Production of interleukin-2 in response to synthetic peptides from hepatitis C virus E1 protein in patients with chronic hepatitis C: relationship with the response to interferon treatment.

BACKGROUND/AIMS: The role of cellular immunity in the clearance of hepatitis C virus after interferon therapy has not yet been elucidated. Here, we analyzed the T cell response to peptides from hepatitis C virus E1 protein in untreated and interferon-treated patients with chronic hepatitis C virus infection. METHODS: We used thirty-six 15-mer synthetic peptides from hepatitis C virus E1 protein (genotype 1a) in a sensitive interleukin-2 production assay in two groups of controls (healthy seronegative individuals and patients with liver diseases unrelated to hepatitis C virus), and three groups of patients with chronic hepatitis C: nine patients who cleared the virus after interferon treatment (group 1), nine patients who failed to respond to the therapy (group 2) and nine previously untreated patients (group 3). RESULTS: None of the controls responded to any of the peptides tested, whereas 8/9 (88%) of patients from group 1 responded positively. In contrast, only 2/9 (22%) of patients from group 2 showed peptide recognition. In group 3, 5/9 patients (55%) displayed positive response against E1 peptides. When E1 peptides from the sequence corresponding to genotype 1b (the commonest in patients who were non-responders to interferon) were tested in nine additional interferon-resistant patients (group 2*) a positive response was detected in only three of them (33%). CONCLUSIONS: T cell recognition of hepatitis C virus E1 peptides in patients with chronic hepatitis C who exhibit sustained response to interferon therapy is increased as compared with interferon-resistant cases, suggesting that T cell immunity to hepatitis C virus structural proteins may play a role in the clearance of this viral infection.

The GCGGAA gene-regulatory motif of herpes simplex virus type-1 is also found in hepatitis C virus.

We have analyzed the sequence of the 5'-untranslated region of hepatitis C virus from 24 patients with chronic hepatitis C and we found a conserved six-nucleotide motif previously described as a modulator of gene expression.

Hepatitis B virus occult infection in subjects with persistent isolated anti-HBc reactivity.

The aim of this study was to investigate the presence of hepatitis B virus occult infection in asymptomatic subjects with persistent anti-HBc reactivity but no other hepatitis B virus serological markers, including HBsAg, anti-HBs, IgM anti-HBc and HBV-DNA. For this purpose we used both polymerase chain reaction assays in sera and immunohistochemistry for HBsAg and HBcAg in liver biopsy specimens. Twenty-four cases were studied: 15 were drug abusers or homosexuals (eight with normal alanine aminotransferase levels) and nine were heterosexuals with raised alanine aminotransferase levels (> 45 U/l) but with no history of blood transfusion or ethanol intake (< 80 g daily). In all but five cases, liver biopsy was performed in subjects with persistent elevated alanine aminotransferase levels. In 10 out of 24 cases (41.66%) hepatitis B virus infection was demonstrated by polymerase chain reaction or immunohistochemistry, and when results from both procedures were available (n = 11) hepatitis B virus infection was detected in 63.63% of the subjects. The only clinical feature associated with HBV infection was the presence of persistent elevated alanine aminotransferase levels (p < 0.05). In conclusion, persistent isolated anti-HBc reactivity may be a relatively common serologic pattern for hepatitis B virus occult infection, at least in patients with chronic liver disease.

[Detection of hepatitis B virus DNA in serum by gene amplification in patients with chronic hepatitis B and in patients chronic hepatitis C]. / Detección del DNA del virus de la hepatitis B en suero mediante amplificación génica en pacientes con hepatitis crónica B y en pacientes con hepatitis crónica C.

BACKGROUND: The polymerase chain reaction (PCR) constitutes important methodological progress for detecting the presence of viral nucleic acids when these are found in small quantities in serum or tissues. The aim of this study was the use of PCR to detect DNA of the hepatitis B virus (HBV) in patients with chronic HBsAg positive hepatitis (HC-B) and in patients with chronic non A non B hepatitis with antibodies against the virus of hepatitis C (anti-HCV) positive (HC-C). METHODS: The DNA of the HBV was determined with PCR in the serum of 40 patients with HC-B and in 15 with HC-C. Moreover, the presence of anti-HCV was studied in the patients with HC-B. RESULTS: The presence of DNA of the HBV was detected by PCR in 69% of the HC-B patients presenting HBeAg positive and DNA of the HBV negative by simple hybridization as well as in 50% of the patients with HBeAg negative, anti-HBe positive and DNA of HBV negative by simple hybridization. In addition, DNA of HBV was detected by PCR in 27% (4/15) of the subjects with HC-C, three of whom had anti-HBc antibodies. On the other hand, 20% of the patients with HC-B had anti-HCV. Anti-HCV positivity was associated to a greater hypertransaminasemia in patients with HC-B in a non replicative phase. CONCLUSIONS: PCR is a sensitive method for detecting viral replication. Its use permits the detection of low DNA concentrations of the HBV in a low but appreciable percentage of chronic negative HBsAg hepatitis. Coinfection by the B and C viruses of hepatitis is not exceptional and explains hypertransaminasemia in some HC-B in a non replicative phase.

[Treatment of chronic hepatitis B with lymphoblastoid alpha interferon]. / Tratamiento de la hepatitis crónica B con interferón alfa linfoblastoide.

Thirty-five patients with active chronic hepatitis B (ACH-B) were evaluated. They were in stable replicative phase (HBeAg +; DNA polymerase and ALT stable in two determinations at least one month apart) and had not been infected by delta virus or HIV-1. Thirty-four patients were heterosexual and no patient was a drug abuser except one. The 23 initial cases were followed up for 15 months without therapy. The subsequent 12 cases were treated with maximal doses of 2.5 megaunits/m2 of lymphoblastoid alpha interferon (IFN-L) daily for two weeks and three times a week during 10 more weeks. While in the controls only two cases (8.69%) lost the DNA-polymerase activity and HBeAg, 5 treated patients (41.66%; p less than 0.05) developed seroconversion to nonreplicative phase. No patient from the control series lost the HBsAg; however, this happened in 2 treated patients (16.66%). These results show that IFN-L is effective in heterosexual patients with ACH-B in replicative phase without delta virus or HIV-I co-infection.