Seroprevalence of hepatitis C virus nucleocapsid antibodies in patients with cryptogenic chronic liver disease.

The serological responses to two different hepatitis C virus antigens were studied by enzyme-linked immunosorbent assay in a variety of chronic liver diseases and in healthy blood donors. The study population comprised 97 cases of cryptogenic chronic liver disease (40% with a history suggestive of parenterally transmitted non-A, non-B hepatitis and 60% without such a history), 87 cases of other well-characterized chronic liver diseases and 96 voluntary blood donors. The commercially available C100-3 assay and a new assay utilizing a 22 kD recombinant protein (c22) from the nucleocapsid region of the virus were used for antibody detection. Overall in the non-A, non-B hepatitis group, 77% were positive for anti-c22, 55% were positive for anti-C100-3 and 24% were negative by both tests. In the parenterally transmitted chronic liver disease group, 82% were positive for anti-C100-3 and 90% were positive for anti-c22 (not significant). In the cryptogenic chronic liver disease cases 36% were positive for anti-C100-3 and 67% were positive for anti-c22 (p less than 0.001). Only in one case (a patient with hepatitis B virus infection) was anti-C100-3 detected without concomitant anti-c22. None of the voluntary blood donors had detectable hepatitis C virus antibodies. The new enzyme-linked immunosorbent assay test for anti-c22 would appear to be a more sensitive indicator of chronic hepatitis C virus infection than the existing commercial test, suggesting a useful diagnostic role in both cases of cryptogenic chronic non-A, non-B hepatitis liver disease and for the screening of blood products for prevention of hepatitis after transfusion.     

慢性肝病者乙型和丙型肝炎病毒重叠感染的研究

对２１３例老年慢性肝病患者的乙型肝炎病毒（ＨＢＶ）和丙型肝炎病毒（ＨＣＶ）血清标志物检测发现：ＨＢＶ感染占７３．２４％、ＨＢＶ和ＨＣＶ重叠感染占重叠感染点１５．４９％、ＨＣＶ感染占７．０４％、其它占４．２６％；ＨＢＶ阴性者ＨＣＶ检出率高于ＨＢＶ阳性者，肝癌和肝硬化患者较慢性肝炎患者高；ＨＢＶ和ＨＣＶ重叠感染患者的血清血蛋白下降显著，γ－球蛋白升高明显，肝硬化并腹水和上消化道出血者了多。结果表明，老     

Detection of hepatitis C virus antibodies and hepatitis C virus RNA in patients with alcoholic liver disease.

The relationship between alcoholic liver disease and hepatitis C virus was studied in 80 patients by searching for hepatitis C virus RNA with the polymerase chain reaction and by measuring hepatitis C virus antibodies. By C-100 enzyme-linked immunosorbent assay, hepatitis C virus antibodies were found in 2 of 10 patients with fibrosteatosis, 8 of 20 patients with alcoholic hepatitis, 14 of 19 patients with chronic hepatitis and 19 of 31 patients with cirrhosis. Percentages of patients with antibodies found by C-100 radioimmunoassay and by enzyme-linked immunosorbent assay based on sequence peptide 42 were lower; of the 16 patients with a low titer by C-100 enzyme-linked immunosorbent assay, 10 were negative by radioimmunoassay and 6 were negative by sequence peptide 42. By a second-generation recombinant immunoblot assay, hepatitis C virus antibodies were found in 1 of 10 patients with fibrosteatosis, 2 of 20 patients with alcoholic hepatitis, 15 of 19 patients with chronic hepatitis and 18 of 31 patients with cirrhosis. Hepatitis C virus RNA was found in 1 of 10 patients with fibrosteatosis, 3 of 20 patients with alcoholic hepatitis, 13 of 19 patients with chronic hepatitis and 20 of 31 patients with cirrhosis. Of the 37 patients with hepatitis C virus RNA, 31 had antibodies by C-100 enzyme-linked immunosorbent assay (25 patients at a high titer [cut-off index greater than 6]), and 31 had antibodies by second-generation recombinant immunoblot assay. Patients with cirrhosis and hepatitis C virus RNA had higher ALT activity than such patients without hepatitis C virus RNA (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of hepatitis C virus in non-B chronic liver disease.

To assess the contribution of the recently identified hepatitis C virus to chronic liver diseases of unknown cause and chronic hepatitis attributed by exclusion to non-A, non-B hepatitis, we tested for antibody to hepatitis C in hepatitis B surface antigen-negative patients with a spectrum of chronic liver diseases. Antibody to hepatitis C virus, a marker of hepatitis C infection, was detected with a first-generation radioimmunoassay at the following frequencies in the following patient groups: 69% of transfusion-associated non-A, non-B hepatitis; 53% of non-transfusion-associated non-A, non-B hepatitis; 26% of hepatitis B surface antigen-negative hepatocellular carcinoma; 8% of cryptogenic cirrhosis; 5% to 7% of autoimmune chronic liver diseases; 19% of patients with miscellaneous types of chronic liver disease; and 0.67% of healthy controls. Among non-transfusion-associated cases, 81% with a history of intravenous drug use but only 18% with occupational exposure as health workers had antibody to hepatitis C virus. Among cases of hepatocellular carcinoma, 63% of Japanese patients but only 11% of American patients had evidence of hepatitis C infection. Comparison in a subgroup of 79 serum samples of a second-generation radioimmunoassay with the first-generation assay demonstrated a 12% increase in antibody frequency from 30% to 42%. We conclude that hepatitis C plays a substantial role in transfusion-associated and non-transfusion-associated non-A, non-B hepatitis as well as in hepatocellular carcinoma, especially in Japan, a limited role in cryptogenic cirrhosis, and essentially no role in autoimmune chronic liver diseases. Application of more sensitive immunoassays will increase the frequency of antibody seropositivity in all subgroups, but relative distinctions among risk groups are likely to remain.     

Cryptogenic chronic liver disease and hepatitis C virus infection in children.

The clinical features of 'cryptogenic' chronic liver disease and the prevalence of antibody to hepatitis C virus (HCV) in serum have been investigated in 33 Italian children (mean age 5 years). The diagnosis was based on the persistence of increased alanineaminotransferase values for longer than 6 months after the exclusion of biliary diseases, of extra-hepatic causes of hypertransaminasemia, of infection with known hepatotropic viruses and of autoimmune or metabolic disorders. Five patients had been transfused early in life, three had undergone surgery and one girl's mother had had acute non-A, non-B hepatitis during pregnancy. The remaining patients had no history of overt parenteral exposure. At presentation only 11 patients were symptomatic, the others had been referred after a check-up for intercurrent diseases. Liver histology performed in 21 cases showed persistent or mild active hepatitis in 18 cases and severe hepatitis or cirrhosis in three cases. Anti-HCV antibodies were found in 48% of the cases, including 88% with obvious exposure and 33% of the remaining cases. During a mean follow-up period of 5 years (range 1-14 years) only 11% of the cases achieved sustained biochemical remission, although none developed signs of liver failure. There was no significant difference in the clinical features and outcome of the disease between anti-HCV-positive and -negative patients. The results of this study suggest that HCV is implicated in most cases of 'cryptogenic' chronic liver disease observed in Italian children with a history of parenteral exposure and in at least one-third of the cases without overt exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevalence of hepatitis C virus antibodies in chronic liver disease and hepatocellular carcinoma patients in India

The prevalence of antibodies to hepatitis C virus (HCV) was investigated in 129 patients with chronic liver disease (85 with chronic active hepatitis and 44 with cirrhosis) and 53 patients with hepatocellular carcinoma. The commercially available second generation anti-HCV enzyme immunoassay kit was used. Antibodies to hepatitis C virus were detected in 16.2% of the patients with chronic liver disease and in 15.1% with hepatocellular carcinoma. Of the HCV positive patients in all groups 51.7% were positive for hepatitis B virus (HBV) markers indicating present or past infection. Prevalence of HBV markers in all the three groups (CAH, cirrhosis and HCC) was higher as compared with anti-HCV prevalence. These results suggest that HCV infection may not be a major cause of chronic liver disease and hepatocellular carcinoma in India and indicate the presence of other aetiological agents.     

Duration and specificity of antibodies to hepatitis C virus in chronic active hepatitis.

To determine the duration and specificity of antibodies to hepatitis C virus in hepatitis B surface antigen-negative chronic active hepatitis, sera from 19 patients seropositive by enzyme immunoassay were assessed by recombinant immunoblot assay. Only 12 of the 19 patients were reactive by immunoblot assay (63%). Patients nonreactive by immunoblot assay had lower signal-cutoff ratios by enzyme immunoassay (1.3 +/- 0.2 vs. 6.5 +/- 0.1; P less than 0.05), higher serum immunoglobulin G levels (4082 +/- 301 vs. 1760 +/- 143 mg/dL; P less than 0.05), and higher serum gamma globulin levels (3.3 +/- 0.5 vs. 2.04 +/- 0.1 g/dL; P less than 0.05) than reactive patients. Twelve of 14 patients with serial studies remained seropositive after 39 +/- 11 months of follow-up (range, 7-113 months). Only patients nonreactive by immunoblot assay became seronegative by enzyme immunoassay during corticosteroid therapy (2/3 vs. 0/6 patients). It is concluded that seropositivity by enzyme immunoassay may not be documented by immunoblot assay. Patients nonreactive by immunoblot assay have lower signal-cutoff ratios and higher gamma globulin levels than reactive patients, and their seropositivity may be nonspecific. Patients nonreactive by immunoblot assay may lose seropositivity by enzyme immunoassay during corticosteroid therapy.     

Low prevalence of hepatitis C antibodies in chronic liver disease in Finland.

High prevalence of hepatitis C antibodies (anti-HCV) have been found in the Middle- and Southern European countries in connection with chronic liver diseases. In a study of Finnish chronic liver disease patients no anti-HCV antibodies were found in 22 autoimmune chronic active hepatitis, in 5 chronic persistent hepatitis and in 38 alcoholic liver disease patients. 2/30 primary biliary cirrhosis patients were anti-HCV positive. As a comparison 3/9 patients with acute community acquired non-A non-B hepatitis and 28/48 i.v. drug addicts had anti-HCV antibodies. The results indicate that HCV infections in Finnish chronic hepatitis patients are rare.     

Prevalence of antibodies to hepatitis C virus among Saudi patients with chronic liver diseases.

The prevalence of antibodies against hepatitis C virus (anti-HCV) was determined in 55 patients with chronic liver diseases including liver cirrhosis (42 patients), liver cirrhosis and hepatocellular carcinoma (8 patients), and chronic active hepatitis (4 patients). A total of 63.6% of these patients were positive for anti-HCV, a significantly higher prevalence than the rate of 3.9% observed in 488 asymptomatic volunteers. Of the 42 patients with liver cirrhosis 16 (38.1%) had positive anti-HCV without any markers of hepatitis B virus (HBV), while 12 (28.6%) had markers of neither HCV nor HBV infection. Our findings suggest that HCV infection may play a significant role in the pathogenesis of chronic liver disease in Saudi Arabia, which is an area of endemic HBV infection. Screening for anti HCV should be considered mandatory in patients with chronic liver disease (CLD) especially where the etiology appears obscure.     

Antiviral therapy in advanced chronic liver disease due to hepatitis C virus infection: pilot study

Background: Antiviral therapy has not been adequately evaluated in patients with hepatitis C virus (HCV)-related advanced liver disease due to apprehensions of adverse events and intolerance. The titrable dose of interferon (IFN)-alpha and ribavirin was evaluated in a flexible regimen in a pilot study. METHODS: Twenty-five patients with HCV-related advanced chronic liver disease received IFN-alpha 1-3 MIU daily with ribavirin 200-600 mg daily for 9 months-3 years. Careful assessment of safety, tolerability and efficacy was made. RESULTS: Improvement in Child-Pugh score (8.4 +/- 1.2 to 7.4 +/- 2.0; P = 0.010) and serum albumin (3.0 +/- 0.5 g/dL to 3.6 +/- 0.5 g/dL; P = 0.007) occurred at follow up after antiviral therapy (median dose and duration: IFN-alpha 1.5 MIU/day for 12 months and ribavirin 400 mg/day for 7.5 months) as compared to baseline. Ascites regressed in 53% of patients (11/21). Thirteen patients (52%) lost HCV-RNA on therapy and eight (32%) achieved sustained virological response (SVR). Death occurred in three patients (12%) while on therapy, in two due to infection. No patient died in the responder group compared to five deaths (29%) in the non-responder group. However, there was no difference in the cumulative probability of survival in the sustained virological responder versus non-responder (P = 0.09). Adverse events were common (92%), but permanent withdrawal was required in only five patients (20%). CONCLUSIONS: Low and titrable dose IFN-alpha and ribavirin therapy in patients with HCV-related advanced chronic liver disease achieves improvement in hepatic synthetic function, Child-Pugh score and ascites. However, close monitoring for serious adverse events is warranted.     

High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus.

OBJECTIVE: To determine the epidemiologic, clinical, serologic, and histologic importance of antibodies to hepatitis C virus (anti-HCV) in blood donors. DESIGN: Cross-sectional identification and prospective evaluation of seropositive donors; retrospective assessment of infectivity; and nested case-control study for risk factors. SETTING: Liver unit of a referral-based university hospital. SUBJECTS: Of 30,231 consecutive donors, 368 (1.2%) were found to be anti-HCV-reactive by enzyme-linked immunosorbent assay (ELISA). Two hundred and fifty-four of these 368 donors were evaluated for risk factors by comparison with 284 age- and sex-matched controls. Eighty-six spouses of seropositive donors were also evaluated. MEASUREMENTS AND MAIN RESULTS: Twenty-four percent of the seropositive donors had a history of percutaneous exposure to blood. This rate increased to 45% when only those donors confirmed to be anti-HCV positive by a second-generation recombinant immunoblot assay (RIBA-2) were considered. A family history of liver disease (odds ratio, 2.8; 95% Cl, 1.6 to 4.8), previous blood transfusion (odds ratio, 6.1; 95% Cl, 3 to 12.5), and a history of tattooing or intravenous drug abuse (odds ratio, 8.4; 95% Cl, 2.3 to 31) were associated with anti-HCV seropositivity. An elevated alanine aminotransferase (ALT) level was found in 58% of the seropositive donors. Of the 150 donors tested, 104 (69%; Cl, 62% to 77%) were confirmed by RIBA-2 to be anti-HCV positive. Of the 105 donors who had a biopsy, 16% had normal histologic findings, 11% had minimal changes, 21% had chronic persistent hepatitis, 45% had chronic active hepatitis, and 7% had active cirrhosis. All 77 donors with RIBA-2-confirmed seropositivity had histologic abnormalities. Of 43 donors evaluated in an infectivity study, 82% were implicated in previous HCV transmission. Only 2.3% of the spouses were anti-HCV positive. The ELISA, RIBA-2, and ALT results correlated with infectivity and abnormal histologic findings. CONCLUSIONS: In our geographic area, almost 70% of donors who are anti-HCV positive by ELISA are confirmed to be positive by RIBA-2; most of these donors appear to be chronic carriers of HCV and have substantial liver disease.     

Efficacy and safety in sitagliptin therapy for diabetes complicated by chronic liver disease caused by hepatitis C virus

Aim: Diabetes is present in patients with chronic liver disease caused by hepatitis C virus (HCV). The aim of this case–control study is to assess the efficacy and safety of dipeptidyl peptidase‐4 inhibitor (sitagliptin) for type 2 diabetes mellitus (T2DM) with chronic liver disease caused by HCV. Methods: Sixteen HCV positive patients with T2DM treated by sitagliptin were retrospectively enrolled. These patients were given sitagliptin between December 2009 and January 2010. Another 16 HCV patients with T2DM treated only with diet and excise for 48 weeks were selected as the control group. Serum levels of fasting plasma glucose (FPG), hemoglobin A1C (HbA1C), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured before and 12, 24, 36 and 48 weeks after the initiation of treatment. Results: In the sitagliptin group, the average HbA1C level decreased approximately 0.8% at 48 weeks after the initiation of sitagliptin. Next, the average FPG level decreased approximately 20 mg/dL during follow up after the initiation of sitagliptin. All the patients were able to take sitagliptin of 50 mg/day without reduction because of sitagliptin‐related side‐effects. On the other hand, in the control group, the average HbA1C and FPG level did not change with statistical significance during follow up of 48 weeks. Regarding aminotransferase, there were no significant changes of average AST and ALT level during follow up of 48 weeks in both the sitagliptin group and control group. Conclusion: Our results indicate that sitagliptin is effective and safe for the treatment of T2DM complicated with HCV positive chronic liver disease.     

Prevalence of hepatitis A virus antibodies in patients with chronic liver diseases.

OBJECTIVE: The age of persons with hepatitis A virus (HAV) infection in the general population has risen; these persons are at increased risk of clinically severe disease, especially patients with chronic liver disease. The aim of the present study was to analyze the prevalence of total antibodies against HAV in patients with chronic liver disease. METHODS: In a prospective study carried out between September 1998 and June 1999, 180 patients seen in the chronic liver disease outpatient department were studied. The prevalence of total anti-HAV antibodies was determined by age group, etiology and degree of histological damage, and according to the antecedents of risk for parenteral infection. A nonconditional logistic regression model was fitted with anti-HAV positivity as the dependent variable. RESULTS: Mean age was 44.1 years, with an anti-HAV prevalence of 77.2% (varying from 42.9% in the 21-25-year-old group to more than 83% in patients > 56-years old). Differences across groups regarding other categories (histological damage, etiology and history of parenteral or drug use) were not statistically significant, but the probability of anti-HAV positivity increased with age and a history of drug addiction. CONCLUSIONS: The prevalence of total anti-HAV antibodies is high among patients with chronic liver disease. We therefore recommend this test before vaccination against HAV, until current recommendations on universal childhood vaccination are implemented, in order to prevent hepatitis A epidemics in the general population.     

Correlation of hepatitis B virus DNA and antigens in the liver. A study in chronic liver disease

Hepatitis B virus deoxyribonucleic acid (DNA) and antigens (HBsAg and HBcAg) were studied in liver biopsy specimens from 105 HBsAg-positive patients with chronic liver diseases. Free or integrated viral DNA, or both, was detected in 83 of 105 (79%) patients, whereas HBsAg and HBcAg were demonstrated immunohistologically in 96 (91%) and 39 (37%), respectively. Of 60 patients with detectable free viral DNA, 38 (63%) were positive for HBcAg, whereas only 1 of 45 (2%) with either integrated viral DNA alone (n = 23) or no detectable viral DNA (n = 22) was positive for HBcAg (p less than 0.001). Furthermore, the amount of HBcAg was positively correlated with the amount of free viral DNA in the liver tissue. In contrast, HBsAg was well expressed not only in the liver with free viral DNA, but also in the liver with integrated DNA. These data suggest that the synthesis of HBcAg is primarily directed by free viral DNA, whereas that of HBsAg may be directed by free as well as integrated viral DNAs.     

Familial clustering of hepatitis C virus infection and chronic liver disease

The present study was undertaken to assess the prevalence of HCV antibodies (anti-HCV) and of chronic liver disease in relatives of anti-HCV positive subjects suffering from chronic active liver disease. We studied 122 subjects from 24 families. Each family had at least one positive anti-HCV component with histologically proven chronic liver disease. Anti-HCV was found in 32% of subjects; 82% of these were suffering from chronic liver disease diagnosed on the basis of physical examination and biochemical parameters. Prevalence of anti-HCV was higher in spouses, parents, and siblings of the index case as compared to the offspring. In conclusion, the transmission of HCV infection and of HCV-related chronic liver disease is contributed to by factors associated with the familial environment.     

New therapies in hepatitis C virus and chronic liver disease: antifibrotics

Fibrotic liver disease occurs after any of the various forms of injury to the liver. Fibrosis is a critical factor leading to hepatic dysfunction and portal hypertension and its complications. The fibrogenic cascade is complex but leads to accumulation of extracellular matrix proteins, followed by nodular fibrosis, tissue contraction, and alteration in blood flow. A critical concept emerging is that activation of effector cells, which produce extracellular matrix, underlies the fibrogenic process. The aggregate data has not only helped lead to an understanding of the pathophysiologic basis of hepatic fibrogenesis, but it has also provided an important context with which to base novel antifibrotic therapy.     

Delta infection in chronic HBs Ag carriers in Tunisia: high prevalence in chronic asymptomatic HBs Ag carriers and in HBs Ag positive cirrhosis

The presence of hepatitis B virus DNA, delta antigen and anti-delta antibodies was examined in 159 Tunisian chronic HBs Ag carriers: 45 were asymptomatic and 114 suffered from cirrhosis. Serum hepatitis B virus DNA was detected in two (4.5%) asymptomatic HBs Ag carriers and in 11 (10%) HBs Ag positive cirrhosis patients. The prevalence of HDV infection determined by the presence of anti-delta was relatively high in asymptomatic HBs Ag carriers (33%) and in HBs Ag positive cirrhosis patients (21%). Active ongoing HDV infection, detected by serum HD Ag and anti-delta IgM, was shown in five patients with cirrhosis and active hepatitis B virus replication. We conclude that hepatitis delta virus may be endemic in Tunisia and does not always inhibit hepatitis B virus replication.     

Analysis of hepatitis B virus DNA, liver disease and influence of antibody to hepatitis C virus in anti-HBe chronic carriers.

Hepatitis B virus DNA (HBV-DNA) in serum was studied in 67 anti-HBe patients using dot-blot hybridization, a modified technique and polymerase chain reaction (PCR). All patients had abnormal aminotransferase (ALT) levels. Serum HBV-DNA was detected in 14/67 cases by dot-blot and in 39/67 (DNA probe) and 45/67 (RNA probe) using the modified technique. The RNA probe was more sensitive than the DNA probe when they were compared, using serial dilutions of HBV-DNA of known concentration (0.1 pg vs 1 pg, respectively). HBV-DNA was found by PCR in 57/67 patients. Ten patients were negative to serum HBV-DNA. The ALT level was significantly higher in patients with serum HBV-DNA by dot-blot as compared to those who had serum HBV-DNA by the modified technique and PCR. With respect to the presence of anti-HCV, 6/67 had anti-HCV confirmed by RIBA test. These 6 patients had serum HBV-DNA. The route of acquisition of HBV infection in anti-HCV positive patients was by parenteral exposure in 67% of the cases and 15% in HCV negative (p less than 0.05). All patients were negative to nonorganic specific autoantibodies. In summary, most of the anti-HBe patients (85%) had viral replication. HCV superinfection plays a minor role in the activity of liver disease.