Virus-related Chronic Liver Disease Research Articles

Urinary transforming growth factor and [formula omitted] levels in hepatitis c virus-related chronic liver disease: Correlation between high levels and severity of disease : Tsai, J.-F., Jeng, J.-E., Chuang, L.-Y., Chang, W.-Y., Tsai, J.-H. Department of Internal Medicine, Kaohsiung Medical College, 100 Shih-Chuan 1 Rd, Kaohsiung 80708, Taiwan Hepatol 1997; 25 (5): 1141–1146

Urinary transforming growth factor and [formula omitted] levels in hepatitis c virus-related chronic liver disease: Correlation between high levels and severity of disease : Tsai, J.-F., Jeng, J.-E., Chuang, L.-Y., Chang, W.-Y., Tsai, J.-H. Department of Internal Medicine, Kaohsiung Medical College, 100 Shih-Chuan 1 Rd, Kaohsiung 80708, Taiwan Hepatol 1997; 25 (5): 1141–1146

In situ investigation of Fas/FasL expression in chronic hepatitis B infection and related liver diseases.

To evaluate Fas/FasL expression in hepatitis B virus-related chronic liver disease, liver biopsies from 44 such cases were studied immunohistochemically. FasL was detected in the infiltrating lymphocytes and both FasL and Fas were found in the hepatocytes. The Fas and FasL-positive cells were mostly found at the advancing edges of interphase hepatitis, and Fas/FasL expression was closely correlated with the inflammatory activity. Unexpectedly, FasL was also expressed in liver cirrhotic nodules, particularly in those with hepatocellular carcinoma with or without inflammation. These results suggest that the factors which induce hepatocyte transformation might also trigger FasL expression and promote FasL/Fas-mediated apoptosis.

Urinary transforming growth factor beta1 levels in hepatitis C virus-related chronic liver disease: correlation between high levels and severity of disease.

To assess the clinical relevance of transforming growth factor beta1 (TGF-beta1) in chronic liver disease, urinary TGF-beta1 and circulating aminoterminal propeptides of type III procollagen (PIIINP) levels were determined by radioimmunoassay in 100 cirrhotic patients, 44 patients with chronic hepatitis, and 50 healthy controls. TGF-beta1 and PIIINP levels in cirrhotic patients were higher than those in patients with chronic hepatitis (each P < .0001) or healthy controls (each P < .0001), respectively. There was a correlation between TGF-beta1 and PIIINP levels in patients (r = .858, P < .0001). The higher the urinary TGF-beta1 level, the worse the severity of chronic liver disease (P < .001). TGF-beta1 levels in cirrhotic patients with antibodies to hepatitis C virus (anti-HCV) were higher than in those without (P < .0001). Compared with cirrhotic patients with hepatitis B surface antigen (HBsAg) alone, those with HBsAg and anti-HCV had higher TGF-beta1 levels (P < .001), a higher frequency of raised TGF-beta1 (P < .005), and a higher frequency of patients with Child-Pugh C (P < .005). Multivariate analysis indicated that the TGF-beta1 level was significantly correlated with the presence of cirrhosis. In conclusion, urinary TGF-beta1 levels may be used as a marker for hepatic fibrogenesis. Higher urinary TGF-beta1 levels correlate with more severe liver disease.

Efficacy of human leukocyte interferon-α treatment in elderly patients with hepatitis-C virus-related chronic liver disease

Sixty-seven aged patients (mean age 69, age range 67-73 years) with hepatitis C virus (HCV)-related chronic liver disease were treated with human leukocyte interferon-alpha at a dose of 9 mU/week for 9 months and then followed up for other 6 months. At the end of treatment, 39 patients (58.2%) showed normalization of alanine aminotransferase (ALT) levels; however, 24 responders (61.5%) had a relapse of the disease in the following 6 months. Fifteen out of 39 responders (38.5%) had a sustained response. Of these, 9 (60%) showed clearance of HCV-RNA from serum. Similar rates were observed in a group of younger patients (mean age 48, age range 17-58 years) treated with the same schedule. In both groups, the most important predictor of response appeared to be the degree of fibrosis at liver histology, rather than the patients' age. These data suggest that interferon-alpha treatment may be as much useful in elderly patients as it may be in younger patients, provided that liver injury is not advanced too much.

P-500 Effects of hepatitis B virus infection and cigarette smoking on hepatocarcinogenesis among patients with heptitis C virus-related chronic liver diseases; A prospective observation and multivariate analysis of 412 patients

P-500 Effects of hepatitis B virus infection and cigarette smoking on hepatocarcinogenesis among patients with heptitis C virus-related chronic liver diseases; A prospective observation and multivariate analysis of 412 patients

Hepatitis B virus genome and genomic expression (antignes) in the liver tissue of the patients with hepatitis B virus related chronic liver diseases

Hepatitis B virus genome and genomic expression (antignes) in the liver tissue of the patients with hepatitis B virus related chronic liver diseases

Expression of IGF-II in hepatitis C virus-related chronic liver disease in humans

Expression of IGF-II in hepatitis C virus-related chronic liver disease in humans

Effects of hepatitis B virus and cigarette smoking on hepatocarcinogenesis among patients with hepatitis C virus-related chronic liver diseases; a prospective observation and multivariate analysis of 412 patients: [formula omitted], Y. Matsuzaki, N. Tanaka, J. Shoda, M. Abei, T. Osuga. Depts. of Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba city, Japan

Effects of hepatitis B virus and cigarette smoking on hepatocarcinogenesis among patients with hepatitis C virus-related chronic liver diseases; a prospective observation and multivariate analysis of 412 patients: [formula omitted], Y. Matsuzaki, N. Tanaka, J. Shoda, M. Abei, T. Osuga. Depts. of Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba city, Japan

Immunoelectron microscopic observations on Leu-7 positive cells in virus-related chronic liver diseases

We investigated the liver biopsies of 78 patients with hepatitis virus-related chronic liver diseases (B type; 14 patients, C type; 64 patients) by immunoelectron microscopy with the Leu-7 monoclonal antibody in order to determine the association of NK/K cells in virus-related chronic liver diseases. Most Leu-7 positive cells in the liver had the Pit cell morphology but a few Pit cells were Leu-7 negative. A few Leu-7 positive cells had neither Pit cell nor typical T cell morphology. No ultrastructural difference was observed in Leu-7 positive cells between hepatitis B virus- and hepatitis C virus-related chronic liver diseases. Regardless of virus type and hepatitis activity, the fine morphology of extravascular Leu-7 positive cells differed considerably from intravascular cells. Leu-7 positive cells were regularly seen in the cellular infiltrates but the ratio of Leu-7 positive cells/whole infiltrates was low. There was no correlation between the inflammatory activity of the disease and the level of Leu-7 positive cell infiltration. A virus aetiology (hepatitis-C or hepatitis-B) did not affect Leu-7 positive cell infiltration. We conclude that NK cells play only a small role in the pathogenesis of hepatitis B virus or hepatitis C virus-related hepatocytolysis, during the chronic stage.

Hepatitis B virus DNA in peripheral blood leukocytes. A comparison between hepatocellular carcinoma and other hepatitis B virus-related chronic liver diseases

Hepatitis B virus (HBV) DNA has been detected in the peripheral blood leukocytes (PBL) during acute and chronic HBV infection. Possible pathobiologic significance includes infectivity and altered immunity. There are few data relating PBL HBV-DNA with severity of the liver disease, in particular with hepatocellular carcinoma (HCC). HBV-DNA was detected by dot-spot hybridization technique in PBL separated from venous blood samples of 209 hepatitis B surface antigen-positive patients (28 healthy carriers and 95 chronic hepatitis, 29 cirrhotic, and 57 HCC patients). Serum HBV-DNA and hepatitis B e-antigen (HBeAg) were also measured. Thirty percent of HCC patients were hepatitis e-antigen-positive compared to 50%, 84% (P < 0.0001), and 69% (P < 0.00001) of healthy carriers and chronic hepatitis and cirrhotic patients, respectively. Furthermore, only 11% of HCC patients had detectable serum HBV-DNA compared to 39% (P < 0.001), 58% (P < 0.001), and 31% (P < 0.05) of these respective patient groups. despite low viral replication among HCC patients, 58% had PBL HBV-DNA. Corresponding figures for healthy carriers and for chronic hepatitis and cirrhotic patients were 39%, 58%, and 56%. Fifty-two percent of HCC patients had positive PBL HBV-DNA in the absence of serum HBV-DNA, compared with 25% in healthy carriers (P < 0.05) and 22% in chronic hepatitis (P < 0.001) and 35% in cirrhotic patients (P = NS). The high detection rate of PBL HBV-DNA among HCC patients may reflect certain pathogenetic processes of HBV infection and indicate a higher risk of development of HCC.

An algorithm to predict hepatitis C virus related chronic liver disease in asymptomatic blood donors

An algorithm to predict hepatitis C virus related chronic liver disease in asymptomatic blood donors

Interferon therapy in liver/kidney microsomal antibody type 1-positive patients with chronic hepatitis C

The association between liver/kidney microsomal antibody type 1 and adult cases of hepatitis C virus-related chronic liver disease has been firmly established. In the presence of both markers, evidence of autoimmunity (liver/kidney microsomal antibody type 1) and actual viremia (serum HCV RNA), the therapeutic dilemma arises between steroids, which are beneficial to autoimmune but deleterious to viral diseases, and interferon-alpha, which may exacerbate an autoimmune disorder. Six patients with liver/kidney microsomal antibody type 1 and serum HCV RNA were given interferon-alpha: three showed a response pattern similar to that observed in autoantibody-negative chronic hepatitis C cases; the other three developed a sharp transaminase peak, which was not followed by HCV RNA clearance. Considering the brisk flare-up of liver cell necrosis, interferon-alpha treatment proved to be dangerous in the above three liver/kidney microsomal antibody type 1/HCV RNA positive cases. Subsequent steroid administration reduced alanine aminotransferase peaks, but may be harmful in viral infections. Therapeutic alternatives are needed: they will probably include pure antivirals (exerting no immunostimulatory effects) with or without immunosuppressive drugs.

A method for detecting specific anti-C100 protein antibodies of IgM isotype in hepatitis C virus infection.

A method for the determination of specific IgM antibodies to C100 protein, a hepatitis C virus-associated antigen, was developed which employed fractionation of serum proteins by gel chromatography and an enzyme-linked immunosorbent assay. Detection of IgM anti-C100 proved to be specific and reproducible in purified IgM fractions. Separation of IgM from IgG was necessary before IgM could be measured, because of the detrimental effect of the simultaneous presence of IgG antibodies with anti-C100 rectivity on IgM determination. IgM anti-C100 was not found in sera containing rheumatoid factors or IgM antibodies to other hepatotropic viruses. IgM anti-C100 was detected in 19 (44%) of 43 patients with hepatitis C virus-related chronic liver disease. When compared with the histological picture of liver disease, IgM anti-C100 was absent in patients with minimal changes and was most common (66.7%) in patients with progressive disease. It is suggested that IgM anti-C100 could reflect an active state of hepatitis C virus infection.

Autoantibodies and circulating immune complexes in sera from patients with hepatitis B virus-related chronic liver disease

Sera from 56 patients with hepatitis B virus-related chronic liver disease (CLD) and 30 normal individuals as controls were examined by enzyme immunoassay (EIA) for the presence of autoantibodies directed against actin, tubulin, myosin, double-stranded (ds) DNA, polymerized human albumin, thyroglobulin, and trinitrophenyl coupled to bovine serum albumin (TNP-BSA). Patients with CLD had consistently elevated levels of IgG, IgA, and IgM antibodies directed against all the panel antigens. The percentage of patients with autoantibodies of the IgA class was particularly high: respectively, 88 and 78% of the patients had strikingly high levels of anti-actin and anti-TNP-BSA IgA autoantibodies. High amounts of IgA and IgG antibodies to polymerized albumin as well as IgG to thyroglobulin were also detected. Circulating immune complexes (CIC) were isolated from patients' sera and their autoantibody activities were tested on the same antigen panel. The autoantibodies thus detected were of the same class and possessed the same activities, although at higher values than those present in the homologous sera. These results indicate that, regardless of their origin, autoantibodies are present in high amounts in the sera of these patients. Moreover, autoantibodies participating in the formation of CIC might play a pathological role.

Frequency of Asymptomatic Hepatitis Types B and C in an Inner City Community and Relation to Possible Risk Factors

The frequency of asymptomatic carriage of the hepatitis virus types B and C in an inner city area (South London) was assessed in a survey of 1002 subjects attending their General Practitioner for minor, non-hepatic complaints. Ten subjects were seropositive for hepatitis B surface antigen (HBsAg) (1 per cent), but only one, who declined liver biopsy, had any clinical laboratory evidence of hepatitis B virus-related chronic liver disease. Carriage of, and exposure to, hepatitis B virus was significantly more frequent among people born outside the UK/Eire and those with a history of jaundice. Among people of Caribbean origin the frequency of hepatitis B virus markers fell from 31 per cent among those born in the Caribbean to 11 per cent amongst second generation subjects born in this country. Despite careful counselling, offers of further investigation and treatment of those affected, and vaccination of vulnerable children or partners, were often declined. Four percent of the same population had antibodies to the hepatitis C virus using the Ortho anti-hepatitis C virus enzyme-linked immunosorbent assay but this figure fell to 0.9 per cent when a second test, based on synthetic peptides rather than a recombinant antigen, was used. None had any abnormality of standard liver function tests. Chronic asymptomatic carriage of hepatitis, particularly in inner city areas, may be more common than previously recognized. Effective use of antiviral agents and vaccination will be limited until appropriate health education dispels the widespread misconceptions and fears associated with a diagnosis of chronic viral hepatitis.

Hepatitis C virus-related chronic liver disease with autoantibodies to liver-kidney microsomes (LKM): Clinical characterization from idiopathic LKM-positive disorders

This study was carried out on 33 patients who were sero-positive for liver-kidney microsomal antibodies (LKM) in order to examine clinical features and the presence of underlying hepatitis C virus infection. Twenty-four sera were positive for antibodies against HCV (anti-HCV) as detected by enzyme immunoassay and confirmed by recombinant immunoblot assay. These patients had chronic liver disease and the majority of those treated with interferon responded favourably. Three of the nine anti-HCV-negative patients had idiopathic chronic hepatitis and two responded favourably to steroids. Two patients were diagnosed as having toxic hepatitis and the other four had various extrahepatic disorders without evidence of liver involvement. The immunoblotting analysis showed reactivity with a 50 kDa microsomal protein which presumably corresponded to cytochrome P-450 db1 both in anti-HCV-positive and -negative sera. In addition a few anti-HCV-positive sera also reacted with a 35 kDa microsomal antigen. Autoimmune markers different from LKM were absent in both groups. The high prevalence of antibodies to the hepatitis C virus among LKM-positive sera confirms that this infection plays a role in forms of chronic hepatitis that had previously been labelled autoimmune. In patients with LKM the presence of anti-HCV may help to forecast a therapeutic response to interferon, while its absence may forecast response to steroid therapy.

Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases

Three-hundred forty-one HBsAg-positive family members of 152 patients with chronic hepatitis B virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis B virus infection in the family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Most of the family members had no history of acute hepatitis, were asymptomatic and were unaware of their carrier status. However, 5.3% had stigmata of chronic liver disease, 6% had serum ALT levels that exceeded two times the upper limit of normal and 78% of those who had biopsies had chronic hepatitis with or without cirrhosis. During a follow-up period of 12 to 90 mo (median = 39 mo), 3% had symptoms of chronic liver disease; 24% had transient, recurrent or persistent elevation in serum ALT levels, 1.4% had cirrhosis and 1% had hepatocellular carcinoma. Neither hepatocellular carcinoma in the index patient nor a previous history of hepatocellular carcinoma in the family was associated with an increase in the morbidity and mortality from chronic hepatitis B virus infection in the HBsAg-positive family members.

Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases

Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases

Hepatic histological findings after transplantation for chronic hepatitis B virus infection, including a unique pattern of fibrosing cholestatic hepatitis

Long-term follow-up of 27 patients with hepatitis B virus-related chronic liver disease treated by transplantation showed that 23 had hepatitis B virus recurrence. In 13 patients late changes in the grafts were similar to those described in other series: minor abnormalities in five cases, chronic active hepatitis in five cases and non-hepatitis B virus-related graft dysfunction in three cases. Three patients had incomplete histological follow-up. Analysis of the histological changes and viral antigen expression in six cases revealed a distinct and novel pattern termed fibrosing cholestatic hepatitis. Development of fibrosing cholestatic hepatitis was associated with rapidly progressive graft dysfunction. It is postulated that this pattern of fibrosing cholestatic hepatitis develops because of a high cytoplasmic expression of viral antigens, including HBsAg. The remaining case had some features of fibrosing cholestatic hepatitis. The main histological features of this unique syndrome include thin, perisinusoidal bands of fibrosis extending from portal tracts to surround plates of ductular-type epithelium; prominent cholestasis; ground-glass transformation; and ballooning of hepatocytes with cell loss and mild mixed inflammatory reaction.

Effect of 28 consecutive days lymphoblastoid interferon (α-IFN) administration on hepatitis B virus related chronic liver disease

Eight HBsAg, HBeAg, DNA-p, HBV-DNA-positive patients with biopsy-proven chronic hepatitis were treated with human lymphoblastoid interferon (Wellferon) given for 28 consecutive days at a dosage ranging from 2.5 to 7.5 MU/m2 i.m.; 10 patients were used as controls. Our results suggest that certain chronic carriers may respond to the treatment with this agent. In fact, the treated patients showed a permanent inhibition of HBV replication sooner and in higher percentage with respect to untreated patients (37.5% vs 20%). IFN administration does not induce any important changes in the immunoregulatory wetwork, but is able to increase significantly the cytolytic activity of NK cells in the patients who respond to the therapy with a permanent inhibition of HBV replication.