AIM： To explore mutations around the interferon sensitivity-determining region （ISDR） which are associated with the resistance of hepatitis C virus lb （HCV-lb） to interferon-α treatment. METHODS： Thirty-seven H...AIM： To explore mutations around the interferon sensitivity-determining region （ISDR） which are associated with the resistance of hepatitis C virus lb （HCV-lb） to interferon-α treatment. METHODS： Thirty-seven HCV-lb samples were obtained from Hong Kong patients who had completed the combined interferon-α/ribavirin treatment for more than one year with available response data. Nineteen of them were sustained virological responders, while 18 were non-responders. The amino acid sequences of the extended ISDR （eISDR） covering 64 amino acids upstream and 67 amino acids downstream from the previously reported ISDR were analyzed. RESULTS： One amino acid variation （I2268V, P = 0.023） was significantly correlated with treatment outcome in this pilot study with a limited number of patients, while two amino acid variations （R2260H, P = 0.05 and $2278T, P = 0.05） were weakly associated with treat- ment outcome. The extent of amino acid variations within the ISDR or eISDR was not correlated with treat- ment outcome as previously reported. CONCLUSION： Three amino acid mutations near but outside of ISDR may associate with interferon treatment resistance of HCV-lb patients in Hong Kong.展开更多
There are cases of hepatitis involving occult hepatitis B virus(HBV)infection in which,even though the HB surface antigen(HBsAg)is negative,HBV-DNA is detected by a polymerase chain reaction(PCR).We con-ducted a seque...There are cases of hepatitis involving occult hepatitis B virus(HBV)infection in which,even though the HB surface antigen(HBsAg)is negative,HBV-DNA is detected by a polymerase chain reaction(PCR).We con-ducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-yearold female.A diagnosis of non-B non-C chronic hepatitis was made.Although HBV markers,such as HBs antibody(anti-HBs),anti-HBc,HBeAg and anti-HBe,were negative,HBV-DNA was positive.Nested PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested PCR.Sequence analysis of the two obtained bands was conducted by direct sequencing.Compared with the control strains,the ATG(Methionine)start codon in the X region had mut ated to GTG(Valine).It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection.展开更多
To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders t...To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODSSequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTSFor both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.展开更多
基金Supported by The National Key Technology Research and Development Program of China, No. 2009ZX10004-104
文摘AIM： To explore mutations around the interferon sensitivity-determining region （ISDR） which are associated with the resistance of hepatitis C virus lb （HCV-lb） to interferon-α treatment. METHODS： Thirty-seven HCV-lb samples were obtained from Hong Kong patients who had completed the combined interferon-α/ribavirin treatment for more than one year with available response data. Nineteen of them were sustained virological responders, while 18 were non-responders. The amino acid sequences of the extended ISDR （eISDR） covering 64 amino acids upstream and 67 amino acids downstream from the previously reported ISDR were analyzed. RESULTS： One amino acid variation （I2268V, P = 0.023） was significantly correlated with treatment outcome in this pilot study with a limited number of patients, while two amino acid variations （R2260H, P = 0.05 and $2278T, P = 0.05） were weakly associated with treat- ment outcome. The extent of amino acid variations within the ISDR or eISDR was not correlated with treat- ment outcome as previously reported. CONCLUSION： Three amino acid mutations near but outside of ISDR may associate with interferon treatment resistance of HCV-lb patients in Hong Kong.
文摘There are cases of hepatitis involving occult hepatitis B virus(HBV)infection in which,even though the HB surface antigen(HBsAg)is negative,HBV-DNA is detected by a polymerase chain reaction(PCR).We con-ducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-yearold female.A diagnosis of non-B non-C chronic hepatitis was made.Although HBV markers,such as HBs antibody(anti-HBs),anti-HBc,HBeAg and anti-HBe,were negative,HBV-DNA was positive.Nested PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested PCR.Sequence analysis of the two obtained bands was conducted by direct sequencing.Compared with the control strains,the ATG(Methionine)start codon in the X region had mut ated to GTG(Valine).It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection.
基金Supported by“Consejería de Salud de la Junta de Andalucía”,No.PI0137/07“Instituto de Salud CarlosⅢ”,No.FISIntrasalud PI010/717
文摘To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODSSequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTSFor both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSIONThe obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.
