Low prevalence of hepatitis C virus antibodies in chronic liver disease in northwest China

To evaluate the prevalence of hepatitis C virus infection in northwest China, 179 chronic liver disease patients in this area were examined for antibody to hepatitis C virus core protein (anti-HCVcore). This antibody was found in only 5 (14 percent) of 37 chronic non-A, non-B liver disease patients, in 11 (16%) of 67 asymptomatic hepatitis B virus carriers, and in 20 (27%) of 75 chronic hepatitis B patients. High titers of anti-HCVcore (cut off index >2) were observed in 3 (60%), 5 (45%), and 9 (45%) of the anti-HCVcore-positive cases of these groups, respectively. We further investigated the seroprevalence of antibodies to hepatitis B virus in the 37 chronic non-A, non-B liver disease patients. All 5 anti-HCVcore-positive cases were positive for a hepatitis B virus marker, with only 44% (14/32) of the anti-HCVcore-negative patients (P < 0.05). Based on these findings, it is concluded that the prevalence of hepatitis C virus infection in chronic non-A, non-B liver disease is unexpectedly low in northwest China and that hepatitis B and C viruses seem to have a similar mode of infection in that area.     

Effect of interferon on GB virus C and hepatitis C virus in hepatitis patients with the co-infection

Of 74 patients who were infected with hepatitis C virus (HCV) and received interferon, 12 (16%) were positive for RNA of GB virus C (GBV-C). RNA of GBV-C was determined in sera from the co-infected patients retrospectively, and the effect of interferon on GBV-C was compared with that on HCV in them. Titers of both GBV-C and HCV RNAs decreased during interferon in all of them. Two patients lost both GBV-C and HCV RNAs and remained clear until 6 months after treatment with interferon, while 2 lost RNA for GBV-C only and 2 for HCV RNA alone. Low pre-treatment RNA titers of GBV-C and HCV correlated with the efficacy of interferon in clearing. Alanine aminotransferase returned to normal only in the patients who lost HCV RNA, regardless of the persistence or loss GBV-C RNA. These results indicate that the response to interferon of GBV-C is comparable to but independent of that of HCV and that the persistence of GBV-C would not prevent the normalization of aminotransferases in response to interferon in patients with chronic hepatitis C. J. Med. Virol. 52:156–160, 1997. © 1997 Wiley-Liss, Inc.     

Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection

Although occult hepatitis B virus (HBV) infection (HBV-DNA in serum in the absence of hepatitis B surface antigen [HBsAg]) is common in chronic hepatitis C, its characteristics are not well known. In this work, the presence of HBV-DNA (by polymerase chain reaction; PCR) and its distribution (by in situ hybridization) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 32 patients with chronic hepatitis C and occult HBV infection and in 20 HBsAg chronic carriers were determined. The results showed that serum HBV-DNA levels were statistically lower (P = 0.001) in patients with occult HBV infection than in HBsAg chronic carriers. The HBV infection pattern in liver cells was identical between patients with occult HBV infection and those with chronic hepatitis B. However, the mean percentage of HBV-infected hepatocytes was significantly lower (P = 0.001) in patients with occult HBV infection (5 +/- 4.44%) than in HBsAg chronic carriers (17.99 +/- 11.58%). All patients with chronic hepatitis B have HBV-DNA in their PBMCs while this occurred in 50% of the cases with occult HBV infection. In conclusion, patients with occult HBV infection have a low number of HBV-infected hepatocytes and this fact could explain the lack of HBsAg detection and low viremia levels found in these cases.     

The role of the hepatitis B virus infection in patients with chronic hepatitis in argentina

Over a seven-year period, we monitored 221 patients with chronic hepatitis from two medical centers. By using the counterelectrophoresis (CEP) test to detect the presence of HBsAg and anti-HBc, or both, we established that 87.7% of them had hepatitis B infection. Serum specimens originally found negative for HBsAg by CEP were further tested by reversed passive hemagglutination (RPH), and those originally found negative for anti-HBc by CEP were further tested by radioimmunoassay (RIA). Five patients were anti-HBc-positive and HBsAg-negative. No sex predominance was observed, but HBsAg incidence increased with increasing age. The HBeAg antigen was detected in 46.8% of the 161 cases tested for it; the most frequent subtype found was adw (63.7%). The present findings indicate that HBV infection largely contributes to the development of chronic hepatitis in Argentinian patients.     

Hepatitis C virus infection in schistosomiasis mansoni in Brazil

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 (sero-positive 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. The findings indicate that concomitant infections with HCV are a major factor contributing to the severity of liver disease in chronic schistosomiasis, and that apparent active replication of the virus in the liver or at extrahepatic sites is strongly associated with severe liver disease. © 1995 Wiley-Liss, Inc.     

IgM anti-hepatitis C virus core antibodies as marker of recurrent hepatitis C after liver transplantation

The differential diagnosis of recurrent hepatitis C following orthotopic liver transplantation (OLT) may be difficult. We evaluated the diagnostic significance of IgM anti-hepatitis C virus (anti-HCV) core antibodies in 27 patients undergoing OLT because of HCV-associated cirrhosis. Serial serum samples collected before and after OLT were tested for the presence of IgM anti-HCV core antibodies. Results were compared with the histological evidence of liver damage, the presence, level, and genotype of serum HCV RNA and the degree of immunosuppression. All patients underwent recurrent HCV infection. Recurrent hepatitis was diagnosed histologically in 21 patients an average of 48 weeks after OLT (range 2–209 weeks): 18 had persistence or (re)appearance of the IgM anti-HCV core after OLT, one lost the IgM anti-HCV core after OLT, and two never secreted IgM anti-HCV core either before or after OLT. The remaining six patients did not develop recurrent hepatitis after a follow-up of 44–241 weeks from OLT; in these patients, IgM anti-HCV core either disappeared (1 case) or decreased (1 case) after OLT or were persistently negative throughout the study (4 cases). Thus, 18/21 patients with recurrent hepatitis, but only one of six without recurrent hepatitis, secreted IgM anti-HCV core after OLT (P < 0.05). The IgM anti-HCV core levels were not correlated with the level or genotype of serum HCV RNA or the degree of immunosuppression. In conclusion, secretion of IgM anti-HCV core antibodies after OLT seems associated with recurrence of HCV-associated liver disease and may have diagnostic significance. J. Med. Virol. 56:224–229, 1998. © 1998 Wiley-Liss, Inc.     

Antibodies to hepatitis C virus in essential mixed cryoglobulinaemia.

Although essential mixed cryoglobulinaemia (EMC) is recognized to be frequently associated with chronic liver disease, aetiology and pathogenesis of liver damage remain unsolved questions. The purpose of this study was to assess the possible causative role of hepatitis C virus (HCV) in the liver impairment occurring in patients with EMC. Twenty-six consecutive EMC patients were evaluated. All patients underwent percutaneous liver biopsy. Anti-HCV antibodies were assayed by ELISA and supported by a recombinant immunoblotting assay (4-RIBA). The prevalence of anti-HCV antibodies in patients with and without chronic active liver disease (CALD) was compared. Anti-HCV antibodies were detected in 13 patients (50%) by ELISA and confirmed in 11 of them (42.3%) by 4-RIBA, the remaining two patients being indeterminate in the supportive assay. CALD correlated significantly with anti-HCV antibodies: indeed, 7/11 (63.6%) anti-HCV+ patients showed histological and clinical pictures of CALD, compared with 1/15 (6.6%) anti-HCV- patients (P less than 0.01). With the exception of the patient who was found to be HBsAg+, no liver tissue expressed hepatitis B virus-related antigens in the hepatocytes. Additional histological findings included discrete lymphoid aggregates in portal tracts, siderosis, fatty changes, hyperplasia of Kupffer cells. It can be concluded that chronic liver damage in EMC is frequently associated with anti-HCV antibodies. Although the cause of EMC remains unknown, this study has obvious implications for clarifying the etiology of associated CALD and further supports the therapeutic use of interferons in this disease.     

Comparison of the hypervariable region of hepatitis C virus genomes in plasma and liver

Nucleotide sequences of the hypervariable region of hepatitis C virus genomes obtained from plasma change rapidly during the course of in fection and are believed to play a part in immunological escape and consequently in the development of persistent infection. It is not known, however, whether these changes also occur in the liver. To clarify this aspect, RNA was extracted from the plasma and liver tissue of eight patients with chronic hepatitis C. After cDNA synthesis, DNA fragments that included the hypervariable region were amplified by the polymerase chain reaction. Consensus nucleotide sequences were determined directly from the polymerase chain reaction products by the dideoxy chain termination method. The diversity of the hypervariable region was analyzed further by the polymerase chain reaction-single strand conformation polymorphism analysis. Consensus nucleotide sequences of the hypervariable region were identical between the plasma and the liver in each patient. The polymerase chain reaction-single strand conformation polymorphism analysis showed multiple DNA bands that represented different hypervariable region sequences. Comparison of the single strand conformation polymorphism patterns revealed that the number, the mobility, and the density of bands were the same between the plasma and the liver. It is concluded that the population and the diversity of hepatitis C virus quasispecies as detected by the hypervariable region sequence are the same between the plasma and the liver despite rapid mutations, indicating that rapid changes in the population of hepatitis C virus quasispecies also occur in the liver. © 1995 Wiley-Liss, Inc.     

IgM antibodies in sera from patients with chronic active hepatitis reacting with the measles virus matrix protein and nucleoprotein

The antigenic specificity of measles virus IgM antibodies in sera from patients with chronic active hepatitis not caused by hepatitis B virus has been examined. An immunosorbent column containing antihuman IgM covalently bound to Sepharose was used to pick up IgM from the sera. Radiolabelled measles virus antigens were then allowed to react with the IgM antibodies. The immune complexes were eluted and analysed by sodium dodecyl sulfate [SDS]-polyacrylamide gel electrophoresis. Four sera from patients with hepatitis B surface antigen [HBsAg]-negative chronic active hepatitis with high measles virus haemagglutination inhibition [HI] and complement fixation [CF] antibody titres and positive enzyme-linked immunosorbent assay [ELISA] for measles-virus-specific IgM were examined. The results were compared with those obtained using sera from patients with an acute measles virus infection and from healthy controls. In both patient groups, IgM antibodies with specificity against the matrix protein represented the major portion of the measles virus IgM. IgM antibodies against the measles virus nucleoprotein and probably against host-cell-derived actin were also present. The patient sera contained only traces of IgM antibodies with specificity against the measles virus haemagglutinin or fusion protein. No specific IgM antibodies were found in sera from healthy controls.     

Antibodies to a putative hepatitis C virus polyprotein in Japanese patients with chronic liver disease.

To investigate the frequency of exposure to hepatitis C virus (HCV) in chronic liver disease, sera from Japanese patients were tested with the original anti-HCV assay (Ortho) and an anti-HCV assay based on synthetic peptides corresponding to a variety of regions in the HCV genome. Thirty-one (67%) of 46 patients with chronic non-A,non-B hepatitis were anti-HCV-positive by the Ortho ELISA, 20 of whom were also positive by ELISA based on synthetic HCV peptides. Eight (53%) of the 15 patients negative by the Ortho ELISA tested positive for anti-HCV by ELISA based on HCV peptides. Serum HCV RNA was detected in all cases positive for antibody to the HCV peptide and in 14 (78%) of 18 cases without antibody. Thirty-seven hepatitis B virus carriers were without anti-HCV by the Ortho ELISA and were negative for serum HCV RNA, six (16%) of whom were positive by ELISA based on HCV peptides. Antibody responses were directed against each synthetic HCV peptide used, with a considerable difference in incidence, indicating possible expression of the corresponding region in the course of HCV propagation. These findings indicate that exposure to HCV may be more common than expected based on the results of the Ortho ELISA.     

Presence of viral replicative intermediates in the liver and serum of patients infected with hepatitis C virus

Hemophilic patients may present immunological dysfunctions resulting from either human immunodeficiency virus (HIV) infection, or other factors like impure factor VIII concentrate and other viral infections. We evaluated prospectively the serologic response to polio vaccination of Israeli hemophilic patients who were vaccinated during an outbreak of poliomyelitis. Eighty-two hemophilic patients, 43 seronegative and 39 seropositive for human immunodeficiency virus (HIV), were vaccinated with enhanced inactivated poliovirus (elPV). Titers of antibodies for poliovirus types 1–3 were determined before and 4 weeks after immunization. T helper and suppressor lymphocytes (T4 and T8), B and T lymphocyte mitogenic response, and natural killer cells were tested and correlated with the response to vaccination. Both groups responded to vaccination with increased titers of antibodies to the three viral types, 4 weeks after immunization. HIV-seronegative patients, however, exhibited higher titers than the HIV-seropositive group. The same pattern was found when 21 patients were tested 1 year after the exposure to elPV. HIV seropositive patients were grouped according to their T4 count (between 16/μ and 500/μ). There was no statistically significant difference in the response of these different groups to vaccination. No correlation was found between the response to vaccination and other immune parameters. These results suggest that asymptomatic HIV-seropositive hemophilic patients respond well to elPV, irrespective of their T4 count. © 1993 Wiley-Liss, Inc.     

Absence of extensive genetic heterogeneity of hepatitis C virus in antibody-negative chronic hepatitis C

Hepatitis C virus (HCV) carriers usually have antibodies to HCV; however, there are viremic individuals without these antibodies. To investigate whether variations of the viral genome are responsible for this discrepancy, the nucleotide and deduced amino acid sequences of HCV capsid and nonstructural regions obtained from 15 viremic patients were examined. These 15 patients were infected with type 1b HCV, and 10 did not have antibody to HCV assayed with second-generation tests. The nucleotide homology of the 5 seropositive and 10 seronegative patients with the HCV prototype sequence were 91.6% and 91.9%, respectively, in the capsid region. There was no apparent difference in the deduced amino acid sequences between the two groups of patients studied (94% vs. 95%). The nucleotide and amino acid sequences of a part of the nonstructural region 3 also showed similar results. These findings suggest that absence of antibodies against both capsid and nonstructural peptides in HCV carriers is not caused by genetic heterogeneity of the viral epitopes. © 1996 Wiley-Liss, Inc.     

Foscarnet therapy in chronic hepatitis B virus E antigen carriers

Foscarnet (trisodium phosphonoformate) is a novel antiviral agent that inhibits viral-specific DNA polymerase. In the present study, eight males with chronic HBV carriage (HBeAg and HBV-DNA seropositivity greater than 12 months) showing chronic persistent hepatitis (CPH) or chronic active hepatitis (CAH) on liver biopsy received either a continuous infusion of foscarnet at 0.15 mg/kg/min for 7 days or 180 mg/kg/day divided into three daily boluses for 2 weeks. In all eight, HBV-DNA levels fell during therapy (median, 401 pg/40 microliters serum; range, 4-3, 100) vs. pretreatment levels (median, 533 pg/40 microliters; range, 30-4, 175), but in none was HBV-DNA undetectable at any stage. Within 1 month, the HBV-DNA had risen to pretreatment levels in all but one patient (with the lowest pretreatment level), who cleared HBeAg and developed anti-HBe within 3 months. Two further patients were anti-HBe positive at 6 months, but their pretreatment serum HBV-DNA levels were already low, suggesting a high probability of spontaneous seroconversion. Toxicity was not evident with the continuous infusion, but for those receiving IV bolus therapy, serum creatinine and phosphate levels rose in three of four patients, necessitating a 25% dose reduction. There was no difference in the effect on serum HBV-DNA between the two regimes. We conclude that foscarnet has only modest antiviral activity in chronic HBV carriers.     

Infection with GB virus C and hepatitis C virus in drug addicts,patients on maintenance hemodialysis,or with chronic liver disease in Nepal

Infection with GB virus C (GBV-C) and hepatitis C virus (HCV) was surveyed in various populations in Kathmandu, Nepal. GBV-C RNA and HCV RNA were detected in four (2%) and none, respectively, of 181 normal controls. Viral RNAs were detected significantly more frequently (P < 0.001) in 32 (44%) and 43 (60%), respectively, of 72 users of illicit intravenous drug, and in three (14%) and one (5%) of 22 patients on maintenance hemodialysis. The three hemodialysis patients with GBV-C RNA had been transfused with more blood units than the 19 without GBV-C RNA (51 ± 21 vs. 5 ± 3 units, P < 0.01), and one was co-infected with HCV. Of 145 patients with chronic liver disease, GBV-C RNA was detected in four (3%) and HCV RNA in 12 (8%); only one patient with GBV-C RNA was without markers of HCV or hepatitis B virus infection. In the 32 drug addicts infected with GBV-C, genotypes were G1 in two (6%), G2 in 26 (81%), G3 in three (9%), and the remaining one (3%) was coinfected with G2 and G3. GBV-C genotypes in the 13 individuals in the populations other than drug addicts were G2 in 11 (85%) and G3 in two (15%). HCV genotypes in the 43 drug addicts with viremia were I/1a in 21 (49%), V/3a in 19 (44%) and I/1a plus V/3a in two (5%); these genotypes were not prevalent in normal controls and patients with chronic liver disease in Nepal. These results indicate that GBV-C infection is prevalent in healthy subjects in Nepal at a frequency (2%) comparable with those in the other countries and that GBV-C transmits efficiently by intravenous drug abuse among drug addicts and by transfusion in hemodialysis patients. J. Med. Virol. 53:157–161, 1997 © 1997 Wiley-Liss, Inc.     

Internalisation of hepatitis C virus core protein by human conjunctival fibroblasts

Recent studies indicate that hepatitis C virus (HCV) proteins can mediate innate immune response and inflammation in conjunctival fibroblasts which contributes to the pathology of dry eye condition associated with chronic HCV infection. The present study investigates the phagocytic potential of human conjunctival fibroblasts (HCFj) for HCV core protein. HCFj cells were incubated with HCV core antigen for different periods of time, and fluorescent micrographs were taken to observe protein internalisation. HCFj cells were capable of internalising HCV core antigen within 1 h; this gives an insight into another molecular mechanism which may contribute towards HCV-associated conjunctival inflammation.     

Intrafamilial transmission of hepatitis C virus in Japan.

To clarify the intrafamilial transmission of hepatitis C virus (HCV), the prevalence of antibody to HCV (anti-HCV) in 107 index patients with type C chronic liver disease was studied and compared with the prevalence of anti-HCV antibody in their 296 family members. Of the 85 index patients who were positive for anti-HCV, 15 (8%) of 196 of their family members were also HCV antibody positive, whereas of the 22 index patients who were anti-HCV antibody negative, none of the family members of the 100 evaluated was positive for anti-HCV antibody, a statistically significant difference between groups (P less than 0.02). No specific relative (spouse, child, parent, and sibling) was linked to HCV positivity in the index cases making it difficult to identify the route of infection that is believed to occur via the parenteral route in the home or community.     

丙型肝炎病毒H株包膜糖蛋白在昆虫细胞中的表达

目的 利用杆状病毒表达系统,在昆虫细胞中表达了丙型肝炎病毒（HCV）H株的包膜糖蛋白E,并应用表达产物对HCV感染患者血清中抗膜蛋白抗体进行检测。方法 将HCVH株E基因片段克隆到杆状病毒转移载体上,转染昆虫细胞,表达包膜糖蛋白,经免疫杂交法鉴定表达产物,并用细胞间接免疫荧光法检测患者血清抗膜蛋白抗体的水平。结果 Western blot显示,表达产物中有多条分子量不同、可与HCV RNA阳性血甭反应的蛋白,细胞免疫荧光染色表明,HCV包膜糖蛋白在细胞浆中表达,用表达产物分别检测HCV患者血清,发现仅11.4%血清中含有膜抗体。结论 成功利用昆虫细胞表达了HCV包膜糖蛋白,为HCV疫苗的研究奠定了基础。     

Detection of IgA class antibody to hepatitis E virus in serum samples from patients with hepatitis E virus infection

A newly developed assay for IgA class antibody to hepatitis E virus (IgA anti-HEV) was used to study 145 serum samples collected during an outbreak of an enterically transmitted hepatitis that occurred in 3 villages in the lower Shebeli region of Southern Somalia between January, 1988 and November, 1989. A total of 52.4% of the afflicted patients were found positive for IgA anti-HEV, and 73.1% of these were also positive for IgM. Both antibodies disappeared during the convalescence period. Similar results were also seen in serum obtained from sporadic cases of acute waterborne hepatitis in Pakistan. © 1993 Wiley-Liss, Inc.