Effect of lamivudinein in BeAg-positive chronic hepatitis B: Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level

AIM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo.RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs 2, P = NS; groups 1 vs 3, P = 0.002; groups 1vs 4, P＜0.0001). HBV DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P = NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02;groups 1 vs 3, P = NS).CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.

Hepatitis C virus protease inhibitor-resistance mutations: Our experience and review

Direct-acting antiviral agents(DAAs)for hepatitis C virus(HCV)infection are one of the major advances in its medical treatment.The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States,Europe,and Japan.When combined with peginterferon plus ribavirin,these agents increase sustained virologic response rates to70%-80%in treatment-na?ve patients and previoustreatment relapsers with chronic HCV genotype 1 infection.Without peginterferon plus ribavirin,DAA monotherapies increased DAA-resistance mutations.Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future.However,it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases.Furthermore,these mutations exhibit cross-resistance to multiple drugs.The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown,and it is as yet uncertain whether such variants are sensitive to DAAs.We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors.Here,we reviewed the literature on resistance variants of HCV protease inhibitors in treatment na?ve patients with chronic HCV genotype 1,as well as our experience.

在有阴暗胃肠的流血的病人的囊内视镜检查法的计算图象修正的功效

AIM:To investigate whether flexible spectral color enhancement(FICE) improves diagnostic yields of capsule endoscopy(CE) for obscure gastro-intestinal bleeding(OGIB).METHODS:The study subjects consisted of 81 patients.Using FICE,there were three different sets with different wavelengths.Using randomly selected sets of FICE,images of CE were evaluated again by two individuals who were not shown the conventional CE reports and findings.The difference between FICE and conventional imaging was examined.RESULTS:The overall diagnostic yields in FICE sets 1,2,3 and conventional imaging(48.1%) were 51.9%,40.7%,51.9% and 48.1%,respectively,which showed no statistical difference compared to conventional imaging.The total numbers of detected lesions per examination in FICE imaging and conventional imaging were 2.5 ± 2.1 and 1.8 ± 1.7,respectively,which showed a significant difference(P = 0.01).CONCLUSION:The diagnostic yield for OGIB is not improved by FICE.However,FICE can detect significantly more small bowel lesions compared to conventional imaging.

Sofosbuvir treatment and hepatitis C virus infection

Hepatitis C virus(HCV) infection is a serious problem worldwide.The use of interferon-based therapy has made HCV eradication challenging.The recent appearance of direct-acting antiviral agents(DAAs) has changed HCV therapy.Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy.Furthermore,the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety.In particular,sofosbuvir,a nucleotide-based NS5 B inhibitor,prevents HCV RNA synthesis by acting as a "chain terminator".Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response.The current review summarizes the efficacy and safety of sofosbuvir therapy.

在有固执地正常的丙氨酸 aminotransferase 的丙肝病毒病人的 IL-28B 多型性和治疗反应

AIM:To examine the association between the interleukin 28B(IL-28B)genotype and treatment response in hepatitis C virus(HCV)-infected patients with persistently normal alanine aminotransferase(PNALT).METHODS:We compared the treatment response of HCV-infected patients with PNALT to that of patients with non-PNALT.Between February 2010 and April2013,278 patients infected with HCV were enrolled in this study.All of the patients were treated with peginterferon-alpha 2a or 2b plus ribavirin.In addition,180μg of peginterferon alpha-2a or 1.5μg/kg peginterferon alpha-2b per week plus weight-based ribavirin(600-1000 mg/d)were typically administered for 24 wk to HCV genotype 2-infected patients or for 48-72 wk to HCV genotype 1-infected patients.In all of the patients,the IL-28B rs8099917 genotype was determined using a TaqMan single-nucleotide polymorphism assay.HCV RNA was measured using the COBAS TaqMan HCV test.RESULTS:Female patients were dominant in the PNALT group(P【0.0001).Among 72 HCV genotype 1-infected patients with PNALT,the early virologic response(EVR)rates(P【0.01)and the sustained virologic response(SVR)rates(P【0.01)were higher in patients with the IL-28B TT genotype than in those with the IL-28B TG/GG genotype.In HCV genotype 1-infected patients with PNALT,multivariate logistic-regression analysis showed that SVR was independently predicted by the IL-28B rs8099917 TT type(P【0.05)and having an EVR(P【0.01).The IL-28B rs8099917 TT genotype strongly correlated with treatment response in HCV genotype 1-infected Asian patients with PNALT.CONCLUSION:The IL-28B genotype may be useful for selecting HCV genotype 1-infected patients with PNALT who should receive interferon-based treatment.

Severe hypercholesterolemia associated with primary biliary cirrhosis in a 44-year-old Japanese woman

A 44-year-old woman developed jaundice and was diagnosed as stage II of primary biliary cirrhosis (PBC). She showed a severely high total cholesterol level. This article focuses on atypical presentations of PBC and the need to test the total cholesterol level of PBC patients.

Prolonged acute hepatitis A mimicking autoimmune hepatitis

AIM: We report a case with a prolonged course of hepatitisA, with alanine aminotransferase (ALT) higher than 500 IU/Lfor more than 2 mo.METHODS: A middle-aged woman had an elevated IgG level of more than 2 000 mg/dL, positive arti-nudear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings were compatible with prolonged acute hepatitis, although acute onset of autoimmune hepatitis could not be ruled out.RESULTS: It was assumed that she developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis. Treatment with UDCAproved to be effective.

Platelet count and sustained virological response in hepatitis C treatment

AIM:To examine the epidemiological data,hematological safety and treatment responses of peginterferonalpha 2a plus ribavirin therapy for hepatitis C.METHODS:Between March 2008 and February 2011,196 hepatitis C virus(HCV)genotype 1 infected Japanese(127 treatment-naive and 69 treatment-experienced patients)patients treated with peginterferonalpha 2a plus ribavirin were enrolled.We examined the epidemiological data and treatment responses were retrospectively analyzed in terms of hematological safety.HCV RNA was measured by the COBAS TaqMan HCV test.RESULTS:Overall sustained virological response(SVR)rates of treatment-naive and treatment-experienced patients were 56% and 39%,respectively.Multivariate logistic regression analysis showed that SVR was attained independently of early virological response in both treatment-naive and treatment-experienced patients.SVR rates did not differ between the pretreatment hemoglobin < 13 g/dL and ≥ 13 g/dL groups.However,in treatment-naive patients,the SVR rate of the pretreatment platelet count < 130000/μL group was significantly lower than that of the pretreatment platelet count ≥ 130000/μL group.CONCLUSION:Attention should be paid to potential thrombocytopenia in the treatment of chronic hepatitis C patients.