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.     

Presumed transfer of hepatitis antibody by blood transfusion to chronic hemodialysis patients

During the winter of 1980 it was noted that some of the patients receiving hemodialysis demonstrated antibody to hepatitis B surface antigen and hepatitis B core antigen. A retrospective study was conducted to determine the number of chronic hemodialysis patients who demonstrated this seroconversion and the reason(s) for the conversion. Because these patients were known to receive numerous blood transfusions during their hemodialysis therapy and the antibody titers were relatively low and continued to diminish until they again became negative, we were led to the suspicion that the passive transfer of antibody was occurring. Eleven of the 12 (91.6%) chronic hemodialysis patients in whom antibody was detected received blood transfusions (packed red cells) during their dialysis therapy. All 11 of these patients received the blood prior to the detection of either the antibodies in their serum. All these patients had negative serologic test results within 1 year. This study indicates that patients who receive blood transfusions, especially numerous transfusions, can passively acquire these hepatitis B markers.     

Hepatitis GB virus C genome in the serum of aplastic anaemia patients receiving frequent blood transfusions

GB virus C (GBV-C) RNA was detected in five of 18 patients with aplastic anaemia who had received blood transfusions, whereas it was not detected in eight patients who had not received any transfusions. Antibody against hepatitis C virus (anti-HCV) was detected in nine patients in the transfusion group, compared with one of eight who had not received any transfusions. Therefore, the route of transmission of both GBV-C and HCV in these patients appeared to have been multiple blood transfusion. Since all of the GBV-C RNA-positive patients harboured anti-HCV, GBV-C seems to frequently superinfect with HCV. Neither GBV-C nor HCV is likely to have been a causative agent of the anaemia in the cases examined.     

Serum Cryoglobulin and Chronic Hepatitis C Virus Disease among Japanese Patients

Objectives: Hepatitis C virus (HCV)-associated mixed cryoglobulins appear to be detected often in hepatitis C-related chronic liver disease. The association of the two phenomenon among Japanese patients is the subject of the present study.
Methods: Serum levels of total hemolytic complement (CH50) and anti-C3d-binding immune complex, as well as the prevalence of cryoglobulins, were studied in 213 patients with chronic liver disease thepatitis C, 155; hepatitis B, 58). Cryoprecipitates were tested for anti-HCV Ah and HCV RNA.
Results: CH50 activity was significantly lower in patients with hepatitis C than in those with hepatitis B except in responders to interferon who showed a sustained loss of HCV RNA. Cryoglobulins were detected in 24 (37%) of 65 patients with hepatitis C; they generally consisted of polyclonal immunoglobulins but one case. Cryoglobulins were more frequently observed in cirrhotic patients and in those with a longer duration of disease. Cryoglobulinemia-related clinical signs such as vasculitis occurred in only three cases. Patients with cryoglobulins had lower CH50 activity and higher immune complex values than those without cryoglobulins. Anti-HCV Ab and HCV RNA were detected in all cryoprecipitates tested.
Conclusions: These findings suggest that HCV is a major cause of cryoglobulins and advanced liver damage. However, serum cryoglobulins with polyclonal immunoglohulins appear to be less frequent among Japanese patients than among those studied in Western countries.     

Hepatitis C virus antibodies among risk groups in Turkey

Summary In order to determine the prevalence of hepatitis C virus (HCV) infection in the Black Sea region in Turkey, 287 serum samples taken from risk groups were investigated for anti-HCV antibodies using HCV EIA system. Anti-HCV antibodies were found to be positive in 51.2% of chronic haemodialysis patients, 20.6% of probable acute non-A, non-B hepatitis patients, 4% of patients who had multiple blood transfusions, 1.5% of the health personnel, while in new haemodialysis patients anti-HCV antibodies were not found.

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Hepatitis C Virus Antikörper in Risikogruppen in der Türkei

Zusammenfassung 287 Serumproben von Personen aus Risikogruppen wurden mit dem HCV EIA System auf anti-HCV Antikörper untersucht, um die Prävalenz des Hepatitis C Virus in der Türkei in der Region am Schwarzen Meer zu bestimmen. Anti-HCV Antikörper fanden sich bei 51,2% der chronischen Hämodialyse-Patienten, bei 20,6% der Patienten mit wahrscheinlicher Non-A, Non-B- Hepatitis, 4% der Patienten, die multiple Bluttransfusionen erhalten hatten und 1,5% des Pflegepersonals. Bei Patienten, die neu in Hämodialyseprogramme aufgenommen wurden, fanden sich keine anti-HCV Antikörper.

     

Hepatitis C viremia and anti-HCV antibodies in alcoholics

We determined serum hepatitis C status using a RIBA2 kit and a sensitive PCR procedure in 62 chronic alcoholics, 36 of whom had anti-HCV antibodies (Ab) detectable in an ELISA1 assay. Anti-HCV antibodies were detected in 22 patients using RIBA2. HCV RNA was detected by means of PCR in 18 patients who were RIBA2 positive and in none who were RIBA2 negative. Liver biopsies, available for 12 HCV RNA-positive patients, revealed histological features of purely alcohol-related lesions in seven and mixed alcohol-viral lesions in five. These results indicate that HCV replication is maintained in most alcoholics who score positive for anti-HCV Ab in the RIBA2 test, and that HCV viremia can be associated with histological features typical of alcoholic liver disease.     

High rate of hepatitis C virus transmission to spouses from hepatitis patients with a history of transfusion

Spouses of hepatitis C virus (HCV)-viremic chronic hepatitis patients were tested for antibodies to the core region-derived synthetic oligopeptides and for antibodies detectable by the second-generation enzyme immunoassay, and HCV RNA was determined in those who were positive for at least one of the above antibodies (anti-HCV). The prevalences of anti-HCV and HCV RNA were both significantly higher in 37 spouses of patients with a history of transfusion than in 55 spouses of patients with no such history: 49% vs. 16% for anti-HCV (P < 0.01) and 41% vs. 5% for HCV RNA (P < 0.05). Anti-HCV was detected in 11 (65%) of 17 spouses who had been married longer than 30 years since the patients received the transfusion, with an incidence significantly higher than in four (20%) of 20 spouses with exposure durations less than 30 years (P < 0.001), and HCV RNA was positive in 11 (65%) of the formers, the incidence being significantly greater than in four (20%) of the latter (P < 0.05). HCV-infected patients, in particular with a history of blood transfusion, are thus possible HCV transmission sources for their spouses, with the risk increasing with the duration of marriage, pointing to a need for follow-up not only for posttransfusion hepatitis C patients, but also for early diagnosis and treatment of their spouses.     

Prevalence of hepatitis C virus antibody in chronic HBsAg-negative non alcoholic hepatopathy]

The presence of antibody to hepatitis C virus was determined in 316 HBsAg-negative patients with non-alcoholic chronic hepatitis who did not receive any blood transfusion once the diagnosis was made. A titre of antinuclear antibodies of 1/40 or lower was found in 18 patients. Persistent chronic hepatitis was present in 21 patients, active chronic hepatitis in 145, hepatic cirrhosis in 128, and hepatocarcinoma in 22 patients. One hundred and three patients had previously received blood transfusion, 76 had undergone previous surgery without transfusion, a clinical episode of hepatitis could be traced in 14, 13 patients were drug addicts (all of them HIV negative), 1 patient had received multiples injections, another had been treated with acupuncture, and 108 patients were free of any of the above. Anti-HCV was present in 76.6% of patients; a significantly higher proportion (87.4%) was found among patients who had received blood transfusion than in patients with previous surgery (72.4%) (p = 0.012), clinical hepatitis (57.1%), or without previous hepatic disease (70.3%) (p = 0.003). The incidence of anti-HCV was lower among cirrhotics (70.3%) than in patients with active chronic hepatitis (84.1%) (p = 0.006); in contrast, previous blood transfusion was significantly higher (p = 0.001) among the latter (40.7%) than in cirrhotics (21.9%). The incidence of anti-HCV was similar among patients with (78.6%) and without (75.8%) type B infection. Our results suggest that infection with virus C may account for a high proportion of non-alcoholic non-B chronic hepatitis.     

Hepatitis C virus infection in patients with haematological diseases: evidence for the association with erythrocytes transfusion and liver disease

We analysed hepatitis C virus risk factors in 131 consecutive patients with haematological malignancies (17.6% anti-HCV positive), 42 with connective tissue diseases (30.9% anti-HCV positive) and 1071 (1.1% anti-HCV positive) new blood donors. Anti-HCV was associated with elevated serum ALT levels (P = 0.0001) and with red cells (P = 0.045), but not with platelets and plasma transfusions. HCV presence in immunocomplexes immunoadhering on the erythrocytes might explain the association between HCV infection and red cell transfusion. However, other risk factors have to be implicated in haematological malignancies to explain the high anti-HCV prevalence in patients who did not receive blood products.     

Genotypic variation, clinical and histological characteristics of chronic hepatitis C detected at blood donor screening

Summary. Since blood donor screening for the hepatitis C virus (HCV) began in 1991 a large number of seropositive subjects have been detected and several reports have suggested a high prevelance of liver disease. The aim of this study was to evaluate the severity of liver disease in HCV-positive blood donors in terms of the clinical, biochemical and histological abnormalities and to investigate the relationships between these features and the mode of transmission, duration of infection and viral genotype. We evaluated 54 consecutive blood donors who were positive for HCV both on serological testing and polymerase chain reaction. Twenty-three (43%) had a history of intravenous drug abuse and 17 (31%) had received blood transfusions. In only two (4%) was no risk factor identified. The mean duration of infection in those with a clear history of HCV exposure was 12 years. Eighty-three percent were HCV genotypes 1 or 3. All had abnormal liver biopsies with chronic hepatitis and several patients had periportal or portal-portal fibrous septa, but there was none with architectural distortion or cirrhosis. There was no correlation between severity of liver disease and duration of HCV infection, mode of transmission or viral genotype.
In the majority of HCV carriers detected at donor screening there is a chronic hepatitis with bridging necrosis in one third, but the degree of fibrosis is minimal and cirrhosis was not present in our patients. The long period of infection of many patients suggests that irreversible liver injury does not necessarily develop at an early stage despite persistent infection.     

Hepatitis C virus infection in patients with nonalcoholic chronic liver disease

STUDY OBJECTIVE: To determine the prevalence and meaning of antibodies to the hepatitis C virus (HCV) in patients with nonalcoholic chronic liver diseases. DESIGN: Cross-sectional study. SETTING: The liver unit of a referral-based university hospital. PATIENTS: Three hundred and forty-six consecutive patients, including 137 with cryptogenic chronic liver disease, 156 with chronic hepatitis B, 47 with primary biliary cirrhosis, and 8 with persistently abnormal aminotransferase serum levels and normal liver histology. Among patients with cryptogenic liver disease, 41 received blood transfusions before discovery of liver disease and 18 had circulating nonorgan-specific autoantibodies. For comparison, 1495 apparently healthy volunteer blood donors were included in the study. LABORATORY INVESTIGATIONS: The presence of anti-HCV antibodies (anti-HCV) was determined by a recently developed enzyme-linked immunoassay. MEASUREMENTS AND MAIN RESULTS: In patients with cryptogenic liver disease, the prevalence of anti-HCV was 82% (95% CI, 76% to 89%), being higher (P = 0.02) in patients with histories of blood transfusion than in those with unknown sources of exposure. Antibodies to HCV were not detected in patients with antinuclear antibodies at high titer. Among patients with chronic hepatitis B, anti-HCV were found in 11% (CI, 5% to 18%) of those with hepatitis B virus (HBV)-associated DNA in serum and in 29% (CI, 17% to 43%) of those with undetectable HBV replication (P less than 0.05). The prevalence of anti-HCV in blood donors was 1.2% (CI, 1.1% to 1.3%). CONCLUSIONS: Our results indicate that HCV infection probably plays an important etiologic role in cryptogenic liver disease and, in some patients, in chronic hepatitis B. Determining whether anti-HCV are present appears to be useful for differentiating viral from autoimmune chronic liver diseases.     

Hepatitis C virus infection in anti-HIV positive and negative French homosexual men with chronic hepatitis: comparison of second- and third-generation anti-HCV testing

ABSTRACT— To determine the prevalence of hepatitis C virus (HCV) infection in homosexuals with chronic hepatitis, we tested for anti-HCV antibodies 113 (47 anti-HIV positive) French non-drug-addicted homosexual men admitted for chronic viral hepatitis. Anti-HCV were detected with second- and third-generation ELISAs (ELISA2 and ELISA3) and RIBAs (RIBA2 and RIBA3). Chronic hepatitis was related to non-A, non-B infection in four, to hepatitis D virus (HDV) infection in five and to hepatitis B virus (HBV) infection in 104 patients. Anti-HCV positivity was found in 50.4% and 12.4% of the 113 patients, with ELISA2 and ELISA3, respectively. Positivity with RIBA2 and RIBA3 was found in only six of the 57 ELISA2 positive patients (all six were ELISA3 positive). The high prevalence of positivity with ELISA2 not confirmed by RIBA2 or RIBA3 suggests false-positive results. ELISA2 positive results were more frequent with frozen serum samples than with fresh serum samples (62% vs 23.5%, p = 0.0003). However, even with fresh serum, ELISA2-positive RIBA-negative results remained frequent in anti-HIV positive patients. ELISA3 seems to give more specific results. We conclude that the prevalence of HCV infection, as assessed with RIBA, was 5.3% among French homosexual men with chronic hepatitis (3.8% after exclusion of transfused patients). This low prevalence suggests that homosexual transmission of HCV is relatively uncommon.     

Clinical and serological differentiation of autoimmune and hepatitis C virus-related chronic hepatitis

Recent reports have focused on the difficulty in differentiating autoimmune hepatitis from chronic hepatitic C due to the high prevalenc of anti-HCV in autoimmune hepatitis. The aim of this study was to identify clinical, biochemical, and serological variables that would help distinguish these two diseases. Pretreatment clinical and biochemical variables were compared from 17 patients with steroid-responsive autoimmune chronic active hepatitis and 62 patients with chronic hepatitis C. Serum samples from these patients were tested for autoantibodies and for anti-HCV by first- and second-generation ELISA, recombinant immunoblot assay, and HCV RNA by polymerase chain reaction. Patients with autoimmune hepatitis were more likely to be symptomatic (94% vs 47%,P<0.005) and jaundiced (76% vs 0%,P<0.005) at the time of referral. Anti-HCV was found in 53% of patients with autoimmune hepatitis, but only two were positive by immunoblot assay and only one of these had detectable HCV RNA. Antinuclear antibody (ANA) was detected in 21% of patients with chronic hepatitis C, although usually at a lower titer than in autoimmune hepatitis (geometric mean titer=1:160 vs 1:500,P<0.003). Patients with chronic hepatitis C who were ANA positive were older than those who were ANA negative, although there were no other differences in clinical or biochemical features between these groups. In particular, there was no difference in response rate to antiviral therapy. Thus, autoantibodies are frequently found in chronic hepatitis C, especially in older subjects, but appear to be clinically insignificant. Anti-HCV is frequently present in autoimmune hepatitis but is rarely confirmed by tests of higher specificity. These findings have important implications in selecting patients for antiviral or immunosuppressive therapy.     

Hepatitis C virus infection among elderly patients in a geriatric hospital

The aim of the study was to determine the prevalence of anti-hepatitis C virus (HCV) antibodies and HCV viremia among elderly patients in a geriatric hospital in Jerusalem, Israel. Serum samples from 273 patients were analyzed for the presence of anti-HCV antibodies. Serum samples of anti-HCV positive patients were analyzed for HCV RNA after amplification with the polymerase chain reaction (PCR). The samples were also analyzed for the presence of HBsAg and the HBsAg positive samples were analyzed for the presence of hepatitis B virus (HBV) DNA. Anti-HCV antibodies were found in 5 patients (1.8%). HCV RNA was detected in one of the 5 patients. HbsAg was found in 2 patients (0.7%). None had detectable HBV DNA. The findings of the study indicate that seropositivity for hepatitis C virus is relatively common among the elderly population studied. Most of those patients are probably not HCV carriers.     

Anti-HCV positivity in sexual partners and offspring of patient with chronic hepatitis C

We investigated the seroprevalence of HCV in stable sexual partners and offspring of chronic hepatitis C patients, and aimed to determine the risk factors involved. 191 anti-HCV and HCV RNA positive subjects who coinhabited with their spouse and/or offspring were included. Risk factors of index cases for disease transmission, liver biopsy results, anti-HCV and HCV-RNA in spouses and/or offspring were evaluated. Together with index cases, a total of 404 family members including 174 stable sexual partners and 230 offspring were included. The most common risk factors among index cases were dental procedures (73.8%), history of surgery (64.9%), and blood transfusions (24.1%). Anti-HCV positivity was established in 11 (2.7%) of the total 404 family contacts--6 sexual partners and 5 offspring. HCV seropositivity was significantly higher in the spouses of index cases with severe hepatitis C compared to those with mild to moderate hepatitis C (p=0.008), but there was no statistically significant correlation between the severity of liver disease in index cases and anti-HCV positivity in their offspring. In conclusion, anti-HCV seropositivity in the spouses and children of patients who are HCV-RNA positive HCV carriers does not appear to be higher than the HCV seroprevalence in our country.     

Prevalence of hepatitis C virus infection in patients with antiphospholipid syndrome.

BACKGROUND/AIMS: The aim of this study was to determine the prevalence and clinical significance of hepatitis C virus (HCV) infection in patients with the antiphospholipid syndrome (APS). METHODS: A series of 88 consecutive patients (78 female and 10 male), with a mean age of 39 years (range 15-79), was prospectively studied. All patients had been diagnosed with APS: 54 (61%) primary APS and 34 (39%) APS associated with systemic lupus erythematosus. A group of 200 apparently healthly blood donors was included in the study. Anti-HCV antibodies were investigated in the serum of all patients using a third-generation ELISA and confirmed by recombinant immunoblot assay. RNA-HCV was investigated in anti-HCV positive samples by polymerase chain reaction. Anticardiolipin, anti-beta2-glycoprotein I and antiprothrombin antibodies were evaluated by ELISA. Lupus anticoagulant was studied by coagulometric assays. RESULTS: Only 2 (2.2%) patients showed positivity for anti-HCV antibodies, but none of them had clinical or biochemical signs of liver disease. Furthermore, RNA-HCV was not detected in serum of any of these patients. Lupus anticoagulant was positive in 57% of patients. Anticardiolipin antibodies were positive in 60% of patients, anti-beta2-glycoprotein I antibodies in 43% of patients, and antiprothrombin antibodies in 56% of patients. The prevalence of anti-HCV in blood donors was 1%. CONCLUSIONS: The prevalence of anti-HCV in patients with APS is low and similar to that in healthy people in our area. HCV infection does not seem to be involved in the etiopathogenesis of this syndrome.     

Spectrum of viral hepatitis in thalassemic children receiving multiple blood transfusions.

AIM: To investigate the prevalence of infection with hepatitis viruses in children with thalassemia receiving multiple blood transfusions. METHODS: Sera from 50 children with thalassemia aged 5-15 years (30 boys), who had each received over 80 units of blood, were evaluated for the presence of markers for hepatitis A virus (HAV; IgG and IgM anti-HAV), hepatitis B virus (HBV; HBsAg, and IgG and IgM anti-HBc), hepatitis C virus (HCV; IgG and IgM anti-HCV, and HCV RNA) and hepatitis E virus (HEV; IgG and IgM anti-HEV). IgM anti-hepatitis D virus (HDV) was looked for only in HBsAg or IgM anti-HBc positive sera. RESULTS: No child had evidence of recent HAV or HDV infection. IgG anti-HAV was positive in 12 children. One patient had acute HBV infection. Nine patients were HBsAg-positive. HCV infection was present in 15 cases; six of them were HCV RNA positive, and three had superinfection with hepatitis B. Recent HEV infection was present in 5 cases. CONCLUSION: Thalassemic patients receiving multiple blood transfusions often acquire hepatitis B (20%) and C (30%) infections. Recent hepatitis E infection was documented in 10% in this one-point study.     

Decrease in serum hepatitis C viral RNA during alpha-interferon therapy for chronic hepatitis C.

OBJECTIVE: To assess the effect of alpha-interferon therapy on hepatitis C viral RNA in serum of patients with chronic hepatitis C. DESIGN: Retrospective testing for hepatitis C viral (HCV) RNA and antibody to the hepatitis C virus (anti-HCV) of stored serum samples from a randomized, double-blind, placebo-controlled trial of alpha-interferon therapy. SETTING: Warren Grant Magnuson Clinical Center of the National Institutes of Health, a tertiary referral center. PATIENTS: Forty-one patients with chronic non-A, non-B hepatitis were entered in this trial. INTERVENTIONS: Twenty-one patients were treated with alpha-interferon, and 20 patients were treated with placebo for 6 months. Seventeen placebo recipients were then treated with alpha-interferon for up to 1 year. METHODS: Samples were tested for anti-HCV by enzyme-linked immunosorbent assay. Hepatitis C viral RNA was detected in serum using the polymerase chain reaction. Titers of both antibody and RNA were determined by serial end-point dilution. MAIN RESULTS: At entry into the trial, 37 (90%) of 41 patients had anti-HCV and 39 (95%) had HCV RNA in serum. Anti-HCV titers decreased slightly with treatment. Serum levels of HCV RNA decreased in all patients who responded to alpha-interferon therapy with improvements in serum aminotransferases; in 17 of 21 responders (81%; 95% Cl, 58% to 95%) HCV RNA became undetectable. In contrast, in only 2 of 16 (12%; Cl, 2% to 38%) patients who did not respond to treatment did HCV RNA become undetectable. In 19 patients treated during the preliminary 6-month period with placebo, HCV RNA remained detectable. Finally, in the 11 patients who relapsed when treatment was stopped, HCV RNA reappeared in the serum, but in 4 of 7 patients with a sustained improvement in serum aminotransferases, HCV RNA remained undetectable. CONCLUSIONS: These results indicate that the clinical and serum biochemical response to alpha-interferon in chronic hepatitis C is associated with a loss of detectable HCV genome from serum.     

Expression of hepatitis B virus (HBV) markers in chronic liver disease positive for antibody to hepatitis C virus (HCV)

We investigated expression of HBV markers in chronic liver disease positive for antibody to HCV (anti-HCV). Sera from 107 patients with chronic non-A, non-B liver disease, 65 HBs antigen carriers with chronic liver disease and 14 asymptomatic HBV carriers were tested for the presence of anti-HCV. Anti-HCV was detected in 83 (78%) patients with chronic non-A, non-B liver disease, irrespective of the past history of blood transfusion, and anti-HCV prevalence was similar in each category of chronic liver disease. Fifty-three (64%) out of these 83 sera positive for anti-HCV has also antibodies to HBV. Anti-HBc antibody was detected frequently in liver cirrhotics with hepatocellular carcinoma than in chronic persistent hepatitis, chronic active hepatitis and cirrhotics without hepatocellular carcinoma. In addition, titers of anti-HBc antibody were significantly higher in cirrhotics with hepatocellular carcinoma than in the other groups. On the other hand, anti-HCV was detected in 7 out of 65 patients with HBV-related liver disease. Four out of these 7 were patients with HBV-related hepatocellular carcinoma. Anti-HCV was detected in none of asymptomatic HBV carriers. These findings suggest that infection with both HBV and HCV is likely to cause more serious liver disease than infection with a single agent.