Hepatitis C virus infection in 2,744 hemodialysis patients followed regularly at nine centers in Hiroshima during November 1999 through February 2003

Patients on maintenance hemodialysis (HD) are at increased risk of infection with hepatitis C virus (HCV). A prospective follow-up study on HCV infection from November 1999 to February 2003 was conducted in nine hemodialysis (HD) units in Hiroshima. A total of 2,744 HD patients were surveyed regularly for HCV RNA in serum. The prevalence of HCV RNA decreased from 15.7% (262/1,664) on the first survey to 12.9% (242/1,882) in the last one (P<0.05). This decrease may be attributed to the inclusion of patients with a lower prevalence of HCV RNA compared to patients leaving dialysis centers (111/1,080 [10.3%] vs. 132/862 [15.3%], P<0.01). During the 40 months of this study, 16 de novo HCV infections were documented in the nine HD units corresponding to an incidence of 0.33% per year. These cases included eight new HCV infections, three re-infections, and five infections that presumably occured in the window period when tested during the first survey. Our study shows that the annual incidence of de novo HCV infection during HD was 0.33%, and emphasizes the need for frequent serum HCV RNA testing and for stringent disinfection procedures in order to prevent the transmission of HCV in these settings.     

Chronic hepatitis A with persistent viral replication

Hepatitis A virus (HAV) usually causes an acute self-limited illness. This report describes a patient with hepatitis A whose serum aminotransferase activities remained above normal and whose serum was persistently positive for immunoglobulin (Ig) M class anti-hepatitis A 31 months after the onset of hepatitis. Liver biopsy carried out 11 months after the onset of hepatitis showed histological changes consistent with chronic hepatitis of moderate severity. HAV RNA was detected by polymerase chain reaction (PCR) in feces collected at the time of the liver biopsy. Furthermore, the patient developed esophageal varices 25 months after the onset of hepatitis. We believe this to be the first reported case in which persistent replication of HAV is implicated in chronic hepatitis with the potential to develop into liver cirrhosis. © 1996 Wiley-Liss, Inc.     

Hepatitis B and hepatitis C among institutionalized psychiatric patients in Taiwan

To investigate the seroprevalence of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) in a psychiatric institution in Taiwan, where hepatitis B virus (HBV) is hyperendemic, a total of 780 patients with psychiatric disorders were studied. Enzyme-linked immunosorbent assays (ELISA) were used for testing HBsAg and anti-HCV. The prevalence of HBsAg was higher than that of anti-HCV among these patients (18.1% vs. 6.8%, P < 0.0001). The HBsAg carrier rate in these patients was consistent with that of the general population, with a trend for HBsAg carrier rate to be lower in the aged and in females. In contrast, the prevalence of anti-HCV was higher in these patients than in general population. Anti-HCV positivity was found more frequently in patients who had received blood transfusion previously (24% vs. 6.4%, P < 0.05). The majority (92%) of patients with positive anti-HCV did not have a history of apparent parenteral exposure. The prevalence of anti-HCV increased significantly with duration of the psychiatric disorder. The prevalence of anti-HCV also tended to increase with duration of hospitalization but without reaching statistical significance. These findings suggest that these institutionalized psychiatric patients contract hepatitis B, as does the general population in Taiwan, and they should be considered as a specific risk group for hepatitis C infection. © 1993 Wiley-Liss, Inc.     

Clinical characteristics and antibody profiles of chronic hepatitis C patients: Relation to hepatitis C virus genotypes

Genotyping of 179 consecutive Japanese chronic hepatitis C patients was carried out based on the variation in the hepatitis C virus (HCV) core gene. The results were correlated with clinical features and antibody responses toward specific HCV proteins deduced from the nucleotide sequence of genotype I/1 a. Genotypes II/1 b, III/2a, and IV/2b were identified in 138 (77%), 24 (13%), and 12 (7%) patients, respectively. Five patients had double infections. Genotype dependence was observed only for antibody response toward the NS4 (5–1–1) protein, which was infrequent in genotype III/2a patients (33%) compared with genotype II/1 b (81%; P < 0.01) and genotype IV/2b (75%; P < 0.05). Following interferon-α therapy, sustained aminotransferase normalisation was achieved by 89% (eight of nine) patients without antibody to the 5–1–1 protein and 33% (17 of 51) with it (P < 0.01). These findings indicate that absence of antibody response to the 5–1–1 protein is frequent in genotype III/2a HCV carriers and may serve to predict responses to interferon therapy. © 1995 Wiley-Liss, Inc.     

Changes in Hepatitis C Virus Genotype Distribution in Chronic Hepatitis C Infection Patients

Purpose: Identification of hepatitis C virus (HCV) genotypes is very important in the selection of antiviral treatment, dose adjustment of antiviral agents, determining the treatment duration and following-up of treatment response. We aimed to determine the distribution pattern of HCV genotypes in chronic hepatitis C infection (CHC) patients. Materials and Methods: We have included 106 CHC patients who were positive in the anti-HCV and HCV-RNA tests performed in our hospital during the 16-month period. Anti-HCV assays were performed on device using a chemiluminescent microparticle immunoassay, while HCV-RNA tests and HCV genotyping assays were performed by real-time polymerase chain reaction. Results: Of the 106 cases; genotype 1b was detected in 67.0%, genotype 3 was detected in 16.0%, genotype 1a was detected in 14.2% and genotype 2 was detected in 2.8% patients. Genotypes 4, 5 and 6 were not detected in our study group. There were no statistically significant differences between the gender and age groups according to the HCV genotype distribution. The genotype 3 detection rate (16%) was the highest rate among the studies compared with the other studies in our country. Conclusions: Events that cause social changes such as war and immigration and intense commercial and touristic activities affect and alter the HCV genotype distribution in HCV-infected patients. For this reason, further multicentre studies are required reflecting all the regions in order to determine the genotype distribution in HCV-infected patients at regular intervals.     

An Ultrastructural Study of Six Cases of Chronic Active C Hepatitis. A Comparison with Chronic Active B Hepatitis

Liver biopsies from six patients affected by chronic active hepatitis (CAH) induced by hepatitis C virus (HCV) have been investigated ultra-structurally and their features compared with those of five cases of CAH induced by hepatitis B virus (HBV). Clusters of deeply packed nuclear inclusions (18 to 22 nm in diameter) were found in patients with HCV-CAH. They were irregularly round and ill-delimited. These inclusions were distinct from the regular round and well-delimited nuclear inclusions associated with HBV. HCV-associated nuclear inclusions were similar to a peculiar type of intranuclear particle described in non-A, non-B hepatitis before the HCV disease had been recognized as a distinct entity. These inclusions have never been hitherto reported in infections caused by HBV or other known hepatotropic viruses. Together, these data suggest that the occurrence of these inclusions can be related to HCV activity in hepatocytes. Changes in the microarchitecture of the liver cell and its microenvironment were similar in HCV- and HBV-CAH. They were heterogeneous in different cases and did not display a clear correlation with the severity of the disease.     

Hepatitis C virus antibody in hepatocellular carcinoma in Taiwan.

The prevalence of antibody to hepatitis C virus (anti-HCV) was investigated in patients with hepatocellular carcinoma (HCC), and correlated with the clinical features. Anti-HCV was detected in 129 histology or aspiration cytology proven HCC patients and 54 healthy controls. Anti-HCV was examined by the HCV EIA (Abbott Laboratories). All healthy controls were anti-HCV-negative. Nineteen of 81 (23.5%) hepatitis B surface antigen (HBsAg)-positive HCC patients were positive for anti-HCV. Anti-HCV was found among 60.4% (29/48) of HCC patients without detectable HB-sAg. Forty-eight of 129 (37.2%) HCC patients were positive for anti-HCV. There was a significant difference in the prevalence of anti-HCV between patients with HBsAg (23.5%) and those without HBsAg (60.4%, P = 0.0001). However, irrespective of the status of HBsAg, there was no statistical difference in sex, age, routine liver function tests, alpha-fetoprotein concentration, or associated cirrhosis between patients with anti-HCV and those without. The results imply that hepatitis C virus may play a role in the pathogenesis of HCC.     

Hepatitis C virus infection as a risk factor for non-alcoholic liver cirrhosis in taiwan

To assess whether hepatitis C virus infection was a risk factor for the development of non-alcoholic liver cirrhosis, antibody to hepatitis C virus (anti-HCV; detected by a second generation HCV enzyme immunoassay), hepatitis B surface antigen (HBsAg; detected by radioimmunoassay) were tested in 150 cirrhotics and 150 sex-matched and age-matched healthy controls. The prevalence of anti-HCV and HBsAg in cirrhotics was higher than in controls (22.0%, 73.3% vs. 2%, 18.7%; P = 0.001). The prevalence of anti-HCV in HBsAgnegative cirrhotics (45.0%) was higher than that in HBsAg-positive patients (13.6%; P =0.001). Both the anti-HCV and carriage of HBsAg were associated significantly with liver cirrhosis, showing odds ratio of 12.0 for HBsAg carriers and 13.8 for patients with anti-HCV. Compared with those without HBsAg and anti-HCV, there was a significantly positive linear trend for developing cirrhosis with the presence of HBsAg alone (odds ratio = 19.9), anti-HCV alone (odds ratio = 49.0), and those positive for HBsAg and anti-HCV (odds ratio = 81.8) (P = 0.00001). The population-attributable risk for developing liver cirrhosis was estimated as 10.8% for anti-HCV alone, 55.2% for HBsAg alone, and 9.4% for both anti-HCV and HBsAg in southern Taiwan. In conclusion, this study shows that hepatitis B and C virus infection act independently and synergistically in the development of non-alcoholic liver cirrhosis among Chinese in Taiwan.     

Hepatitis C genotypes in patients with dual hepatitis B and C virus infection

In patients with chronic hepatitis B and C virus (HBV, HCV) infection, an inverse relationship in the replicative activity of the two viruses has been reported. In the present study the genotype of HCV was evaluated in 34 consecutive cases found with hepatitis B surface antigen (HBsAg) and anti-HCV in the serum, in order to identify its possible influence in determining the pattern of HBV/HCV interaction. Nineteen patients were HCV-RNA positive and could be genotyped: 8 were infected by HCV-1 (3 by HCV-1a and 5 by HCV-1b), 10 by HCV-2, and only 1 by HCV-3. Among these, 3 were HBV-DNA positive, compared to 10 of 15 HCV-RNA-negative patients (P = 0.003), and all 3 were coinfected with HCV-2. Mean alanine aminotransferase (ALT) levels were similar between patients infected with HCV-1 and HCV-2. Among 7 patients with cirrhosis 5 were infected by HCV-2, while 6 of 12 of those without cirrhosis had HCV-1 infection. In conclusion, HBV replication was inhibited more efficiently by HCV-1 than by HCV-2. Cirrhosis was frequently found in patients with dual HBV and HCV-2 infection. © 1996 Wiley-Liss, Inc.     

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.     

Hepatitis C virus and liver diseases

Hepatitis C virus (HCV) was identified molecularly and a procedure for its diagnosis was developed. In Japan, 70–80% of all cases of chronic liver disease, including hepatocellular carcinoma, are associated with HCV infection. Hepatitis C virus is a typical RNA virus with a high mutation rate. At least six variants of HCV have been identified by their nucleotide sequences. These variants are still classified into three types each containing at least two subtypes; that is, 1a (type I) and 1 b (type II), 2a (type III) and 2b (type IV), and 3a (type V) and 3b (type VI). Type 1 b (type II) is the predominant HCV in Japan. Even HCV cDNA clones isolated from a single patient showed mutations of HCV, especially in envelopecoding regions. Thus HCV may change during the course of chronic hepatitis due to the high mutation rate of HCV itself and elimination of some clones by immune reactions or interferon therapy. These findings explain the higher rate of chronic HCV infection and indicate that production of an effective vaccine is difficult.     

Prevalence and significance of antibodies to hepatitis C virus among Saudi haemodialysis patients.

Seventy-four patients who were maintained on chronic haemodialysis in King Khalid University Hospital, Riyadh, Saudi Arabia were tested using the recently available ELISA to determine the prevalence of antibodies to hepatitis C virus (anti-HCV) in a haemodialysis unit. The prevalence rate of anti-HCV antibodies of 41.9% in the haemodialysis patients was significantly higher than the rate of 3.9% detected in 488 asymptomatic blood donors who were similarly tested. In the haemodialysis patients, anti-HCV positivity was related to previous blood transfusion (greater than 5 units of blood) and to the duration of haemodialysis (greater than 4 years); but was unrelated to sex, age, positive HBV markers or to past or current elevation of serum ALT. The results indicate a relatively higher prevalence of anti-HCV antibodies in our patients compared to rates of 1-20% reported from Europe and the U.S.A. An effective control strategy for HCV infection in this high risk group is urgently indicated.     

Genetic variability of hepatitis C virus in chronically infected patients with viral breakthrough during interferon-ribavirin therapy

Little is known about hepatitis C virus (HCV) breakthrough during antiviral therapy, although it would help in understanding HCV resistance to current antiviral treatments. To analyse the implication of virological factors and the vigour of humoral immune responses in this phenomenon, we studied nine chronic hepatitis C patients with a viral breakthrough during IFN/ribavirin combination therapy, as well as five responders and five non-responders. The IRES and regions coding for the capsid protein, the PePHD domain of envelope glycoprotein E2 and the NS5A and 5B proteins were amplified by RT-PCR before treatment, before and during breakthrough, and after treatment. The major variant sequence was obtained by direct sequencing. The heterogeneity of quasispecies was studied by SSCP in all patients and sequencing after cloning in seven genotype 1b-infected patients. Humoral responses against HCV epitopes were also analysed. The major sequences of IRES, PePHD, and NS5B remained stable during treatment, regardless of the treatment response. However, the capsid protein and the regions flanking PePHD showed sequence variations in breakthrough patients, although no specific mutation was identified. The variable V3 region of NS5A, but not the PKR-binding domain and the ISDR, seemed to be associated with differences in response to treatment. The analysis of HCV quasispecies revealed no characteristic pattern during treatment in breakthrough patients, whose HCV genome profiles looked most similar to that of non-responders. The humoral response was similar between groups. In conclusion, viral breakthrough does not seem to be due to selection of resistant strains with signature mutations.     

Interference of replication between hepatitis B and C viruses in patients infected with HIV

The clinical and cellular interactions between hepatitis B virus (HBV) and hepatitis C virus (HCV) were investigated in patients co-infected with the human immunodeficiency virus (HIV). One hundred ninety-nine patients followed for 6 years were evaluated to compare the level of HBV DNA and HCV RNA in patients co-infected with HIV and HBV, and patients co-infected with HIV, HBV, and HCV. A full-length HBV genome and HCV JFH1 RNA were co-transfected into HuH-7.5.1 cells in vitro to examine the impact of co-infection and dependence on the HBV PreC mutant for replication interference. Before 2',3'-dideoxy-3'-thiacytidine (3TC)-based antiretroviral therapy (ART) was initiated, HBV DNA was found in 56/123 (45.4%) patients co-infected with HIV and HBV, and in 19/76 (25.0%) patients co-infected with HIV, HBV, and HCV. After 3TC-based ART was initiated, detectable HBV DNA decreased to 7/76 (9.2%) in patients co-infected with HIV, HBV, and HCV, but HCV RNA increased from 43/76 (56.6%) to 60/76 (78.9%) (P = 0.003). In vitro HBV and HCV co-infection led to decreased replication of both viruses. The primary factors that influenced the decreased replication were the order of the HBV and HCV infection and the HBV PreC mutation.     

输血后肝炎病例中丙型肝炎的分析

７３例输血后肝炎经血清学检测，乙型肝炎病毒表面抗原和／或抗ＨＢｃ阳性２１例，抗丙型肝炎病毒抗体阳性６２例，显示输出后肝炎以丙型肝炎为主，在６２例输后血丙肝中，８２．２６％的患者输血或输血浆后６个月血清抗ＨＣＶ阳转；输血血组与输血浆组比较，输注量与输血后丙型肝炎的发生无关。提示血浆比全血更易传播丙型肝炎。部分随访病例说明丙型肝炎慢性化趋势较高。     

Autoimmune forms of chronic hepatitis associated with hepatitis C virus (HCV) infection with and without HCV-RNA: histological differences from pure autoimmune hepatitis and chronic hepatitis C

Liver biopsy specimens of pure autoimmune hepatitis (pAIH), autoimmune forms of chronic hepatitis with positivity for anti-hepatitis C virus (anti-HCV) and negativity for HCV-RNA (cAIH-RNA(-)), autoimmune forms of chronic hepatitis with positivity for anti-HCV and HCV-RNA (cAIH-RNA(+)), and chronic hepatitis C (CHC) were compared histologically and statistically to clarify the histological character of the autoimmune form of chronic hepatitis with HCV infection. The following representative histological features were used to investigate: inflammation, fibrosis, plasma cell infiltration, lymphoid aggregates/follicles, non-suppurative destructive cholangitis, and the shape of the enlarged portal tracts. While a considerable overlap in histological features between the pAIH and cAIH-RNA(-) groups and between the CHC and cAIH-RNA(+) groups was recognized, the overlap between the pAIH and CHC groups was small. Significant differences were found between cAIH-RNA(-) and cAIH-RAN(+) groups, especially in necroinflammatory findings. In conclusion, most cases of cAIH-RNA(-) with histological features similar to those of pAIH were shown to be AIH. The remaining cases might be CHC with subsidence of viral duplication. Conversely, many cases of cAIH-RNA(+) with histological findings similar to those of CHC were shown to be CHC clinically mimicking pAIH. The remaining cases might represent coexistence of pAIH and HCV infection.     

Distribution of Hepatitis C Virus Genotypes in Istanbul,Turkey

Purpose: The hepatitis C virus (HCV) has seven main genotypes and multiple subtypes. The distribution of HCV genotypes varies across geographical regions worldwide. Updated estimates of HCV genotype distributions have a critical importance for developing strategies to manage or eliminate HCV infection. The aim of this study was to determine the distribution of HCV genotypes in patients with HCV admitted to a university hospital in Istanbul, Turkey. Materials and Methods: A total of 412 HCV RNA positive patients with 46.6% of males and 53.4% of females between January 2013 and September 2016 were included in the study. Genotyping of HCV of the study population was performed by a commercial reverse hybridisation line probe-based assay. Results: Genotype 1 (82.5%) was dominant genotype, followed by genotype 3 (10.7%), genotype 2 (4.6%) and genotype 4 (2.2%). Among patients with genotype 1, subtype 1a, 1b and undetermined subtype were 6.3%, 38.8% and 37.4%, respectively. It was observed that genotype proportion was dependent on gender and age of the patients. Genotype 1 and genotype 2 were more prevalent in females, whereas genotypes 3 and 4 were more prevalent in males. Genotype 1 in the older patients and genotype 3 in the younger patients were more prevalent. Conclusion: The majority of patients with HCV infection had genotype 1 (82.5%), followed by genotype 3, 2 and 4. Monitoring the change in HCV genotype distribution is critical for the development of effective strategies for HCV elimination.     

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.     

Interferon therapy in chronic hepatitis C virus: Evidence of different outcome with respect to different viral strains

The aim of the study was to assess the role of different viral strains of hepatitis C virus (HCV) in determining the outcome of the alpha-interferon (IFN) therapy. Fifty-seven patients (34 from Italy and 23 from Japan) with HCV-positive liver disease were enrolled in the study. The NS4 region of HCV was amplified in sera by “nested” polymerase chain reaction (PCR) using a primer pair synthesized according to the sequence of JK-1. The NS4 region was positive in 14 (41%) Italian and in 13 (56%) Japanese patients. In positive patients the sequence of the NS4 region was also obtained. Subsequently, HCV genotype was determined in all patients by PCR amplification of the core region. All patients received recombinant alpha2a-interferon (IFN), 6 million units 3 times a week for 1 month followed by 3 million units 3 times a week for 5 months. The patients were followed for 1 year after the end of treatment. At the end of the follow-up, 17 (30%) had sustained normal levels of serum alanine aminotransferase (ALT). The outcome of treatment was not correlated with race, age, sex, histology, and pretreatment ALT level, but was significantly (P < 0.00001) associated with the presence of both the NS4-JK-1 region and HCV type II. Among the 27 NS4-positive patients, only 1 patient (3.7%) achieved a complete response, whereas the remaining 26 patients (96.3%) either were non-responders or relapsed after IFN was discontinued. In contrast, among the 30 NS4-JK-1-negative patients, 15 (53%) had a sustained remission. HCV genotyping showed type I in 3 (6%), type II in 40 (74%), type III in 4 (7%), and type IV in 3 (6%) cases. Coinfection was present in 4 (7%), while in 3 cases amplification was not obtained. Patients with type II were all non-responders or relapsers, while a response to the treatment was oberved in 17 of 17 (100%) of the remaining patients. These data indicate that the presence of JK-1 variant of HCV or HCV type II is almost always predictive of a poor response rate Of IFN therapy. © 1995 Wiley-Liss, Inc.