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.     

Antibody to hepatitis C virus in cryptogenic chronic liver disease.

The prevalence of antibody to hepatitis C virus (HCV) was studied in 207 patients with chronic liver disease of unknown etiology, in relation to clinical, epidemiological and histological features. Serum antibody to C-100 epitope of HCV was detected by ELISA in 82.6% of patients, with a significant difference compared with a group of patients with primary biliary cirrhosis (10%). The presence of anti-HCV antibody in serum did not correlate with age, sex, histological diagnosis, and activity and duration of the disease, nor with serum anti-HBc, used as a marker of exposure to hepatitis B virus infection. These results strongly support the view that most cases that were previously defined as cryptogenic forms of chronic liver disease are in fact related to HCV infection. There was a correlation between serum anti-HCV antibody and history of risk for parenteral exposure or of acute hepatitis. This correlation was particularly evident for transmission by parenteral route, suggesting that HCV infection may be transmitted often by this route (36.8% among anti-HCV antibody-positive patients and 11.1% among anti-HCV-negative patients). Liver disease in patients without risk factors for parenteral transmission and with lower prevalence of anti-HCV antibody may be caused by other as yet unidentified non-A, non-B (non-C) agents or may be of nonviral origin.     

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.     

Seroprevalence of hepatitis C antibody in Peru.

The prevalence in Peru of antibody to hepatitis C virus (anti-HCV) was determined in a survey of populations living in the northern jungle region and in groups at high risk of parenterally and sexually transmitted diseases. All sera were initially screened for anti-HCV using commercial first and second generation ELISAs; repeatedly reactive sera were further verified with a second generation immunoblot assay. Serum samples were also tested by ELISA for HBsAg, anti-HBs, and anti-HBc. None of 2,111 sera obtained in the survey of jungle residents was positive for anti-HCV by immunoblot assay. Twelve of 16 HIV-1 antibody positive hemophiliacs, one of 103 HIV-1 antibody positive homosexuals, and three of 602 HIV-1 negative registered female prostitutes were positive for anti-HCV. A high prevalence of total markers of hepatitis B infection was found in all subjects, especially in older subjects and groups at high risk of parenterally and sexually transmitted diseases. The findings of this study indicate that seropositivity for hepatitis C virus antibody is uncommon in Peru except in high risk groups and suggest that the epidemiology of hepatitis C differs substantially from hepatitis B.     

Mother to infant transmission of hepatitis C virus infection

Eight women with chronic hepatitis C virus (HCV) infection during pregnancy gave birth to 11 children. Five of these children had elevated ALT, but only two had increased levels in more than one sample. All children tested before 6 months of age were positive for anti-HCV at most up to 7 months of age and then became negative. One child with a maximum ALT level of 8.4 mukat/l however, regained anti-HCV positivity at 12 months of age, and a liver biopsy at 21 months of age showed resolving hepatitis. Passively acquired HCV antibodies are obviously found in newborns of anti-HCV-positive mothers with chronic hepatitis. In 1 of 11 children, active anti-HCV production and concomitant liver disease suggested mother to infant transmission of hepatitis C virus infection.     

A prospective study of post-transfusion non-A, non-B (type C) hepatitis following cardiovascular surgery in Taiwan

In an attempt to investigate the incidence and clinical course of non-A, non-B (NANB) hepatitis following blood transfusion in Taiwan, 288 patients who underwent cardiovascular surgery and received blood transfusion were followed prospectively with serum liver aminotransferase levels and viral hepatitis markers for at least six months. None had any past history of liver disease or drug abuse. All blood donors were tested for serum hepatitis B surface antigen and alanine aminotransferase (ALT) (greater than 45 U/L). Thirty-seven (12.8%) patients developed PTH. 34 (91.9%) were considered to be cases of NANB hepatitis, 2 (5.4%) were cytomegalovirus hepatitis, and one (2.7%) was caused by Epstein-Barr virus. No one developed hepatitis B post-transfusion hepatitis (PTH). Of the 34 NANB PTH patients, 15 (44.1%) were asymptomatic, 16 (47.1%) had clinical symptoms, and 9 (26.5%) had serum total bilirubin levels higher than 2 mg/dl. There was no case of fulminant hepatic failure. Of 26 NANB PTH patients who were followed up for more than one year, 15 (57.7%) still had abnormal serum ALT levels. The incubation period of NANB PTH ranged from 2 to 16 (mean 6.1 +/- 3.2) weeks. Of the 37 PTH patients, 32 (86.5%) were found to have anti-HCV seroconversion during one year follow-up period. NANB PTH is as common in Taiwan as in the United States and Japan, and is demonstrated by this study to be due mostly to HCV.     

Minimal role of hepatitis C virus infection in childhood liver diseases in an area hyperendemic for hepatitis B infection

To investigate the role of hepatitis C virus (HCV) in childhood liver disease in Taiwan, an area hyperendemic for hepatitis B, we studied antibody to HCV (anti-HCV) with a second generation enzyme immunoassay in 195 infants and children, including 96 hepatitis B surface antigen (HBsAg) positive children (66 with chronic hepatitis B, 23 children with hepatocellular carcinoma, and 7 with fulminant hepatitis B), 6 children with fulminant non-A, non-B hepatitis, 42 infants with neonatal hepatitis, 11 with biliary atresia, and 40 prospectively followed blood recipients. For comparison, another 748 apparently healthy children (from neonates to 12 years) were also screened for anti-HCV. The positive rate of anti-HCV was low in both apparently healthy children (0.13%) and patients with various liver disorders (0 to 4.4%) except fulminant hepatitis. The seropositive rate in 6 cases of non-A, non-B fulminant hepatitis was higher (16.7%) although the case number was too small. We conclude that HCV is generally not a major etiologic factor in the liver diseases of Taiwanese children. © 1993 Wiley-Liss, Inc.     

Hepatitis C virus RNA in plasma and blood mononuclear cells in patients with chronic hepatitis C treated with alpha-interferon

Hepatitis C virus (HCV), a positive stranded RNA virus, is the main causative agent of post-transfusion and sporadic non-A non-B hepatitis worldwide. Paired samples of plasma and peripheral blood mononuclear cells (PBMC) from 11 patients with chronic hepatitis C treated with α-interferon (IFN) were tested, using a single step polymerase chain reaction (PCR), for the presence of HCV RNA. Before treatment, the viral genome was detected in all the plasma samples and 81.8% of PBMC. After 3 months of treatment, HCV RNA was still present in 63.6% of plasma samples but in only 27.3% of PBMC. A good correlation was observed between serum alanine aminotransferase level normalisation and disappearance of the viral genome in plasma. Among the six responder patients, five relapsed shortly after IFN withdrawal; HCV RNA became detectable again, especially in PBMC. These results show the presence of HCV in PBMC from most patients infected chronically. IFN therapy had an inhibitory effect on viral replication in lymphoid cells, but frequent relapses observed after cessation of treatment with IFN suggested persistence Of HCV in these Cells. © 1995 Wiley-Liss, Inc.     

Hepatitis C virus and its genotypes in patients suffering from chronic hepatitis C with or without a cryoglobulinemia-related syndrome

Recently, evidence has been presented for a possible association between hepatitis C virus (HCV) infection and essential mixed cryoglobulinemia (EMC). Eleven consecutive patients with EMC and two with cryoglobulinemia type I were examined for the presence of markers of HCV infection. Eleven of 13 patients (10 with EMC and 1 with type I cryoglobulinemia) had anti-HCV antibodies (as determined by a second generation anti-HCV assay) and HCV-RNA in plasma or serum. HCV-RNA was also detected in liver biopsies of five patients. Genotyping showed that HCV genotype 1 was found in 10 of 11 patients with HCV-RNA (9 genotype 1b and 1 genotype 1a) and only one patient had HCV genotype 2. However, a similar high prevalence of genotype 1b (100%) was found in a group of 14 consecutive patients with chronic hepatitis C, who had no clinical evidence of cryoglobulinemia. Concomitant infection was present in three patients with genotypes 2, 3 and 4, respectively. These findings stress the high prevalence of HCV infection in patients with EMC and further study shows that a difference in genotype prevalence was not found between HCV-related EMC and chronic hepatitis C without clinical manifestations of EMC. © 1994 Wiley-Liss, Inc.     

Non-A, non-B hepatitis in persistent carriers of hepatitis B virus

There are reports in the literature that infection with hepatitis A virus in hepatitis B carriers can result in resolution of the carrier state. In an attempt to induce clearance of the carrier state of hepatitis B virus in two persistently infected chimpanzees, the chimpanzees were infused with documented non-A, non-B infectious material. Biochemical and histopathological evidence of hepatitis was accompanied by the unique abnormalities of endoplasmic reticulum associated with non-A, non-B hepatitis in the chimpanzees. Elevation of alanine aminotransferase was accompanied by fourfold reduction in one chimpanzee and sixfold reduction in the other in the plasma levels of HBV-associated DNA polymerase activity and simultaneously by twofold reduction in the concentration of hepatitis B surface antigen in both chimpanzees. A mediator may account for these changes in markers of hepatitis B virus infection, and this mechanism may also explain the occurrence of spontaneous regression in some persistently infected carriers. The significance of transient red cell anaemia in non-A, non-B hepatitis, which was observed in one of the chimpanzees, is yet to be established.     

Experimental infection of Tamarins with human non-A, non-B hepatitis virus

Non-A, non-B (NANB) viral hepatitis was successfully transmitted to two colony-born Tamarins following inoculation with antihaemophilic factor VIII concentrate or the "H" inoculum. Both animals showed histological and ultrastructural evidence of viral hepatitis, with raised alanine aminotransferase (ALT) levels from the second week after inoculation through to the end of follow-up, 5 months later.     

Patterns of serological markers in transfusion-transmitted hepatitis C virus infection using second-generation HCV assays.

A semiautomated dot blot assay and cDNA polymerase chain reaction (PCR) were used to study longitudinal anti-hepatitis C virus (HCV) recognition patterns in relation to presence of HCV-RNA in transfusion recipients and their infectious donors. In 9 recipients, 4 different patterns of HCV infection were observed: (A) persistent HCV carriage accompanied by chronic hepatitis in 6, (B) acute resolved hepatitis, but persistent HCV replication in one, and (C) continuous HCV replication without hepatitis in one and (D) acute resolved hepatitis with clearance of infection in one. This last self-limited infection was characterized by the disappearance of HCV-RNA as well as anti-HCV reactivity. In contrast, antibody reactivity persisted in 7 of 8 patients with chronic HCV infection who could be followed until 1990. Seven of the 9 recipients developed antibodies to all recombinant peptides in dot blot assay; one became positive for anti-C33 and anti-core and one developed anti-core only. The sequence of appearance of antibodies differed among individual patients. In 7 patients with full anti-HCV recognition patterns, the sequence of events was (mean and limits in days after transfusion): onset of hepatitis at day 50 (22-74), seroconversion of anti-C33 at day 91 (59-129), anti-core at day 133 (54-203), and anti-C100 at day 143 (59-365). The incorporation of C33 and core proteins, in addition to C100, in the second generation anti-HCV ELISA enhanced the detection rate in the HCV-infected transfusion recipients from 7/9 (78%) to 9/9 (100%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Association of hepatitis C virus carrier state with the occurrence of hepatitis C virus core antibodies.

An enzyme immunoassay (EIA) was developed for the determination of antibodies against the "putative" core protein of hepatitis C virus (HCV). Antigens used were recombinant fragments (amino acids 6-77 or 6-143) of the HCV core protein, produced in Escherichia coli with truncated hepatitis B core (HBc) as fusion protein. Evaluation of 385 sera positive for HCV antibodies by first generation EIA, revealed 98 (25.4%) with HCV core antibodies. HCV-RNA, determined by the polymerase chain reaction (PCR), was exclusively found in the sera positive for HCV core antibodies (89 PCR positives). In random screening of 3,708 sera, 3 sera with HCV core antibodies were found PCR positive. Only 2 of these sera were positive in the first generation EIA. It is concluded that HCV core antibody determination is a reliable test for identifying HCV carriers among blood donors.     

Serum antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma

Antibodies against hepatitis C virus (anti-HCV) were detected in 60.8% of 78 patients with hepatocellular carcinoma (HCC). Cirrhosis, present in most of the patients, as well as alcohol abuse, age, sex, and alpha-fetoprotein were equally distributed in the anti-HCV-positive and -negative groups. HBsAg positivity was significatively higher in negative anti-HCV group. By contrast, hepatitis B virus (HBV) antibodies were detected more frequently in positive anti-HCV patients than in the negative anti-HCV group. These data must be considered with caution because of the small number of HBsAg-positive patients. It is concluded that the high prevalence of anti-HCV in patients with HCC may suggest an etiological role of the hepatitis C virus, although in relationship to age, alcohol abuse and cirrhosis, the similarity in the two groups questions this hypothesis.     

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.     

Non-A,non-b hepatitis virus: identification of a core antigen-antibody system that cross reacts with hepatitis b core antigen and antibody

Using immunodiffusion, a major cross-reactivity had been previously demonstrated between hepatitis B(HBe/3 Ag) and the antigen reported in the serum of non-A, non-B hepatitis patients, therefore redesignated NANBe Ag. By direct immunofluorescence a new antigen associated with, but distinct from, NANBe Ag has now been identified in the liver of 14/26 patients with NANB chronic active hepatitis. The homologous antibody was detected in the serum of these 14 patients. Behaving like HBc Ag and cross reacting with it by immunofluorescence, the new antigen was termed NANBc Ag. Anti NANBc also became detectable in serial acute phase and convalescence sera from 5/5 NANB Ag-positive posttransfusion hepatitis cases. Further characterization of NANBe and NANBc antigens achieved by fractionation of a NANB virus-infected liver showed NANBc Ag to be expressed on 22–25 nm HB core-like particles containing DNA polymerase activity. Cross-reactivity between NANBc and HBc antigens was confirmed by immunodiffusion. Liver-derived NANBe Ag identical to serum NANBe Ag exhibited the same physical properties as HBe/3 Ag and could be similarly released by disruption of the non-A, non-B virus cores. These results indicate that hepatitis B and NANB virions not only share the same structure and DNA polymerase activity but are also antigenically related and belong to the same new class of DNA viruses.     

Prevalence of hepatitis C virus antibodies among patients infected with human immunodeficiency virus.

A study was undertaken to determine the prevalence and risk factors for serological evidence of hepatitis C virus (HCV) infection in patients infected with the human immunodeficiency virus (HIV). Tests for anti-HCV antibody were carried out by enzyme-linked immunoassay (EIA) on 101 HIV-infected patients from two university-based outpatient clinics. Anti-HCV antibody reactive samples were tested by using a recombinant immunoblot assay (RIBA) for HCV antibodies. Fourteen of 101 (13.9%) HIV-infected patients were anti-HCV reactive by EIA. Of these 14, only seven were reactive by RIBA: four were intravenous drug users as a sole risk factor for HIV infection; and the remaining three acquired HIV by blood transfusion, contaminated instrument exposure or IV drug use and sexual contact. Acquisition of HIV by sexual activity alone was not associated with HCV infection. It is concluded that HCV infection is found in approximately 7% of a university HIV clinic population. False-positive anti-HCV antibody serology may lead to overestimation of the prevalence of HCV infection. Female sex and intravenous drug use are significantly associated with HCV infection among HIV-infected individuals.     

Absence of detectable hepatitis B virus DNA in sera and liver of chimpanzees with non-A, non-B hepatitis

The risk of hepatitis B infections has been reduced by screening of blood donors for hepatitis B surface antigen (HBsAg). However, recipients remain at significant risk of developing post-transfusion hepatitis. Studies have shown that non-A, non-B hepatitis virus(es) are responsible for the majority of post-transfusion hepatitis infections. In spite of many efforts, these non-A, non-B hepatitis viruses have not yet been identified. Epidemiological studies, however, suggest that non-A, non-B hepatitis shares many features with hepatitis B. Recently, Wands et al [1982] showed, in chimpanzees infected with non-A, non-B hepatitis agents, the presence of antigenemia or viremia by radioimmunoassay with monoclonal antibodies directed toward distinct determinants of HBsAg and by molecular hybridization analysis. They suggested that non-A, non-B hepatitis agents may be related, but distinct variant(s) of hepatitis B virus (HBV). In this study, five chimpanzees were inoculated with three different agents that have been shown to transmit non-A, non-B hepatitis. The following inocula were used (I) a factor VIII preparation kindly provided by D.W. Bradley, (II) acute phase serum from a chimpanzee infected with the F strain kindly provided by A.J. Zuckerman, and (III) a DS-antigen serum previously shown by us to transmit non-A, non-B hepatitis [Duermeyer et al, 1983]. All chimpanzees developed a rise in transaminase levels between 8 and 10 weeks after inoculation. None of the chimpanzees was positive for any markers of HBV infection. No evidence was obtained of infection with hepatitis A, cytomegalovirus, or Epstein-Barr virus. One chimpanzee developed chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Post-transfusion hepatitis: antigen/antibody systems correlated with non-A, non-B hepatitis

In seven patients post-transfusion hepatitis (PTH) was due to non-A, non-B virus(es) (38.9% of all PTH, while 61.1% were due to hepatitis B virus (HBV). No clinical or biochemical differences were observed in non-A, non-B PTH when compared with PTH due to HBV, while incubation period was very ample, from 15 days to nine months (generally 45 days to two months). An antigen/antibody system was shared by five of our patients (their sera showed precipitin lines when assayed by immunodiffusion with known sources of antigen or antibody), while in one patient an antigen/antibody system was detected when onset serum was assayed with self-recovery serum but not when assayed with known sources of antigen and antibodies, nor with sera of the other five patients. Antigen was detected during the first weeks of illness, antibody at recovery, for both systems. The results suggest that there may be at least two antigen/antibody systems correlated to non-A, non-B hepatitis not necessarily linked to incubation period.