Persistent Hepatitis C viremia after acute self-limiting posttransfusion Hepatitis C

Persistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (antiHCV). We tested HCV-RNA and anti-HCV in serial serum samples from 41 patients with posttransfusion non-A, non-B hepatitis, followed for an average of 6 years after transfusion. Serum HCV-RNA was measured by nested polymerase chain reaction, which used primers from the 5′ untranslated region of the HCV genome. Anti-HCV were tested with first- and second-generation enzyme-linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second-generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV-RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow-up period in every case with chronic hepatitis and in the remaining 5 patients with self-limiting hepatitis. Anti-HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti-HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1. Anti-HCV (anti C-33 and anti-c22) were cleared in the five patients with transient hepatitis C viremia, but remained detectable in those with chronic viremia. In conclusion, serum HCV-RNA is detected at the onset of acute posttransfusion hepatitis C and persists in patients progressing to chronic hepatitis. Some patients with self-limiting hepatitis become HCV-RNA negative soon after the onset of hepatitis, whereas in others it persists throughout follow-up, suggesting the development of a silent carrier state.     

Short and long-term effects of interferon on serum markers of hepatitis C virus replication

Abstract Hepatitis C virus RNA (HCV-RNA) and serological markers of HCV infection were measured in 30 patients with chronic hepatitis C who had been treated with interferon (IFN). Patients were classified into four groups according to serum alanine aminotransferase (ALT) levels after treatment. These were: as complete responders (CR); partial responders (PR); transient responders (TR); and non-responders (NR). In all 11 patients in the CR group, HCV-RNA disappeared from serum for at least 24 months and anti-c100-3 decreased progressively during this time. In the PR group, four of five patients were positive for HCV-RNA in spite of the improvement of ALT levels and decline of anti-c100-3. In the TR and NR groups, HCV-RNA disappeared transiently or remained persistently positive. The results indicate that IFN-mediated improvement of ALT and decrease of anti-HCV (anti-c100-3) were not always related to the disappearance of HCV-RNA from serum. On the other hand, sustained disappearance of HCV-RNA from serum was demonstrated in the patients who did not have post-treatment ALT relapse. This indicates that IFN can eradicate HCV from serum in some patients and provide a clinical remission of chronic hepatitis C.     

HCV不同编码区抗体在慢性丙型肝炎干扰素治疗中的变化

采用含ＨＣＶ不同编码区三种重组抗原（Ｃ２２，Ｃ３３ｃ，Ｃ１００－３）的重组免疫印迹试验，对２０例接受干扰素（ＩＦＮ）治疗的慢性丙型肝炎患者血清相应的三种抗体进行动态监测，同时观察ＨＣＶＲＮＡ及ＡＬＴ的变化，并进行对比分析。结果表明：ＨＣＶＲＮＡ持续清除与Ｃ３３ｃ及Ｃ１００－３抗体滴度的持续下降及转阴有关（Ｐ值分别＜０．０１及＜０．００５），与Ｃ２２抗体变化无关（Ｐ＞０．０５）；ＩＦＮ治疗后ＡＬＩ稳定正常与ＨＣＶ病毒血症清除之间无相关性（Ｐ＞０．０５）。提示动态观察抗－Ｃ１００－３及抗－Ｃ３３ｃ可预测ＣＨＣ病人ＩＦＮ治疗后病毒血症的变化，而ＩＦＮ治疗后ＡＬＴ转为稳定正常不一定预示病毒血症消失。     

Circulating HCV-RNA,HCV genotype,and liver histology in asymptomatic individuals reactive for anti-HCV antibody and their follow-up study

Abstract: The present study was aimed to clarify the virologic status, liver histologies, and the results of follow-up liver tests in symptom-free individuals with anti-HCV antibodies and normal liver tests. Forty-nine individuals with normal liver tests and positive second generation anti-HCV antibody assay were entered into this study. Cases with hepatitis C viremia were evaluated for HCV genotype, amount of circulating HCV-RNA, and liver histology and were followed-up for more than one year. Of the forty-nine individuals, 36 had hepatitis C viremia, indicated by polymerase chain reaction (PCR) assay. Liver histology was as follows: 3 had non-specific changes, 25 had chronic persistent hepatitis (CPH), and 8 had chronic active hepatitis (CAH). Twenty-four cases with CPH and CAH developed an elevated AST and/or ALT concentration (> 30IU/1) between 12 and 32 months of follow-up. The amount of circulating HCV-RNA ranged from 10² to 10⁷ copies/50 μl serum. The distribution of HCV genotypes was nearly the same as that for symptomatic CAH. These data suggest that the histological examination and follow-up examination are very important for following symptom-free individuals with hepatitis C viremia because there are some candidates for interferon therapy among them. There are few individuals who will remain healthy among asymptomatic HCV carriers.     

A severe hepatitis flare in an HBV-HCV coinfected patient during combination therapy with Α-interferon and ribavirin

We report a reactivation of hepatitis B virus infection and a severe hepatitis flare in a patient with chronic hepatitis due to dual infection with hepatitis B and C viruses during combination therapy with alpha-interferon and ribavirin. Pretreatment, HCV was the dominant virus, with detectable serum HCV-RNA but undetectable HBV-DNA. The patient responded to therapy, with the disappearance of HCV-RNA and normalization of serum alanine aminotransferase (ALT) at months 1 and 6. In the seventh month of therapy, an ALT flare was observed, and serum HBV-DNA became detectable. The patient had a severe hepatitis flare leading to impending hepatic failure. Treatment was discontinued and the patient had marked clinical and biochemical improvement and recovered with normalization of liver function test results within 1 month. Two months later, serum HBV-DNA was again undetectable, both by hybridization and polymerase chain reaction (PCR) assays. The patient had a rapid progression to cirrhosis in a year. At month 24, 17 months after the end of therapy, serum HCV-RNA reappeared, with a level of 2.4 × 10⁵ copies/ml. In conclusion, severe HBV reactivation may occur during interferon plus ribavirin therapy in patients with chronic hepatitis C who are also hepatitis B surface antigen (HBsAg)-positive, and thus more careful monitoring than usual should be considered. Longterm follow-up is recommended, because very late HCV relapses may occur in coinfected patients. These data exemplify the complexity of viral dominance in patients infected with multiple hepatitis viruses, and this has significant importance for treatment decisions. Lamivudine may be administered early in HCV-RNA/HBsAg-positive patients who are at high risk of liver failure once reactivation of HBV occurs during interferon therapy.     

Hepatitis C virus serum markers and liver disease in children with leukemia during and after chemotherapy

The pattern of hepatitis C virus (HCV) serum markers and liver disease was investigated in 11 leukemic children showing anti-HCV reactivity at least once during long-term observation to define the role of HCV infection and the behavior of HCV serologic markers in this patient cohort. Antibodies to HCV by first- and second-generation enzyme-linked immunosorbent assay (ELISA) and by second-generation (four antigens) recombinant immunoblotting assay (RIBA) and HCV-RNA by nested polymerase chain reaction (PCR) were serially examined in serum. Liver disease was defined according to transaminase levels. Seven of 11 patients were found HCV-RNA positive during chemotherapy and after blood transfusion, 3 of 11 became viremic during follow-up, and 1 of 11 was always HCV-RNA negative. Seroconversion to anti-HCV positivity by second-generation ELISA occurred in all the HCV-RNA positive children either during or after chemotherapy. Alanine aminotransferase (ALT) levels were elevated in all the HCV-RNA positive patients during antileukemic treatment and normalized in seven of them after therapy withdrawal, despite persisting viremia. These results indicate that HCV- RNA testing by polymerase chain reaction is required to correctly identify HCV infection in patients with leukemia while on chemotherapy. Viremia did not correlate with ALT levels and anti-HCV patterns.     

Presence of hepatitis C virus (HCV)-RNA in peripheral blood mononuclear cells in HCV serum negative patients during interferon and ribavirin therapy

Identification of hepatitis C virus (HCV)-RNA in blood serum is crucial for hepatitis C diagnosis and for appropriate treatment. Detection of HCV-RNA in blood serum is used for therapy monitoring of patients with hepatitis C. Despite HCV-RNA elimination from blood serum during treatment in some patients, HCV viremia appears again after the completion of therapy. The aim of this study was to assess HCV-RNA in peripheral blood mononuclear cells (PBMCs) of hepatitis C patients in relation to HCV-RNA and antibodies to HCV in the serum. The study involved 71 patients undergoing anti-viral therapy (interferon and ribavirin). RNA isolated from serum and PBMCs was examined for the presence of HCV-RNA by an RT-PCR technique using specific oligonucleotide primers or by commercially available kits. In order to show the possible presence of HCV sequences in PBMCs, molecular DNA probes were constructed with a PCR amplicon and biotin-labelled by nick translation, and FISH and extended chromatin fibers in situ hybridization (ECFs-FISH) techniques were used. A 24-month follow-up study revealed that 34 out of 59 patients (58%) eliminated HCV-RNA from their sera. In the serum negative group, HCV-RNA was detected in PBMCs of 2 patients. The presence of HCV-RNA in PBMCs was confirmed by the FISH technique. In the ECFs-FISH procedure, no signal was found in all examined patients. Our data suggest that PBMCs infected with HCV can serve as a virus reservoir. HCV-RNA serum negative patients who have HCV-RNA in their leukocytes after completion of anti-viral therapy would be at great risk of hepatitis C recurrence. These HCV-RNA serum negative but PBMCs positive patients would be a potential source of HCV spread.     

Fluctuation patterns of HCV-RNA serum level in patients with chronic hepatitis C

The serum level of hepatitis C virus (HCV)-RNA is clinically important as a predictor of the response to interferon (IFN) therapy in patients with chronic hepatitis C. If serum HCV-RNA levels fluctuate during follow-up, and IFN therapy is begun at the time of a low HCV-RNA level, the IFN therapy may be more effective. We evaluated the fluctuation of HCV-RNA serum levels for 2 years in 212 patients with chronic hepatitis C, untreated with IFN who had HCV genotype 1b and an HCV-RNA level of 10 Meq/ml or more at first consultation. The HCV-RNA level was measured monthly for 2 years with an HCV branched DNA probe assay (b DNA probe assay). We classified HCV-RNA patterns into three types by the ratio of maximum HCV-RNA level (a) to minimum HCV-RNA level (b). In pattern 1 (constant type, 151 patients; 71.2%) the a/b ratio was 1–5. In pattern 2 (slight fluctuation type, 46 patients; 21.7%) the a/b ratio was 5–10. In pattern 3 (severe fluctuation type, 15 patients; 7.1%), the a/b ratio was 10 or more. Next, we evaluated the factors associated with the three patterns. Acute exacerbation of chronic hepatitis was regarded as an increase in serum alanine aminotransferase (ALT) level to more than 250 IU/l. The incidence of acute exacerbation for a 2-year follow-up was 13.9% (21/151) in pattern 1, 19.6% (9/46) in pattern 2, and 53.3% (8/15) in pattern 3. Multivariate analysis showed that acute exacerbation was the most important factor in the manifestation pattern 3. In conclusion, we found that: (1) about 70% of patients had a constant HCV-RNA levels for 2 years. (2) A few patients had severe fluctuation of serum HCV-RNA level after acute exacerbation of chronic hepatitis. Received: July 23, 1999 / Accepted: September 24, 1999     

Hepatitis type C virus infection in patients with type B chronic liver disease

Anti-c100-3 (Ortho) was determined in the sera of 152 patients with HBs antigen-positive chronic liver diseases to assess coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Eleven patients (7.2%) were positive for anti-c100-3. Anti-CP-9 (Okamoto) and HCV-RNA (RT-PCR) were also examined in these 11 patients. Anti-CP-9 was detected in 7 patients and HCV-RNA was detected in all 11 patients. Four of the 11 anti-c100-3-positive patients were positive for HBe antigen (HBeAg) and others were negative. In 8 of the 11 patients, HCV was suspected to be superinfected by blood transfusion. In HBeAgpositive patients, serum glutamic pyruvic transaminase (SGPT) was elevated in relation to active replication of HBV shown by DNA-polymerase activity. The histological findings showed chronic active hepatitis, with or without cirrhosis. On the other hand, in HBeAg-negative patients, SGPT fluctuated without evidence of active replication of HBV. Active inflammation in the liver was observed in 3 of 5 HBeAg-negative patients by liver biopsy. These findings suggest that HBV might play an important role in chronic active inflammation in HBeAg-positive patients coinfected with HCV, and that HCV might be responsible for continuous inflammation in HBeAg-negative patients coinfected with HCV.     

Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum

Background/Aims: Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment.Methods: ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV).Results: After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders (p=0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this times was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum.Conclusions: A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.     

Hepatitis C virus does not cause nonalcoholic steatohepatitis

The pathogenesis of nonalcoholic steatohepatitis (NASH) remains poorly understood. Since inflammation and fatty changes are associated with hepatitis C (HCV) infection, we have tested the role of HCV in the genesis of NASH. Five consecutive cases of classic NASH were tested by Abbott anti-c100-3 EIA and polymerase chain reaction (PCR) to detect HCV-RNA. All serum specimens were negative for anti-c100-3 (or anti-HCV EIA) and HCV PCR. Based on this study, we conclude that HCV does not play a causative or contributing role in the pathogenesis of NASH.     

HCV and HBV coexist in HBsAg-negative patients with HCV viraemia: Possibility of coinfection in these patients must be considered in HBV-high endemic area

Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with hepatitis B virus (HBV) infection in Korea. The role of HBV and hepatitis C virus (HCV) in HCC patients who are negative for hepatitis B surface antigens (HBsAg) remains poorly defined. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. Therefore, routine enzyme immunoassay may not detect HBV, in spite of the presence of HBV viraemia in low titres. The aim of this study was to confirm the coexistence of HBV viraemia in hepatitis C-infected patients with HCC who have apparent HBsAg seronegativity and to establish the need for clinical reinterpretation of enzyme immunoassay (EIA) serological tests of HBsAg in patients with HCV viraemia and HCC. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and the coinfection rate of HCV and HBV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV-RNA positive but HBsAg negative, and tested for HBV by polymerase chain reaction (PCR). Eleven non-A and non-B chronic hepatitis patients without HCC who had the same profiles of anti-HCV, HCV-RNA, and HBsAg were tested for HBV by PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A and non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of the 616 patients with HCC, 450 (73.1%) had current HBV infection, 48 (7.8%) had anti-HCV antibodies, and nine (1.5%) had viral markers of both HCV and HBV by serological profiles. Of the 27 patients with HCV viraemia and HBsAg seronegativity (16 with HCC; 11 with non-A non-B chronic hepatitis), 14 (51.9%) showed HBV viraemia by PCR. In contrast, of the 75 patients in the control group (45 with HCC; 30 with non-A and non-B chronic hepatitis) who were both HCV PCR negative and HBsAg negative, five (11.1%) showed HBV viraemia by PCR. The PCR for HBV revealed coexistent HBV viraemia in HCV viraemia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viraemia should be considered and molecular analysis for HBV-DNA performed.     

Antibody testing and RT-PCR results in hepatitis C virus (HCV) infection: HCV-RNA detection in PBMC of plasma viremia-negative HCV-seropositive persons

Summary To evaluate the concordance between viremia and antibody testing in hepatitis C virus (HCV) diagnosis, 682 serum or plasma samples collected from patients with known or suspected HCV infection were tested. An overall concordance of 77% between serological and PCR results was found, 5% was RNA positive/antibody negative and 18% antibody positive/RNA negative. The relationship between HCV infection, risk group and clinical diagnosis was studied in 116 patients: the presence of anti-HCV antibody without viremia was shown in 72.7% of asymptomatic subjects and 17.6% of chronic hepatitis subjects without interferon treatment. However, the detection of HCV-RNA in peripheral blood mononuclear cells (PBMC) in four out of 38 plasma viremia-negative HCV-seropositive subjects (10.5%), showed that HCV-RNA could persist in PBMC and could begin the viral replication again at different times. The detection of HCV-RNA in PBMC in anti-HCV-positive subjects without viremia could reduce false-negative results of HCV-RNA testing by RT-PCR in serum or plasma.     

A prospective study of hepatitis C virus infection after needlestick accidents

Abstract: There have been few prospective studies of hepatitis C virus (HCV) infection after needlestick accidents in hospital employees. In the present study, the prevalence and features of HCV infection after needlestick accidents were evaluated prospectively measuring serum HCV-RNA. Subjects were 56 employees who had HCV needlestick accidents. To monitor the development of hepatitis, the serum ALT levels and HCV-related seromarkers, such as first generation anti-HCV (RIA), second generation anti-HCV (PHA) and HCV-RNA (RT-PCR) were measured every month for at least 12 months after the accidents. Three of 56 (5.4%) recipients developed HCV infection. HCV-RNA was detected in all three recipients within 4 months after the exposure, and second-generation HCV antibody was detected in two of three recipients. The detection of HCV-RNA was earlier than that of HCV antibody. Two of three HCV-infected recipients developed type C acute hepatitis and one of two received interferon therapy; however, the other case received no medication. The detection of HCV-related seromarkers and the elevation of ALT levels were transient in these three recipients; thus, none developed chronic hepatitis. In conclusion, HCV infection developed in 5.4% of recipients within 4 months after HCV accidents. All of these HCV-infected recipients showed fair prognosis. HCV-RNA was a beneficial parameter for early detection of HCV infection.     

Chronic hepatitis C responds poorly to combination therapy in chronic hepatis B carriers

BACKGROUND: The effect of conventional interferon-based therapy of hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection is controversial. Yet, no studies have been carried out into pegylated interferon treatment for chronic HBV/HCV coinfection. We aimed to evaluate the response rate and side effects of conventional or pegylated interferon combined with ribavirin on chronic HBV/HCV coinfection therapy. METHODS: The study included 36 chronic hepatitis patients (M/F: 28/8, mean age 47+/-12 years) who were positive for HBsAg and anti-HCV. They were tested for the presence of HBV-DNA by hybridisation assay, and the samples giving negative results were retested by polymerase chain reaction (PCR). All patients were tested for HCV-RNA using PCR, and the HCV genotype was determined. RESULTS: Nineteen patients were given standard interferon either alone or in combination with ribavirin, whereas 17 were given pegylated interferon and ribavirin combination therapy. None of the patients had HBV-DNA positivity; however, all had HCV-RNA detectable by PCR. All the patients had HCV genotype 1b. The mean alanine aminotransferase and aspartate aminotransferase levels were 118+/-65 U/l and 90+/-95 U/l respectively. Five patients in each group discontinued the treatment due to side effects. Only two patients (one from each group) reached sustained virological response. CONCLUSION: Neither pegylated nor conventional interferon based regimes were effective for HBV/HCV coinfection, in which the dominant virus was HCV. Pegylated interferon and ribavirin therapy was not superior to conventional interferon based regimes in the treatment of HBV/HCV coinfection.     

Hepatitis C virus infection of salivary gland epithelial cells: Lack of evidence

Background: Hepatitis C virus genome (HCV-RNA) has been detected in whole salivary gland tissue of chronically infected patients. However, contamination of the tissue by plasma or blood cells was not excluded by the previous reports.Aims: To assess whether HCV infects the salivary gland epithelial cells in patients with chronic HCV liver disease.Methods: Twenty unselected patients with chronic active hepatitis (11 cases) or active cirrhosis (nine cases) were examined. Serum and saliva samples were obtained from all patients, 12 of whom (seven, chronic active hepatitis; five, active cirrhosis) underwent salivary gland biopsy. PCR for HCV-RNA was performed on RNA extracted from serum, saliva and salivary gland epithelial cells collected by isokinetic gradient separation after trypsin digestion of whole salivary gland tissue. Saliva samples were also examined for the presence of secretory IgA anti-HCV by gel chromatography and ELISA testing.Results: HCV-RNA was detected in all sera with titers ranging from 5.42×10⁵ genome equivalents/ml to 123.2×10⁵ genome equivalents/ml. Thirteen patients were infected with genotype 1b, four patients had genotype 1a, two patients had genotype 2a and one patient was unclassifiable. Low titer HCV-RNA (<2×10⁵ genome equivalents/ml) was detected in saliva samples (15%) from highly viremic patients infected with 1b genotype. RNA extracted from salivary gland epithelial cells consistently tested negative for HCV-RNA. In addition, all saliva specimens tested negative for secretory-IgA (S-IgA) anti-HCV, even after a 10-fold concentration of the samples.Conclusions: There was no evidence that HCV infects the salivary gland epithelial cells in our viremic patients with HCV chronic liver disease. Low level HCV-RNA in saliva is most probably due to virus spillover from blood.     

Low prevalence of chronic hepatitis C, but high prevalence of elevated aminotransferases in a cohort of 2026 patients referred for orthopaedic surgery in the eastern part of Germany

INTRODUCTION: The prevalence of chronic hepatitis C in Germany is about 0.2 - 0.4 %. However, there seems to be regional differences between western and eastern states of the country. Thus, the present study analysed the prevalence of chronic hepatitis C in a cohort of orthopaedic patients in Thuringia. METHODS: Tests for antibodies against hepatitis C virus (anti-HCV) were performed on serum samples of 2026 patients (1183 females, 843 males) admitted for orthopaedic surgery to a university hospital in Thuringia. If anti-HCV was positive, serum was tested for HCV-RNA by polymerase chain reaction (PCR). For the sake of anonymity only age and gender were reported in all patients. In 1465 cases, values of alanine (ALT) and aspartate (AST) aminotransferases were additionally available. The low HCV prevalence was confirmed in a second cohort of orthopaedic patients (n = 929, 599 females, 330 males) investigated at a university hospital in Saxonia. RESULTS: In the Thuringian cohort, anti-HCV was detectable in 12/2026 (0.6 %) individuals (10 females (0.85 %) and 2 males (0.24 %: p = 0.14 %). HCV-RNA was positive in 3/10 of anti-HCV positive females (0.15 % of the study cohort). HCV infection was already known in two cases. Anti-HCV positive patients seemed to be older than anti-HCV negative individuals (64.25 vs. 59.48 years; p = 0.17), as well as HCV-RNA positive cases compared to non-viraemic patients (66.3 vs. 63.6 years; p = 0.32). All HCV-RNA positive females had elevated ALT values. However, ALT and AST were also elevated in 18.2 % and 11.7 % of anti-HCV negative individuals. There was no significant difference between males and females (p = 0.32). In the Saxonian cohort none of 929 individuals were HCV positive. CONCLUSION: The prevalence of chronic hepatitis C is low in the investigated cohorts of orthopaedic patients in Thuringia and Saxonia. However, elevation of aminotransferases occurs surprisingly often. The reasons for elevated aminotransferases and a reliable analysis of the HCV prevalence in different subgroups of the Eastern German population require further evaluation.     

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.     

Detection of specific antibodies to HCV-ARF/CORE+1 protein in patients treated with pegylated interferon plus ribavirin

Hepatitis C virus (HCV) infection is a major cause for chronic liver disease and hepatocellular carcinoma. The HCV-ARF/core+1 protein is an alternative product of HCV core-encoding sequence of unknown biological function. Highly purified HCV core and ARF/core+1 recombinant proteins from HCV genotype 1a and HCV-ARF/core+1 recombinant protein from HCV genotype 3a were expressed in Escherichia coli. Using an enzyme-linked immunosorbent assay, we assessed the prevalence of anti-ARF/core+1 antibodies in 90 chronic hepatitis C patients infected with HCV genotypes 1a/1b or 3a, treated with pegylated interferon (Peg-IFN-a-2a) plus ribavirin. Samples derived from 92 healthy blood donors were used as negative controls. All HCV-RNA-positive serum samples reacted with core 1a antigen, while 15 (37.5%) of 40 and 14 (28%) of 50 patients infected with HCV-1a/1b and HCV-3a, respectively, were found to have anti-ARF/core+1 antibodies into their serum before treatment initiation. These antibodies were persistently present during treatment follow-up and linked to elevated levels of HCV-RNA at baseline.