Recent studies have focused on whether different hepatitis C virus (HCV) genotypes are associated with different profiles of pathogenicity, infectivity, and response to antiviral therapy. The establishment of a simple and precise genotyping system for HCV is essential to address these issues. A new genotyping system based on PCR of the core region with genotype-specific PCR primers for the determination of HCV genotypes 1a,

Response to a 1-yr course of interferon-alpha 2b was assessed in 18 patients with chronic hepatitis C virus infection in relation to clinical, biochemical and histological parameters and to the presence or absence of hepatitis C virus RNA and the presumed replicative form of the virus (negative-strand hepatitis C virus RNA) in serum, liver and peripheral blood mononuclear cells. The findings were compared with those in seven untreated patients studied over the same period. At the start of the study, positive-strand hepatitis C virus RNA was found in sera of all 25 patients, in livers of 24 and in peripheral-blood mononuclear cells of 19 of 22 tested; negative strand was found in livers of 11 and in peripheral-blood mononuclear cells of 15 of 22. Negative-strand hepatitis C virus RNA was not found in the serum of any patient at any stage. All of the five treated patients considered to show complete response during the study period cleared hepatic hepatitis C virus RNA, and four also became seronegative, but three had evidence suggestive of viral replication in their peripheral-blood mononuclear cells; two of these last patients subsequently relapsed. Loss of hepatic hepatitis C virus RNA was the only significant difference between these five and the seven partial and six nonresponders, but it is uncertain whether the observed changes were due specifically to interferon-induced modulation of virus expression because similar (apparently spontaneous) changes were seen in four of the untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The involvement of the hepatitis C virus (HCV) in the severity of liver disease in chronic schistosomiasis was investigated in 215 Brazilian patients with S. mansoni infections, but without evidence of hepatitis B surface antigen (HBsAg). Forty-three had hepatointestinal (HIS) and 172 had hepatosplenic schistosomiasis (HSS), and 135 had compensated (HSSC), and 37 had decompensated (HSSD) liver disease. Fifty-two (24%) were found to have evidence of HCV infection (seropositive for anti-HCV antibodies and/or HCV-RNA). These comprised 35 (95%) of the 37 with HSSD, 16 (12%) of the 135 with HSSC, and 1 (2.4%) of the 43 with HIS, compared with only 1 (2%) of 50 control patients without S. mansoni. Testing of matched liver tissue and peripheral blood mononuclear cells (PBMCs) from 25 patients (6 HSSC and 19 HSSD) with HCV infections showed that 17 (68%) had "active" viral infections, in that negative strand HCV-RNA (the presumed replicative intermediate of the virus) could be detected in liver and/or PBMCs. Among these 25, negative strand HCV-RNA was found in 16 (84%) of the 19 with chronic active hepatitis, but in only 1 (17%) of the 6 with mild or inactive disease (P < 0.01). HCV-RNA was detected in matched spleen specimens from 9 of 10 patients (all of whom were also positive in PBMCs), suggesting that the spleen is an important extrahepatic reservoir of the virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Serial serum samples from 16 Italian patients presenting with acute hepatitis C virus (HCV) infections (which progressed to chronic hepatitis in six) were screened for the non-organ-specific autoantibodies most frequently associated with autoimmune hepatitis (AIH), as well as for antibodies against the hepatic asialoglycoprotein receptor (ASGP-R) and against the GOR peptide. One patient had low titres (1:10-1:80) of liver-kidney microsomal (LKM-1) antibodies during the recovery phase and three others had transient low titres of anti-smooth muscle (IgM class, 1:10) or anti-ASGP-R (1:150-1:300). Anti-GOR was detected in 43 (65%) of 66 sera from 13 of these patients. There was no correlation between any of these findings and progression to chronicity. By comparison, 18 patients with AIH studied concurrently before institution of immunosuppressive therapy all had antinuclear and/or smooth muscle antibodies, or LKM-1, at 1:40-1:640 and anti-ASGP-R at 1:300-1:2,100. None of these 18 had evidence of HCV infection and all were seronegative for anti-GOR. The findings indicate that the autoantibodies usually associated with AIH are rare in HCV infections but the virus can very occasionally induce a transient autoimmune response. Anti-GOR appears to be an antibody specifically related to HCV infection and is probably not a marker of induced autoimmunity, and it does not predict progression to chronic hepatitis.

Schistosomiasis and hepatitis B virus (HBV) infection are very common in Brazil but the interrelationships between the two infections are poorly understood. We have undertaken a detailed serological study of the prevalence of HBV markers in 189 Brazilian patients with chronic schistosomiasis mansoni, 46 with hepatointestinal (HIS) and 143 with hepatosplenic (HSS) schistosomiasis, 12 of the latter having decompensated liver disease (HSSD), and in 50 control patients. Sera were tested for HBsAg, anti-e, anti-HBc, anti-HBs and HBV-DNA. Eighty-three (44%) of the 189 schistosoma patients had at least one marker of HBV infection, 18 of whom (10%) were seropositive for HBsAg. All the controls were HBsAg negative, but ten (20%) had anti-HBc and anti-HBs. There was no significant difference in the frequency of these markers between HIS (14/46, 30.4%), HSSC (43/131, 34.5%), and the controls. Among the HBsAg-positive patients, one had HIS (HBV-DNA negative), seven had HSSC (one HBV-DNA positive) and ten had HSSD (six HBV-DNA positive), a significant association of HBV carriage with HSSD (P << 0.001). Mean (+/- SD) ALT values were significantly (P < 0.001) higher in HBsAg-positive HSSD patients (70.7 +/- 18 IU/liter) than in those with HSSC (29.5 +/- 15 IU/liter). Liver biopsies were performed in 12 HBsAg-positive patients (one with HIS, three with HSSC, and eight with HSSD) and in 50 HBsAg-negative HSSC patients. Seven of the eight HSSD patients had chronic active hepatitis with cirrhosis, and one had inactive cirrhosis. All three patients with HSSC and the one with HIS had chronic persistent hepatitis, with periportal fibrosis in three.(ABSTRACT TRUNCATED AT 250 WORDS)