Levels of plasma malondialdehyde and erythrocyte antioxidant enzyme activities in patients with chronic hepatitis B

BACKGROUND/AIMS: Hepatitis B virus infection, extensively seen throughout the world, can become highly chronic. Pathogenesis of chronic hepatitis is not yet known fully. It is shown that oxidative stress may play a role in pathogenesis and may regulate collagen synthesis and thus may contribute to the process of liver damage. This study is aimed at investigating the existence of oxidative stress in chronic hepatitis B cases and its relation with alanine aminotransferase and aspartate aminotransferase which are the serum indicators of liver damage; along with interaction of erythrocyte antioxidation enzyme activities in the same cases. METHODOLOGY: Eighty patients with chronic hepatitis B under follow-up, and 40 healthy volunteers were included in this study. In the control and patients groups, together with serological markers for viral etiology, alanine aminotransferase and aspartate aminotransferase levels; plasma malondialdehyde level; erythrocyte superoxide dismutase, glutathione peroxidase and catalase activities were analyzed. RESULTS: Malondialdehyde levels of chronic hepatitis B cases were statistically high compared to control group (p < 0.05). There was correlation between serum malondialdehyde levels and serum alanine aminotransferase, aspartate aminotransferase levels in the patient group (r = 0.324, p < 0.01, r = 0.273, p < 0.05). Average superoxide dismutase and catalase activities were found to be significantly low compared to control group (p < 0.001); average glutathione peroxidase activity were significantly high when considered statistically (p < 0.001). No correlation between serum alanine aminotransferase and aspartate aminotransferase levels and glutathione peroxidase, catalase and superoxide dismutase activities was found in the patients group (p > 0.05). CONCLUSIONS: In the study we showed that there is correlation between serum malondialdehyde level and alanine aminotransferase and aspartate aminotransferase levels of chronic hepatitis B patients. According to the results of our study, it might be thought that serum malondialdehyde level might be a marker of hepatocellular damage in chronic hepatitis B cases. We suggest that antioxidant treatment for chronic hepatitis B patients should be examined in future studies.     

Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood

Seventy-six children aged 1-13 years who were known to be positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months and who had biopsy-proven chronic hepatitis have been followed longitudinally for 1-12 years (mean, 5 years). Twenty-three of them are now young adults. Eight patients had acute type B hepatitis 12-24 months before entering the study, while 68 patients came to observation during a chronic phase. At the beginning of follow-up, all 76 children were positive in serum for hepatitis B virus DNA, and 44 (58%) had chronic active hepatitis, associated with cirrhosis in two cases. During follow-up, 23 (30%) patients remained hepatitis B e antigen-positive, most with unchanged biochemical and histological features. The other 53 (70%) cases seroconverted to hepatitis B e antibody and cleared hepatitis B virus DNA from serum, including 7 of 8 (87%) patients with acute hepatitis at presentation. After seroconversion, alanine aminotransferase levels normalized in all patients and remained normal in 49 patients (92.5%) throughout a mean observation period of 3 years. Five of these children, including 2 of 7 (29%) with previous acute hepatitis, eventually cleared hepatitis B surface antigen from their sera. Finally, 4 (7.5%) patients experienced a mild increase of alanine aminotransferase levels several months after seroconversion in the absence of hepatitis B virus replication or of delta virus superinfection. Clinical and virological parameters did not significantly differ between patients with or without acute onset; however, seroconversion occurred earlier, and the rate of hepatitis B surface antigen clearance was greater in the former than in the latter group. The present data indicate that approximately two thirds of children with hepatitis B e antigen- and hepatitis B virus DNA-positive chronic hepatitis clear hepatitis B virus DNA from their sera before reaching adulthood. After termination of viral replication, most patients achieve a sustained biochemical remission, suggesting the disappearance of disease activity. Reactivation of virus replication after hepatitis B e antibody seroconversion has never been observed in this series, although mild alanine aminotransferase level abnormalities could be detected in a minority of cases.     

Serum levels of alpha-interferon and gamma-interferon in patients with acute and chronic viral hepatitis

We measured activities of alpha- and gamma-interferon simultaneously in 198 sera of 70 patients with acute and chronic viral hepatitis using specific and sensitive enzyme immunoassay and immunoradiometric assay. The results were compared with those in patients with influenza and in healthy controls. Twelve out of 28 patients with acute viral hepatitis showed positive alpha-IFN and/or gamma-IFN activities. alpha-IFN was detectable throughout the clinical course while gamma-IFN levels rose in the convalescent phase regardless of etiology. Conversely, in patients with influenza, both alpha-IFN and gamma-IFN levels of initial samples tended to be higher than those of late samples. Six out of 12 patients with chronic active type B hepatitis showed increased alpha-IFN and/or gamma-IFN values during acute deterioration with marked elevation of serum alanine aminotransferase. However, the two interferons did not always appear simultaneously, although either was detectable in both acute and chronic hepatitis. Enhanced alpha-IFN or gamma-IFN activity was not found in asymptomatic chronic hepatitis B carriers or in patients with chronic persistent hepatitis and liver cirrhosis with chronic hepatitis B virus infection, with the exception of 2 cases. Our results indicated that circulating multiple IFN species were present during the clinical course in some patients with acute and chronic viral hepatitis.     

Efficacy of ursodeoxycholic acid therapy in chronic viral hepatitis C with high serum γ-glutamyltranspeptidase levels

We administered ursodeoxycholic acid (UDCA) orally, at a daily dose of 600 mg, for 4 months to 36 patients with chronic viral hepatitis C. Another 36 patients with chronic viral hepatitis C, treated with placebo for 4 months, served as controls. None of the patients were alcoholics and none suffering from auto-immune hepatitis. Of the 36 patients in the UDCA-treated group, 13 had high levels of serum -glutamyl-transpeptidase (GGT), i.e., exceeding 150U/l (normal <50U/l). Histological examination of liver biopsy specimens obtained from 10 patients in this group before treatment suggested that damage of the interlobular bile ducts was prominent in patients with higher levels of serum GGT. After 1 month of UDCA treatment, significant decreases in the levels of serum GGT, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed (P<0.05 for GGT and AST), and the decreases continued for the 4-month treatment period. The reduction of GGT levels was the most prominent change in the liver function indices; the percent change in the GGT level was –25.2±4.4 (mean percent change ± SE) at 1 month and –38.0±5.0 at 4 months. A significant correlation was observed between the serum AGGT level (GGT value before treatment minus value after 3 months of treatment) and the total score for morphological injury of the bile ducts (P<0.05). These results suggested that UDCA has the potential to reverse hepatocellular damage in patients with chronic viral hepatitis C, in whom high GGT levels may be due, in part, to a damaged interlobular bile duct. UDCA may be useful for the treatment of chronic viral hepatitis C, especially in patients exhibiting a high level of GGT.     

A pilot study of thymosin alpha1 therapy for chronic hepatitis B patients

OBJECTIVE: The efficacy of thymosin alpha 1 (Talpha1) in patients with chronic hepatitis B still requires confirmation. We, therefore, evaluated the efficacy of therapy in patients with chronic hepatitis B. METHODS: Sixteen patients were randomly assigned into one of two groups, treated with 0.8 mg of Talpha1 (low dose group; n = 8) or 1.6 mg Talpha1 (high dose group; n = 8), administered six times weekly for two weeks, followed by twice weekly for another 22 weeks. Responders were defined as patients having clearance of hepatitis B e antigen by radioimmunoassay and negativity of hepatitis B virus (HBV)-DNA by branched DNA signal amplification and normalization of serum alanine aminotransferase (ALT) 24 months after initiation of Talpha1 therapy. Transient acute exacerbation was defined as an increase of more than 300 IU/I in serum ALT level during Talpha1 therapy. RESULTS: The response rate was 37.5% (6/16). Talpha1 therapy had a significant effect when, 1) transient acute exacerbation was present (p = 0.0029), 2) the serum HBV-DNA level was < 100 Meq/ml prior to the commencement of Talpha1 therapy (p = 0.0063). The difference between low and high dose groups was not statistically significant (p = 0.608). CONCLUSION: The results of this trial show that: 1) a 24-week course of Talpha1 could be a worthwhile strategy for chronic hepatitis B patients with a serum HBV-DNA level of less than 100 Meq/ml; and 2) patients with a transient acute exacerbation during Talpha1 therapy generally often respond well.     

Do serum ALAT values reflect the inflammatory activity in the liver of patients with chronic viral hepatitis?

Abstract: A retrospective study was carried out in 40 patients with chronic viral hepatitis, to assess whether serum alanine aminotransferase reflects the inflammatory process in the liver. Twenty liver biopsy specimens were included for each disease. Five histological aspects were scored: periportal inflammation, lobular inflammation, ballooning, Councilman bodies and lymphocyte follicles. Logarithmic values of alanine aminotransferase were correlated with each aspect using the Spearman correlation coefficient. For the hepatitis B cohort a statistical significant correlation was found between alanine aminotransferase and periportal inflammation (p=0.0001), lobular inflammation (p=0.0002) and Councilman bodies/area (p=0.003). In the hepatitis C study population alanine aminotransferase correlates with both periportal inflammation (p=0.007) and lymphocyte follicles/Area (p=0.02). In conclusion, these results suggest that alanine aminotransferase can be used as an indicator of inflammatory activity. A prospective study is needed, to further analyze the use of alanine aminotransferase, as a monitor of disease activity in patients with chronic viral hepatitis.     

Persistence of serum hepatitis B virus deoxyribonucleic acid in hepatitis B surface antigen-positive patients with chronic persistent hepatitis treated with prednisone

The effect of a short course of prednisone therapy was evaluated in 8 patients with liver biopsy-verified chronic persistent hepatitis B. In 6 of the 8 (75%) patients, an abrupt fall in serum alanine aminotransferase levels after the initiation of prednisone was noted, and in 4 patients, there was an increase in serum alanine aminotransferase values after prednisone was discontinued. However, the serum levels of hepatitis B virus deoxyribonucleic acid were consistently greater than or equal to 200 pg before, during, and after the course of treatment in 7 of the 8 (87.5%) patients. All patients were initially hepatitis B e antigen-positive and remained so during the study period. These findings indicate that, unlike some patients with chronic active hepatitis B, immunosuppression with prednisone had no effect in altering hepatitis B viral replication in patients with chronic persistent hepatitis.     

Improvement of alanine aminotransferase by administration of suplatast tosilate plus ursodeoxycholic acid in patients with resistance to ursodeoxycholic acid monotherapy on hepatitis C virus-related chronic liver disease

OBJECTIVE: Inflammatory liver damage and viral persistence after hepatitis C virus (HCV) infection are known to be related in host immunity. Suplatast tosilate is an immunomodulator that selectively inhibits type 2 cytokine production by helper T cells. We investigated the efficacy and safety of the administration of suplatast tosilate for patients with HCV infection by examining the level of serum alanine aminotransferase (ALT) and viremia. PATIENTS AND METHODS: Thirty-eight patients who had shown resistance to ursodeoxycholic acid (UDCA) therapy (600 mg/day tid) over 6 months for HCV-related chronic liver disease were randomized into two groups and received UDCA alone (600 mg/day tid) or UDCA (600 mg/day tid) plus suplatast tosilate (300 mg/day tid) by means of sealed envelopes. RESULTS: After 24 weeks, serum ALT was decreased in the patients receiving UDCA plus suplatast tosilate, with the mean reduction being 40.2% (from 132 to 79 IU/l; p=0.001). In the patients receiving UDCA alone, ALT decreased by 8.3% (from 133 to 122 IU/l; ns). Multiple comparison of individual ALT changes showed that the UDCA plus suplatast tosilate achieved significantly greater improvement (p = 0.001). However, serum HCV RNA was unchanged in both groups. Two patients developed adverse reactions to suplatast tosilate, which resolved promptly after the discontinuation of the therapy. CONCLUSION: These findings suggest that suplatast tosilate promotes biochemical improvement in the patients with chronic hepatitis C.     

Effects of indomethacin on viral replication markers in asymptomatic carriers of hepatitis B: a randomized, placebo-controlled trial

OBJECTIVES: Previous studies have suggested some benefits of nonsteroidal antiinflammatory drugs (NSAIDs) use in patients with chronic viral hepatitis. We evaluated potential effects of indomethacin in asymptomatic carriers of hepatitis B surface antigen (HBsAg). DESIGN: Randomized, placebo-controlled, double-masked clinical trial. METHODS: One hundred and twelve patients who were confirmed to be HBsAg carriers for at least 6 months and had normal liver function tests, normal abdominal sonography, and no sign of cirrhosis were randomly assigned into two groups. One group (56 participants, mean age (+/-SD) 31.7 (+/-9.6) yr, 29 male, mean serum alanine aminotransferase (ALT) (+/-SD) 24.9 (+/-9.2)) received indomethacin capsules (25 mg) three times daily and the other group (56 participants, mean age (+/-SD) 33.8 (+/-10.2) yr, 33 male, mean serum ALT (+/-SD) 24.5 (+/-8.7)) took placebo capsules with identical package and appearance. All participants were under treatment for 6 months and were followed 3 months thereafter. Statistical analyses were performed both by intention-to-treat and on-treatment methods. RESULTS: Nine participants in the indomethacin group (16%) and 8 in the placebo group (14%) did not complete the trial. HBsAg seroconversion did not differ by treatment group (2 subjects in each group became seronegative). Hepatitis B virus DNA (HBV-DNA) became negative in sera of 7 participants in the indomethacin group but only in 1 in the placebo group (intention-to-treat p= 0.06; on-treatment p= 0.03). Seroconversion of HBeAg to anti-HBe occurred only in 5 participants in the indomethacin group (intention-to-treat p= 0.06; on-treatment p= 0.03). Adverse events included one case of hepatotoxicity and two cases of gastritis in the indomethacin group and one suspected gastritis in the placebo group. CONCLUSIONS: We suggest use of indomethacin only in the subgroup of asymptomatic HBsAg carriers who have detectable HBV-DNA or HBeAg in their sera.     

Individualization of interferon therapy using serum hepatitis B virus DNA to reduce viral relapse in patients with chronic hepatitis B: a randomized controlled trial

OBJECTIVE: In patients with chronic hepatitis B, viral relapse following interferon (IFN) therapy may be the result of a treatment duration that is too short to prevent hepatitis B virus (HBV) from replicating later. To reduce viral relapse in patients with chronic hepatitis B who responded to IFN, we individualized the duration of therapy according to serum HBV-DNA levels. METHOD: Treatment duration was prolonged to maintain negative serum HBV-DNA levels for the next 6 months in 30 patients who became HBV-DNA-negative following IFN therapy (group A). Another 35 patients were treated for only 6 months (group B). All patients had HBV-DNA as well as hepatitis B surface antigen (HBsAg) in their sera for more than 6 months and were proven histologically to have chronic hepatitis. Interferon alfa (IFN-alpha) was administered subcutaneously at a dose of 5 MU/m2 three times a week. RESULTS: There were no differences in age, gender, hepatitis B e antigen (HBeAg) positivity, serum alanine aminotransferase (ALT) levels, or serum HBV-DNA levels between the two groups. The mean duration of IFN therapy in group A was 7.2 months. At the end of treatment, serum HBV-DNA was negative in 16 patients in group A and in 18 patients in group B. The loss of serum HBV-DNA was maintained to the end of follow-up in 13 patients in group A but in only eight patients in group B. Similarly, serum ALT levels were normal in 14 patients in group A but in only nine patients in group B at the end of follow-up. CONCLUSION: Individualization of the duration of treatment to maintain serum HBV-DNA negativity for at least 6 months may reduce the viral relapse rate following IFN therapy.     

病毒性肝炎与糖尿病关系的临床研究

目的探讨病毒性肝炎与糖尿病发病的关系。方法对84例慢性乙型肝炎与83例慢性丙型肝炎患者,76例同期住院患者（对照组）进行病例分析研究,明确其是否合并糖尿病。结果慢性乙型肝炎患者糖尿病并发率为5．9％,慢性丙型肝炎患者糖尿病并发率为13．3％,对照组患者糖尿病并发率为7．9％,慢性丙型肝炎组糖尿病的并发率明显高于慢性乙型肝炎组和对照组患者（P〈0．05）,慢性乙型肝炎组和对照组患者糖尿病并发率差异无统计学意义（P〉0．05）。慢性肝炎合并糖尿病男女比例为2．2：1。三组中合并糖尿病与未合并糖尿病的患者均为中老年人,在年龄、体质量指数、空腹血糖方面差异无统计学意义。合并糖尿病的慢性乙型肝炎和慢性丙型肝炎患者血清丙氨酸氨基转移酶、门冬氨酸氨基转移酶及总胆红素水平高于未合并糖尿病者（P〈0．05）。结论慢性丙型肝炎病毒感染易合并糖尿病,丙型肝炎病毒感染可能是糖尿病的发病因素之一。     

Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. Interim analysis of a double-blind multicentre randomized trial. The UDCA-PBC Study Group

Based on uncontrolled observations, we have proposed ursodeoxycholic acid (UDCA) as a novel therapeutic approach in primary biliary cirrhosis (PBC). To confirm and extend our original findings, we have designed a double-blind multicentre randomized clinical trial. An interim analysis was planned at 6 months, involving all subjects included in the trial, with a final analysis at 2 years. The UDCA-PBC trial began in June 1987 and will be completed in March 1990. Seventy patients were randomized to receive UDCA and 68 a placebo. The two groups were well matched with respect to age, sex, duration and prevalence of symptoms and histologic severity (50% of the UDCA group had stage III-IV disease vs. 37% of the placebo group). During the first 6 months of follow-up, six patients withdrew from the trial. At 6 months, the proportion of patients with jaundice was significantly lower (p less than 0.01) in UDCA recipients than in the placebo group. There was a similar decrease in the proportion of patients with pruritus and fatigue in both groups. The following laboratory test values were significantly lower in UDCA recipients than in the placebo group after 6 months of therapy: serum bilirubin, alkaline phosphatase, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltranspeptidase activities (p less than 0.001), cholesterol (p less than 0.003) and IgM levels (p less than 0.03). The results of this interim analysis confirm and extend the biochemical data provided by our previous pilot study. However the final analysis of the trial is necessary for a definitive assessment of the safety and efficacy of UDCA therapy in PBC.     

Improved quality of life in patients with refractory or recidivant ascites after insertion of transjugular intrahepatic portosystemic shunts

BACKGROUND AND AIMS: A substantial proportion of patients with chronic hepatitis C virus infection have persistently normal serum transaminase levels. The aim of this study was to assess the efficacy and safety of interferon plus ribavirin combination therapy in this population. METHODS: In this prospective open trial 152 patients with biopsy-proven chronic hepatitis C were enrolled, 32 of whom had persistently normal alanine aminotransferase levels (group A). The remaining 120 patients served as a comparison (group B). Patients were treated for 12 months with 4.5 million units of interferon-alpha(2a) thrice weekly in combination with ribavirin 1,000 or 1,200 mg daily. They were followed up for at least 6 months after therapy. Serum hepatitis C RNA was detected by polymerase chain reaction and quantified by a branched DNA assay. RESULTS: At the end of treatment, 12 (37.5%) and 48 patients (40%) were negative for HCV-RNA in groups A and B, respectively (p = 0.33). After 24 weeks of follow-up, 9 patients (28%) from group A and 36 patients (30%) from group B were still HCV-RNA negative (p = 0.4). Treatment was well tolerated by both groups. There were no alanine transferase elevations among group A patients during therapy. CONCLUSION: Interferon-ribavirin combination therapy was safe and induced a sustained virologic response in a significant proportion of patients with chronic hepatitis C and repeatedly normal serum transaminase levels.     

Long-term follow-up of a randomized trial of interferon therapy for chronic hepatitis B in a predominantly homosexual male population

BACKGROUND/AIMS: Extended follow-up of a previously published therapeutic trial with interferon alfa is now available to further clarify the long-term outcome of HIV-negative and HIV-positive subjects with chronic hepatitis B virus infection after interferon alfa therapy. METHODS: Forty-five subjects with compensated liver disease and chronic hepatitis B infection with evidence of active hepatitis B replication were studied. These subjects were enrolled between 1986 and 1991 and had been randomized, stratified by HIV status, to either receive interferon therapy (10 MU/m2 of lymphoblastoid interferon alfa 3 times per week for 12 weeks) or no treatment. Hepatitis B serology, serum hepatitis B viral DNA and alanine aminotransferase were measured on an annual to biannual basis. CD4-positive T lymphocyte counts and HIV RNA concentration were also obtained. RESULTS: From 9 months post-interferon alfa treatment to the end of the extended follow-up (4 to 9 years), the relative risk of seroconverting to anti-HBe positive for subjects who had received interferon alfa therapy compared to those who did not was not significant in either HIV-negative (p = 0.80) or HIV-positive (p = 0.62) subjects. CONCLUSIONS: Unlike the first 9 months following interferon alfa therapy, the rate of elimination of markers of hepatitis B virus replication, regardless of HIV status, was not increased above the natural rate beyond 9 months following interferon alfa therapy.     

Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of patients.The remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the illness.Nearly a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular carcinoma.The indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity levels.The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.     

Liver enzyme values in injection drug users with chronic hepatitis C

BACKGROUND: Liver enzymes fluctuate in chronic hepatitis C virus infection. However, the range that can be attributed to the course of hepatitis C virus (versus an intercurrent cause of hepatitis) is unknown. AIMS: To characterise the range of liver enzyme values as a function of the upper limit of normal (ULN) of the assay among persons chronically infected with hepatitis C virus. PATIENTS: One thousand and fifty-nine hepatitis C virus chronically infected individuals with > or =5 semi-annual evaluations. METHODS: Alanine aminotransferase and aspartate aminotransferase levels were prospectively obtained. Potential causes of elevations were examined using serologic testing. RESULTS: Among 1059 individuals, 11,463 enzyme measurements were obtained over 6.5 years, of which 63.5% were <1.25x ULN, 26.5% were 1.25-2.5x ULN, 8.3% were 2.5-5x ULN, and 1.6% were 5-10x ULN; only 0.2% were >10x ULN. Elevations >10x ULN were transient, the alanine aminotransferase/aspartate aminotransferase ratio tended to be different at the time of the elevation compared to before and after and 24% were associated with acute viral hepatitis. On the other hand, subjects with elevations 5-10x ULN tended to have elevated levels throughout follow-up and only 8% were associated with acute viral hepatitis. CONCLUSIONS: Liver enzymes fluctuate up to 5x ULN in most hepatitis C virus-infected persons; clinicians should seek alternate explanations for those with higher alanine aminotransferase or aspartate aminotransferase levels, especially among hepatitis C virus-infected persons with greater than 10-fold elevations.     

Hepatitis B virus in the State of Alagoas,Brazil: genotypes characterization and mutations of the precore and basal core promoter regions

The aims of this study were to investigate the genotypes of hepatitis B virus and to identify the precore G1896A and basal core promoter A1762T/G1764A mutations in HBsAg and anti-HBc-positive patients. Eighty-three asymptomatic individuals, three with acute hepatitis B and 33 with chronic hepatitis B referred to viral hepatitis centers in the State of Alagoas, Brazil were analyzed according to their viral load, HBeAg/anti-HBe profile and alanine aminotransferase serum level. The genotypes identified were: A (92.5%), C (5%), D (1.25%) and F (1.25%). The precore mutation was detected in 3.8% of sequences and basal core promoter mutation in 52.4%. These were identified in 45.45% of the asymptomatic individuals and 54.55% of the patients with chronic hepatitis, irrespective of viral load and alanine aminotransferase serum level. In genotype C, only the basal core promoter mutation was identified and no mutations were identified in genotypes D and F.     

Interferon and ursodeoxycholic acid combined therapy in the treatment of chronic viral C hepatitis: Results from a controlled randomized trial in 80 patients

Because 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy, and because ursodeoxycholic acid(UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis, we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [mu]three times a week), and in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined as the normalization of alanine transaminase (ALT) levels. The results showed that 6 months after cessation of IFN, 59% of responders had relapsed in group I but only 27% had relapsed in group II (P = .03). There was no difference between the two groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential for long-term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and, therefore, whether it could be advocated as an adjunct to antiviral therapy.     

Famciclovir in chronic hepatitis B: results of a dose-finding study

BACKGROUND/AIMS: Famciclovir, an orally available nucleoside analogue with potent in vitro activity against HBV, is being investigated for treatment of chronic hepatitis B. METHODS: A dose-finding study was conducted in patients with hepatitis B e antigen present in serum. Patients received famciclovir 125 mg, 250 mg, 500 mg three times daily (tid) or placebo for 16 weeks, followed by 8 months post-treatment observation, and 16 weeks open-label treatment. More than 90% of patients had previously received alpha-interferon or had baseline characteristics indicating a high likelihood of poor response to alpha-interferon. RESULTS: Famciclovir induced rapid, dose-dependent suppression of viral replication and reduction in alanine aminotransferase (ALT), with greatest efficacy in the 500-mg tid treatment group. HBV DNA reduction was maintained throughout the treatment period. ALT also steadily declined during the treatment period. Approximately 40% of patients with pretreatment ALT>upper limit of normal (ULN) receiving famciclovir 500 mg tid, experienced sustained normalization of ALT at the end of the 8-month follow-up. Anti-HBe seroconversion occurred more frequently in patients receiving famciclovir 500 mg tid compared with placebo (p=0.04). Famciclovir was generally well tolerated; the incidence of adverse events was comparable to placebo. Exacerbation of liver disease or serious ALT flares were not observed. CONCLUSION: Famciclovir 500 mg three times daily may offer an alternative to alpha-interferon for treatment for chronic hepatitis B. Anti-HBe seroconversion in the famciclovir 500-mg tid group suggests that 16 weeks treatment has the potential for HBV clearance. Further studies with a longer treatment duration are warranted.     

Thymosin treatment of chronic hepatitis B: a placebo-controlled pilot trial

Chronic hepatitis B is a severe and frequently progressive disease. We assessed the safety and efficacy of thymosin fraction 5 and thymosin-alpha 1 in a prospective, placebo-controlled trial in 12 patients with chronic hepatitis B. All patients had histological and biochemical evidence of active liver disease for at least 6 mo before treatment and were positive for serum hepatitis B virus DNA and HBsAg. Seven patients received thymosin fraction 5 or thymosin-alpha 1 and five patients received placebo twice weekly for 6 mo. By the conclusion of the study (1 yr), serum aminotransferase levels had improved significantly in thymosin-treated patients, but not in the placebo group. Six (86%) of the thymosin treated patients and one (20%) patient given placebo cleared hepatitis B virus DNA from serum (p less than 0.04, Fisher's exact test). After treatment, replicative forms of hepatitis B virus DNA were present in the liver specimens of four of five placebo-treated patients but in only one of seven thymosin-treated patients (p less than 0.04, Fisher's exact test). Response to thymosin therapy was associated with significant improvements in peripheral blood lymphocyte and CD3 and CD4 counts and in in vitro production of interferon-gamma over initial values. No significant side effects were observed in patients given thymosin or in placebo-treated patients. Clinical, biochemical and serological improvement in patients responding to thymosin were sustained during 26 +/- 3 mo of follow-up. The results of this pilot trial suggest that thymosin therapy promotes disease remission and cessation of hepatitis B virus replication in patients with chronic viral infection.