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Introduction: Chronic hepatitis B (CHB) remains common in endemic regions, causing significant healthcare burden. Patients with CHB may need to be adherent to nucleoside analogue (NA) for a long period of time to prevent complications. This study aims to investigate the safety, efficacy and patient experience of a virtual monitoring clinic (VMC) in monitoring stable patients taking NA for CHB. Methods: Patients on NA and regular follow-up were randomised to either VMC alternating with doctors' clinic visit or to a control group in which they continued standard follow-up by doctors. Therapy adherence was measured by medication possession ratio (MPR) for NA therapy, incidence of virological breakthrough and hepatocellular carcinoma (HCC) development at two years of follow-up. Patient acceptance was measured on a Likert scale of 1–10. Results: A total 192 patients completed follow-up: 94 and 98 patients in the VMC and control groups, respectively. Mean age was 60.6 ± 10.8 years, with 95.3% Chinese ethnicity and 64.1% males. Age, gender, race, educational, employment and financial status were similar in both groups. Upon study completion, the majority of patients – 76 (80.9%) in VMC group and 74 (75.5%) in control group – had MPR ≥0.8; 88.8% were satisfied and rated VMC better than a traditional follow-up clinic with doctors only. More than 85% of patients rated ≥8/10 on the Likert scale for VMC, and preferred VMC over traditional clinic visits. Clinical outcomes observed were HCC development in one (1.1%) in the VMC group and four (4.1%) in the control group (p = 0.369). Two (2.1%) and one (1.0%) virological breakthroughs were observed in the VMC and control groups, respectively (p = 0.615). No incidence of HCC or abnormal blood tests were missed in the VMC arm. Discussion: VMC is a viable and safe clinical model for monitoring stable CHB patients on NA therapy without compromising patients' adherence to medications and is preferred by patients. [ABSTRACT FROM AUTHOR]

Background: Chronic hepatitis B (CHB) is endemic to Asia and is a leading cause of liver‐related morbidity. The prevalence of concomitant CHB and hepatic steatosis (HS) is increasing in Asia. Non‐invasive tests (NITs) including FIB‐4, NFS and APRI assess fibrosis in populations with a single aetiology, but not in subjects with concomitant CHB and HS. Aim: To explore the accuracy of NITs in predicting advanced fibrosis in patients with concomitant CHB and HS. Methodology: This multicentre study of CHB patients who underwent liver biopsy explored clinical characteristics of these subjects, stratified by presence of HS. Fibrosis scores from NITs were compared against histological fibrosis stage in CHB subjects with and without HS. Results: 2262 subjects were enrolled, 74.5% were males, and the mean age was 39.5 years ±11.8 SD. 984 (44.4%) had HS, 824 (36.4%) had advanced fibrosis. In the CHB group, the AUROC for advanced fibrosis were 0.65 (95% CI 0.62–0.69) for FIB‐4 and 0.63 (95% CI 0.60–0.66) for APRI. The specificities were 0.94 for FIB‐4 greater than 3.25 and 0.81 for APRI greater than 1.5. In the CHBHS group, the AUROC for advanced fibrosis were 0.67 (95% CI 0.63–0.71) for FIB‐4, 0.60 (95% CI 0.56–0.64) for APRI and 0.65 (95% CI 0.61–0.69) for NFS. The specificities were 0.95 for FIB‐4 greater than 3.25, 0.88 for APRI greater than 1.5 and 0.99 for NFS greater than 0.675. Conclusion: The performance of NITs to exclude advanced fibrosis did not differ greatly regardless of HS. FIB‐4 and NFS have the best negative predictive values of 0.80 and 0.78, respectively, to exclude advanced fibrosis in CHBHS subjects. [ABSTRACT FROM AUTHOR]

Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti‐hepatitis C virus antibody (anti‐HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at‐risk population, such as immunocompromised hosts and end‐stage renal failure patients on hemodialysis. HCV antigen (Ag) could be useful in identifying the ongoing infection in such clinical scenarios. Hence, we aimed to study the utility of HCV Ag testing for the diagnosis of acute and chronic hepatitis C. Of 89 samples studied, 19 were from acute hepatitis C patients who were immunocompromised or were on hemodialysis, 43 were from active chronic hepatitis C patients and 27 were from patients treated for chronic hepatitis C. All samples were tested for HCV Ag using the Abbott ARCHITECT HCV Ag assay. HCV Ag was reactive in 19/19 samples from acute hepatitis C patients and 42/43 samples from active chronic hepatitis C patients. It was nonreactive in all samples from treated patients. The test showed a sensitivity and specificity of 98.4% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 96.4%, respectively. The HCV antigen test has high clinical sensitivity and specificity and is useful for the diagnosis of acute and chronic hepatitis C infection in at‐risk and immunocompromised patients. Its short turnaround time and relatively low cost are advantageous for use in patients on hemodialysis and other at‐risk patients who require monitoring of HCV infection and reinfection. Highlights: ‐ Anti HCV antibody is used as screening test/ ‐ Anti HCV antibody test is falsely negative in immunocompromised hosts. ‐ HCV antigen testing can be used as screening test in this group. [ABSTRACT FROM AUTHOR]

Background: Pre‐emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear. Objectives: We aim to describe the prescription pattern of PGx drugs among adult medical outpatients. Methods: We estimated the 5‐year cumulative incidence (CI) for receiving three groups of PGx drugs using competing risks analysis: (i) all PGx drugs, (ii) PGx drugs with guidelines and (iii) PGx drugs with serious clinical effects. Comparisons of CIs were also done by patient characteristics using Gray's test. Results: The 5‐year CIs of receiving any new PGx drug, PGx drug with guidelines and serious clinical effects were 42.6%, 37.3% and 13.7%, respectively. The 5‐year CI of receiving any new PGx drug was higher for patients >40 years old (43.6% vs ≤40 years old 36.0%, P < 2.2 × 10−22), Malays and Indians (50.3% and 49.8% vs Chinese 31.1%, P < 2.2 × 10−22), those who attended one of the following four specialties at the index visit compared to other specialties (infectious diseases [46.2% vs 42.6%, P = 2.9 × 10−4], psychiatry [48.3% vs 42.3%, P = 7.4 × 10−13], renal [49.8% vs 40.9%, P < 2.2 × 10−22], and rheumatology and immunology [54.8% vs 41.7%, P < 2.2 × 10−22]) and those prescribed ≥5 drugs at index visit (51.7% vs 0‐4 drugs 41.7%, P < 2.2 × 10−22). Conclusions: Medical outpatients have a substantial probability of benefiting from pre‐emptive PGx testing and this is higher in certain subgroups of patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Non‐alcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome. Worryingly, it has been increasingly reported among nonobese patients. This study aims to analyse patient characteristics of biopsy‐proven NAFLD in an Asian cohort and explore differences stratified by body mass index (BMI). Methods: Clinical, laboratory, and histological data were collected from 263 adults with biopsy‐proven NAFLD. Patients with and without obesity (BMI cut‐off 25) were compared. The ability to predict advanced liver fibrosis with three non‐invasive scores, the NAFLD Fibrosis score (NFS), Fibrosis‐4 (FIB4), and the aspartate aminotransferase to platelet ratio index (APRI), was compared. Results: Obese subjects had a lower mean age (49.5 ± 12.5 vs 54.0 ± 12.9 years, P = 0.017), a higher prevalence of diabetes (52.4% vs 36.8%, P = 0.037), and a higher waist circumference (113.9 ± 16.0 cm vs 87.0 ± 18.4 cm, P = 0.022). The prevalence of dyslipidaemia (68.0% vs 61.4%, P = 0.353) and hypertension (61.7% vs 49.1%, P = 0.190) was comparable between the two groups. The distribution of non‐alcoholic steatohepatitis (NASH) (63.1% versus 61.4%, P = 0.710) and advanced fibrosis (31.6% versus 26.3%, P = 0.447) were also similar in both groups. All three non‐invasive scores (NFS, FIB4, and APRI) performed poorly in predicting advanced fibrosis in nonobese patients with NAFLD. The FIB4 was the most accurate non‐invasive score in predicting advanced fibrosis in the obese group. Conclusions: Obese and nonobese patients are equally at risk of NASH and advanced fibrosis. While the FIB4 is the most accurate non‐invasive score in predicting advanced fibrosis among obese individuals, further research is warranted to develop a nonobese specific score to correctly identify nonobese NAFLD patients with advanced fibrosis. [ABSTRACT FROM AUTHOR]

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) patients often have dyslipidemia, and optimal treatment of dyslipidemia lowers the risk of cardiovascular disease and mortality. Our aim was to study the prescription of statin and low‐density lipoprotein cholesterol treatment targets in NAFLD patients. Methods: Consecutive NAFLD patients attending five clinics in Asia were included in this study. The 10‐year cardiovascular disease risk was calculated based on the Framingham Heart Study, and patients were categorized as moderate, high, or very high risk for cardiovascular disease on the basis of the American Association of Clinical Endocrinologist 2017 Guidelines. The low‐density lipoprotein cholesterol treatment goal for each of the risk groups was 2.6, 2.6, and 1.8 mmol/L, respectively. Results: The data for 428 patients were analyzed (mean age 54.4 ± 11.1 years, 52.1% male). Dyslipidemia was seen in 60.5% (259/428), but only 43.2% (185/428) were on a statin. The percentage of patients who were at moderate, high, and very high risk for cardiovascular disease was 36.7% (157/428), 27.3% (117/428), and 36.0% (154/428), respectively. Among patients who were on a statin, 58.9% (109/185) did not achieve the treatment target. Among patients who were not on a statin, 74.1% (180/243) should be receiving statin therapy. The percentage of patients who were not treated to target or who should be on statin was highest among patients at very high risk for cardiovascular disease at 79.6% (78/98) or 94.6% (53/56), respectively. Conclusion: This study highlights the suboptimal treatment of dyslipidemia and calls for action to improve the treatment of dyslipidemia in NAFLD patients. [ABSTRACT FROM AUTHOR]

Introduction: Despite the widespread use of transient elastography for non-invasive assessment of liver fibrosis, the optimal cut-off liver stiffness measurement (LSM) values remain unclear. This study aimed to validate the optimal cut-off LSM values for significant fibrosis and cirrhosis in patients with chronic liver disease (CLD).Methods: Prospective multicentre data of CLD patients who underwent paired liver biopsy and LSM was analysed to determine the optimal cut-off LSM values for predicting significant fibrosis (METAVIR F ≥ 2) and cirrhosis (METAVIR F4). A high-quality cohort was selected by excluding those with failed LSM and invalid LSM readings.Results: Of the 481 patients recruited, 322 fulfilled the pre-defined quality criteria. CLD aetiology was chronic hepatitis B (CHB) in 49%, non-alcoholic steatohepatitis (NASH) in 16% and chronic hepatitis C (CHC) in 12%. Area under the receiver operating characteristic curve for LSM was 0.775 (95% confidence interval [CI] 0.724-0.826) for significant fibrosis and 0.810 (95% CI 0.738-0.882) for cirrhosis. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 13 kPa for cirrhosis in the general cohort. Optimal cut-off LSM values were 9 kPa for significant fibrosis and 12 kPa for cirrhosis for both CHB and CHC, while the corresponding values for NASH were 11 kPa and 15 kPa.Conclusion: Optimal cut-off LSM values should be selected based on disease aetiology. In Singapore, the optimal cut-off LSM values for CHB and CHC are 9 kPa for significant fibrosis and 12 kPa for cirrhosis. Optimal cut-off values for NASH require further validation. [ABSTRACT FROM AUTHOR]

Introduction: To study the prevalence of hepatitis C virus (HCV) infection in blood donor (BD), haemodialysis (HD) and intravenous drug user (IVDU) populations in Singapore and assess the IL28B polymorphism if HCV positive.Methods: The BD population were healthy volunteers, the HD population were patients who were on haemodialysis for at least six months of follow-up between January 2009 and December 2014. IVDU population was from inmates at halfway houses who consented.Results: Between 2011 and 2014, of 161,658 individuals who underwent screening prior to blood donation, 95 (0.059%) were positive for HCV. Of the 42 sera available, common genotypes (GTs) were GT-3 (47.6%) and GT-1 (31.0%). Of 1,575 HD patients, 2.2% were anti-HCV positive. The HCV GT distribution was HCV GT-1 (32.4%), HCV GT-3 (20.5%) and GT-6 (8.8%). 83 halfway house inmates were screened. Of the 47 IVDUs, 36.2% were anti-HCV positive with predominant GT-3 (%). IL28B polymorphism was noted to be CC predominantly 85.3%.Conclusion: Prevalence of HCV infection has decreased in both the BD and HD populations. However, it remains high in the IVDU population. GT-1 remains the most common in the HD population; however, GT-3 infection is now more common among the BD population in Singapore. IL28B - CC is the predominant variant among the HCV-infected individuals in Singapore. [ABSTRACT FROM AUTHOR]

Hepatitis B is leading cause of liver related morbidity in Asia with predominant genotypes B and C in East-Asia. Data on Serum, intrahepatic viral-markers, and long-term follow-up of prevalent genotypes (GT) B and C in patients with biopsy proven advanced fibrosis are sparse. To compare serum, intrahepatic viral-markers and development of hepatocellular carcinoma (HCC) in GT-B and C in patients with advanced fibrosis (Ishak ≥ 4). Sixty-three treatment-naïve patients identified with advanced fibrosis on liver-biopsy performed between 1998 and 2000 at Singapore General Hospital. FFPE tissue was available for 59 patients and serum for 42 patients. HBV-DNA was quantified in serum and liver while qHBsAg quantified in serum. Patients were followed-up till December 2015. The median age was 47 ± 16 years, with 77.7% males. About 19 were GT-B, 43 patients were GT-C, and 1 had both GT-B and C. Mean follow-up was 13.5 years. The median serum HBV-DNA was 6.25 ± 2.17 and 6.58 ± 1.85 log IU/ml, serum HBsAg was 3.29 ± 0.80 and 3.45 ± 1.85 log IU/ml, and intrahepatic HBV-DNA was 0.52 ± 3.73 copies/cell and 0.4 ± 1.37 copies/cell in the GT-B and C, respectively ( P > 0.1 in all). Complete cirrhosis (Ishak-6) was present in 47.6%, Ishak-5 fibrosis in 33.3%, and Ishak-4 fibrosis in 19% at recruitment. On follow-up HCC developed in 8/43 in GT-C and in 3/19 GT-B ( P = 0.86). Advanced age and cirrhosis were significant factors for development of HCC. No difference in serum HBV-DNA, qHBsAg or intrahepatic HBV-DNA was seen in the two genotypes. HCC development seen over long-term follow-up was independent of genotypes in patients with advanced fibrosis. J. Med. Virol. 89:845-848, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]