Influence of Host and Viral Factors on Patients with Chronic Hepatitis C Virus Genotype 6 Treated with Pegylated Interferon and Ribavirin: A Systematic Review and Meta-Analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis of the influence of host and viral factors on the sustained virologic response (SVR) in hepatitis C virus genotype 6 (HCV-6) patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV). METHODS: Data were retrieved from Medline, Embase, PubMed and the Cochrane Library for 'genotype 6' studies published up to December 2014 and for abstracts from international scientific meetings. Inclusion criteria were efficacy of PEG-IFN+RBV based on SVR, 24- or 48-week therapy and treatment-naïve patients. Patients with hepatitis B, D and E and HIV coinfection or another concurrent liver disease were excluded. Pooled standard difference, odds ratio and confidence intervals (CIs) were calculated using a random-effect model with STATA 11. RESULTS: Fourteen studies were included in the meta-analysis. The pooled SVR rate was 80% (95% CI: 0.78-0.83, p < 0.0001; I2 = 71.2%). SVR of the PEG-IFN+RBV-treated HCV-6 patients was markedly higher than that of HCV-1 patients (80.1 vs. 55.3%). The SVR rate was significantly higher for the 48- than the 24-week treatment, but not different among HCV-infected patients with rs12979860 and ss469415590 polymorphisms of the ILFN4 gene (80.6% CC vs. 66.7% non-CC, p = 0.593; 81.1% TT/TT vs. 60% non-TT/TT, p = 0.288). Gender and type of PEG-IFN did not affect SVR rates. CONCLUSIONS: Treatment outcomes for HCV-6 patients are superior to those for HCV-1 patients and comparable to those of HCV-2 and HCV-3 patients, especially at 48 weeks. The level of fibrosis affects treatment outcome, but SVR rates are not significantly different between genders. IL28B and IFNL4 polymorphisms are not significantly associated with HCV-6 treatment outcome.

The correlation between hepatitis C core antigen and hepatitis C virus RNA levels with respect to human immunodeficiency virus status, hepatitis C virus genotype and interferon-lambda-4 polymorphism.

OBJECTIVES: Serum hepatitis C virus (HCV) core antigen (HCVcAg) concentrations correlate with HCV RNA levels in HCV monoinfected patients. Data in HCV/HIV coinfected patients are still limited. We aim to compare the use of HCVcAg measurement with respect to HIV status, HCV genotypes, interferon-lambda-4 (IFNL4) polymorphism and clinical parameters. METHODS: We analyzed an untreated cohort of 104 patients with HCV monoinfection and 85 patients with HCV/HIV coinfection. Serum HCVcAg was measured by a commercial chemiluminescent microparticle immunoassay. The presence of IFNL4 polymorphism ss469415590 was identified by real-time PCR. RESULTS: log10 HCVcAg levels were significantly correlated with corresponding log10 HCV RNA levels (r = 0.889, p < 0.001), but not with ALT levels and liver stiffness. The correlation between HCV RNA and HCVcAg was particularly high in coinfected patients and those with high viremia. Mean log10 HCVcAg concentration was significantly higher in coinfected patients than in monoinfected patients. Patients harboring the TT/TT genotype of ss469415590 had significantly higher levels of log10 HCVcAg than those with the non-TT/TT genotype. HCVcAg levels were similar across HCV genotypes. CONCLUSIONS: HCVcAg concentrations had an excellent correlation with HCV RNA levels, particularly in HCV/HIV-coinfected individuals and might be associated with IFNL4 polymorphism. HCVcAg testing could be used as an alternative to HCV RNA assays in resource-limited settings.

IFNL3 (IL28B) and IFNL4 polymorphisms are associated with treatment response in Thai patients infected with HCV genotype 1, but not with genotypes 3 and 6.

Recent studies have shown an association between single nucleotide polymorphisms (SNPs) in the interferon lambda-3 (IFNL3 or IL-28B) and IFNL4 genes and treatment response to hepatitis C virus genotype 1 (HCV-1) infection. The importance of these SNPs for HCV genotype 3 (HCV-3), and particularly HCV genotype 6 (HCV-6), remains to be elucidated. We analyzed a cohort of 225 Thai individuals with chronic HCV infection treated with pegylated-interferon and ribavirin, of whom 69 (30.7%), 114 (50.7%) and 42 (18.6%) patients were infected with HCV-1, HCV-3, and HCV-6, respectively. DNA extracted from blood samples was analyzed for the SNPs rs12979860 and ss469415590. The distribution of CC, CT, and TT genotypes of rs12979860 was 189 (84%), 28 (12.4%) and 8 (3.6%), respectively, while the distribution of TT/TT, ΔG/TT, and ΔG/ΔG genotypes of ss469415590 was 192(85.3%), 28(12.5%), and 5(2.2%), respectively. Significantly lower frequencies of the favorable genotypes CC (for rs12979860) and TT/TT (for ss469415590) were found in the HCV-1 group in comparison with the other groups. The favorable genotypes were associated significantly with rapid and sustained virological response in the HCV-1 group. However, they were only associated with rapid virological response in the HCV-3 and HCV-6 groups. Furthermore, both SNPs were associated equally with the treatment outcome in the HCV-1 group. In contrast, the role of these SNPs in predicting treatment response was attenuated in the HCV-3 and HCV-6 groups. Thus, identification of these SNPs may be useful only in patients with refractory HCV-1 infection.

Correlation of Serum Transaminase Levels with Liver Fibrosis Assessed by Transient Elastography in Vietnamese Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a cause of chronic liver disease, often resulting in liver cirrhosis, portal hypertension, and hepatocellular carcinoma damaging outcomes. Alanine transaminase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury. Several studies have demonstrated that high ALT levels are correlated with higher nonalcoholic steatohepatitis (NASH) risk. The aim was to determine the correlation of serum alanine aminotransferase and aspartate transaminase with liver stiffness in Vietnamese patients with NAFLD. PATIENTS AND METHODS: The study included 18 to 80 years old patients diagnosed with fatty liver on ultrasound at the University of Medical Center (UMC) liver clinic. Liver stiffness was measured using transient elastography. The histopathological, demographic, and laboratory data of the participants were also collected. The baseline and clinical characteristics of NAFLD patients were stratified by serum ALT levels. RESULTS: There were 138 NAFLD patients, including 82 men (59.4%) and 56 women (40.6%) (mean ± SD age of 41 ± 11 years). Liver fibrosis (F0) between the two groups showed no significant difference (p = 0.469). Similarly, no difference was found in the mild fibrosis level (F2) of the two groups of patients (p = 0.371). ALT level was significantly higher in NAFLD patients with advanced fibrosis (F3, F4) (3.2% vs 15.9%, p = 0.0013; 3.2% vs 13.2%, p = 0.0047, respectively). NAFLD patients with mild to moderate fibrosis (F1-F2) were detected at 59 U/L cut-off value with 67% sensitivity and 51% specificity. However, severe fibrosis and/or cirrhosis patients (F3-F4) had a cut-off value of 81 U/L with 53% sensitivity and 67% specificity in patients. CONCLUSION: Using ALT level as a marker for severe NAFLD would consider high-risk patients as mild cases, even though there is still the risk of progressive and severe hepatic disease. Our study underlines the small contribution of ALT as an independent factor for detecting NAFLD severity.

Factors associated with the severity of hypertriglyceridemia induced acute pancreatitis.

ABSTRACT: Hypertriglyceridemia induced acute pancreatitis (HTGP) was associated with increased risk of local complications, recurrent acute pancreatitis (AP), the frequency of other complications, and its high mortality as compared to other causes. Determining the factors associated with the severity of HTGP was necessary and important in the management of patients with AP.This study aims to examine the clinical and biochemical characteristics of HTGP patients, and to determine the factors associated with the severity of HTGP according to the revised Atlanta classification.This retrospective and prospective study enrolled 157 HTGP patients from January 2016 to May 2019 at Cho Ray Hospital who had serum TG levels measured within the first 48 hours of admittance with a TG concentration ≥ 1000 mg/dL and excluded other causes. The clinical features and outcomes of patients with HTGP were determined in terms of demographics, clinical symptoms, laboratory data, system complications, local complications, disease severity, and length of hospital stay. The primary outcome was the severity of HTGP as based according to the revised Atlanta classification. We evaluated the relationship between general information, clinical factors and laboratory data in the study population.There were 157 HTGP patients participated in this study. Patients with HTGP had evidence of obese or overweight range (61.2%), history of diabetes mellitus (32.5%) or undiagnosed diabetes (28.0%), history of AP (35.7%), alcohol use (23.6%), hypertension (15.9%), dyslipidemia (13.4%). The patients had typical symptoms of AP, including pancreatic abdominal pain (upper abdominal pain) (93%), nausea/vomiting (80.9%), fever (59.2%), distension abdomen (84.7%), and resistance of abdominal wall (24.8%). The severity of HTGP was significantly associated with fever, altered mental status, rapid pulse, and hypotension (P < .05). Patients with severe HTGP had significantly more pancreatic necrosis, higher values of Blood urea nitrogen and creatinine, longer prothrombin time and activated partial thromboplastin time on admission and higher CRP48 than not severe HTGP (P < .05).The severity of HTGP was significantly related to clinical factors including fever, altered mental status, rapid pulse, hypotension, and pancreatic necrosis. The value of Blood urea nitrogen, creatinine, prothrombin time, and activated partial thromboplastin time at admission is higher and longer in the severe AP group with P < .05.

Effectiveness of educational intervention carried out by clinical pharmacists for the quality of life of patients with irritable bowel syndrome: A randomized controlled trial.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is associated with repetitive gastrointestinal symptoms that greatly reduce the patient's quality of life (QoL). Training regarding IBS-related knowledge, medication adherence, lifestyle, and diet adjustments has been demonstrated to strengthen patient QoL. The aim of this study was to evaluate the effectiveness of an educational intervention carried out by clinical pharmacists to improve the QoL of patients with IBS. METHODS: Our research included data collected at the University Medical Center, Ho Chi Minh City, from April 2018 to December 2018, and was designed as a randomized controlled clinical trial. Patients with IBS were randomized into an intervention group (IG) and nonintervention group (NIG). The intervention program included training about IBS-related knowledge, the importance of medication adherence, symptom recognition, lifestyle, and diet adjustments. Participants were followed up by monthly telephone calls. The outcome was the change in patient QoL scores (IBS-QoL) 8 weeks after they took part in the research. RESULTS: Of 273 patients in the trial, there were 132 patients in the IG cohort and 141 in the NIG cohort. At 8 weeks, IG QoL score changes were statistically higher than those of NIG: 20.1 ± 12.1 (IG) versus 13.2 ± 13.4 (NIG). Furthermore, pharmacist intervention played an important role in increasing QoL after 8 weeks, as confirmed by multivariate regression analysis (B = 5.9; 95% confidence interval 2.4-9.4, P = 0.001). CONCLUSIONS: Patient education, lifestyle, and dietary intervention, administered by clinical pharmacists, improves IBS-QoL compared to standard medical therapy over 8 weeks.

Investigation of antibiotic use in patients with acute pancreatitis in a Vietnamese hospital.

BACKGROUND AND AIM: The aim of this study was to investigate the antibiotics used in patients with acute pancreatitis and evaluate their appropriateness. METHODS: We conducted a descriptive cross-sectional study on 136 patients aged 18 years or older who were diagnosed with acute pancreatitis and admitted to a national hospital in Ho Chi Minh City from January 2017 to December 2018. Medical records of patients were reviewed for data analysis, including epidemiological characteristics, pathological characteristics, treatment methods, and treatment effectiveness. RESULTS: There were 69.9% men and 30.1% women with a median age of 49.9 years. The most common etiologies included alcohol (21.3%), gallstones (23.6%), and hypertriglyceridemia (19.9%). The proportions of mild, moderate, and severe disease were 54.4, 39.0, and 6.6%, respectively. Antibiotics were given in 52.2% of patients. Although antibiotic prophylaxis was not recommended, 23.5% of cases used prophylactic antibiotics when there were no suspicion or evidence of infection. CONCLUSIONS: Our study suggests that it is necessary to optimize the appropriateness of antibiotic indications for patients with acute pancreatitis.

Awareness, knowledge, and practice for hepatitis B infection in Southeast Asia: a cross-sectional study.

INTRODUCTION: The prevalence of hepatitis B virus (HBV) infection in Southeast Asia is high. Awareness and early detection are essential for timely prevention and treatment. METHODOLOGY: We examined the awareness of, knowledge about, practices and views on treatment for HBV infection in Southeast Asia. A cross-sectional survey was conducted from December 2016 to February 2017 among individuals from six nations in Southeast Asia-Myanmar, Thailand, Vietnam, Cambodia, the Philippines, and Singapore. The study population comprised healthcare and non-healthcare personnel. RESULTS: In total, 799 healthcare personnel and 1079 non-healthcare personnel completed an online survey. The prevalence of the awareness of their own HBV infection status and risk of this regionally endemic infection was 85.6% (684/799) among healthcare personnel and 54.0% (583/1079) among non-healthcare personnel. Similarly, 85.9% of healthcare personnel and 45.5% of non-healthcare personnel had good knowledge about disease transmission, complications, and the need for treatment, and 76.6% of healthcare personnel and 39.8% of non-healthcare personnel followed good HBV infection-prevention practices. Overall, 90.6% found the idea of treatment acceptable. Awareness had a significant impact on both knowledge and practice scores among both healthcare personnel and non-healthcare personnel (p < 0.01) but without statistically significant differences in treatment acceptance between the two groups (p = 0.61). CONCLUSIONS: Awareness of HBV infection was relatively low among non-healthcare personnel in Southeast Asian populations. The provision of additional hepatitis B awareness campaigns is crucial to eliminating viral hepatitis in the region.

Prevalence of Thymine--Adenine Dinucleotide Repeat, IL28B and IFNL4 in Thai Population and Correlation with Spontaneous Clearance and Treatment Outcome of Hepatitis C Infection.

BACKGROUND: The interleukin-28B (IL28B) gene polymorphism is a strong baseline predictor of sustained virological response (SVR) in hepatitis C virus (HCV) treatment. The length of thymine--adenine dinucleotide repeats, or (TA)n, in the regulatory region of IL28B can affect interferon transcription. In order to determine predictive values in HCV infection, we explored the correlation among factors including (TA)n genotypes, clinical features, interferon-λ-3 (IFNL3) and interferon-λ-4 (IFNL4) polymorphisms, and HCV treatment outcome. METHODS: Sera from 492 patients with chronic HCV infection, 101 individuals with spontaneous HCV clearance and 123 healthy blood donors (control group) were analyzed. Genotyping of the (TA)n was performed by direct sequencing. The rs12979860 (IFNL3) was identified using nested PCR and sequencing, while ss469415590 (IFNL4) was identified by real-time PCR. RESULTS: The distribution of (TA)n was similar between individuals with spontaneous HCV clearance and chronic HCV infection, but differed significantly from healthy controls. Individuals with both (TA)n alleles ≥ 12 had significantly higher SVR rate compared to individuals with at least one (TA)n <12 allele. This strong correlation was seen for patients infected with HCV-1, HCV-3, and HCV-6. The (TA)n genotypes were not associated with HCV viral load, ALT levels and liver stiffness, but were correlated with platelet counts (p<0.001). In contrast, rs12979860 (CC) and ss469415590 (TT/TT) genotypes were associated with higher SVR rated only in patients with HCV-1. CONCLUSIONS: The (TA)n genotypes were not associated with spontaneous clearance of HCV infection but associated with treatment response in patients infected with HCV-1, HCV-3 and HCV-6. In contrast, IFNL3 and IFNL4 polymorphisms were predictive of treatment outcome only for patients infected with HCV-1.

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 with 23 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-LiPA II; 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.

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 genotype 6 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 whom 15 (23.1%), 16 (24.6%) and 34 (52.3%) patients were infected with hepatitis C genotype 1 (HCV-1), genotype 3 (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.