Serological pattern ＂anti-HBc alone＂： Characterization of 552 individuals and clinical significance

AIM: To investigate the prevalence and clinical significance of "anti-HBc alone" in an unselected population of patients and employees of a university hospital in southern Germany. METHODS: All individuals with the pattern "anti-HBc alone" were registered over a time span of 82 mo. HBV-DNA was measured in serum and liver samples, and clinical charts were reviewed. RESULTS: Five hundred and fifty two individuals were "anti-HBc alone" (of 3004 anti-HBc positive individuals; 18.4%), and this pattern affected males (20.5%) more often than females (15.3%; P<0.001). HBV-DNA was detected in serum of 44 of 545 "anti-HBc alone" individuals (8.1%), and in paraffin embedded liver tissue in 16 of 39 patients tested (41.0%). There was no association between the detection of HBV genomes and the presence of biochemical, ultrasonic or histological signs of liver damage. Thirty-eight "anti-HBc alone" patients with cirrhosis or primary liver carcinoma had at least one additional risk factor. HCV-coinfection was present in 20.4% of all individuals with "anti-HBc alone" and was the only factor associated with a worse clinical outcome. CONCLUSION: In an HBV low prevalence area, no evidence is found that HBV alone causes severe liver damage in individuals with "anti-HBc alone". Recommendations for the management of these individuals are given.     

Alpha-interferon therapy in chronic hepatitis due to active dual infection with hepatitis B and C viruses

BACKGROUND: Nearly 14% of non-alcoholic chronic liver disease in India is related to hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection. There are no clear data available from the literature on the therapeutic management of these patients who often suffer an unfavourable course. METHODS: Fourteen consecutive cases of biopsy-proven chronic liver disease fulfilling the following criteria were included: Child's A or B liver disease, hepatitis B surface antigen positive, HBV-DNA positive, antibody to HCV positive and HCV-RNA positive. Seven patients had chronic liver disease (group I), while the remaining seven patients (group II) had additional disorders (non-Hodgkin's lymphoma (two), acute leukaemia (two), thalassaemia (two), chronic renal failure (one). Interferon alpha-2b (IFN) was given in a dose of 6 MIU thrice weekly for 6 months. Complete response was defined as loss of HBV-DNA and HCV-RNA at 6 months and sustained response (SR) as the sustained loss of HBV-DNA and HCV-RNA for more than 6 months during the follow-up period. RESULTS: At the end of 6 months, alanine aminotransferase (ALT) levels remained unchanged (120 +/- 40 vs 136 +/- 64 IU/L), but six of the seven (86%) patients in group I lost HBV-DNA. All three hepatitis Be antigen (HBeAg)-positive patients lost HBeAg with an early flare of ALT (at 45 +/- 12 therapy days). Two of these patients (29%) lost HCV-RNA. Thus, SR was seen in 29%, while HBV-DNA loss was found in 100% during the follow-up period. In group II patients, there was a significant decrease in ALT (308 +/- 14 vs 65 +/- 25 IU/L, P < 0.001), but only three (43%) patients lost HBV-DNA and two (29%) lost HCV-RNA. One patient with acute leukaemia and another with renal failure had a complete response to IFN, but none of the lymphoma patients showed any antiviral response. CONCLUSIONS: In chronic hepatitis due to dual infection with HBV and HCV, interferon therapy is: (i) safe; (ii) effective (more so in clearing HBV); (iii) often associated with early ALT flare; and (iv) may be less effective if non-Hodgkin's lymphoma is present.     

Hepatitis B virus multiplication in the absence of usual serological markers. A study of 146 chronic alcoholics

The possible role of HBV infection in the progression of alcoholic liver disease remains debated. However, serum HBV markers in alcoholics, although present with a high frequency, mainly consist of anti-HBs and/or anti-HBc antibodies. In order to detect an HBV multiplication that could be missed by the usual markers, we looked for HBV-DNA in the serum of 146 chronic alcoholics; the results were compared with those of the usual serological HBV markers. Sixty-eight of the 146 patients could be studied for HBV-DNA both in the liver and the serum. The 146 alcoholics were divided in 48 with normal liver function (group I); 67 with non-cirrhotic alcoholic liver disease (group II); 31 with alcoholic cirrhosis (group III). Among the 146 patients, 17 had a viral multiplication reflected by serum positive HBV-DNA, as against none of 100 healthy controls (P less than 0.01). Six of the 17 had a normal liver function (6/48 = 12.5%), 7 were of group II (7/67 = 10.4%) and 4 had cirrhosis (4/31 = 12.9%). Serum HBV-DNA was associated with HBsAg in 3 occasions; in addition serum HBV-DNA was also present in 5 HBsAg-negative patients with anti-HBc and/or anti-HBs and even in 9 without any usual HBV marker. The overall prevalence of HBV markers in the 146 patients went from 30.8% to 37.0% when serum HBV-DNA was taken into account; it was similar in the 3 groups studied. Eight patients, of the 68 studied, were liver HBV-DNA-positive.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

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

Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients

Purpose  The presence of hepatitis B virus (HBV) DNA in liver tissue and/or in serum in the absence of detectable hepatitis B surface antigen (HBsAg) is called occult HBV infection. This pattern was identified in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the role of antibodies to hepatitis B core antigen (anti-HBc) as a screening test for occult HBV infection in Egyptian chronic HCV patients. Methods  One hundred chronic HCV patients negative for HBsAg were included and subdivided into two groups according to anti-HBc-IgG seroreactivity. Group A included 71 patients positive for anti-HBc (53 men and 18 women, mean age ± SD 48.8 ± 9.6 years), and group B included 29 patients negative for anti-HBc (18 men and 11 women, mean age ± SD 46.6 ± 11.7 years). All patients were subjected to full clinical assessment, routine laboratory investigations, abdominal ultrasonography and quantification of HBV-DNA by real-time PCR. Results  Chronic HCV patients positive for anti-HBc have more severe liver disease compared with anti-HBc negative patients. Although HBV-DNA in the serum was detected in 22.5% of anti-HBc-positive chronic HCV patients, it was not detected in any of anti-HBc-negative chronic HCV patients. There was no significant difference in any of the clinical and laboratory data tested between anti-HBc-positive patients with and without HBV-DNA in the serum. Conclusion  A significant number of patients with anti-HBc had detectable levels of HBV-DNA in the serum. Egyptian chronic HCV patients have a high prevalence of occult HBV infection.     

A randomized, controlled trial of maintenance interferon therapy for patients with chronic hepatitis C virus and persistent viremia.

BACKGROUND & AIMS:: At least half of patients with chronic hepatitis C virus (HCV) fail to respond to interferon or interferon/ribavirin therapy. Histological improvement is observed in some nonresponders. We conducted a randomized, controlled trial to determine if maintenance interferon therapy could prevent histological progression in this subset of nonresponders. METHODS: Fifty-three patients with chronic HCV were enrolled. All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response. Twenty-seven of the patients were randomly assigned to continue interferon (3 MU 3 times weekly) for 24 months; 26 patients discontinued treatment and were observed prospectively. Alanine aminotransferase (ALT) level and HCV-RNA titer were monitored, and liver biopsy was repeated every 12 months. RESULTS: Before interferon therapy, the 2 groups were well matched for all demographic factors, serum ALT (94.0 +/- 15.6), log HCV-RNA titer (5. 85 +/- 0.15 copies/mL), histology score (9.5 +/- 0.2), and percentage with cirrhosis (25%). After 6 months of treatment, significant reductions (P < 0.05) in serum ALT level (62.6 +/- 9.6), log HCV-RNA titer (4.79 +/- 0.13 copies/mL), and hepatic inflammation (4.0 +/- 0.2) were observed. These improvements were maintained in the patients randomized to continue interferon. Stopping treatment was associated with an increase in serum ALT, log HCV-RNA, and hepatic inflammation back to baseline. After 30 months of treatment, mean fibrosis score declined from 2.5 to 1.7 and 80% of patients had histological improvement (P < 0.03). Discontinuation of interferon was associated with an increase in mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30% of patients (P < 0.01). CONCLUSIONS: These data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic.     

Effect of Alcohol Intake on the Efficacy of Interferon Therapy in Patients with Chronic Hepatitis C as Evaluated by Multivariate Logistic Regression Analysis

The effect of alcohol intake on the efficacy of interferon (IFN) therapy was evaluated retrospectively in patients with chronic hepatitis C diagnosed by liver histology and positive serum hepatitis C virus (HCV)-RNA. Patients included 119 given IFN therapy and 11 no IFN therapy. Serum HCV-RNA was measured 6 months after discontinuation of IFN therapy in 92 treated patients, 27.2% of whom showed disappearance of serum HCV-RNA. Multivariate logistic regression analysis revealed that this disappearance was affected by alcohol intake, the presence of its history ( p < 0.05) or cumulative alcohol consumption (kg) (p < 0.01), and serum HCV-RNA levels ( p < 0.001). The odds ratio associated with serum HCV-RNA still positive at 6 months was 7.016 (95% confidence interval: 1.444-34.082) and 1.004 (1.001-1.007) for the presence of alcohol intake history and the cumulative alcohol consumption, respectively. Other predictor variables–such as sex and age of patients, history of blood transfusion, HCV genotype, histological findings of the liver, and types of IFN– had no influence on the efficacy of the therapy. Cumulative alcohol consumption showed a negative correlation with serum HCV-RNA levels pretreatment, when the outcome variable was divided into two categories based on serum HCV-RNA levels: 10⁶ copy/ml or less and 10⁷ copy/ml or more. Alcohol intake was positively correlated with histological extent of alcoholic fibrosis, but affected neither grading nor staging of chronic viral hepatitis. We conclude that alcohol intake was a risk factor on the efficacy of IFN therapy in chronic hepatitis C patients. This effect was independent of serum HCV-RNA levels and histological findings specific for viral hepatitis in the liver.     

Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers

AIM: To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS: Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS: After a mean follow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy (10%) had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection. The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION: The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.     

Pathological and virological findings in patients with persistent hypertransaminasaemia of unknown aetiology

BACKGROUND: The histopathological spectrum and role of hepatitis viruses in cases of hypertransaminasaemia of unknown aetiology have not been correctly analysed in a sufficiently large number of patients. METHODS: We studied 1075 consecutive patients referred for liver biopsy because of elevation of alanine aminotransferase (ALT) levels for more than six months. From this population we selected those cases in whom the aetiology could not be defined from clinical, biochemical, and serological data obtained before biopsy. In these patients liver biopsies were reviewed, and hepatitis B virus (HBV)-DNA and hepatitis C virus (HCV)-RNA were assayed in serum by polymerase chain reaction (PCR). Serum hepatitis G virus (HGV)-RNA was determined by PCR in 74 patients. RESULTS: Of 1075 patients studied, the cause of the increased serum ALT levels remained elusive after appropriate testing in 109 patients (10.1%). Liver biopsies from these patients showed non-specific changes in 32.7% of cases, non-alcoholic steatohepatitis (NASH) in 15.8%, and chronic hepatitis or cirrhosis in 51.5%. HBV-DNA and/or HCV-RNA was detected more frequently in cryptogenic liver disease than in healthy blood donors (26.7% v 3.4%; p<0.001). HGV-RNA was found in only one patient. The proportion of cases with detectable HBV-DNA or HCV-RNA was 14.3% in patients with non-specific changes or NASH, 30.7% in patients with chronic hepatitis, and 61.5% in patients with cirrhosis. Cirrhosis was found more frequently in patients with positive HBV-DNA and/or HCV-RNA in serum than in those who tested negatively (p=0.005). CONCLUSIONS: In our series, patients in whom biochemical and serological data did not determine the aetiology of the disease represented 10% of all cases referred for liver biopsy for persistent elevation of serum transaminases. Approximately 50% of patients had chronic hepatitis or cirrhosis and the remainder had NASH or non-specific changes. Occult viral infections were found in a high proportion of cases in the first group and in a low percentage of patients in the second.     

Serum thioredoxin levels as an indicator of oxidative stress in patients with hepatitis C virus infection

BACKGROUND/AIM: It has recently been suggested that oxidative stress may be associated with hepatitis C virus (HCV) infection. Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX levels in patients with HCV-related chronic liver diseases. METHODS: Serum TRX levels were determined with a sandwich enzyme-linked immunosorbent assay kit in 174 serum HCV-RNA positive patients, including 6 asymptomatic carriers, 124 chronic hepatitis, 20 liver cirrhosis, and 24 hepatocellular carcinoma, and in 15 healthy volunteers. RESULTS: The serum TRX levels (medians and [ranges], ng/ml) were significantly elevated in the HCV-infected patients; 30.9 [20.7-37.7] in asymptomatic carriers, 34.5 [8.6-135.6]* in chronic hepatitis, 42.5 [21.4-97.2]* in liver cirrhosis, and 43.9 [11.7-180.3]** in hepatocellular carcinoma (*p<0.05, **p<0.001, vs. 24.9 [1.3-50.7] in healthy controls). Serum TRX levels were significantly correlated with the serum levels of ferritin and fibrogenesis markers, and with the histological stage of hepatic fibrosis. The serum TRX levels before interferon treatment of patients whose serum HCV-RNA was still positive on day 14 following interferon treatment (42.6 [20.1-90.0]) were significantly higher than those of patients whose serum HCV-RNA was negative on day 14 following interferon treatment (25.8 [7.4-59.8], p<0.05). CONCLUSIONS: The serum TRX levels of patients with HCV infection increased with their serum ferritin levels and the progression of liver fibrosis. Patients with higher serum TRX levels exhibited resistance to interferon therapy. Oxidative stress may therefore be responsible for the pathological mechanism of HCV-related liver diseases and be one of the impediments to eradication of HCV during interferon treatment.     

Outcome of anti-HBe positive chronic hepatitis B in alpha-interferon treated and untreated patients: a long term cohort study

BACKGROUND/AIMS: We studied the influence of biochemical and virologic patterns and interferon on the outcome of anti-HBe positive chronic hepatitis B in 164 (103 treated) consecutive patients, followed-up prospectively for a mean of 6 years (21 months-12 years). METHODS: Histology, biochemical and virologic profiles were characterized by monthly monitoring during the first 12 months of follow-up. Thereafter patients underwent blood and clinical controls every 4 and 6 months, respectively. Cirrhosis at follow-up histology or end stage complications of cirrhosis served as end points for the analysis of factors influencing disease progression in patients with baseline chronic hepatitis or cirrhosis, respectively. RESULTS: Disease progression was associated with older age (P<0.001), absence of previous HBeAg history (P=0.017) and higher serum HBV-DNA levels (P=0.009) (more frequently observed in unremitting disease profile, P=0.012) at multivariate analysis. Fluctuations of IgM anti-HBc levels (associated with disease exacerbations, P=0.045) correlated with end stage complications in cirrhotics (P=0.011). Disease improved in 14.6 and 1.6% of treated and untreated patients, respectively (P=0.015): interferon slowed disease progression (P<0.001). CONCLUSIONS: The outcome of anti-HBe positive chronic hepatitis B is worsened by older age and persistent viral replication or hepatitis exacerbations in chronic hepatitis or in cirrhotic patients, respectively. Interferon reduces by 2.5-folds disease progression.     

Mutations in the NS5A gene predict response to interferon therapy in Japanese patients with chronic hepatitis C and cirrhosis.

The virus genotype, serum HCV-RNA level and liver histology are reported to be important factors in the response to interferon therapy. Recent studies have revealed that HCV NS5A 2209-2248 amino acid changes affect the response to interferon therapy of genotype 1b chronic hepatitis C. In contrast, some studies done in western countries have reported no such correlation. In the present study, interferon therapy was given to 58 Japanese patients, including 15 liver cirrhosis patients. NS5A 2209-2248 changes, the serum HCV level, ALT level, age and histology were examined in relation to the interferon effect. Twenty-four of the 58 patients (41%) showed a sustained virological response to the therapy. The responses to interferon therapy were significantly correlated with NS5A 2209-2248 changes (p < 0.0001), the HCV-RNA level (p < 0.0001) and histology (p < 0.0060). Among 15 liver cirrhosis patients, 3 of 6 mutant type patients showed a sustained virological response; 5 intermediate and 4 with wild type virus infected patients showed no responses. In conclusion, NS5A 2209-2248 changes may be a useful predictive marker of response to interferon therapy in addition to the serum HCV RNA level even in histologically advanced patients.     

Combined treatment of relapse of chronic hepatitis C with high-dose alpha2b interferon plus ribavirin for 6 or 12 months

BACKGROUND/AIMS: Retreatment of relapses of chronic hepatitis C with a standard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b. We aimed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness, and also to evaluate the tolerability, and to identify the determinants of sustained response. METHODS: Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of a-interferon monotherapy were randomised to receive alpha2b interferon (6 MU tiw) plus ribavirin (1000-1200 mg daily) for 6 or 12 months. ALT normalisation and serum HCV-RNA clearance at the end of treatment and 6 months after stopping therapy were used as markers for sustained response. RESULTS: End-of-treatment response was achieved in 48 patients (96%) and 27 (54%) had a complete sustained response. Patients treated for 12 months had a higher rate of sustained response (18/25, 72%; 95% C.I. 0.54-0.89) than those treated for 6 months (9/25, 36%; 95% C.I. 0.17-0.55, p=0.01). Twelve months of therapy was significantly more effective for patients with genotype 1b and baseline serum HCV-RNA greater than 450 000 copies/ml (p=0.005). Seven subjects (14%) discontinued treatment because of side effects. Logistic regression analysis showed 12 months of therapy, young age and low pre-treatment serum HCV-RNA to be independent predictors of sustained response. CONCLUSIONS: Relapsers with genotype 1b and high levels of HCV-RNA will benefit from a 12-month course of 6 MU tiw interferon plus ribavirin, while subjects with genotype 1b and low levels of serum HCV-RNA or with genotype other than 1b may be treated for 6 months.     

Treatment of patients with chronic hepatitis C not responding to interferon with high-dose interferon alpha with or without ribavirin: final results of a prospective randomized trial. Austrian Hepatitis Study Group.

OBJECTIVE: To investigate the efficacy of high-dose interferon alpha (IFN-alpha) with or without ribavirin in interferon (IFN) non-responders. STUDY DESIGN: 304 chronic hepatitis C patients received 5 MU IFN-alpha2b (IntronA, Schering-Plough, Kenilworth, NJ, USA) three times a week for 3 months. Non-responders were randomized either to continue with IFN (IFN 5 MU/TIW followed by 10 MU/TIW, each for 3 months) alone (group A: n = 76, m: f = 54: 22, age 45.7 +/- 12 years, 16% cirrhosis, alanine aminotransferase [ALT] 66 +/- 35 U/l) or in combination with ribavirin (approximately 14 mg/kg/day) (group B: n = 81, m: f = 57: 24, age 48.2 +/- 12 years, 17% cirrhosis, ALT 71 +/- 40 U/l). At the end of treatment, patients were followed for 6 months. MAIN OUTCOME MEASURES: Virological response at end of treatment and 6 months thereafter. SETTING: University hospitals and tertiary referral centres. RESULTS: At the end of treatment, eight (10.8%) and 25 (31.3%, P= 0.0066) patients were HCV-RNA negative, and 51 and 39 were HCV-RNA positive, in groups A and B, respectively. There were 17 drop-outs in each group. Six months after treatment, only one patient in group A (1.3%) and seven patients (8.6%, P= 0.06) in group B had normal ALT and undetectable serum HCV-RNA. CONCLUSIONS: A combination of high-dose IFN with ribavirin induces a short-lasting complete response in about one-third of IFN-non-responders.     

Interferon therapy does not prevent hepatocellular carcinoma in HCV compensated cirrhosis

BACKGROUND/AIMS: Recent experiences suggest that interferon may significantly decrease the incidence of hepatocellular carcinoma. We conducted a randomized study with interferon versus no therapy in hepatitis C virus Child A cirrhosis with abnormal alanine aminotransferase and HCV-RNA positive serum with the aim to investigate the incidence of hepatocellular carcinoma, worsening of cirrhosis's stage and death or orthotopic liver transplantation. METHODOLOGY: A cohort of 122 patients prospectively followed was analyzed retrospectively to assess the effect of interferon therapy (mean follow-up: 96 +/- 18.3 months). We only chose patients with hepatitis C virus infection who had undergone blood transfusion before 1980. Hepatitis C virus serotype was determined by hepatitis C virus serotyping 1-6 assay (Murex Biothec Limited Temple Hill, Dartford, Kent, UK). HCV-RNA level was determined by bDNA, Chiron Corporation Emeryville, CA. Diagnosis of hepatocellular carcinoma was made on the basis of the appearance of local lesions at periodic ultrasound examination of the liver and confirmed with spiral computed tomography. Fine needle biopsy under sonographic guidance was effected. Fifty-nine patients (mean age: 55.3 +/- 7) received interferon (3MU three times a week for 12 months), 8 stopped therapy for side effects, 71 did not receive interferon (mean age: 56.8 +/- 8). Baseline characteristics were similar. RESULTS: It emerges how interferon does not reduce the risk of hepatocellular carcinoma in compensated cirrhosis. In interferon treated patients an improvement in relation with worsening and death/orthotopic liver transplantation has been noted. CONCLUSIONS: The use of the interferon seems to be scarcely useful when structural alterations of the cirrhotic kind show up, as cirrhosis represents by itself a risk factor for hepatocellular carcinoma. Nevertheless, in relation to the worsening of cirrhosis's stage the interferon therapy can be useful in compensated cirrhosis.     

Pegylated interferon plus ribavirin for recurrent Hepatitis C infection after liver transplantation in naïve and non-responder patients on a stable immunosuppressive regimen

BACKGROUND: Hepatitis C virus recurrence after liver transplantation is universal, leading to chronic hepatitis and cirrhosis. AIMS AND PATIENTS: We evaluated the efficacy and safety of pegylated interferon and ribavirin in 20 patients with recurrent Hepatitis C virus after liver transplantation (10 na?ve and 10 non-responders to a previous interferon course). METHODS: Treatment consisted of pegylated interferon alfa-2b (1.0 microg/kg once weekly) and ribavirin (600 mg/daily) for at least 6 months. Therapy continued for an additional 6 months only in patients with undetectable serum Hepatitis C virus-RNA or >2 log drop from baseline levels. RESULTS: Eleven out of 20 patients (55%) completed 1 year of treatment. Nine patients (45%) had undetectable Hepatitis C virus-RNA at the end of treatment, six of them were na?ves and three non-responders. In all of them, virological response persisted 6 months after discontinuation of therapy, so the sustained virological response rate was 60% in na?ve patients and 30% in non-responders. CONCLUSIONS: Our results suggest that pegylated interferon plus ribavirin combination therapy may be effective in patients with post-liver transplantation recurrent chronic Hepatitis C, even in those previously non-responders to interferon plus ribavirin. These results need to be confirmed by large studies.     

Treatment of chronic hepatitis C in patients who failed interferon monotherapy: effects of higher doses of interferon and ribavirin combination therapy. The Virginia Cooperative Hepatitis Treatment Group

OBJECTIVE: The present study was designed to evaluate the effectiveness of interferon-ribavirin combination therapy for treatment of chronic hepatitis C virus (HCV) in patients who failed previous treatment with interferon monotherapy. METHODS: A total of 140 patients with well-documented chronic HCV who failed to achieve a virological (if HCV-RNA was assessed) or biochemical response (if HCV-RNA was not assessed) to interferon monotherapy, 3 mU three times weekly (TIW) for 3-18 months, were randomly assigned to one of three treatment groups. Group A patients were treated with 5 mU interferon TIW for 6 months. Ribavirin (1000-1200 mg daily) was added in those patients HCV-RNA positive at month 3. Group B patients were treated with 3 mU interferon TIW plus ribavirin (1000-1200 mg daily) for 6 months. The dose of interferon was increased to 5 mU TIW in those patients HCV-RNA positive at month 3. Group C patients were treated with 5 mU interferon TIW plus ribavirin (1000-1200 mg daily) for 6 months. Serum ALT and HCV-RNA were monitored during and after treatment for a total of 15 months. RESULTS: Seventeen percent of patients in group A became HCV-RNA negative by treatment month 3. Adding ribavirin resulted in one additional patient becoming HCV-RNA negative. However, none of the patients in this group achieved sustained virological response. Twenty-six percent of patients in group B became HCV-RNA negative by treatment month 3. Increasing the dose of interferon from 3 to 5 mU TIW increased virological response to 30%. However, sustained virological response was observed in only 14%. Thirty percent of patients in group C became HCV-RNA negative, but sustained virological response was observed in only 12%. Sustained virological response was found to be significantly greater in patients with a nontype I HCV genotype (p < 0.002) and in patients who had a decline in HCV-RNA titer to a value < 100,000 copies/ml during their previous course of interferon monotherapy (p < 0.0001). None of the 12 sustained responders were African Americans (p < 0.013). CONCLUSIONS: Retreatment of nonresponders with interferon-ribavirin combination therapy results in limited benefit; only 13% of patients achieved sustained virological response. Response was extremely poor in African Americans and those with HCV genotype 1.     

Anti-HBe-positive chronic hepatitis B with HBV-DNA in the serum response to a 6-month course of lymphoblastoid interferon.

Eighteen heterosexual HBsAg carriers with anti-HBe- and HBV-DNA-positive chronic hepatitis B (CHB) were randomly assigned to receive human lymphoblastoid interferon (ly-IFN) at a dose of 5 MU/m2 i.m. three times a week for 6 months (ten cases) or no treatment (eight cases). All patients were followed for 24 months after IFN discontinuation and received a second liver biopsy. During the 6 months of treatment all patients had a progressive reduction of serum HBV-DNA levels, and at the end of therapy nine out of ten were HBV-DNA-negative and had normal ALT values. None of the untreated patients became persistently HBV-DNA-negative or showed significant variations of ALT levels. During the post-treatment follow-up, from 1 to 17 months after ly-IFN discontinuation, eight of the nine responders (89%) had recurrent or persistent reappearance of HBV-DNA in the serum and reactivation of the liver disease activity, with an ALT peak in four of them. On the post-trial liver biopsy seven of the eight relapsed patients showed persistence of HBcAg reactivity with no significant difference in the percentage of positive cells with respect to the pre-treatment liver specimen. Histological features improved in four treated patients, worsened in one untreated case and were unchanged in the remaining patients. These results indicate that ly-IFN shows a transient antiviral effect in the therapy of anti-HBe- and HBV-DNA-positive CHB. The 6-month treatment regimen employed in this study seems insufficient for eradicating the replicating virus from the liver cells in the majority of patients and consequently does not appear to prevent HBV reactivation after IFN discontinuation.     

Effects of Zhaoyangwan on chronic hepatitis B and posthepatic cirrhosis

AIM: To study the therapeutic effects of zhaoyangwan (ZYW) on chronic hepatitis B and hepatic cirrhosis and the anti-virus, anti-fibrosis and immunoregulatory mechanisms of ZYW. METHODS: Fifty cases of chronic hepatitis B and posthepatic cirrhosis with positive serum HBsAg, HBeAg, anti-Hbc and HBV-DNA were divided randomly and single-blindly into the treatment group (treated with ZYW) and the control group (treated with interferon). After 3 month treatment, the effects of the treatment group and the control group were evaluated. RESULTS: The serum ALT normalization was 83.3% (30/36) in the treatment group and 85.7% (12/14) in the control group, with no significant difference (chi2=0.043, P>0.05). After the course, the negative expression rates of the serum HBV-DNA and HBeAg were 44.4% (16/36) and 50% (18/36) in the treatment group, and 50% (7/14) and 50% (7/14) in the control group, respectively, with no significant difference (chi2=0.125, chi2=0.00, both P>0.05). Negative HBsAg and positive HBsAb appeared in 4 cases of the treatment group and 1 case of the control group. Serum anti-HBc turned negative in 6 cases of the treatment group and 1 case of the control group, respectively. After the ZYW treatment, serum CD3+, CD4+, CD8+, CD4+/CD8+ and NK cell activation were significantly increased. Only serum CD3+ and NK cell activation were significantly increased in the control group with a significant difference between the two groups. The serum C4, C1q, C3, B and C9 were significantly increased in the treatment group. In the control group only the serum C4 was increased. The concentration of serum interferon had no change after treatment with ZYW, while it was significantly increased in the control group after treatment with interferon. The ultrastructure of the liver restored, which helped effectively to reduce the degeneration and necrosis of hepatic cells,infiltration of inflammatory cells and hepatic cirrhosis. CONCLUSION: ZYW is a pure Chinese herbal medicine. It can exert potent therapeutic effects on chronic hepatitis B and posthepatic cirrhosis. ZYW has similar therapeutic effects to those of interferon. It is cheap and easily administered with no obvious side-effects. It can be widely used in clinical practice.