Mutation pattern of lamivudine resistance in relation to hepatitis B genotypes: hepatitis B genotypes differ in their lamivudine resistance associated mutation pattern.

Little is known about differences between individual hepatitis B genotypes and mutation patterns associated with lamivudine resistance. This study analyses the lamivudine-associated mutation pattern in relation to the four major HBV genotypes A-D. The PubMed database was screened for keywords "HBV OR Hepatitis B," "YMDD," "genotype," and "lamivudine"; all identified publications published till June 2009 were analyzed for differences in mutation pattern. To confirm the literature-based findings the databases of two reference laboratories in Tübingen (Germany), and Melbourne (Australia) were analyzed. Twenty-nine studies were identified reporting 827 patients with known hepatitis B genotype who underwent lamivudine treatment and developed resistance mutations. The literature data revealed that genotype A favors the rtM204V mutation unlike the other major genotypes (P<0.001), which corresponds to a significant difference in the mutation pattern of genotypes endemic in Asian countries and those found in the rest of the world. These significant findings of the literature-review could be reproduced in the analysis of the databases from Tübingen and Melbourne. Furthermore, the rtL180M mutation is significantly connected to the rtM204V mutation in genotypes A, B, and C, respectively. It is concluded that there is proof that HBV genotypes differ in their mutation pattern of lamivudine resistance. Future studies will need to evaluate whether this will translate into genotype-specific differences in resistance emergence on either entecavir or telbivudine as these antivirals differ in their mutation profile, rtM204V for entecavir and rtM204I for telbivudine.

Molecular and clinical characteristics of hepatitis B virus in Korea.

Korea is an endemic area of hepatitis B virus (HBV) infection but very little is known about the molecular characteristics of HBV isolates from Korean patients or the association with disease progression. The complete HBV genome sequences from 53 Korean patients with chronic hepatitis B, advanced cirrhosis, or hepatocellular carcinoma (HCC) were analyzed to identify (i) subgenotype distribution and genetic diversity and (ii) signature mutations associated with liver disease progression. With the exception of 1 patient infected with HBV/B, all 52 patients (98.1%) were infected with HBV/C, subgenotype C2. These strains were 98.4% identical and the frequency of amino acid substitutions occurring within key immunological epitopes increased with disease severity. A number of amino acid/nucleotide substitutions were associated with HCC, namely sR24K (HBsAg), SI126T (HBsAg), and pcA1846T (precore gene) mutations (P = 0.029, 0.001, and 0.008, respectively). HBV harboring deletions in the pre-S region were also associated with increased liver disease severity (chronic hepatitis B vs. cirrhosis, P = 0.040; chronic hepatitis B vs. HCC, P = 0.040). Despite the high degree of sequence conservation, several key HBV mutations were associated with disease progression. Prospective studies with larger cohorts of patients are required to evaluate further the clinical manifestation of HBV/C2 in Korea.

Kinetics of hepatitis C viral RNA and HCV-antigen during dialysis sessions: evidence for differential viral load reduction on dialysis.

Hepatitis C infection is a common problem in dialysis units. The prevalence ranges from 3% to more than 50%. Several reports have described a variable reduction of HCV-RNA during hemodialysis treatment sessions. But so far nothing is known about the HCV antigenemia or the kinetics of the reduction of HCV-RNA and HCV antigenemia during these sessions. HCV-RNA was monitored using the VERSANT HCV bDNA assay 3.0 (Bayer Healthcare Diagnostics, Leverkusen, Germany) or the HCV-Monitor TaqMan (Roche Diagnostics). HCV antigenemia was tested by using Ortho-trac-C assay (Ortho Clinical Diagnostics, Neckargemünd, Germany). Kinetics of HCV-RNA were available in 15 dialysis sessions measured by bDNA assay and in 5 dialysis sessions measured by rt-PCR. Quantitative HCV-antigenemia was available in fourteen dialysis sessions. Not only HCV-RNA but as expected also the HCV-antigenemia fell during the dialysis session. However, while the average reduction of HCV-antigen appears steady and linear, the level of HCV-RNA seems to be stable during the first 3 hr of dialysis, and decreases rapidly during the last 2 hr. The results seem to be independent of the HCV-RNA detection method. The different kinetics of HCV RNA and HCV antigen load suggest that there are different mechanisms responsible for the reduction of the HCV antigen and HCV-RNA, respectively. Reduction of viral load during dialysis session indicates a potential benefit of dialysis in case of HCV associated antiviral therapy.