Editorial Board: Emmet B. Keeffe, MD (Chair); Anna Lok, MD; Brian McMahon, MD; Albert Min, MD; Myron Tong, MD; Naoky Tsai, MD; Bruce Tung, MD
HBV Watch^™
Timely Information for Practicing Physicians

JULY 2005

LIVER TRANSPLANTATION

Prophylaxis of HBV recurrence. Alfredo Marzano and colleagues retrospectively analyzed 22 HBsAg-positive patients with cirrhosis who developed YMDD mutation while on lamivudine therapy prior to liver transplantation (LT). Of these, 13 patients had a rebound of serum HBV DNA to > 5 log₁₀ copies/mL (phenotypic resistance), and 9 patients did not have phenotypic resistance but were found at the time of LT to have YMDD mutants in stored sera (genotypic resistance). Of the 13 patients with phenotypic resistance, 11 were treated with adefovir dipivoxil (ADV) 10 mg daily in addition to lamivudine and underwent LT after HBV DNA levels fell below 5 log₁₀ copies/mL. Following LT, prophylaxis with ADV, lamivudine, and hepatitis B immunoglobulin (HBIG) were given. The 9 patients with genotypic resistance received lamivudine and HBIG after LT. During 35 months of post-LT follow-up, none of the 11 patients with phenotypic resistance who received ADV in addition to lamivudine and HBIG, and none of 7 patients with genotypic resistance only who received lamivudine and HBIG, had HBV recurrence. HBV recurred in 2 patients with phenotypic resistance within the first 2 months; these patients were not treated with ADV before surgery and underwent LT with an HBV DNA level >5 log₁₀ copies/mL, which likely exceeded the neutralizing capacity of HBIG. HBV also recurred in 2 patients with genotypic resistance only, both of whom stopped HBIG after LT. These results show that the addition of ADV can reduce HBV recurrence in patients with high viremic lamivudine-resistant HBV. An editorial by Anna Lok reviews this report and concludes that further studies are needed to determine the optimal HBIG dose after ADV is added and whether lamivudine therapy should be maintained. (Marzano A, et al. Liver Transpl. 2005;11:532–538; Lok ASF. Liver Transpl. 2005;11:490–493)

CHRONIC HBV INFECTION

Efficacy and safety of thymalfasin. Thymalfasin (thymosin alpha-1), an immune-modulating agent that enhances Th1 cytokine production and T-cell differentiation and maturation, is used in many countries around the world to treat chronic hepatitis B. S. Iino and others conducted a study in which 316 Japanese patients with chronic HBV were randomized to receive thymalfasin 0.8 or 1.6 mg for 24 weeks. At week 72, ALT normalization, HBV DNA clearance, and HBe antigen clearance were achieved in 36.4%, 30%, and 22.8% of patients in the 1.6 mg group, respectively. Similar results were observed in the 0.8 mg group. Patients were not stratified by liver biopsy results, and subsequent intragroup analysis showed that patients with advanced fibrosis had significantly better response rates with the 1.6 mg dose. Thymalfasin was tolerated well. All adverse reactions were mild, and most involved elevation of aminotransferase levels, most likely related to the immune effects of thymalfasin. These results suggesting that thymalfasin is effective therapy against chronic HBV infection need to be confirmed in a controlled study. In addition, studies of combination therapy with thymalfasin and interferon are underway to determine whether combination therapy will be superior to thymalfasin or interferon mono-therapy. (Iino S, et al. J Viral Hepat. 2005;12:300–306)

Long-term follow-up of peginterferon and lamivudine combination therapy. H.L. Chan and colleagues compared long-term treatment outcomes between HBeAg-positive patients who received 52 weeks of lamivudine monotherapy (n=47) and those who received combination therapy with 32 weeks of peginterferon alfa-2b plus 52 weeks of lamivudine (n=48). At the end of treatment, HBeAg loss occurred in 63% of patients in the combination group but in only 28% in the lamivudine group (P=0.001). Post-treatment follow-up intervals were 124 ± 29 and 117 ± 34 weeks for the patients in the monotherapy and combination therapy groups, respectively. The probability of sustained response (defined as HBeAg loss and HBV DNA <100,000 copies/mL) was greater with combination therapy than with monotherapy: rates of sustained response in the respective groups were 33% vs 13% at 24 weeks, 31% vs 11% at 52 weeks, and 29% vs 9% at 76 weeks after cessation of treatment (P=0.0015). None of the sustained responders developed biochemical relapse during follow-up. These findings demonstrate that combination peginterferon and lamivudine therapy resulted in a higher rate of long-term sustained response than did lamivudine monotherapy. (Chan HL, et al. Hepatology.2005;41:1357–1364)

Prognostic determinants. M.F. Yuen and colleagues monitored 3,233 Chinese patients with chronic HBV for a median of 46.8 months to determine risk factors for the development of complications in Asian HBV patients. They observed that patients with serum ALT levels of 0.5 to 2 times ULN had an increased risk for complications as compared with patients with ALT levels < 0.5 times ULN (P<0.0001). Design flaws in this study include the short period of follow-up (mean, 30 months), absence of histologic data, cross-sectional analysis of HBV DNA, definition of exacerbation as ALT >1.5 times ULN, lack of available HBV DNA results at presentation, and lack of an analysis of the impact of treatment. In addition, most patients who had high serum ALT levels at baseline did not have persistently high levels during follow-up. Thus, the conclusion that serum ALT level at baseline is predictive of the development of complications in Asian patients with chronic HBV requires further, well-designed, confirmatory studies. (Yuen MF, et al. Gut. 2005; Epub ahead of print)

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