Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay

To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.     

Predictive value of IgM antibodies to hepatitis C virus in patients with chronic hepatitis C undergoing interferon-α therapy. Analysis by two different methods

SUMMARY. To determine the predictive value of IgM anti-hepatitis C virus (HCV) testing in patients with chronic hepatitis C infections undergoing interferon-α (IFN-α) therapy, IgM anti-HCV reactivity was analysed by two different methods (non-commercial and commercial) in 19 patients and monitored at times 0 (pre-treatment), 3, 6, 12. and 24 months during follow-up. Eight patients were non-responders, five remained in sustained response 1 year after stopping treatment, and six had a relapse. No correlation between alanine transaminase (ALT) levels and IgM anti-HCV reactivity was found by either method in baseline samples. In addition, neither the presence nor absence of IgM anti-HCV in baseline samples, nor the loss of specific IgM reactivity during treatment, had any predictive value. Finally, no other parameters analysed (age, sex, risk group and histological diagnosis), were significantly associated with IgM anti-HCV reactivity in our study. In summary, these results suggest that baseline detection and monitoring of IgM anti-HCV reactivity are not useful in predicting the sustained response to IFN-α therapy in chronic hepatitis C infection.     

Detectable levels of IgM antibodies to hepatitis C virus core protein predict breakthrough in patients with chronic hepatitis C treated with interferon-α

Summary. The predictive value of IgM antibodies to hepatitis C virus core antigen (HCcAb) is controversial. We studied 79 patients undergoing interferon-α (IFN-α) treatment and we found that detectable levels of IgM HCcAb could predict breakthrough on treatment.     

Cellular immune response to the hepatitis C virus

Hepatitis C virus (HCV) infection is most often clinically inapparent and rarely associated with symptoms of acute hepatitis. Most patients, however, fail to resolve the acute infection and proceed to develop chronic hepatitis with the risk of liver cirrhosis and hepatocellular carcinoma later in life. Since the kinetics of the earliest events of virus–host interaction are likely to determine the outcome of infection, research has focused on the characterization of the strength and kinetics of the antiviral immune response in different stages of disease. The identification of the immunological correlates of viral clearance is pivotal for the development of vaccines and efficient therapies.     

Anti-hepatitis C virus core IgM antibodies correlate with hepatitis C recurrence and its severity in liver transplant patients

BACKGROUND: The significance of immunoglobulin (Ig) M antibody to hepatitis C virus (HCV) core antigen was studied in 60 patients with HCV infection after orthotopic liver transplantation (OLT) diagnosed by polymerase chain reaction. METHODS: Patients were followed up for a mean of 28 months after transplantation. Sera collected three months before transplantation, and one and 12 months after transplantation were analysed for anti-HCV core IgM (HCV-IgM EIA 2.0 assay). After OLT protocol biopsies, procedures were performed routinely every six months. Semiquantitative histopathological assessment of allograft hepatitis was performed using Knodell's score. The results were correlated with clinical features, liver histology findings, and virological features, such as genotype and viraemic levels assessed by a branched DNA assay. RESULTS: One year after liver transplantation, 29/60 (48%) patients had chronic hepatitis on graft biopsy. The presence of anti-HCV core IgM one month (p=0.004) and 12 months (p=0.003) after OLT was positively correlated with recurrence of chronic hepatitis. The positive predictive value of anti-HCV core IgM detected one month after transplantation was 0.88. A significant relationship was observed between severity of graft disease and presence of anti-HCV core IgM 12 months after transplantation. The mean Knodell score was 8.9 in anti-HCV core IgM positive patients compared with 3.6 in those who were anti-HCV core IgM negative (p=0.001). The presence of IgM anti-HCV did not correlate with serum HCV RNA level or HCV genotype. CONCLUSION: We confirm that the presence of anti-HCV core IgM after OLT is a marker of HCV induced graft damage. The recurrence and severity of HCV hepatitis in patients undergoing OLT for HCV cirrhosis is related to the presence of anti-HCV core IgM after liver transplantation. These findings have diagnostic relevance and confirm that measurement of IgM anti-HCV core may help to better monitor the treatment of HCV recurrence after transplantation.     

Evidence that use of a second-generation hepatitis C antibody assay prevents additional cases of transfusion-transmitted hepatitis

SUMMARY. The aim of this study was to determine if using hepatitis C antibody (anti-HCV) enzyme immunoassay version 2.0 (EIA2) in addition to version 1.0 (EIA1) increased the safety of the blood supply. Blood non-reactive by anti-HCV EIA1 was transfused in 1990-92. Stored samples from 40098 units, donated prior to 13 March 1992 were later tested by EIA2. For donor units reactive for anti-HCV by EIA2. a recombinant immunoblot assay (RIBA2) was also carried out. In 63 cases, recipients of transfusions which were EIAZ negative or EIA2 reactive were tested for anti-HCV and elevated alanine aminotransferase (ALT) levels 9-1 2 months after transfusion: pretransfusion anti-HCV status of recipients was unknown. Among these multitransfused patients receiving units that were negative by both EIA1 and EIA2, 1/26 (4%) had anti-HCV. Among transfusion recipients of units negative by EIA1, but who received at least one unit reactive by EIA2,4/37 recipients (11%) were anti-HCV reactive (P = 0.59). For the recipients of EIA2 reactive blood, when the donor unit was RIBA2 non-reactive. 0/23 recipients were reactive by anti-HCV. Among the recipients of a RIBA2 indeterminate unit, 1/10 recipients had anti-HCV, but for patients who received at least one RIBA2 reactive unit, 3/4 recipients had anti-HCV (P = 0.0 3). Hence. second-generation anti-HCV testing detected additional units capable of transmitting hepatitis C that were not detected by first-generation testing. However, RIBA2 is a more specific method than EM2 for determining units capable of transmitting HCV.     

Effect of hepatitis C antibody screening in blood donors on post-transfusion hepatitis in Taiwan

A national screening programme for antibody to hepatitis C virus (HCV) in blood donors in Taiwan began in July 1992 using a second-generation immunoassay. To study the impact of this screening on post-transfusion hepatitis in Taiwan, a prospective study on post-transfusion hepatitis, that was started in 1987, was continued. As of June 1994, 245 patients who received a blood transfusion after July 1992 had completed a follow-up period for more than 6 months post-transfusion. Of them, seven (2.8%) recipients developed acute post-transfusion hepatitis. The hepatitis in six cases could not be attributed to infection by hepatitis A, B, C, D, E viruses or cytomegalovirus (CMV) or Epstein-Barr virus (EBV). The remaining patient seroconverted to both IgG and IgM anti-CMV. All seven patients recovered in 6 months without development of chronicity, and the mean peak alanine aminotransferase level was lower compared with that of the cases before anti-HCV screening (i.e. pre-July 1992). These results indicate that the current anti-HCV screening has effectively interrupted HCV transmission through blood transfusion in Taiwan.     

Intrafamilial transmission of hepatitis C virus in Japan

To study the intrafamilial transmission of hepatitis C virus (HCV), 36 family members of 16 patients with anti-HCV (anti-C100-3)-positive chronic liver disease were screened for anti-HCV by an enzymelinked immunosorbent assay (ELISA). Clusters of anti-HCV -positive individuals were observed in 2 of 16 families (12.5%). Four of 35 family members (11.4%) with no history of blood transfusion were positive for anti-HCV. Two of 17 offspring (11.8%) of anti-HCV-positive females were positive for anti-HCV, while 1 of 5 spouses (20.0%) was positive for anti-HCV. These data suggest that intrafamilial transmission is one of the possible routes of infection for HCV.     

Serum levels of anti-hepatitis C virus IgM core antibodies may predict the response to interferon-α therapy in chronic hepatitis C

SUMMARY. We measured the optical densities (OD) of serum anti-hepatitis C virus IgM core antibodies in 40 HCV-positive patients (24 males and 16 females) with histologically proven chronic active hepatitis but without cirrhosis. All patients were treated with i.m. injections of 3 MU thrice weekly of interferon-α (IFN-α) for 6 months and followed-up monthly. Optical densities were evaluated in thawed sera before beginning treatment and 6 months after completion, and in fresh sera obtained at the end of an 8–12-month follow-up period. Patients were grouped into three categories according to the OD obtained: <0.3 (negative test): 0.3-0.6 (intermediate positivity): >0.6 (high positivity). According to the response to treatment during the follow-up period, patients were further divided into three classes: sustained responders: relapsers or partial responders: non-responders. In each patient, the OD values were similar in the three determinations before, after therapy and at the end of the follow-up period. All patients with an intermediate positive test for anti-HCV IgM core antibodies were relapsers or partial responders, and all patients with high OD values were non-responders. Conversely, 71% of the patients with a negative test were sustained responders. We conclude that this cheap and easily performed test may be useful in predicting the response to IFN therapy.     

Epidemiological characteristics of the incidence of hepatitis C virus (C100-3) antibodies in patients with liver diseases in the Inshore Area of the Yangtze River

Abstract The Nantong area is an endemic region of hepatitis B virus (HBV) infection in the inshore area of the Yangtze River. However, no detailed data are available about hepatitis C virus (HCV) infection in this area. In this study recent reports are reviewed about the incidence of viral hepatitis and primary hepatocellular carcinoma (PHC) in China, and it is shown that the Nantong area is a high risk region for PHC. This study reports on the incidence of antibody to HCV (anti-HCV) in patients with chronic liver diseases in the Nantong area; investigated in collaboration with members of the Nantong Medical College, Jiangsu Province, the People's Republic of China. The incidence of anti-HCV (C100-3) in the Nantong area was: 0.67% (three of 451) in donor blood; 0.0% (none of 89) in patients with acute hepatitis; 2.7% (five of 186) in those with chronic hepatitis, 4.5% (two of 44) in those with liver cirrhosis; 6.3% (one of 16) in those with PHC; and 1.3% (one of 78) in patients without liver disease. The incidence of hepatitis B surface antigen in the Nantong area was: 15.7% (14 of 89) in patients with acute hepatitis; 81.2% (151 of 186) in those with chronic hepatitis; 81.8% (36 of 44) in those with liver cirrhosis; 87.5% (14 of 16) in those with PHC; and 20.5% (16 of 78) in patients without liver disease. Although the Nantong area is a high risk region for PHC, these data suggest that HCV infection is not an important aetiological factor for PHC in this area.     

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications...     

Antibody to the hepatitis C virus in acute hepatitis and chronic liver diseases in Japan

ABSTRACT— In a 6-month follow-up study of acute hepatitis in Japan, 31 out of 41 (75.6%) cases of post-transfusion non-A and non-B hepatitis (NANB-PTH) and 14 out of 40 (35.0%) cases of sporadic non-A non-B hepatitis (NANB-SPO) were found to be positive for antibody to the hepatitis C virus (HCVAb). After 12 months of follow-up, 30 cases (81.1%) became chronic among 37 HCVAb positive acute NANB hepatitis cases. This figure shows a significantly higher rate of chronicity as compared with HCVAb negative acute NANB hepatitis. The prevalences of HCVAb in hepatitis B surface antigen (HBsAg) negative cases of chronic hepatitis and liver cirrhosis were 76.3% (200/262) and 66.7% (106/159), respectively, which were significantly different from the values of 5.1% (13/255) and 10.6% (13/123) observed in HBsAg positive cases. Of chronic liver disease cases positive for HCVAb, 45.8% (152/332) had a history of blood transfusion, in contrast to the value of 3.7% (13/352) observed in HBsAg positive cases of chronic liver disease that were negative for HCVAb.     

Intrafamilial transmission of hepatitis C virus

Abstract The intrafamilial transmission pattern of hepatitis C virus (HCV) was examined in 118 family members of 61 index patients with type C chronic liver disease using anti-HCV antibodies and HCV RNA assay. The study subjects consisted of eight parents, 49 spouses, 50 children, eight siblings and three other relatives. The positivity rates of anti-C100, anti-JCC, second-generation anti-HCV and HCV RNA were 6.8, 12.7, 12.7 and 11.0%, respectively. Positivity in one or more anti-HCV antibody assay was detected in 3/24 (12.5%) father-child pairs, 3/17 (17.6%) mother-child pairs, 2/8 (25%) sibling pairs, 6/38 (15.8%) husband-wife pairs and 2/13 (15.4%) wife-husband pairs. In spouses, positivity for anti-HCV antibody or HCV RNA was observed after 40 years of age. None of 11 spouses married < 15 years was positive for any anti-HCV assay or HCV RNA. In spouses whose age was > 50 years and duration of marriage was > 25 years, anti-HCV or HCV RNA was frequently detected (32.0%). However, when seven pairs involving four spouses, one mother-daughter pair and two sibling pairs were subtyped, the same HCV subtypes were found in only four pairs (type II in three pairs and type III in one pair). Further, the agreement rate between anti-HCV and HCV RNA was > 90%. These results suggest that intrafamilial transmission of HCV, revealed by the subtyping method, is considered lower than the percentage of positivity for anti-HCV antibodies or HCV RNA in family members of patients with type C chronic liver disease. Thus, the intrafamilial transmission of HCV seems to be quite rare and much less common than that of HBV.     

Long-term follow-up of anti-hepatitis C virus antibodies in patients with acute nonA nonB hepatitis and different outcome of liver disease

Abstract: We screened 74 patients with nonA nonB acute hepatitis (37 of post-transfusion PTH, and 37 of non-post-transfusion, NPTH, origin) for the presence of anti-HCV by tests detecting either C100–3 antibodies alone (ELISA I) or C100–3 plus C33c plus C22–3 antibodies (ELISA II). Samples were taken at the onset of disease and then serially for a period of time ranging from 12 to 60 months. An increased number of anti-HCV positive cases (86% vs 69%) and an earlier seroconversion were observed with the second compared to the first generation ELISA. Positive samples were confirmed by recombinant immunoblot assay (RIBA), which was also used to study the kinetics of the antibody response to individual HCV antigens. Anti-C33c and anti-C22–3 antibodies were the first detectable markers of HCV infection in 80% and 20% of the patients, respectively. Thirty-two percent of the patients studied showed complete and persistent biochemical recovery, whereas 68% maintained a chronic elevation of the transaminase values. Among the 20 patients who showed early and persistent normalization of the transaminase values, complete disappearance of all antibody reactivities was limited to five of them, whereas in four cases only anti-C100–3 and anti-5–1-1 became negative.     

Incidence of hepatitis C virus (HCV) antibodies and HCV-RNA in blood donors and patients with liver diseases in the Inshore Area of the Yangtze River

The Nantong area is a high risk region for primary hepatocellular carcinoma (PHC) in the inshore area of the Yangtze River. However, no detailed data are available about hepatitis C virus (HCV) infection in this area. We examined the incidences of anti-HCV and HCV-RNA in blood donors with hepatitis B surface antigen (HBsAg)- and hepatitis B core antibody (HBcAb)-negative and patients with chronic liver diseases in the Nantong area at Nantong Medical College, Jiangsu Province, the People's Republic of China. The incidences of HBV markers (HBsAg and/or HBcAb), anti-HCV (C100-3), second generation anti-HCV, HCV-RNA and any marker of HCV in the Nantong area were found to be: 0.0, 0.7, 0.4, 0.2 and 0.7% in donor bloods; 16.9, 0.0, 3.4, 15.7 and 16.9% in patients with acute hepatitis; 82.8, 2.7, 4.8, 7.5 and 10.2% in those with chronic hepatitis; 86.4, 4.5, 9.1, 4.5 and 11.4% in those with liver cirrhosis; 87.5, 6.3, 0.0, 0.0 and 6.3% in those with PHC; and 21.8, 1.3, 1.3, 0.0 and 1.3% in patients without liver diseases, respectively. Although the Nantong area is a high risk region for PHC, these data suggest that HCV infection is not an important aetiological factor for PHC in this area.     

Clinical evaluation of a newly established anti-HCV assay for the diagnosis of hepatitis C in Japan

To develop a more dependable method of diagnosing hepatitis C, serum anti-hepatitis C virus (HCV) was examined by using a new assay (anti-HCV second generation). The results were compared with those of either the conventional assay (anti-HCV first generation) or HCV-RNA analysis. With the first generation assay, anti-HCV was detected in 69% of post-transfusion acute hepatitis (AH), 44% of sporadic AH, 50% of needlestick exposed AH, 72% of chronic hepatitis (CH), 77% of liver cirrhosis (LC) and 86% of hepatocellular carcinoma (HCC). These results were remarkably increased by using the second generation assay (92% in post-transfusion AH, 72% in sporadic AH, 100% in needlestick exposed AH, 96% in CH, 96% in LC and 97% in HCC). Furthermore, in the early stages of AH (from 1-5 weeks after onset), anti-HCV was not detected in all 18 patients by the first generation assay, but was found in 10 of them by using the second generation assay. The failure to detect anti-HCV with the first generation assay was mainly due to a lack of the core region coding peptide (C22-3) in this assay. In the AH-resolving group, anti-HCV second generation did not disappear, but the titre tended to be lower than that in the CH-developing group. Thus, the second generation assay for anti-HCV was considered to be a more useful tool for not only the diagnosis of hepatitis C but also for determining prognosis.     

Outcome of acute symptomatic non-A,non-B hepatitis: a 13-year follow-up study of hepatitis C virus markers

ABSTRACT— Thirty-nine of 61 prospectively followed patients who had had acute non-A, non-B hepatitis in 1978 were clinically reexamined in 1991 and tested for antibodies to hepatitis C virus (anti-HCV) with a second generation ELISA and RIBA and for HCV RNA by PCR. Acute hepatitis C was diagnosed in stored sera from 1978 in 24 patients, who were found still to be anti-HCV positive in 1991, and 16 of them were also HCV RNA positive. The majority of anti-HCV positive patients with or without HCV RNA had elevated serum ALT levels 13 years after onset of their acute hepatitis C. After 13 years follow-up, 1.6% of the patients had died of end-stage liver disease, 8% of anti-HCV positive patients had histologically confirmed liver cirrhosis, 79% of anti-HCV positive patients were judged to have chronic infection, whereas 21% seemed to have recovered. To conclude, we found that a majority of our patients with acute symptomatic hepatitis C continued to be viraemic 13 years after onset of hepatitis C, and that all continued to be anti-HCV positive by second-generation ELISA.