is central to the regulation of host immune responses. The NF-kappaB activation status and its morphological sources were assessed by immunohistochemistry in allograft biopsy specimens of orthotopic liver transplantation patients with recurrent hepatitis C virus (HCV). Hepatocellular NF-kappaB immunostaining was detected in HCV cases compared with controls (nontransplant: P <.001; transplant: P =.006), which correlated with the number of NF-kappaB positive hepatocytes (P =.007) and contrasted to the absent to weak staining of controls (nontransplant: P =.001; transplant: P =.009). Enhanced NF-kappaB staining of cytokeratin 19-positive bile ducts and proliferating ductules in the HCV group was in contrast to controls. Intense NF-kappaB immunoreactivity was detected in CD68-positive Kupffer cells and macrophages of all HCV specimens compared with a few controls (nontransplant: P <.001; transplant: P =.001) and contrasted to the weak staining of controls (nontransplant: P <.001; transplant: P =.001). NF-kappaB-positive immunoreactivity correlated with the number of T cell receptor (TCR) alpha/beta-positive lymphocytes (P <.001), which was not observed in controls. In those HCV cases showing evidence of necroinflammatory activity (grade) and individual features of portal inflammation, periportal inflammation/piecemeal necrosis, lobular inflammation, and fibrosis (stage), higher NF-kappaB staining intensity scores within bile ducts, proliferating ductules, hepatocytes (piecemeal necrosis: P =.016; stage: P =.030), and lymphocytes (stage: P =.044) and increased number of NF-kappaB-positive cells within bile ducts, proliferating ductules (grade, lobular inflammation, piecemeal necrosis, stage: P =.022), hepatocytes, and lymphocytes were observed. Increased staining intensity and frequency of NF-kappaB-positive cells were similarly observed in HCV-positive allografts obtained from patients under tacrolimus- compared with cyclosporine-based immunosuppression. These data implicate an immunoregulatory role of intragraft NF-kappaB activation in the pathogenesis and progression of posttransplantation HCV disease recurrence.

Prior to performance of gastrointestinal endoscopic procedures, physicians are generally required to appraise patients of potential risks, benefits, and alternatives. Components of the informed consent process require that: (1) consent be voluntary; (2) the patient be sufficiently mentally capable to engage in rational decision-making; and (3) "adequate information" be conveyed. Controversies reflected in both medical and legal literature concern the definition of "adequate information." To sample current opinion regarding consent for both diagnostic and therapeutic ERCP, members of the Indiana Gut Club and Midwest Gut Club were polled. From this group of academic and private practice physicians, 81 completed evaluations were compiled. Greater than 90% of physicians believed that pancreatitis and pancreatitis/bleeding/perforation must be mentioned for diagnostic and therapeutic ERCP, respectively. There was variation of opinion as to whether patients must be informed of potential need for surgery, prolonged hospital stay, or death. The performing physician was felt to be ultimately responsible for obtaining consent, although other health-care team members, excluding a secretary, could participate.