Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients: A pilot study

BACKGROUND: In chronic hepatitis B, long-term use of alpha interferon is hampered by side effects, and long-term treatment with nucleos(t)ide analogues is burdened by drug-resistant mutants. We hypothesized that alternate rounds of lamivudine and alpha interferon might circumvent previous shortcomings. AIM: To evaluate efficacy of sequential lamivudine or IFN-alpha2b monotherapies in preventing occurrence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants and achieving virological and biochemical response. METHODS: Fifteen patients with hepatitis B surface antigen, anti-HBe-positive chronic hepatitis received four consecutive rounds of monotherapy with lamivudine (100 mg/day), IFN-alpha2b (5MU/tiw), lamivudine, IFN-alpha2b. Serum HBV-DNA levels were evaluated during and off treatment, HBV polymerase and pre-core/core regions sequenced. RESULTS: End-of-treatment response was achieved in 10 patients (67%). One patient did not respond, a second developed genotypic resistance at week 24. A rebound in viremia occurred in three patients at week 48. Six patients (40%) remained sustained responders. Triple promoter mutations at nucleotides 1762-1764-1896 prevailed in non-responders (60%) as compared to responders (20%). L180M/M204V mutations were identified during virological breakthrough. CONCLUSION: Sequential approach of alternate rounds of lamivudine or interferon may help patients to tolerate a prolonged schedule of therapy and protect them from emergence of viral strains.     

Efficacy of ursodeoxycholic acid in association with alpha-interferon for chronic hepatitis C in alpha-interferon non-responder patients

BACKGROUND: The aim of the present study was to evaluate the effect of combined treatment with alpha-interferon (alpha-IFN) and ursodeoxycholic acid (UDCA) on liver function tests and serum HCV-RNA in patients with chronic hepatitis C who had not responded to alpha-IFN alone. METHOD: One hundred and three patients (60 men, 43 women, mean age 49 +/- 1.3 years) who had not responded (both HCV-RNA positive and increased serum ALT levels) to 4 consecutive months of treatment with alpha-IFN (3 MU three times weekly) were randomly assigned to receive UDCA (IFN-UDCA, 53 patients, 600 mg/day) in addition to the same alpha-IFN dose, or to continue alpha-IFN alone (IFN-controls, 50 patients). After stopping alpha-IFN, patients who had received UDCA continued to receive UDCA for an additional 6-month period. The two groups were comparable for sex, basal ALT, basal yGT, genotype distribution and liver histology, while mean age was lower in controls (53 +/- 1.8 vs 46 +/- 1.8 years; P< 0.01). RESULTS: Twenty (38%) out of 53 IFN-UDCA patients had normal ALT, compared with only six (12%) out of 50 IFN-control patients (P < 0.01). HCV-RNA became undetectable in four IFN-UDCA patients. Three months after withdrawal of alpha IFN, 15 IFN-UDCA responders, but none of the IFN-controls, had normal ALT values (P< 0.01); 6 months after withdrawal, nine IFN-UDCA responders still had normal ALT (P= NS) and HCV-RNA was still undetectable in four of them. Portal and periportal inflammation showed a statistically significant improvement (Fisher's exact test P< 0.01) in IFN-UDCA patients as compared with IFN-controls, while no effect was observed on portal fibrosis. CONCLUSIONS: These data demonstrate that UDCA improves the response rate to alpha-IFN. Furthermore, in 8% of IFN-UDCA patients the response rate was sustained and associated with HCV-RNA clearance.     

Amantadine for chronic hepatitis C: pilot study in 14 patients

BACKGROUND: Amantadine, a widely available antiviral drug, has been previously reported to be effective in patients with chronic hepatitis C who failed to respond to interferon-alpha therapy. Nevertheless, its efficacy has not been fully studied, particularly in naive patients. OBJECTIVE AND DESIGN: We conducted a pilot study to determine the efficacy and the safety of amantadine as initial therapy in patients with chronic hepatitis C. METHODS AND PARTICIPANTS: Fourteen consecutive patients (mean age, 40 years; M/F ratio, 9/5) with chronic hepatitis C, elevated alanine aminotransferase (ALT) and without cirrhosis were treated with a 6-month course of amantadine, 100 mg orally twice daily. Main outcome measures were ALT concentrations and serum hepatitis C virus-RNA (HCV-RNA) levels at the end of therapy. RESULTS: All adverse events were mild or moderate and were not treatment limiting. At the end of treatment, all patients had detectable serum HCV-RNA and only one patient had a normal ALT level. The serum HCV-RNA median level and the ALT median level were not significantly different at the end of treatment as compared to baseline levels. CONCLUSIONS: Our results show that amantadine alone cannot be recommended as an alternative therapy in patients with chronic hepatitis C.     

A pilot study of beta-interferon for treatment of patients with chronic hepatitis B who failed to respond to alpha-interferon

BACKGROUND/AIMS: Alpha-interferon achieves persistent loss of hepatitis B virus (HBV) in about 30-40% of patients with chronic hepatitis B. In non-responder patients, the disease may progress leading to complications such as cirrhosis and hepatocellular carcinoma. The aim of the current study was to evaluate the efficacy of beta-interferon in patients with chronic hepatitis B who did not respond to one course of alpha-interferon. METHODS: Twenty nine alpha-interferon-non-responder patients with chronic hepatitis B (11 hepatitis B e antigen, HBeAg-positive; 18 HBeAg-negative) were treated with 6 million units beta-interferon five times a week for 24 weeks. The post-treatment follow-up lasted for 48 weeks. RESULTS: At the end of treatment, 38% of patients (18% HBeAg-positive; 50% HBeAg-negative) had normal serum aminotransferase levels and negative serum HBV DNA. At the end of follow-up, HBV DNA was no longer detectable in serum in 21% of patients (18% HBeAg-positive; 22% HBeAg-negative). Beta-interferon was well tolerated and safe. CONCLUSIONS: This pilot study suggests that beta-interferon therapy is effective and safe in the retreatment of patients with chronic hepatitis B who had not responded to a previous alpha-interferon cycle.     

A pilot study of ribavirin therapy for chronic hepatitis C.

Interferon-alpha therapy is of proven efficacy in chronic hepatitis C, but it is not universally effective and may be associated with intolerable side effects. Ribavirin is a nucleoside analog with a broad spectrum of antiviral action. We conducted an uncontrolled pilot study of ribavirin therapy in 13 patients with chronic hepatitis C. Ribavirin was given for 6 mo, in a dose that was increased, at 2-mo intervals, from 600 mg to 1,000 mg to 1,200 mg/day. Serum ALT levels gradually decreased in all 13 treated patients; the mean percentage of decrease was 67% (from 210 U/L [range = 109 to 593] to 63 U/L [range = 22 to 108 U/L]; p = 0.0006) after 6 mo of treatment. Serum aminotransferase levels fell to the normal range in four patients (31%). In the 3 to 6 mo after cessation of ribavirin therapy, serum aminotransferase activities gradually rose to near pretreatment levels in all but one patient. Therapy was associated with a significant decrease in the geometric mean titer of hepatitis C virus RNA in serum (1:1,981 vs. 1:199; p less than 0.02) although no patients lost hepatitis C virus RNA from serum during therapy. No significant improvement was seen in liver histological appearance. Ribavirin therapy resulted in mild, reversible hemolysis; no patient exhibited symptomatic anemia. These findings suggest that ribavirin has a beneficial effect in patients with chronic hepatitis C, although further studies are needed to determine how ribavirin is best used.     

Effect of alpha-interferon on hepatitis C virus chronic infection in mixed cryoglobulinemia patients

Summary Since a striking association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia has been demonstrated, the aim of this study is to investigate the effect of alpha-interferon (-IFN) on HCV viraemia and clinico-serological manifestations of 15 patients (ten female and five male, mean [±SD] age 53±7 years). In 14/15 patients pre-study steroid dosage remained unchanged during treatment. -IFN was administered at a dose of 2×10⁶ IU daily for a month, then every other day for five months. On the whole, a statistically significant improvement of purpura (p<0.001), serum transaminases (p<0.001), and cryocrit (p<0.01) was observed after -IFN treatment. HCV viraemia was detected by polymerase chain reaction technique in 13/15 patients with mixed cryoglobulinemia and anti-GOR antibodies, expression of HCV-related autoimmunity, were present in 8/15. After -IFN treatment, HCV RNA levels showed a clear-cut reduction in five persons and disappeared in another, while anti-HCV antibodies (Chiron ELISA and RIBA II) did not change after the six-month period of therapy. These data further support the possible etiopathogenetic role of HCV in patients with mixed cryoglobulinemia and suggest that -IFN may be regarded as the elective treatment in this disease.

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Wirksamkeit von alpha-Interferon bei Patienten mit gemischter Kryoglobulinämie und chronischer HCV-Infektion

Zusammenfassung Zwischen der Hepatitis C Virus-Infektion (HCV) und gemischter Kryoglobulinämie wurden bemerkenswerte Beziehungen festgestellt. Bei 15 Patienten mit gemischter Kryoglobulinämie wurde daher die Wirkung von alpha- Interferon (-IFN) auf die HCV-Virämie und die klinischen und serologischen Parameter der Kryoglobulinämie geprüft (zehn Frauen, fünf Männer, mittleres Alter (±SD) 53±7 Jahre). -IFN wurde während eines Monats täglich in einer Dosis von 2×10⁶ IU und dann fünf Monate lang jeden zweiten Tag verabreicht. Die Kortikosteroiddosen blieben dabei in 14/15 Fällen unverändert. Nach der -IFN-Therapie war eine signifikante Besserung der Purpura (p<0,001), der Serumtransaminasen (p<0,001) und des Kryokrit (p<0,01) festzustellen. Bei 13/15 Patienten wurde mittels Polymerase-Kettenreaktion (PCR) eine HCV-Virämie nachgewiesen. Bei 8/15 fanden sich anti-GOR-Antikörper, die als Zeichen der HCV-assoziierten Autoimmunreaktion zu werten sind. Die HCV-RNA-Spiegel waren nach Behandlung mit -IFN in fünf Fällen deutlich zurückgegangen und in einem Fall verschwunden. Zu einer änderung der anti-HCV Antikörper (Chiron ELISA und RIBA II) kam es während der sechsmonatigen Behandlung mit -IFN jedoch nicht. Die Ergebnisse unterstützen die Annahme einer ätiopathogenetischen Beziehung zwischen HCV-Infektion und gemischter Kryoglobulinämie. Möglicherweise stellt -IFN eine gezielte Therapie bei dieser Krankheit dar.

     

Hepatocellular carcinoma in HIV-infected patients with chronic hepatitis C

OBJECTIVES: Chronic hepatitis C is frequently seen in HIV-positive subjects infected through needle sharing or transfusion of contaminated blood products. Progression to end-stage liver disease seems to occur faster in these patients. As the life expectancy of HIV-infected persons has dramatically improved since the introduction of highly active antiretroviral therapies, cirrhosis and eventually hepatocellular carcinoma (HCC) may be recognized at an increasing rate in patients coinfected with HIV and hepatitis C virus (HCV). METHODS: We identified the main features of HIV-infected individuals with end-stage liver disease due to HCV infection and diagnosed with HCC in three HIV/AIDS referral centers, and compared these features to those of a control group of patients with HCV-related HCC but without HIV infection. RESULTS: Seven HIV-infected patients were identified. Of these, six were <45 yr of age and had been intravenous drug users. The mean time between exposure to HCV and the development of HCC was estimated to be 17.8 yr. Two subjects were coinfected with hepatitis B and delta viruses, respectively. Only one individual had been diagnosed of an AIDS-defining condition before the diagnosis of HCC was made. However, all subjects had < 500 CD4+ T cells at the time of HCC diagnosis. Five died within the first 4 months of follow-up. Patients in the control group (n = 31) were significantly older (68.9 +/- 8.9 vs 42.2 +/- 10.4; p < 0.001) and the duration of HCV infection was significantly longer (28.1 +/- 10.9 vs 17.8 +/- 2.7; p < 0.05) than in those with HIV-HCV coinfection. CONCLUSIONS: HCC seems to occur at a younger age and after a shorter period of HCV infection in subjects coinfected with HIV. Thus, treatment of CHC should be encouraged in HIV-positive patients, and in those with HCV-related cirrhosis the periodic monitoring of alpha-fetoprotein and abdominal ultrasonography should be recommended.     

A pilot study of rimantadine for patients with chronic hepatitis C unresponsive to interferon therapy

OBJECTIVE: Therapeutic options are limited for chronic hepatitis C patients who have not responded to a course of interferon therapy. Recently, a 6-month course of amantadine was shown to result in a sustained virological response in chronic hepatitis C patients who were unresponsive to interferon therapy. The aim of this study was to evaluate the effect of rimantadine on chronic hepatitis C patients who had not responded to interferon therapy. METHODS: This was an open label trial involving 17 patients who were treated with rimantadine 100 mg b.i.d. for 6 months. Changes in serum aminotransferase activities and HCV-RNA levels were determined. RESULTS: Mean alanine aminotransferase activities and HCV RNA levels did not change significantly during therapy. HCV RNA remained detectable in all patients throughout therapy. Neurologic symptoms (headaches, nervousness, and dizziness) developed in 29% of patients. A total of 12% of patients required dose reduction after 12 wk of therapy because of dizziness. CONCLUSION: Rimantadine has no significant antiviral activity against HCV.     

Long-term follow up of chronic hepatitis C patients after alpha-interferon treatment: a functional study

AIM: To evaluate the long-term functional outcome of chronic hepatitis C (CHC) patients treated with interferon (IFN) therapy. METHODS: Thirty-six patients with CHC were followed up for a mean of 36 months (+/- 19, SD) after a course of IFN therapy. Biochemical, virological (qualitative hepatitis C virus (HCV)-RNA and HCV genotype), and functional (monoethylglycinexylidide (MEGX) test) evaluations were carried out at the time of liver biopsy. Patients were divided into long-term responders (LTR), relapsers (RR), or non-responders (NR) according to IFN therapy outcome. At the end of follow up, patients were non-invasively re-evaluated by means of biochemistry, qualitative HCV-RNA, MEGX test, and liver ultrasonography. RESULTS: A significant decrease in MEGX values was observed in all patients. However, when patients were examined according to treatment outcome, only NR and RR showed a significant decrease in liver function as compared to pretreatment levels (MEGX30, 80.5 +/- 26.8-62.9 +/- 24.2 ng/mL, P< 0.01; MEGX60, 72.9 +/- 18.1-60.5 +/- 19.7 ng/mL, P< 0.05; MEGXAUC, 3,816 +/- 1,243-3,095 +/- 1,205 ng/mL per h, P< 0.05). On the contrary, LTR patients showed no significant modifications in MEGX values at each sampling time (MEGX,5, 72.9 +/- 31.4-70.3 +/- 29.7 ng/mL; MEGX30, 84.0 +/- 27.6-71.5 +/- 21.8 ng/ mL; MEGX60, 69.5 +/- 26.8-63.2 +/- 14.4 ng/mL; MEGXAUC 4028 +/- 1,378-3,620 +/- 1,041 ng/mL per h). At the end of follow up, LTR patients showed normal liver biochemistry and negativity of serum HCV-RNA, while NR and RR patients showed a significant decrease in platelets. CONCLUSIONS: In CHC patients long-term response to IFN therapy, besides favoring positive clinical and virologic long-term outcome, results in maintaining preserved liver function. Furthermore, IFN therapy seems to determine a decrease in the rate of functional disease progression, even in NR and RR. The MEGX test may be considered as a useful tool for performing serial follow up of CHC patients.     

Long-term follow-up of patients with chronic hepatitis C treated with alpha-interferon.

We reanalyzed the results of a pilot study of recombinant alpha-interferon therapy for chronic non-A, non-B hepatitis in light of the recent discovery of the hepatitis C virus and the development of diagnostic assays for this agent. Stored serum samples from 10 patients treated between 1984 and 1986 were tested for antibody to hepatitis C virus and hepatitis C virus RNA before, during and after therapy. In addition, the current clinical, serum biochemical and virological statuses of these patients were evaluated to determine the long-term effects of interferon therapy. All patients had evidence of hepatitis C virus infection, with hepatitis C viral RNA, antibody to hepatitis C virus or both markers detectable in serum. Serum hepatitis C virus RNA was found to disappear in seven of eight patients whose aminotransferase levels became normal with interferon therapy but remained present in two patients who did not respond to therapy. Levels of hepatitis C virus RNA decreased and disappeared when serum aminotransferases fell to normal levels but rose with subsequent elevation of aminotransferase levels in two patients who had relapses in disease when interferon was stopped. During a follow-up of 3 to 6 yr, hepatitis C virus RNA remained undetectable in the six patients whose serum aminotransferase levels remained normal after interferon therapy. However, neither initial titers of hepatitis C virus RNA nor disappearance of viral RNA from serum during treatment predicted a sustained response. Thus long-term beneficial responses to alpha-interferon can occur in patients with chronic hepatitis C and are associated with sustained loss of hepatitis C virus RNA from serum.     

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

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

Eosinophilic enteritis observed during alpha-interferon therapy for chronic hepatitis C

We report a patient with chronic hepatitis C who developed eosinophilic enteritis while being treated with recombinant interferon α-2b. He had no history of either allergic disorders or recurring episodes of abdominal cramps, nausea, or diarrhea. He also had had a normal eosinophil count prior to the interferon treatment. After a 12-week course of interferon α-2b, he began to complain of severe abdominal pain, diarrhea, and abdominal fullness. His peripheral eosinophil count increased to 45% (absolute count, of 7610/μl). Abdominal ultrasonography and computed tomography revealed diffuse thickness of the intestinal wall with gross ascites that contained numerous eosinophils. An upper gastrointestinal barium study with small bowel follow-through showed an edematous mucosal layer of the jejunum and ileum. There was a spectacular relief of the patient's subjective symptoms after the administration of prednisolone. Follow-up studies revealed resolution of the ascites and the mucosal layer edema and normalization of the peripheral eosinophil count. Prednisolone was tapered off, but the eosinophilic enteritis did not recur. As there had been no evident exposure to common causative factors for eosinophilic enteritis, we suggest that interferon α-2b could thus have played a role in the triggering of the eosinophilic enteritis. Received: August 19, 1999 / Accepted: November 26, 1999     

Clearance of hepatitis C virus in HIV-infected patients with multiple chronic viral hepatitis

Viral interferences between hepatitis C (HCV) and hepatitis B (HBV) viruses were investigated in a case-control study conducted in 107 human immunodeficiency virus (HIV)-infected patients with HCV antibodies. Overall, 15 (68%) of 22 hepatitis B surface antigen (HBsAg)-positive patients had negative serum HCV-RNA while it occurred in only nine (10%) of 85 HBsAg-negative counterparts (P = 0.02). After adjusting for age, antiretroviral therapy, plasma HIV-RNA and CD4 counts, being HBsAg-positive was strongly associated with having negative serum HCV-RNA (odds ratio: 23; 95% confidence interval: 6-59; P < 0.001). Thus, HBV may favour the elimination of HCV in HIV-infected patients, which may influence liver disease and therapeutic decisions.     

Pharmacokinetics,efficacy and safety of daclatasvir plus asunaprevir in dialysis patients with chronic hepatitis C: pilot study

The aim of this study was to evaluate the pharmacokinetic profile of daclatasvir (DCV) and asunaprevir (ASV) dual therapy in haemodialysis patients infected with hepatitis C virus (HCV). Eighteen haemodialysis patients and 54 patients with normal renal function were treated with DCV and ASV dual therapy for 24 weeks. We evaluated the pharmacokinetic profiles of DCV and ASV and examined the rate of sustained virological response 12 weeks after the end of treatment (SVR₁₂) and incidence of adverse events during treatment of haemodialysis patients infected with chronic HCV genotype 1 infection. To adjust for potential differences in baseline characteristics between haemodialysis patients and patients with normal renal function, we used propensity scores case–control matching methods. Area under the plasma concentration time curve from 0 to 6 h (AUC_{0–6 h}) of DCV was slightly lower in haemodialysis patients than in patients with normal renal function (P > 0.6). AUC_{0–6 h} of ASV was significantly lower in haemodialysis patients (P = 0.012). SVR₁₂ rates were 100% (18/18) for haemodialysis and 96.2% (52/54) for patients with normal renal function. Changes in mean log₁₀ HCV RNA levels and viral response were higher in haemodialysis patients compared to patients with normal renal function. No discontinuations due to adverse events occurred. In conclusion, DCV and ASV dual therapy for HCV infection is effective and safe with similar results in haemodialysis patients compared to patients with normal renal function.     

High rate of sustained response to consensus interferon plus ribavirin in chronic hepatitis C patients resistant to alpha-interferon and ribavirin: a pilot study

Background: The aim of this study was to evaluate an alternative treatment (consensus interferon plus ribavirin) for chronic hepatitis C patients resistant to combined therapy. Methods: Fourteen patients previously resistant to interferon alpha plus ribavirin were consecutively assigned to receive 15 μg of consensus interferon plus ribavirin (1000 mg) daily for 4 weeks, and 9–15 μg every other day plus daily ribavirin for the following 44 weeks. Alanine aminotransferase and hepatitis C virus (HCV) RNA (Amplicor Monitor; Roche) levels were monitored during therapy and for 24 weeks after its completion. Results: A rapid and marked decrease of HCV RNA viremia of more than 2 logs was observed in 10 (71%) of 14 patients at week 2 of treatment. At the end of therapy, 10 (71%) of 14 patients had undetectable HCV RNA. The end-of-treatment response rates were 6 of 9 (67%) patients for genotype 1 and 4 of 5 (80%) for other genotypes. Sustained response was observed in 4 (36%) of 11 patients who completed 24 weeks of follow-up. Conclusions: A marked and rapid decrease of viral load was observed during therapy with high doses of consensus interferon plus ribavirin in patients previously resistant to combined therapy, even in those infected with genotype 1. Of 11 patients who completed the post-treatment follow-up, 36% presented a sustained response. Received July 23, 2001 / Accepted: January 25, 2002 Reprint requests to: S.K. Ono-Nita Editorial on page 766     

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study

Background/Aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination.Methods: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3′TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction.Results: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance).Conclusions: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotheraphy appears disappointing, and other treatment strategies should be investigated.