Hepatitis C virus genotype 6:Virology,epidemiology,genetic variation and clinical implication

Hepatitis C virus(HCV)is a serious public health problem affecting 170 million carriers worldwide.It is a leading cause of chronic hepatitis,cirrhosis,and liver cancer and is the primary cause for liver transplantation worldwide.HCV genotype 6(HCV-6)is restricted to South China,South-East Asia,and it is also occasionally found in migrant patients from endemic countries.HCV-6 has considerable genetic diversity with23 subtypes(a to w).Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping,there are also now rapid genotyping tests available such as the reverse hybridization line probe assay(INNO-LiPAⅡ;Innogenetics,Zwijnaarde,Belgium).HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes.Based on current evidence,the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk,although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response.In addition,the development of direct-acting antiviral agents is ongoing,and they give high response rate when combined with standard therapy.Herein,we review the epidemiology,classification,diagnosis and treatment as it pertain to HCV-6.

Hepatitis E virus infection: Epidemiology and treatment implications

Hepatitis E virus(HEV) infection is now established as an emerging enteric viral hepatitis. Standard treatments in acute and chronic hepatitis E remain to be established. This study undertakes a review of the epidemiology, treatment implication and vaccine prevention from published literature. HEV infection is a worldwide public health problem and can cause acute and chronic hepatitis E. HEV genotypes 1 and 2 are primarily found in developing countries due to waterborne transmission, while the zoonotic potential of genotypes 3 and 4 affects mostly industrialized countries. An awareness of HEV transmission through blood donation, especially in the immunocompromised and solid organ transplant patients, merits an effective anti-viral therapy. There are currently no clear indications for the treatment of acute hepatitis E. Despite concerns for side effects, ribavirin monotherapy or in combination with pegylatedinterferon alpha for at least 3 mo appeared to show significant efficacy in the treatment of chronic hepatitis E. However, there are no available treatment options for specific patient population groups, such as women who are pregnant. Vaccination and screening of HEV in blood donors are currently a global priority in managing infection. New strategies for the treatment and control of hepatitis E are required for both acute and chronic infections, such as prophylactic use of medications, controlling large outbreaks, and finding acceptable antiviral therapy for pregnant women and other patient groups for whom the current options of treatment are not viable.

Characteristics and outcomes of cholangiocarcinoma by region in Thailand: A nationwide study

AIM To identify the potential risk factors of cholangiocarcinoma, we determined the characteristics of cholangiocarcinoma patients among 5 different regions of Thailand. METHODS All patients diagnosed with cholangiocarcinoma between 2008 and 2013 were identified using the Nationwide Hospital Admission Data registry(n = 39421). Baseline characteristics, comorbidities and survival were abstracted. RESULTS The annual incidence during the study period was stable in all regions. Most patients lived in the Northeast(62.8%), followed by the North(16.9%), Central(12.3%), Bangkok(5.4%), and South(n = 2.6%) regions(P < 0.0001). Significantly more cholangiocarcinoma patients had diabetes, cirrhosis, and chronic viral hepatitis B/C infection than noncholangiocarcinoma participants(diabetes: 11.42% vs 5.28%; cirrhosis: 4.81% vs 0.92%; hepatitis B: 0.74% vs 0.12%; and hepatitis C: 0.50% vs 0.10%, P < 0.0001 for all, respectively). The overall 1-year mortality rate was 81.7%, with a stable trend over time. CONCLUSION Diabetes and chronic liver diseases may be associated with cholangiocarcinoma in the Thai population.

Risk factors and molecular characterization of acute sporadic symptomatic hepatitis E virus infection in Thailand

Objective:To report clinical outcomes and viral genotypes of acute symptomatic hepatitis E virus(HEV)infection in Thailand.Methods:Forty patients with acute symptomatic HEV infection were recruited during 2009-2013.Clinical,demographic and laboratory data were collected.Diagnosis was accomplished by detection of anti-HEV IgM and/or HEV RNA in the serum or stool.HEV genotypes were classified by direct sequencing of RT-PCR products and phylogenetic analysis.Results:The high risk group,comprising immune-compromised,liver cirrhosis and very elderly(>80 years)patients(17 cases),had higher levels of serum alkaline phosphatase at presentation compared with the low risk group.Two fatal cases resulted from acute hepatitis E in the high risk group,initial clinical presentation did not show statistically significant differences.In six cases(6/40),the virus could be detected in serum or stool by RT-PCR and sequencing.Upon molecular characterization,the viruses were classified as HEV genotype 3f and were in the same cluster as Thai swine HEV.Conclusions:Our data showed that acute HEV infection has various clinical presentations and outcomes.Higher levels of serum alkaline phosphatase were observed in high risk patients.All isolated viruses were identified as HEV genotype 3f possibly originating from swine.

Early viral kinetics during hepatitis C virus genotype 6 treatment according to IL28B polymorphisms

AIM:To investigate the early viral kinetics and interleukin-28B(IL28B)polymorphisms of hepatitis C genotype6 during pegylated interferon and ribavirin therapy.METHODS:Sixty-five patients with chronic hepatitis C virus(HCV)infection treated with pegylated interferon and ribavirin(PEG-IFN/RBV)were included,of whom15(23.1%),16(24.6%)and 34(52.3%)patients were infected with hepatitis C genotype 1(HCV-1),genotype3(HCV-3)and genotype 6(HCV-6),respectively.Serum HCV-RNA levels were measured frequently during the first 4-wk of therapy.DNA extracted from samples was analyzed for the IL28B single nucleotide polymorphism(SNP)rs12979860 by polymerase chain reaction and direct sequencing.RESULTS:During the first 4-wk of therapy,the mean viral decline for patients with HCV-6(5.55±1.82 log10IU/mL)was comparable to that of patients with HCV-3(5.55±1.82 log10IU/mL vs 5.86±1.02 log10IU/mL,P=0.44)and was significantly higher than patients with HCV-1(5.55±1.82 log10IU/mL vs 4.23±1.99 log10IU/mL,P=0.04).In the HCV-6 group,the first phase(days 0-2)viral decline was significantly higher in patients with the favorable rs12979860 CC than non-CC genotypes(2.46±1.01 log10IU/mL/wk vs 1.70±0.67 log10IU/mL,respectively,P=0.045).A statistically insignificant decrease in the second-phase(days 7-28)decline was also found in patients with the CC genotype than those with the non-CC genotype,though not significantly different(1.24±0.64 log10IU/mL/wk vs 0.80±0.65 log10IU/mL/wk,respectively,P=0.172).At baseline,the SNP genotype was an independent predictor of rapid virological response but not of sustained virological response.CONCLUSION:The IL28B genotype was linked to an impact on early viral kinetics in response to PEG-IFN/RBV therapy in HCV-6 infected patients.

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease:Results from the Thai Association for the Study of the Liver(THASL)DILI Registry

Background and Aims:The impact of drug-induced liver injury(DILI)on patients with chronic liver disease(CLD)is unclear.There are few reports comparing DILI in CLD and non-CLD patients.In this study,we aimed to determine the incidence and outcomes of DILI in patients with and without CLD.Methods:We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies,causes,and the severity of DILI.We compared the causative agents,clinical features,and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry.Subjects with definite,or highly likely DILI were included in the analysis.Results:A total of 200 subjects diagnosed with DILI were found in the registry.Of those,41 had CLD and 159 had no evidence of CLD in their background.Complementary and alternative medicine(CAM)products were identified as the most common class of DILI agents.Approximately 59%of DILI in the CLD and 40%in non-CLD group were associated with CAM use.Individuals with pre-existing CLD had similar severity including mortality.Twelve patients(6%)developed adverse outcomes related to DILI including seven(3.5%)deaths and five(2.5%)with liver failure.Mortality was 4.88%in CLD and 3.14%in non-CLD subjects over median periods of 58(8–106)days and 22(1–65)days,respectively.Conclusions:In this liver disease registry,the causes,clinical presentation,and outcomes of DILI in subjects with CLD and without CLD patients were not different.Further study is required to confirm our findings.