Chapter of Gastroenterologists professional guidance for management of patients with liver disease in Singapore during the COVID-19 pandemic

In this paper, we aim to provide professional guidance to clinicians who are managing patients with chronic liver disease during the current coronavirus disease 2019 (COVID-19) pandemic in Singapore. We reviewed and summarised the available relevant published data on liver disease in COVID-19 and the advisory statements that were issued by major professional bodies, such as the American Association for the Study of Liver Diseases and European Association for the Study of the Liver, contextualising the recommendations to our local situation.

Comparisons between non-alcoholic steatohepatitisand alcohol-related hepatocellular carcinoma

Background/Aims@#Non-alcoholic liver disease and alcoholic liver disease begin as simple steatosis that may progress to steatohepatitis and ensuing liver-related complications such as cirrhosis and hepatocellular carcinoma (HCC). We explored differences in characteristics between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitisrelated (ASH) HCC. @*Methods@#NASH and ASH patients were identified from our department’s prospective HCC database. A total of 54 and 45 patients met predefined inclusion and exclusion criteria for the NASH-HCC and ASH-HCC groups, respectively. Clinical, biochemical and tumor characteristics were studied. @*Results@#NASH-HCC patients were older compared to ASH-HCC patients (72±9 vs. 66±9 years, P<0.001) and less male predominant (65% vs. 98%, P<0.001). Prevalence of diabetes mellitus (78% vs. 36%, P<0.001) and hypertension (80% vs. 58%, P<0.001) were significantly higher in the NASH-HCC group. Liver function tests and Child-Pugh scores were similar. There were no differences in alpha-fetoprotein level, lesions found at diagnosis (unifocal/multifocal) or prevalence of portal vein invasion. In both groups, almost half of the patients were in TNM stage 4 at the time of diagnosis and more than 50% of patients were not suitable for any therapy. Median survival in the NASH-HCC and ASH-HCC groups were 13 and 7 months respectively (P=0.113). @*Conclusions@#Despite significant differences in demography of the NASH-HCC and ASH-HCC groups, liver and tumor characteristics were comparable. Most patients were diagnosed late and were not amenable to curative or locoregional therapies. Better characterization of patients with NASH and ASH at risk of HCC is necessary to optimize screening, surveillance, and management strategies.

Chapter of Gastroenterologists professional guidance on risk mitigation for gastrointestinal endoscopy during COVID-19 pandemic in Singapore

In this paper, we aimed to provide professional guidance to practising gastrointestinal (GI) endoscopists for the safe conduct of GI endoscopy procedures during the current coronavirus disease 2019 (COVID-19) pandemic and future outbreaks of similar severe respiratory tract infections in Singapore. It draws on the lessons learnt during the severe acute respiratory syndrome (SARS) epidemic and available published data concerning the COVID-19 pandemic. It addresses measures before, during and after endoscopy that must be considered for both non-infected and infected patients, and provides recommendations for practical implementation.

Optimal liver stiffness measurement values for the diagnosis of significant fibrosis and cirrhosis in chronic liver disease in Singapore

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.

Epidemiology and Clinical Evolution of Liver Cirrhosis in Singapore

<p><b>INTRODUCTION</b>Liver cirrhosis is a common cause of morbidity and mortality and an important burden on the healthcare system. There is limited literature on liver cirrhosis in Singapore. We aimed to describe the epidemiology and clinical characteristics of cirrhotic patients seen in an ambulatory setting in a tertiary referral centre.</p><p><b>MATERIALS AND METHODS</b>This is a retrospective observational cohort study of cirrhotic patients attending the ambulatory clinic of Singapore's largest tertiary hospital over 5 years. Cirrhosis was diagnosed on characteristic radiological features and/or histology. Aetiology of cirrhosis was determined by history, serology, biochemistry and/or histology. Data on decompensation events and death were retrieved from computerised hospital records.</p><p><b>RESULTS</b>The study included 564 patients with median follow-up of 85 months. Mean age was 60.9 ± 12.5 years with 63.8% males. Main aetiologies of cirrhosis were chronic hepatitis B (CHB) (63.3%), alcohol (11.2%), cryptogenic (9%) and chronic hepatitis C (CHC) (6.9%). CHB was the predominant aetiology in Chinese and Malays whereas alcohol was the main aetiology in Indians. CHC cirrhosis was more common in Malays than other races. Majority had compensated cirrhosis with 76.8%/18.3%/5%; Child-Pugh A/B/C respectively. Decompensation events occurred in 155 patients (27.5%) and 106 of them (18.8%) died. Diagnosis of cirrhosis via surveillance ultrasound was associated with improved 10-year survival. Age at diagnosis, portal vein thrombosis, Child-Pugh class and decompensation within 1 year of diagnosis were independent predictors of mortality.</p><p><b>CONCLUSION</b>CHB is the primary cause of liver cirrhosis in Singapore. The major aetiologies of cirrhosis vary amongst the different ethnic groups. Cirrhotics with advanced age, portal vein thrombosis, poorer liver function and early decompensation have a higher mortality risk.</p>

Successful extracorporeal liver dialysis for the treatment of trimethoprim-sulfamethoxazole-induced fulminant hepatic failure

Trimethoprim-sulfamethoxazole (TMP-SMZ) is a commonly used antibiotic that has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. DRESS syndrome is characterised by fever, rash, lymphadenopathy, eosinophilia and one or more major organ involvement. Although rare, TMP-SMZ is a recognised cause of fulminant hepatic failure. We report a 17-year-old Chinese male adolescent who presented with fever, myalgia, generalised maculopapular rash and lymphadenopathy after taking TMP-SMZ for acne vulgaris. He subsequently developed hepatic encephalopathy and was worked up for urgent liver transplantation. He responded well to extracorporeal liver dialysis (originally intended as a bridging therapy) and subsequently recovered without the need for liver transplantation. This case report highlights the importance of early recognition of TMP-SMZ-induced DRESS syndrome and the need for early discontinuation of the drug in the affected patient. Extracorporeal liver dialysis and transplantation should be considered in the management of TMP-SMZ-induced fulminant hepatic failure.