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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]

We aimed to compare the severity of liver disease, metabolic profile and cardiovascular disease (CVD) risk of chronic hepatitis B (CHB) patients with and without hepatic steatosis and patients with non‐alcoholic fatty liver disease (NAFLD). Patients with NAFLD and CHB were prospectively enrolled from 10 Asian centres. Fibroscan was performed for all patients and hepatic steatosis was defined based on controlled attenuation parameter >248 dB/m. CVD risk was assessed using the Framingham risk score. The data for 1080 patients were analysed (67% NAFLD, 33% CHB). A high proportion (59%) of CHB patients had hepatic steatosis. There was a significant stepwise increase in alanine aminotransferase, aspartate aminotransferase, gamma‐glutamyl transpeptidase, controlled attenuation parameter and liver stiffness measurement, from CHB patients without hepatic steatosis to CHB patients with hepatic steatosis to NAFLD patients (p < 0.001 for all comparisons). There was a significant stepwise increase in the proportion of patients with metabolic syndrome and in CVD risk, with very high or extreme CVD risk seen in 20%, 48% and 61%, across the groups (p < 0.001 between CHB patients with and without hepatic steatosis and p < 0.05 between CHB patients with hepatic steatosis and NAFLD patients). In conclusion, there was a high proportion of CHB patients with hepatic steatosis, which should be diagnosed, as they may have more severe liver disease, so that this and their metabolic risk factors can be assessed and managed accordingly for a better long‐term outcome [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]

Study Objective: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. Design: Prospective, single‐arm study. Setting: National Cancer Centre, Singapore. Patients: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab‐based treatment. Intervention: Close monitoring of HBV DNA levels, ie. every 4–6 weeks during rituximab treatment, every 6–8 weeks in the first year post‐treatment, and every 3–4 months in the second year post‐treatment. Measurements: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation‐related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost‐minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. Main Results: A total of 66 patients provided analyzable data with a follow‐up period of 966.6 months. No hepatitis flare or reactivation‐related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. Conclusions: The surveillance protocol is an effective, feasible and cost‐saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab. [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 & Aims: Lifestyle modification is the cornerstone for the management of non‐alcoholic fatty liver disease (NAFLD). We aim to understand lifestyle habits of NAFLD patients, compare across Asian regions and identify area of deficiency. Methods: In the multi‐centre controlled attenuation parameter (CAP)‐Asia study, we collected clinical data and lifestyle habit data of NAFLD patients from Singapore, mainland China, Hong Kong, Taiwan and Malaysia. Physical activity was assessed using the International Physical Activity Questionnaire. Results: A total of 555 patients were included in the final analysis (mean age 54.5 ± 11.2 years, 54.1% men and median liver stiffness 6.7 kPa). More patients from mainland China (27.4%) and Taipei (25.0%) were smokers. Modest drinking was more common in Taiwan (25.0%) and Hong Kong (18.2%); only 1.3% had binge drinking. Majority of patients drank coffee (64.0%) and tea (80.2%), with varying amounts and durations in different regions. Soft drinks consumption was most common in Singapore (62.2%) and Malaysia (57.7%). Only 29.7% of patients met the Physical Activity Guidelines Recommendations, with no major differences across regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity, and sitting time was an independent factor associated with high CAP. Tea and coffee consumption were independently associated with high CAP and liver stiffness, respectively. Conclusions: Despite some heterogeneity, unhealthy lifestyle and physical inactivity are common across Asian regions. Patients with liver stiffness <10 kPa were more likely to report any vigorous activity. Healthcare providers may use the comparative data to identify areas of deficiency. [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]

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]

Background & Aim Diabetes mellitus has been linked to cirrhosis-related mortality in Western populations, but less is known about this relationship in Asian populations. We studied the impact of diabetes on the risk of cirrhosis mortality in a population-based cohort among Chinese in Singapore. Methods We used data collected and analysed from the Singapore Chinese Health Study, a prospective community-based cohort of 63 275 subjects aged 45-74 years during enrolment between 1993 and 1998. Information on diet, lifestyle and medical history was collected via structured questionnaire. Mortality cases from cirrhosis in the cohort were identified via linkage with nationwide death registry up to 31 December 2014. Cox proportional regression models were used to estimate the associations with adjustment for risk factors of cirrhosis. Results After a mean follow-up of 16.9 years, there were 133 deaths from cirrhosis. Diabetes was associated with an increased risk of cirrhosis mortality (hazard ratio [ HR]: 2.80; 95% confidence interval [ CI]: 2.04-3.83), and for both viral ( HR: 2.20; 95% CI: 1.18-4.11) and non-viral hepatitis-related cirrhosis mortality ( HR: 3.06; 95% CI: 2.13-4.41). The association between diabetes and non-viral hepatitis-related cirrhosis mortality was stronger among participants of body mass index ( BMI) less than 23 kg/m2 ( HR: 7.11; 95% CI: 3.42-14.79) compared to heavier individuals ( HR: 2.28; 95% CI: 1.20-4.35) ( Pinteraction=0.02). Conclusion Diabetes is a risk factor for cirrhosis mortality, especially for non-viral hepatitis-related cirrhosis in population with BMI considered low or normal in Asia. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatitis B and C viruses (HBV and HCV) are two clinically distinct but related diseases. Pooled data from five studies of peginterferon alpha-2a in patients with chronic HCV infection (CHC) were compared with two studies of the drug in patients with chronic HBV infection (CHB). Method: The HBV studies included both hepatitis B e antigen (HBeAg)-positive ( n=271) and HBeAg-negative ( n=177) patients; 791 patients took part in the HCV trials. In all studies, patients were treated with 180 μg peginterferon alpha-2a monotherapy once weekly for 48 weeks. The number of adverse events (AEs), discontinuations and dose modifications were documented. Health-related quality of life (HRQL) was assessed using the Short-Form 36 questionnaire. Safety was assessed throughout the treatment period. A 24-week treatment-free follow-up period was also included. Results: Differences (HBV vs HCV) were observed in the incidence of AEs (88–89 vs 96–100%), serious AEs (4–5 vs 7–16%) and treatment withdrawals (6–8 vs 17–33%). The frequency of depression-related events was lower in CHB patients (4 vs 22%, P<0.001), as was the impact of treatment on HRQL. Conclusions: The safety and tolerability of peginterferon alpha-2a in patients with CHB compares favourably with that observed in CHC patients, with a lower incidence of common interferon-related AEs and a significantly lower incidence of depression. [ABSTRACT FROM AUTHOR]

Abstract This paper addresses two difficult issues in the treatment of hepatitis C: patients who fail to achieve a sustained response after the first course of treatment, and those who simultaneously suffer from chronic renal failure. With the recent improvements in firstline treatment, retreatment is mainly applicable to those who have previously received 6-month of interferon monotherapy at 3 MU thrice weekly. For those who had an end-of-treatment response but relapsed, there is a choice between interferon monotherapy at increased dose and/or duration of treatment, or a 6-month course of combination therapy. Retreatment of non-responders is generally unsuccessful, but some patients may respond to interferon-alpha 3 MU and ribavirin 1.0–1.2 g/day. For patients with chronic renal failure and hepatitis C, combination treatment is not possible because ribavirin is contraindicated. Interferon given at a dose of 1.5 MU thrice weekly was reported to be fairly well tolerated by patients who were on dialysis and resulted in end-of-treatment and sustained biochemical and virological response in some cases. Interferon given in the usual doses may be associated with severe adverse effects in patients with renal failure, and can precipitate allograft rejection in patients who have undergone renal transplantation. [ABSTRACT FROM AUTHOR]

Explores the role of surgical intervention in the blue rubber bleb nevus syndrome characterized by cutaneous and gastrointestinal cavernous hemangiomas. Correlation between number and distributions of skin and gastrointestinal tract lesions; Multiple skin hemangiomas; Long-term remission of gastrointestinal bleeding.

A response from authors of the article "Association between diabetes mellitus and cirrhosis mortality: the Singapore Chinese Health Study" in a 2017 issue is presented.