Displaying publications 1 - 20 of 31 in total

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  1. Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, et al.
    Hepatol Int, 2024 Apr;18(2):299-383.
    PMID: 38416312 DOI: 10.1007/s12072-023-10629-3
    Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
  2. Zhou XD, Targher G, Byrne CD, Somers V, Kim SU, Chahal CAA, et al.
    Hepatol Int, 2023 Aug;17(4):773-791.
    PMID: 37204656 DOI: 10.1007/s12072-023-10543-8
    BACKGROUND: Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists.

    METHODS AND RESULTS: A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management.

    CONCULSIONS: The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

  3. Lee WS, Chew KS, Ng RT, Kasmi KE, Sokol RJ
    Hepatol Int, 2020 May;14(3):305-316.
    PMID: 32356227 DOI: 10.1007/s12072-020-10048-8
    Premature infants and children with intestinal failure (IF) or short bowel syndrome are susceptible to intestinal failure-associated liver disease (IFALD, previously referred to as parenteral nutrition-associated liver disease, or PNALD). IFALD in children is characterized by progressive cholestasis and biliary fibrosis, and steatohepatitis in adults, and is seen in individuals dependent upon prolonged administration of PN. Many factors have been proposed as contributing to the pathogenesis of IFALD. In recent years, the focus has been on the potential synergistic roles of the intestinal microbiome, increased intestinal permeability, activation of hepatic innate immune pathways, and the use of intravenous soybean-oil-based intravenous lipid emulsions (SO-ILE). In vitro and in vivo studies have identified stigmasterol, a component of the plant sterols present in SO-ILE, as playing an important role. Although various strategies have been adopted to prevent or reverse IFALD, most suffer from a lack of strong evidence supported by well-designed, prospective clinical trials with clearly defined endpoints. Reduction in the amount of SO-ILEs or replacement with non-SO-ILEs has been shown to reverse IFALD although safety and long-term effectiveness have not been studied. Medical and surgical modalities to increase intestinal adaptation, advance enteral feedings, and prevent central line bloodstream infections are also important preventative strategies. There is a continued need to conduct high-quality, prospective trials with clearly define outcome measures to ascertain the potential benefits of these strategies.
  4. Maiwall R, Pasupuleti SSR, Choudhury A, Kim DJ, Sood A, Goyal O, et al.
    Hepatol Int, 2023 Jun;17(3):662-675.
    PMID: 36571711 DOI: 10.1007/s12072-022-10463-z
    BACKGROUND AND AIM: Acute-on-chronic liver failure (ACLF) is a severe form of alcoholic hepatitis (SAH). We aimed to study the natural course, response to corticosteroids (CS), and the role of the Asian Pacific Association for the Study of Liver (APASL) research consortium (AARC) score in determining clinical outcomes in AH patients.

    METHODS: Prospectively collected data from the AARC database were analyzed.

    RESULTS: Of the 1249 AH patients, (aged 43.8 ± 10.6 years, 96.9% male, AARC score 9.2 ± 1.9), 38.8% died on a 90 day follow-up. Of these, 150 (12.0%) had mild-moderate AH (MAH), 65 (5.2%) had SAH and 1034 (82.8%) had ACLF. Two hundred and eleven (16.9%) patients received CS, of which 101 (47.87%) were steroid responders by day 7 of Lille's model, which was associated with improved survival [Hazard ratio (HR) 0.15, 95% CI 0.12-0.19]. AARC-ACLF grade 3 [OR 0.28, 0.14-0.55] was an independent predictor of steroid non-response and mortality [HR 3.29, 2.63-4.11]. Complications increased with degree of liver failure [AARC grade III vs. II vs I], bacterial infections [48.6% vs. 37% vs. 34.7%; p 

  5. Singh V, De A, Mehtani R, Angeli P, Maiwall R, Satapathy S, et al.
    Hepatol Int, 2023 Aug;17(4):792-826.
    PMID: 37237088 DOI: 10.1007/s12072-023-10536-7
  6. Maiwall R, Singh SP, Angeli P, Moreau R, Krag A, Singh V, et al.
    Hepatol Int, 2024 Apr 05.
    PMID: 38578541 DOI: 10.1007/s12072-024-10650-0
    Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.
  7. Lee WS, Lum SH, Lim CB, Chong SY, Khoh KM, Ng RT, et al.
    Hepatol Int, 2015 Apr;9(2):292-302.
    PMID: 25788179 DOI: 10.1007/s12072-014-9558-0
    BACKGROUND: Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population.

    METHODS: Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia.

    RESULTS: At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012].

    CONCLUSIONS: Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.
  8. Liaw YF, Kao JH, Piratvisuth T, Chan HL, Chien RN, Liu CJ, et al.
    Hepatol Int, 2012 Jun;6(3):531-61.
    PMID: 26201469 DOI: 10.1007/s12072-012-9365-4
    Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier "Asian-Pacific consensus statement on the management of chronic hepatitis B" was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.
  9. Lau G, Yu ML, Wong G, Thompson A, Ghazinian H, Hou JL, et al.
    Hepatol Int, 2021 Oct;15(5):1031-1048.
    PMID: 34427860 DOI: 10.1007/s12072-021-10239-x
    BACKGROUND & AIM: Hepatitis B reactivation related to the use of immunosuppressive therapy remains a major cause of liver-related morbidity and mortality in hepatitis B endemic Asia-Pacific region. This clinical practice guidelines aim to assist clinicians in all disciplines involved in the use of immunosuppressive therapy to effectively prevent and manage hepatitis B reactivation.

    METHODS: All publications related to hepatitis B reactivation with the use of immunosuppressive therapy since 1975 were reviewed. Advice from key opinion leaders in member countries/administrative regions of Asian-Pacific Association for the study of the liver was collected and synchronized. Immunosuppressive therapy was risk-stratified according to its reported rate of hepatitis B reactivation.

    RECOMMENDATIONS: We recommend the necessity to screen all patients for hepatitis B prior to the initiation of immunosuppressive therapy and to administer pre-emptive nucleos(t)ide analogues to those patients with a substantial risk of hepatitis and acute-on-chronic liver failure due to hepatitis B reactivation.

  10. Chen T, Yang Z, Choudhury AK, Al Mahtab M, Li J, Chen Y, et al.
    Hepatol Int, 2019 Nov;13(6):695-705.
    PMID: 31650510 DOI: 10.1007/s12072-019-09992-x
    BACKGROUND AND AIM: Cirrhosis is a controversial determinant of mortality in HBV-related acute-on-chronic liver failure (HBV-ACLF). The present study aimed to explore the effects of cirrhosis and the associated risk factors, especially its complications, on the outcome of HBV-ACLF.

    METHODS: A prospective-retrospective cohort of 985 patients was identified from the APASL-ACLF Research Consortium (AARC) database and the Chinese Study Group. Complications of ACLF (ascites, infection, hepatorenal syndrome, hepatic encephalopathy, upper gastrointestinal bleeding) as well as cirrhosis and the current main prognostic models were measured for their predictive ability for 28- or 90-day mortality.

    RESULTS: A total of 709 patients with HBV-ACLF as defined by the AARC criteria were enrolled. Among these HBV-ACLF patients, the cirrhotic group showed significantly higher mortality and complications than the non-cirrhotic group. A total of 36.1% and 40.1% of patients met the European Association for the Study of Liver (EASL)-Chronic Liver Failure consortium (CLIF-C) criteria in the non-cirrhotic and cirrhotic groups, respectively; these patients had significantly higher rates of mortality and complications than those who did not satisfy the CLIF-C criteria. Furthermore, among patients who did not meet the CLIF-C criteria, the cirrhotic group exhibited higher mortality and complication rates than the non-cirrhotic group, without significant differences in organ failure. The Tongji prognostic predictor model score (TPPMs), which set the number of complications as one of the determinants, showed comparable or superior ability to the Chinese Group on the Study of Severe Hepatitis B-ACLF score (COSSH-ACLFs), APASL-ACLF Research Consortium score (AARC-ACLFs), CLIF-C organ failure score (CLIF-C OFs), CLIF-C-ACLF score (CLIF-C-ACLFs), Model for End-Stage Liver Disease score (MELDs) and MELD-sodium score (MELD-Nas) in HBV-ACLF patients, especially in cirrhotic HBV--ACLF patients. Patients with two (OR 4.70, 1.88) or three (OR 8.27, 2.65) complications had a significantly higher risk of 28- or 90-day mortality, respectively.

    CONCLUSION: The presence of complications is a major risk factor for mortality in HBV-ACLF patients. TPPM possesses high predictive ability in HBV-ACLF patients, especially in cirrhotic HBV-ACLF patients.

  11. Chan WK, Nik Mustapha NR, Mahadeva S
    Hepatol Int, 2015 Oct;9(4):594-602.
    PMID: 25788185 DOI: 10.1007/s12072-014-9596-7
    BACKGROUND: The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is indeterminate in a proportion of NAFLD patients. Combining the NFS with liver stiffness measurement (LSM) may improve prediction of advanced fibrosis. We aim to evaluate the NFS and LSM in predicting advanced fibrosis in NAFLD patients.

    METHODS: The NFS was calculated and LSM obtained for consecutive adult NAFLD patients scheduled for liver biopsy. The accuracy of predicting advanced fibrosis using either modality and in combination were assessed. An algorithm combining the NFS and LSM was developed from a training cohort and subsequently tested in a validation cohort.

    RESULTS: There were 101 and 46 patients in the training and validation cohort, respectively. In the training cohort, the percentages of misclassifications using the NFS alone, LSM alone, LSM alone (with grey zone), both tests for all patients and a 2-step approach using LSM only for patients with indeterminate and high NFS were 5.0, 28.7, 2.0, 2.0 and 4.0 %, respectively. The percentages of patients requiring liver biopsy were 30.7, 0, 36.6, 36.6 and 18.8 %, respectively. In the validation cohort, the percentages of misclassifications were 8.7, 28.3, 2.2, 2.2 and 8.7 %, respectively. The percentages of patients requiring liver biopsy were 28.3, 0, 41.3, 43.5 and 19.6 %, respectively.

    CONCLUSIONS: The novel 2-step approach further reduced the number of patients requiring a liver biopsy whilst maintaining the accuracy to predict advanced fibrosis. The combination of NFS and LSM for all patients provided no apparent advantage over using either of the tests alone.

  12. Kamarajah SK, Chan WK, Nik Mustapha NR, Mahadeva S
    Hepatol Int, 2018 Jan;12(1):44-55.
    PMID: 29372507 DOI: 10.1007/s12072-018-9843-4
    INTRODUCTION: The value of repeated liver stiffness measurement (LSM) in non-alcoholic fatty liver disease (NAFLD) has not been shown before.

    METHODS: A longitudinal study of biopsy-proven NAFLD patients was conducted at the Asian tertiary hospital from November 2012 to January 2017. Patients with paired liver biopsies and LSM were followed prospectively for liver-related and non-liver related complications, and survival.

    RESULTS: The data for 113 biopsy-proven NAFLD patients (mean age 51.3 ± 10.6 years, male 50%) were analyzed. At baseline, advanced fibrosis based on histology and LSM was observed in 22 and 46%, respectively. Paired liver biopsy and LSM at 1-year interval was available in 71 and 80% of patients, respectively. High-risk cases (defined as patients with advanced fibrosis at baseline who had no fibrosis improvement, and patients who developed advanced fibrosis on repeat assessment) were seen in 23 and 53% of patients, based on paired liver biopsy and LSM, respectively. Type 2 diabetes mellitus was independently associated with high-risk cases. The median follow-up was 37 months with a total follow-up of 328 person-years. High-risk cases based on paired liver biopsy had significantly higher rates of liver-related complications (p = 0.002) but no difference in other outcomes. High-risk patients based on paired LSM had a significantly higher rate of liver-related complications (p = 0.046), cardiovascular events (p = 0.025) and composite outcomes (p = 0.006).

    CONCLUSION: Repeat LSM can predict liver-related complications, similar to paired liver biopsy, and may be useful in identifying patients who may be at an increased risk of cardiovascular events. Further studies in a larger cohort and with a longer follow-up should be carried out to confirm these observations.

  13. Ng RT, Chew KS, Choong CL, Song ZL, Teh JKL, Koay ZL, et al.
    Hepatol Int, 2022 Dec;16(6):1390-1397.
    PMID: 36131224 DOI: 10.1007/s12072-022-10417-5
    OBJECTIVE: Outcome of pediatric acute liver failure (PALF) in countries with limited availability of LT is not well described. We evaluated the outcome and prognostic indicators of PALF in Malaysia where emergency LT for ALF is limited.

    METHODS: In this retrospective review on children  452 μmol/L and peak GGT 

  14. Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, et al.
    Hepatol Int, 2016 Jan;10(1):1-98.
    PMID: 26563120 DOI: 10.1007/s12072-015-9675-4
    Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
  15. Chan WK, Bahar N, Razlan H, Vijayananthan A, Sithaneshwar P, Goh KL
    Hepatol Int, 2014 Jan;8(1):121-7.
    PMID: 26202413 DOI: 10.1007/s12072-013-9510-8
    PURPOSE: Previous studies on multiracial Malaysian populations found inordinately high prevalence of NAFLD among Malays and Indians. Whether the prevalence of NAFLD is different among young adults of different ethnic origins is not known. We aimed to determine racial differences in NAFLD in a young multiracial Malaysian population and associated factors.

    METHODS: This was a cross-sectional study on medical students from the University of Malaya. Diagnosis of NAFLD was by transabdominal ultrasonography and following exclusion of significant alcohol intake and other causes of chronic liver disease.

    RESULTS: Data of 469 subjects were analyzed (mean age 23.2 ± 2.4 years, 40.3 % male). The racial distribution was: Chinese 53.9 %, Malay 30.5 % and Indian 15.6 %. The overall prevalence of NAFLD was 7.9 %. Subjects with NAFLD were older, had greater BMI and WC, higher SBP and DBP, higher FBS, serum TG and LDL levels, and lower serum HDL level. The prevalence of NAFLD was higher among males compared to females (17.9 % vs. 3.3 %, p 

  16. Goh SC, Ho EL, Goh KL
    Hepatol Int, 2013 Jun;7(2):548-54.
    PMID: 26201786 DOI: 10.1007/s12072-012-9359-2
    BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) in the Malaysian population is not known. Malaysia has a multiracial Asian population with three major Asian races: Malay, Chinese, and Indian living together. The aim of the study is to determine the prevalence and risk factors in a suburban Malaysian population.

    METHODS: Consecutive subjects who came for a health checkup at a suburban medical facility were recruited for the study. All individuals had clinical assessments, anthropometric measurements, blood tests, and ultrasonography of the liver performed. Those with significant alcohol consumption and history of chronic liver disease were excluded.

    RESULTS: Of the 1,621 "health screened" individuals analyzed, 368 (22.7 %) were found to have NAFLD. They comprised Chinese 1,269 (78.3 %), Malay 197 (12.1 %), and Indian 155 (9.6 %). Males and "older" age group ≥45 years had high prevalence rates with the highest in Indian (68.2 %) and Malay (64.7 %) males. Chinese females <45 years had the lowest prevalence of 5.2 %. A significant increase in the prevalence of fatty liver between age <45 years and ≥45 years was seen in female of all three races but in male, this increase was seen only among the Indians. NAFLD was strongly associated with diabetes mellitus, glucose intolerance, body mass index ≥23, low high-density lipoprotein cholesterol, hypertriglyceridemia, and hypertension.

    CONCLUSION: NAFLD is common in suburban Malaysian population. Older Indian and Malay males have an inordinately high prevalence of the disease.

  17. Chan WK, Goh KL
    Hepatol Int, 2013 Mar;7(1):65-71.
    PMID: 26201622 DOI: 10.1007/s12072-012-9384-1
    Non-alcoholic fatty liver disease (NAFLD) is rapidly increasing in the Asia-Pacific and affects up to 30 % of the general population. In younger children, prevalence has been reported to be between 2.1 and 4.5 %. The prevalence of NAFLD increases with increasing age. NAFLD is more prevalent in men than women, but this trend fades in older age group. NAFLD is one of the most common causes of raised serum ALT levels and the latter is closely related to the presence of features of metabolic syndrome. NAFLD may contribute to metabolic syndrome in a similar way as visceral adiposity and can be an early predictor of metabolic disorders. NAFLD increases the risk of developing diabetes mellitus and is closely related to degree of glucose intolerance. A significant proportion of patients with NAFLD have impaired glucose tolerance or diabetes mellitus but with normal fasting blood glucose, highlighting the importance of oral glucose tolerance test in NAFLD patients with normal fasting blood glucose. Besides liver-related complications, NAFLD has been associated with cardiovascular complications, hyperuricemia, gout, chronic kidney disease, gallstone disease, colorectal adenomatous polyp, and polycystic ovarian syndrome. NAFLD seems to be related to host metabolic factors rather than viral factors and does not seem to affect severity of the liver disease in patients with chronic hepatitis B. On the other hand, hepatic steatosis may be related to both host metabolic and viral factors in patients with chronic hepatitis C and seems to adversely impact on the severity of liver disease and possibly response to antiviral therapy.
  18. Eslam M, Sarin SK, Wong VW, Fan JG, Kawaguchi T, Ahn SH, et al.
    Hepatol Int, 2020 Dec;14(6):889-919.
    PMID: 33006093 DOI: 10.1007/s12072-020-10094-2
    Metabolic associated fatty liver disease (MAFLD) is the principal worldwide cause of liver disease and affects nearly a quarter of the global population. The objective of this work was to present the clinical practice guidelines of the Asian Pacific Association for the Study of the Liver (APASL) on MAFLD. The guidelines cover various aspects of MAFLD including its epidemiology, diagnosis, screening, assessment, and treatment. The document is intended for practical use and for setting the stage for advancing clinical practice, knowledge, and research of MAFLD in adults, with specific reference to special groups as necessary. The guidelines also seek to improve patient care and awareness of the disease and assist stakeholders in the decision-making process by providing evidence-based data. The guidelines take into consideration the burden of clinical management for the healthcare sector.
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