Maria G. Koutelou

Role of hepatitis C virus in acute non-A, non-B hepatitis in Greece: A 5-Year prospective study

The prevalence of hepatitis C virus (HCV) infection in 182 prospectively followed adult patients (110 males, 72 females) with acute non-A, non-B hepatitis and its correlation with progression to chronic hepatitis were studied. These patients were followed for a mean of 24.7 +/- 13.1 (range, 6-57) months. By using a specific enzyme immunoassay for the detection of antibodies against C100-3 polypeptide of HCV, 96 (52.7%) were found antibody positive. HCV was implicated in 64/89 (71.9%) of the cases with classical parenteral exposure but only in 18/64 (28.1%) of the community-acquired cases. Progression to chronic hepatitis was observed more frequently in antibody-positive than in antibody-negative cases (60/96 or 62.5% vs. 27/86 or 31.4%, P = 0.00002). Progression was also observed more often in males than in females (66/112 or 58.9% vs. 21/70 or 30.0% P = 0.0001), both in the antibody positive (48/68 or 70.6% vs. 12/28 or 42.9%, P = 0.01) and in the antibody negative (18/44 or 40.9% vs. 9/42 or 21.4%, P = 0.043) cases. These data indicate that (a) acute hepatitis due to HCV is characterized by a high rate of chronicity, especially in males, and (b) a non-A, non-B, non-C agent or a different strain of HCV may be responsible for the majority of the community-acquired cases of non-A, non-B hepatitis in Greece.

Differential diagnosis of acute HBsAg positive hepatitis using IgM anti-HBc by a rapid, fully automated microparticle enzyme immunoassay

BACKGROUND/AIMS We determined the diagnostic significance of IgM anti-HBc by a rapid, fully automated microparticle enzyme immunoassay (IMx CORE-M) in acute HBsAg positive hepatitis. METHODS We studied prospectively for at least 6 months 100 patients with acute self-limited hepatitis B (group A) and 40 patients with acute hepatitis superimposed on histologically confirmed chronic hepatitis B (group B). On admission, all patients in group A were positive and those in group B were negative for IgM anti-HBc by a commercially available enzyme immunoassay. RESULTS Based on the assay criteria, the rates of IMx CORE-M (> 1.2) positive serum samples on admission, 4, 12 and 24 weeks later were: in group A: 100%, 95%, 72%, 44% and in group B: 20%, 27.5%, 17.5%, and 15%, respectively. Misclassification was observed in 20-27.5% of the acute on chronic hepatitis B cases. However, the mean IMx CORE-M index value was found to be significantly higher in group A during the whole follow-up. In particular, on admission the mean IMx CORE-M index value was 2.504 +/- 0.435 (range: 1.508-3.482) in group A and 0.747 +/- 0.346 (range: 0.062-1.384) in group B (p < 0.001). Discriminant function analysis showed that the cutoff level between the two groups for IMxCORE-M index on admission was 1.5. Four to 12 weeks from admission, in the group with acute on chronic hepatitis B cases, 13 patients with HDV and/or HCV superinfection had significantly lower IMx-CORE M index values compared with 27 patients with acute hepatitis due to exacerbation of chronic hepatitis B. CONCLUSIONS IMx CORE-M appears to be an accurate diagnostic test to differentiate acute from acute on chronic HBsAg positive hepatitis, but the cut-off level seems to be higher (1.5 instead of 1.2).

Clinical and Laboratory Features of Acute Community-acquired Non-A, Non-B, Non-C Hepatitis

Hepatitis C virus (HCV) infection, the main cause of post-transfusion non-A, non-B hepatitis worldwide, appears much less commonly in community-acquired non-A, non-B (CA-NANB) hepatitis. To further define the role of HCV or other known hepatitis viruses, we studied a well-defined cohort of 71 patients with acute CA-NANB hepatitis in Athens, Greece. Four of 46 biopsied cases were classified as chronic hepatitis. HCV was responsible for only 10 of 67 (14.9%) acute cases. Clinically and histologically, severe hepatitis was exclusively observed in non-A, non-B, non-C (NANBNC) (20/36 or 55.6% vs 0/6, P = 0.014) cases. Progression to chronic hepatitis was more frequent in anti-HCV-positive (6/10 or 60%) than in anti-HCV-negative (15/57 or 26.3%) cases (P = 0.044). Six of the 9 biopsied chronic NANBNC cases developed cirrhosis within 10–21 months. Seven NANBNC cases were tested for anti-HEV as well as HCV RNA and HBV DNA in serum and liver, and all were found to be negative. In conclusion, this study indicates that HCV is implicated in a minority of cases of acute CA-NANB hepatitis in Greece. Based on clinical severity and rate of chronicity, acute CA-NANBNC hepatitis differs from acute HCV infection. CA-NANBNC hepatitis is not caused by any known hepatitis virus. Although the viral etiology of the non-(A-E) hepatitis remains to be proven, this study lends further support to the existence of hitherto unkown hepatitis viruses.

Quantitative detection of hepatitis B virus DNA in sera from patients with acute hepatitis B

Two hundred forty-four serial serum samples from 30 adults hospitalized with benign (nonfulminant) acute hepatitis B were tested for the presence of hepatitis B virus (HBV) DNA by a quantitative solution hybridization assay using a125I-labeled DNA probe complementary to HBV-DNA sequences. Acute hepatitis B was self-limiting in 28 and progressed to chronicity in the remaining two patients. Of the 28 patients with self-limiting hepatitis, 21 (75%) were hepatitis B e antigen (HBeAg) positive, 26 (93%) were HBV-DNA positive, and one patient (3.6%) was negative for both markers on admission to the hospital. HBV-DNA cleared after HBeAg clearance in 20 (71.4%), before HBeAg clearance in five (17.9%) and simultaneously with the loss of HBeAg in the remaining two (7.1%) of the 27 initially HBV-DNA- and/or HBeAg-positive patients. Moreover, HBV-DNA remained detectable in serum for 13.3±6.6 (range: 4–22) days after the appearance of anti-HBe in 71.4% of these patients. In contrast, HBV-DNA and HBeAg remained persistently positive in the two patients who developed chronic HBV infection. These data show that: (1) viremia frequently persists after disappearance of HBeAg and (2) appearance of anti-HBe does not indicate the cessation of HBV replication in adults with acute self-limiting hepatitis B.