Wait-listed (n ϭ 226) or post-liver transplantation (n ϭ 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (Ͻ1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively. Among posttransplantation patients, serum HBV DNA levels became undetectable in 40% and 65% at weeks 48 and 96, respectively. After 48 weeks, ALT, albumin, bilirubin, and prothrombin time normalized in 51%, 81%, 76%, and 56% of posttransplantation patients, respectively. Among wait-listed patients who underwent on-study liver transplantation, protection from graft reinfection over a median of 35 weeks was similar among patients who did (n ϭ 34) or did not (n ϭ 23) receive hepatitis B immunoglobulin (HBIg). Hepatitis B surface antigen was detected on the first measurement only in 6% and 9% of patients who did or did not receive HBIg, respectively. Serum HBV DNA was detected on consecutive visits in 6% and 0% of patients who did or did not receive HBIg, respectively. Treatment-related adverse events led to discontinuation of adefovir dipivoxil in 4% of patients. Cumulative probabilities of resistance were 0%, 2%, and 2% at weeks 48, 96, and 144, respectively. In conclusion, adefovir dipivoxil is effective and safe in wait-listed or posttransplantation CHB patients with lamivudine-resistant HBV and prevents graft reinfection with or without HBIg. Liver Transpl 13:349-360, 2007.

This study aimed to estimate the overall HCV genotype distribution and to reconstruct the HCV genotypespecific incidence in Greece during the recent decades. It also focused at the identification of genotype 4 subtype variability in Greek isolates. A total of 1686 chronically infected HCV patients with detectable serum HCV RNA by RT-PCR, belonging to different risk groups were studied. Amplified products from the 5¢-noncoding region were typed using a commercially available assay based on the reverse hybridization principle. The HCV genotype-specific incidence was estimated using a previously described back calculation method. HCV genotype 1 was the most prevalent (46.9%) followed by genotype 3 (28.1%), 4 (13.2%), 2 (6.9%) and 5 (0.4%). A high prevalence of genotype 1 (66.3%) in haemophilia patients was recorded whereas HCV genotype 3 was found mainly among patients infected by I.V. drug use (58.2%). Data on the temporal patterns of HCV genotype-specific incidence in Greece revealed a moderate increase (1.3-1.6 times) for genotypes 1 and 4, and a decrease (1.5 times) for genotype 2 from 1970 to 1990, whereas there was a sharp (13-fold) increase for genotype 3. The molecular characterization of 41 genotype 4 HCV isolates belonging to various risk groups revealed that, subtype 4a was the most frequently detected (78%). Phylogenetic comparison of the Greek 4a isolates with all HCV-4a isolates reported worldwide so far revealed a topology which does not discriminate Greek isolates from the others. HCV-4 does not represent a recent introduction in Greece.

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I nterferon alfa (IFN), lamivudine, and adefovir dipivoxil are the only approved treatments for chronic hepatitis B. IFN treatment has a moderate efficacy and frequent side effects, and is associated with an inconvenient 3-timesweekly dosing regimen. Lamivudine and adefovir have significant antiviral activity, although viral rebound after cessation of therapy and development of resistance after long-term lamivudine therapy are major clinical limitations.The new pegylated forms of IFN (pegylated interferon alfa-2a or 2b) are currently being evaluated among chronic hepatitis B patients. The benefit of conjugation of IFN with polyethylene glycol is the improvement of delivery of IFN by significantly prolonging its plasma halflife and thereby providing protracted activity, which allows once-per-week dosing. Results from trials among hepatitis B e antigen (HBeAg) (ϩ) or HBeAg (Ϫ) chronic hepatitis B patients indicate that treatment with pegylated interferon alfa-2a is superior to conventional interferon alfa-2a or lamivudine monotherapy. 1-3 The combination of pegylated interferon alfa-2a or alfa-2b and lamivudine was not found to improve sustained response rates over pegylated interferon monotherapy in HBeAg (Ϫ) or HBeAg (ϩ) chronic hepatitis B patients, respectively. 3,4 Mathematical modeling of the dynamics of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection during antiviral therapy has provided useful insight into viral replication, host cell death rate, and treatment efficacy. [5][6][7] In the last years, similar studies have been Abbreviations: IFN, interferon alpha; HCV, hepatitis C virus; HBV, hepatitis B virus; ALT, alanine aminotransferase; LMV, lamivudine; QD, daily; QW, once weekly. From the

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A 1700 base cDNA fragment coding for the putative structural gene(s) of hepatitis E virus (HEV) was inserted into the pATH 10 expression vector. The fusion protein (C2) expressed by this plasmid was found to contain epitopes recognized by anti-HEV antibodies. C2 protein was used in a Western blot format to examine its usefulness in detecting anti-HEV antibodies in well documented human cases of HEV and non-human primates infected with HEV. Both IgM and IgG anti-HEV could be detected in our Western blot assay. This Western blot assay was found not to detect antibodies from acute-phase sera from patients with either HAV or HBV. The C2 protein contains broadly cross-reactive epitopes, and the Western blot assay was able to detect anti-HEV antibodies in patient sera from Asia, Africa, and North America. The optimum serum dilution for the detection of both IgM and IgG was 1:25.