The prevalence of antibody to hepatitis C virus (anti-HCV) in patients with acute and chronic liver diseases in Jakarta, Indonesia

The seroepidemiology of HBV and HCV infections in the patients with acute and chronic liver diseases in Jakarta was investigated. The sera from 141 cases with acute hepatitis, 176 liver cirrhosis and 70 hepatocellular carcinoma (HCC) were exmained. Anti-HA IgM, HBsAg, antiHBc IgM and anti HCV (Ortho) were detected by Elisa method. In acute hepatitis, 83 cases (58.9%) out of 141 cases were hepatitis A and 9 cases (6.4%) hepatitis B. The others were diagnosed non-A, non-B (NANB) hepatitis and anti-HCV in 4 cases (11.8%) out of 34 cases with NANB hepatitis was positive. The low prevalence of antiHCV in acute NANB hepatitis seems to be due to inadequate date of serum sampling. HBsAg and anti-HCV in liver cirrhosis were positive 36.5% and 73.9% respectively, including 22.7% of double infection. HBsAg and anti-HCV in HCC were 58.6% and 34.2%, including 17.1% of double infection. In 16.7% fo chronic liver disease (liver cirrhosis and HCC), neither HBsAg nor anti-HCV were detected.     

Prevalence of anti-HCV among Chinese patients with acute and chronic liver disease

To assess whether the hepatitis C virus plays an important role in Chinese patients with acute and chronic liver disease, antibodies to HCV (anti-HCV) were measured by enzyme immunoassay in 67 patients with type A and B acute viral hepatitis, 165 patients with non-A, non-B (NANB) hepatitis, 438 patients with chronic hepatitis, 200 patients with postnecrotic liver cirrhosis, 72 patients with alcoholic liver disease, 55 patients with non-alcoholic fatty liver, 24 patients with toxic and drug-induced hepatitis, and 20 patients with other chronic liver diseases. Anti-HCV was not detected in sera from patients with type A and B acute viral hepatitis, toxic and drug-induced hepatitis, primary biliary cirrhosis, Wilson's disease, or lupoid hepatitis. The anti-HCV prevalence was found to be highest in patients with NANB hepatitis (59% in sporadic and 73.2% in transfusion-associated), 16.4% in non-alcoholic fatty liver, 5.6% in alcoholic liver disease, 6.8% in chronic hepatitis, and 16% in postnecrotic liver cirrhosis. In patients with chronic hepatitis, the anti-HCV prevalence was significantly higher in HBsAg-negative (15/34, 44.1%) than in HBsAg-positive cases (15/404, 3.7%; P less than 0.0001). The results indicate that HCV is a major agent of NANB hepatitis and plays an important role in HBsAg-negative chronic liver disease in Taiwan.     

Clinical study of IgA antibody against hepatitis C virus core antigen in patients with type C chronic liver disease

Immunoglobulin A class antibody to hepatitis C virus core antigen (IgA anti-HCc) was measured in the serum of 128 patients with type C chronic liver disease. Fifty-eight patients (45.3%) were seropositive. IgA anti-HCc was detected in only one of 20 patients with chronic persistent hepatitis; however, 52.3% (46/88) of patients with chronic active hepatitis and 55% (11/20) of patients with liver cirrhosis were seropositive. Histological examination revealed that 22 (71.0%) of 31 patients with severe disease activity were seropositive compared to 35 (44.9%) of 78 patients with moderate (P<0.05) and one (5.3%) of 19 patients with mild (P<0.01) histological changes. IgA anti-HCc was measured sequentially in 65 patients who underwent interferon therapy. There was a significant difference between responders and other patients in the mean ratio of IgA anti-HCc titers one month after therapy. Three months after therapy, IgA anti-HCc was detectable in only two of 15 responders who were IgA anti-HCc seropositive at the start of therapy. In contrast, IgA anti-HCc reappeared three months after therapy despite a temporary decrease to undetectable levels in all nonresponders. We conclude that IgA anti-HCc is a useful marker to identify the presence of active type C liver disease and that the disappearance of IgA anti-HCc three months after interferon therapy predicts a good response in treated patients.     

Hepatitis C: basic and clinical studies.

The HCV, a single stranded RNA virus belonging to the family of flavivirus, has been identified as the probable cause of the majority of cases of transfusion-associated NANB hepatitis and community-acquired NANB hepatitis in Japan. The hepatitis virus is present in a least 2% of the blood donor population and is extremely common in high risk groups, such as hemophiliacs and hemodialysis patients. The contribution of HCV infection to sporadic, acute and chronic hepatitis, liver cirrhosis and primary liver cancer has been established. Furthermore anti-HCV in 20% of alcoholic patients with liver injury suggest that HCV may be etiologically associated with liver disease previously attributed to other causes. Therapy of acute and chronic liver disease associated with HCV infection is likely to be undertaken with recombinant IFN alpha in the future to prevent the progression of the disease from acute hepatitis to chronic hepatitis, and from chronic hepatitis to liver cirrhosis or primary liver cancer. However the prevention of HCV infection will be the goal, in addition to screening of donor blood and exclusion to a large degree of positive units likely to decrease the incidence of post-transfusion hepatitis.     

Hepatitis C: Basic and clinical studies

The HCV, a single stranded RNA virus belonging to the family of flavivirus, has been identified as the probable cause of the majority of cases of transfusion-associated NANB hepatitis and community-acquired NANB hepatitis in Japan. The hepatitis virus is present in a least 2% of the blood donor population and is extremely common in high risk groups, such as hemophiliacs and hemodialysis patients. The contribution of HCV infection to sporadic, acute and chronic hepatitis, liver cirrhosis and primary liver cancer has been established. Furthermore anti-HCV in 20% of alcoholic patients with liver injury suggest that HCV may be etiologically associated with liver disease previously attributed to other causes. Therapy of acute and chronic liver disease associated with HCV infection is likely to be undertaken with recombinant IFN alpha in the future to prevent the progression of the disease from acute hepatitis to chronic hepatitis, and from chronic hepatitis to liver cirrhosis or primary liver cancer. However the prevention of HCV infection will be the goal, in addition to screening of donor blood and exclusion to a large degree of positive units likely to decrease the incidence of post-transfusion hepatitis.     

Clinical evaluation of titration of hepatitis C virus core antibody and its subclasses

Abstract Titrations of anti-hepatitis C core (anti-HCc) immunoglobulin G (IgG) antibodies and its subclasses were studied in 90 patients with acute and chronic hepatitis C virus (HCV) infection, including 27 patients who underwent interferon (IFN) therapy. The positivity rates for each anti-HCc subclass were as follows: 95.2% for IgG1, 12.0% for IgG2, 69.9% for IgG3 and 19.3% for IgG4. The total anti-HCc IgG titre correlated well with the IgG1 titre, indicating that IgG1 was the main virus-specific IgG. Changes of IgG1 production mainly contributed to fluctuations of the anti-HCc IgG titre and corresponded well to positivity for HCV-RNA during and after IFN therapy. IgG3 was detected prior to IgG1 during the early phase of acute hepatitis in some cases and also appeared with relapse after IFN therapy. The serial assay of anti-HCc subclasses showed the patients' humoral immune response to HCV infection, and might be useful for evaluation of anti-viral immunity influenced by IFN therapy.     

Chronic evolution of acute hepatitis B: the significance of simultaneous infections with hepatitis C and D. Copenhagen Hepatitis Acuta Programme

Seventy-six of 77 consecutive patients with hepatitis B surface antigen (HBsAg)-positive acute hepatitis were reevaluated using anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), and IgM anti-hepatitis B core (HBc) testing. Anti-HCV and/or anti-HDV was found in 32 patients (42%). The presence of these markers was significantly associated with intravenous drug abuse (p less than 10(-6). Sixty-nine patients were IgM anti-HBc-positive, of whom two (3%) (95% confidence limits, 1-12%) became chronic HBsAg carriers with histologically verified chronic liver disease; both were anti-HCV and anti-HDV-negative. Among the remaining 67 IgM anti-HBc-positive patients 8 had HBV and HDV co-infection, 3 had HBV and HCV co-infection, and 1 had HBV, HCV, and HDV co-infection. Twenty-two had evidence of preceding or past HCV infection; two developed chronic active hepatitis in spite of HBsAg clearance. Seven patients with IgM anti-HBc negative. One was a chronic HBsAg carrier with HDV superinfection. One had subclinical acute HBV infection and became a chronic HBsAg carrier. In a further two patients reactivation of replication in a chronic HBV infection could not be disregarded. Three patients could not be classified; all had acute recent onset of symptoms, cleared HBsAg within 6 months, but lacked IgM anti-HBc. It is concluded that HCV and HDV superinfections in HBV carriers mimicking acute HBV infection with chronic evolution are rarely encountered in the present population in spite of high frequency of both HCV and HDV markers.     

Hepatitis C virus antibody in Poland.

To assess the epidemiology of hepatitis C virus (HCV) in Poland, anti-HCV was studied in patients with acute and chronic non-A, non-B (NANB) hepatitis, in healthy adults, and in subjects at risk. Anti-HCV prevalence was 2% in 152 blood donors, 78% in 95 parenteral drug addicts, 21% in 112 alcoholics, and 86% in 42 patients with chronic NANB hepatitis. Among 34 prospectively followed patients with acute NANB hepatitis 17 (50%) developed anti-HCV. It seems that HCV infection is responsible for the majority of NANB hepatitis in Poland and is common in parenteral drug abusers and alcoholics.     

Non-A, Non-B Fulminant Hepatitis is also Non-E and Non-C

Objectives : to define the roles of the hepatitis C and E viruses (HCV and HEV) in non-A, non-B (NANB) fulminant hepatitis. Methods : we utilized the polymer-ase chain reaction to amplify HCV and HEV RNA sequences and assays to detect antibodies to HCV and HEV in the acute phase sera of eight presumed viral NANB and seven nonviral NANB fulminant hepatic failure (FHF) patients. Results : none of the 15 patients had detectable HCV or HEV RNA or elevated HCV and IgM-HEV antibody titers in their acute phase sera. Three patients, all with features of autoimmune hepatitis, had raised IgG-HEV antibody titers. Due to the possibility of serologically undetectable hepatitis B virus (HBV) infection in fulminant hepatitis patients, we performed polymerase chain reaction amplification of HBV genomic DNA in acute phase sera of the presumed viral NANB FHF patients and subsequently found no evidence of HBV DNA. Conclusions: we did not find evidence implicating HCV or HEV in presumed viral NANB FHF or as agents contributing to or causing the liver failure in nonviral NANB FHF patients with au-toimmune hepatitis, drug-induced hepatotoxicity, or ha-lothane hepatotoxicity.     

Prevalence of hepatitis C virus antibody in a liver transplantation population

The development of a serologic assay to detect antibodies directed at an antigen (C-100-3) of the hepatitis C virus (anti-HCV) has been a major breakthrough in the long search for causative agents of non-A, non-B (NANB) hepatitis. The frequency of HCV in those who have end-stage liver disease is not known. Moreover, the rate of recurrence after liver transplantation (OLTx) and the rate of acquisition of new HCV infection as a result of the OLTx experience is as yet unknown. This study was performed in an attempt to answer these questions. The prevalence of HCV in 372 patients undergoing OLTx at the University of Pittsburgh was determined. Those transplanted for HBV-related liver disease with hepatoma had the highest rate of HCV antibody positivity (45.4%) followed by those with metabolic liver disease (42.5%), putative NANB liver disease (41.4%), and cryptogenic cirrhosis (20.9%); those with cholestatic liver disease exhibited the lowest rate (16.2%). HCV antibody was positive in only 26.3% of patients with hepatoma. Of those patients who were negative prior to transplantation, 12.2% acquired HCV antibody post-OLTx. In the putative NANB group, no difference was detected in the AST and ALT prior to transplantation in either the HCV antibody-positive or -negative patients. In patients with cryptogenic cirrhosis, those who were positive for HCV antibody had higher transaminase levels prior to transplantation than did those patients who were HCV antibody negative.     

Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis C infection

BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera of patients with acute or chronic hepatitis. The prevalence and clinical significance of B19 DNA in serum samples from patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS: Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53 normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme-linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR), Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti-B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51 serum samples from patients with HCV infection. B19 DNA was detected in serum samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51 patients with HCV infection, but not in 53 serum samples from normal controls. The occurrence of liver dysfunction was not affected by B19 infection in patients with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA from patients with chronic HBV infection and all of the 12 serum samples with B19 DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9 subtype, respectively. The variant subtypes of B19 were found to be distinctive in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that human parvovirus B19 infection was frequently found in patients with chronic HBV or HCV infection. The variant genotypes were present in patients with different chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the frequency of liver dysfunction in patients with chronic hepatitis. Long-term longitudinal studies are required to determine the natural course of parvovirus B19 infection and whether its coinfection affects the natural history of chronic hepatitis B or hepatitis C.     

Hepatitis C virus detection is facilitated by the combined use of c100 protein and GOR epitope.

Assay for the antibody to the c100 protein (anti-c100) lacks sensitivity in terms of detection of hepatitis C virus (HCV) in all samples. The author used anti-c100 and antibody to the GOR epitope (anti-GOR) by the enzyme-linked immunosorbent assay to examine 524 patients with chronic liver disease and 682 volunteer blood donors in Fukuoka, Japan. The prevalence of HCV infection, as revealed by the presence of anti-c100 and/or anti-GOR, was 3.9% in 540 volunteer blood donors, 12.7% in 142 volunteers with abnormal liver function, 7.4% in 135 patients with HBsAg-positive liver disease and 89.5% in 389 patients with non-A, non-B (NANB) liver disease. These results show a higher prevalence than demonstrated only by the anti-c100 in NANB liver disease patients (82.5%, P < 0.01). The concurrence of anti-c100 and anti-GOR in subjects with HCV infection was 23.8% in 21 volunteer blood donors, 44.4% in 18 volunteers with abnormal liver function and 61.2% in 348 NANB liver disease patients. The concurrence seems to increase with deterioration of liver function. We concluded that combination assay for anti-c100 and anti-GOR demonstrated a more accurate prevalence of HCV infection than single assay for anti-c100 among NANB liver disease patients, and that the presence of anti-GOR plays a role in liver disease in anti-HCV-positive subjects.     

Hepatitis C virus RNA genome in plasma of patients with non-A,non-B hepatitis

Recently, the assay system of anti-hepatitis C virus antibody (HCV-Ab) was developed. However, there is no clinically useful method to detect hepatitis C virus (HCV) itself. The authors recently developed a method to detect the HCV-RNA genome in plasma using polymerase chain reaction (PCR). In the present study, the specificity of this assay in detecting HCV infection was investigated. Freshly obtained 1 ml plasma specimens from 100 patients with various liver diseases and from 11 control subjects were studied. In patients with non-A, non-B (NANB) hepatitis-related liver diseases, HCV-RNA was detected in 2 out of 7 cases of acute hepatitis, in 29 out of 31 cases of chronic hepatitis, in 17 out of 21 cases of cirrhosis and in 2 out of 6 cases of hepatocellular carcinoma. On the other hand, no HCV-RNA was detected in 15 cases of various types of alcoholic liver diseases, in 12 cases of hepatitis B related liver diseases, and in 11 controls. HCV-RNA was detected in 2 of 6 drinkers with chronic hepatitis. The prevalence of HCV-RNA was not closely related to a history of blood transfusions. These results suggest that our method for HCV-RNA is specific for HCV infection and HCV infection is the likely etiology of most chronic NANB hepatitis cases. The clinical usefulness of our method is illustrated by the fact that we were able to study 100 patients and needed only 1 ml plasma per HCV-RNA assay.     

Anti-HCV immunoglobulin M antibody in patients with hepatitis C

Anti-hepatitis C virus (HCV) immunoglobulin M antibody titres were measured by an enzyme-linked immunosorbent assay method in 16 patients with non-A, non-B acute hepatitis (NANB AH), 13 with non-A, non-B fulminant hepatitis (NANB FH) and nine with type C chronic hepatitis. Anti-HCV IgM was positive in one of the 16 patients with NANB AH, six of the 13 with NANB FH, and five of the nine with type C chronic hepatitis. Anti-HCV IgG was positive in eight of the 16 patients with NANB AH and eight of the 13 with NANB FH. Either anti-HCV IgM or anti-HCV IgG were positive in 10 of the 13 patients with NANB FH. All of the five anti-HCV IgM positive patients with type C chronic hepatitis were undergoing an exacerbation of the diseases, while all of the anti-HCV IgM negative patients were in a remission stage which had lasted for more than 6 months. The findings of this study suggest that anti-HCV IgM is useful for the early diagnosis of type C FH and may be a useful marker of diseases activity in type C chronic hepatitis.     

Hepatitis C virus RNA genome in plasma of patients with non-A, non-B hepatitis.

Recently, the assay system of anti-hepatitis C virus antibody (HCV-Ab) was developed. However, there is no clinically useful method to detect hepatitis C virus (HCV) itself. The authors recently developed a method to detect the HCV-RNA genome in plasma using polymerase chain reaction (PCR). In the present study, the specificity of this assay in detecting HCV infection was investigated. Freshly obtained 1 ml plasma specimens from 100 patients with various liver diseases and from 11 control subjects were studied. In patients with non-A, non-B (NANB) hepatitis-related liver diseases, HCV-RNA was detected in 2 out of 7 cases of acute hepatitis, in 29 out of 31 cases of chronic hepatitis, in 17 out of 21 cases of cirrhosis and in 2 out of 6 cases of hepatocellular carcinoma. On the other hand, no HCV-RNA was detected in 15 cases of various types of alcoholic liver diseases, in 12 cases of hepatitis B related liver diseases, and in 11 controls. HCV-RNA was detected in 2 of 6 drinkers with chronic hepatitis. The prevalence of HCV-RNA was not closely related to a history of blood transfusions. These results suggest that our method for HCV-RNA is specific for HCV infection and HCV infection is the likely etiology of most chronic NANB hepatitis cases. The clinical usefulness of our method is illustrated by the fact that we were able to study 100 patients and needed only 1 ml plasma per HCV-RNA assay.     

Clinical evaluation of three anti-HCV ELISAs in patients with various liver diseases

We measured antibodies to hepatitis C virus (HCV) in 380 patients with various liver diseases by three enzyme-linked immunosorbent assays (ELISAs): HCV antibody ELISA test (C100), KCL-163 (KCL) corresponding to the nonstructural protein of HCV, and JCC based on the translation product of the presumptive HCV core gene. Of 233 cases of non-A, non-B (NANB) liver disease, 63.9% were anti-C100 positive, 69.1% were anti-KCL positive, and 79.8% were anti-JCC positive. Detection of serum HCV-RNA in 213 cases of chronic NANB liver disease revealed that the concordance was 80.3% for C100, 86.4% for KCL, 94.8% for JCC, and 95.3% for all three ELISAs. Overall, 85.4% of chronic NANB cases were considered to have type C disease with HCV infection. The most reliable assays for diagnosing chronic NANB liver disease as type C appeared to be the KCL and JCC ELISAs.This work was supported in part by a grant from the Sagawa Science Foundation.     

42例丙型肝炎病毒感染的临床血清学分析

本文分析了42例丙型肝炎患者的临床资料和病毒感染的血清学标志物。在42例患者中,抗-HCV-lgM、抗-HCV-IgG和HCV RNA检出率分别为66.7％、71.4％和59.5％。其中抗-HCV-IgM和HCVRNA检出率,在急性肝炎患者(88.9％,66.7％)明显高于慢性肝炎患者(50.0％,54.2％);肝损害严重者(79.3％,72.4％)显著高于肝损害轻微者(38.5％,30.8％)。结果显示,抗-HCV-IgM、抗-HCV-IgG和HCV RNA同时检测不仅可提高丙肝病原诊断阳性率并对病情和预后的判断有一定作用。     

Incidence, prevalence, and clinical course of hepatitis C following liver transplantation.

Hepatitis C virus (HCV) is the agent responsible for posttransfusion hepatitis. The incidence, timing, and clinical course of HCV positive hepatitis in liver transplant recipients are unknown. Three hundred and seventeen donor-recipient liver transplant pairs were grouped on the basis of their pretransplant HCV antibody status. The biopsy findings were examined. Four distinct groups were identified on the basis of HCV serology: group I, both were negative; group II, donor was negative and recipient was positive; group III, donor was positive and recipient was negative; group IV, both were positive. The prevalence of anti-HCV positivity in recipients was 13.6%. The rate of seroconversion was 9.2%. Histologic hepatitis not ascribable to any specific cause other than non-A, non-B (NANB) hepatitis occurred in 13.8%. The incidence of histologic chronic active hepatitis was 1.6%, and none progressed to cirrhosis. The concordance rate for a positive anti-HCV serology and NANB hepatitis was 2.8%. Of the 35 patients (group II and IV) with positive anti-HCV serology pretransplant, only 17 were positive posttransplantation. Based on these data it can be concluded that posttransplant NANB hepatitis occurred in 13.8% of liver recipients. Twenty percent of these were anti-HCV positive. Progression to histologic chronic active hepatitis occurs over a period of 1-5 years in 1.6% of cases.     

Serodiagnosis of hepatitis C in acute and chronic liver disease in southwestern Saudi Arabia.

The extent of involvement of hepatitis C, as compared to hepatitis A and hepatitis B, virus infection in acute and chronic liver disease in the Asir Region, southwestern Saudi Arabia, was assessed in 898 patients hospitalized during the period from June 1990 to November 1991. Acute icteric hepatitis cases with severe onset were distinguished by their referral to the fever hospital while cases with milder onset and those with chronic hepatitis were followed at two general hospitals. Antibodies to the c-100-3 antigen of hepatitis C virus (anti HCV) were detected in a significant proportion of patients with chronic liver disease (chronic active hepatitis (65%), cirrhosis (44%)). Anti HCV was also detected in patients with acute hepatitis with milder onset at the general hospitals (10.9%) but proportionately much less in patients at the fever referral hospital (< 1%) where hepatitis A (52%) and, to a lesser extent hepatitis B (11%), were mostly diagnosed. These results indicate that HCV is a major identifiable infection in hospitalized patients with chronic liver disease in this region but that anti HCV antibodies (c-100-3) are not detected, at least at onset, in sporadic cases with acute manifestations. Testing for additional viral antigens or RNA and a longer follow-up period would be required before exclusion of a role for HCV in acute disease. Alternatively, other viral and non-viral agents may be sought in this illness.     

The significance of blood transfusion in non-A, non-B chronic liver disease in Japan

We performed a follow-up study on 70 patients with acute non-A, non-B (NANB) posttransfusion hepatitis and a retrospective study on 283 chronic hepatitis, 70 cirrhosis and 53 hepatocellular carcinoma patients of type NANB. In acute NANB post-transfusion hepatitis, as judged by the transaminase levels, th duration of the disease exceeded 6 months in 46/70 = 65.7% and 1 year in 32/70 = 45.7%. The histological diagnosis of the 32 cases persisting for more than 1 year was chronic active hepatitis in 5, chronic persistent hepatitis in 2 and unresolved hepatitis in 6. The frequency of previous transfusion in chronic hepatitis, cirrhosis and hepatocellular carcinoma of type NANB was 42.8, 37.1 and 15.1%, respectively, whereas the incidence of early posttransfusion hepatitis was 8.5, 8.6 and 7.5%, respectively. in chronic liver diseases with a history of jaundice and/or hepatitis, previous transfusions are more frequently associated with type NANB than with type B disease. The present study demonstrates that NANB posttransfusion hepatitis tends to develop to chronic liver disease when analyzed prospectively as well as retrospectively.