Familiar clustering and spreading of hepatitis delta virus infection

The prevalence of hepatitis delta virus (HDV) infection was significantly higher among the relatives of 79 carriers of HBsAg with antibody to HDV (index cases) than among relatives of 111 carriers without serological evidence of HDV infection (controls). Antibody to HDV was found in 45 of the 80 (56%) carriers of HBsAg in families of index cases but only in 2 of 59 (3%) carriers in families of controls (P less than 0.0001). During follow-up new HDV infection developed in 31% of 13 susceptible carriers in families of index cases, but only in 1.2% of 162 susceptible carriers in families of controls (P less than 0.001). None of the family members previously unexposed to the hepatitis B virus had HDV markers in serum or developed this infection during the follow-up. Familial clustering shows that HDV is transmitted by personal contacts, presumably through the inapparent permucosal or percutaneous passage of virus during close or intimate contact. The family model indicates that endemic HDV is maintained and spread through the network of carriers in the community, and that HBsAg carriers in contact with HBsAg/HDV carriers are at high risk of contracting HDV.     

The clinical value of serum ferritin in hepatocellular carcinoma

Serum ferritin is often elevated in patients with hepatocellular carcinoma (HCC). Its use as a disease marker has been proposed. We have measured serum ferritin levels in 85 patients with HCC and in 62 comparable subjects with cirrhosis. Abnormal values (greater than or equal to 300 ng/ml) were found in 54% of the patients with HCC and in 35% of those with cirrhosis (median 323 and 204 ng/ml, respectively). The overlap of the range of concentration in HCC and cirrhosis was so great that no discriminant level could be chosen. No relationship was found between alpha-fetoprotein and ferritin concentrations. Among 61 patients who received Adriamycin treatment, no discernible fall in ferritin levels was observed, while alpha-fetoprotein increased progressively during the follow-up. Serum ferritin has no role in diagnosing and/or monitoring the response to treatment of patients with HCC.     

The epidemiology of hepatitis delta infection in Italy. Promoting Group.

The epidemiology of HDV infection in Italy was assessed in a retrospective study involving 1556 HBsAg chronic carriers on their first presentation at one of the 35 Liver Units in 1987. Total anti-HD was detected in 23.4% of HBsAg carriers and was significantly more frequent in southern than in northern Italy (26.6% vs. 19.1%, p less than 0.01). Age distribution showed that 73% of the anti-HD-positive subjects, but only 56% of the anti-HD-negative subjects, were under 40 years of age (p less than 0.01). Anti-HD prevalence increased with the severity of the liver disease from 3.8% in healthy carriers to 42.5% in cirrhosis. No geographical statistical difference was found among HBsAg healthy carriers or subjects with chronic persistent hepatitis (CPH), while among patients with chronic active hepatitis (CAH) or cirrhosis anti-HD prevalence was much higher in the south (p less than 0.01). The various potential risk factors were evaluated by multiple logistic regression analysis. HDV infection was independently related to young age, residence in the south, i.v. drug abuse, a large family and household contact with an anti-HD-positive carrier. No association was found with blood transfusion or male homosexuality. These findings confirm that HDV infection is endemic in Italy, particularly in some southern areas, where intrafamily contact probably at a young age may favour the spread of the infection.     

Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa‐2a/ribavirin

Summary. It is unclear whether the current threshold for ‘high’ hepatitis C virus (HCV) RNA level (800 000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono‐infected and 176 HIV–HCV co‐infected patients treated with peginterferon alfa‐2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono‐infected patients, the difference in SVR rates between those with low and high baseline HCV RNA levels was 27% (70%vs 43%) when 400 000 IU/mL was used and 16% (59%vs 43%) when 800 000 IU/mL was used. In HIV–HCV genotype 1 co‐infected patients, the difference was 51% (71%vs 20%) when 400 000 IU/mL was used and 43% (61%vs 18%) when 800 000 IU/mL was used. A lower threshold (200 000 IU/mL) was identified for genotype 1 mono‐infected patients with ‘normal’ alanine aminotransferase (ALT) levels. No threshold could be identified in HCV genotype 2 or 3 patients. A threshold HCV RNA level of 400 000 IU/mL is optimal for differentiating high and low probability of SVR in genotype 1‐infected individuals with elevated ALT.     

Hepatitis C virus replication in 'autoimmune' chronic hepatitis.

Both high and low anti-hepatitis C virus antibody (anti-HCV) prevalence has been reported in autoimmune chronic active hepatitis. Therefore, we studied 15 consecutive HBsAg-negative, ELISA anti-HCV-positive, autoantibody-positive patients with biopsy proven chronic active hepatitis in order to confirm ELISA specificity by immunoblot test (RIBA-HCV), and to evaluate HCV replication by serum HCV-RNA. Nine patients were anti-nuclear, three type 1 anti-liver-kidney microsomal and three anti-smooth muscle antibody positive. None had associated autoimmune disease. All cases showed mild clinical disease and only moderate necroinflammatory activity. Response to prednisone was poor. RIBA-HCV confirmed ELISA results in all patients. HCV-RNA was found in the serum from 10 patients. Institution of alpha-interferon treatment in three steroid non-responsive patients was followed by prompt normalization of transaminases. Thus, a subgroup of autoantibody-positive chronic active hepatitis can be recognized as HCV-related and should be clinically and etiologically distinguished from autoimmune chronic active hepatitis. Trials of alpha-interferon treatment are worthwhile in this condition.     

Hepatitis C virus antibodies in chronic liver diseases of different aetiology.

To define the prevalence of Hepatitis C Virus (HCV) infection in patients with chronic hepatitis or cirrhosis of any aetiology, we tested a group of 372 consecutive subjects with biopsy-proven chronic liver disease (CLD) for anti-HCV antibodies, excluding active drug-addicts and alcoholics. Our results show that in Southern Italy HCV infection is widespread among subjects with cryptogenic chronic liver disease, as well as in liver diseases with features of autoimmunity (71.7% and 66.7% anti-HCV positive, respectively). Anti-HCV is infrequent among non drug-addicted HBsAg positive subjects (4.7%), and bears no relation to hepatitis D superinfection. Subjects with CLD and a history of parenteral exposure are almost always anti-HCV positive (89.2%). Patients with HBV-related CLD and previous drug-addicts are on the average younger than other disease groups, irrespective of their HCV status. Among subjects whose CLD is related to parenteral exposure, cryptogenic or autoimmune no increase in the rate of anti-HCV positivity seems to bear a parallel relationship to age. No known risk factor for parenteral transmission, other than use of blood or blood products and previous drug-addiction, can be clearly related to HCV infection. No trend to familiar clustering of HCV-induced liver disease is apparent. Liver disease severity, as assessed by transaminase levels and liver histology, does not correlate to anti-HCV status.     

Genetic and sex-linked factors influencing hbs antigen clearance 1. nonimmune clearance in inbred strains of mice

Differences in the clearance values of polyvinylpyrrolidonc (K_PVP) and HBs antigen (K_HBs) were seen in several strains of inbred mice. In addition, in all strains studied K_HBs was greater in females than in males, while K_PVP was not significantly different in the two sexes. In the strain with the lowest K_HBs values, the incidence of HBs antibody formation was lower than in the other strains. These data indicate that genetic and sex-linked factors influence nonimmune clearance of HBs antigen in mice. If similar factors exist in man they may explain some of the variation in clinical manifestation of HBV infection.