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  1. Zhang X, Goh GB, Chan WK, Wong GL, Fan JG, Seto WK, et al.
    Liver Int, 2020 11;40(11):2719-2731.
    PMID: 32799384 DOI: 10.1111/liv.14638
    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.

  2. Wu J, Wang HL, Liu X, Ding C, Zhou Y, Fu X, et al.
    Liver Int, 2020 02;40(2):298-307.
    PMID: 31674705 DOI: 10.1111/liv.14289
    BACKGROUND & AIMS: Trends in long-term mortality rates for viral hepatitis in East and Southeast Asia have been rarely reported. The aim of our study was to explore the long-term trends in viral hepatitis mortality rates in East and Southeast Asian countries between 1987 and 2015 and provide predictions of mortality to 2030.

    METHODS: We obtained viral hepatitis mortality data from the WHO Mortality Database for six East and Southeast Asian countries between 1987 and 2015. We produced choropleth maps of viral hepatitis mortality rates in 1987 and 2015 in East and Southeast Asia to illustrate geographic variations. We made predictions of mortality rates for each included country until the year 2030 using a series of joinpoint models.

    RESULTS: Viral hepatitis mortality rates declined in China (the average annual percent change (AAPC) = -5.1%, 95% CI: -7.5, -2.6), Singapore (AAPC = -5.4%, 95% CI: -7.5, -3.2), and the Philippines (AAPC = -3.4%, 95% CI: -4.9, -1.8). In contrast, Japan, the Republic of Korea, and Malaysia have experienced increasing trends in mortality rates, followed by decreasing trends. Our predictions indicate that all countries will experience slight to moderate downward trends until 2030.

    CONCLUSION: Favourable decreasing trends have been noted in East and Southeast Asian countries, which may not only inform the control and management of viral hepatitis in this region but also guide the prevention of viral hepatitis deaths in another region with a similar viral hepatitis epidemic.

  3. Verma N, Choudhury A, Singh V, Duseja A, Al-Mahtab M, Devarbhavi H, et al.
    Liver Int, 2023 Feb;43(2):442-451.
    PMID: 35797245 DOI: 10.1111/liv.15361
    BACKGROUND AND AIMS: We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF).

    METHODS: We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90-days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision.

    RESULTS: Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30-day outcomes. The AUC and accuracy of the XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7 AARC model (p 

  4. Schröeder SE, Pedrana A, Scott N, Wilson D, Kuschel C, Aufegger L, et al.
    Liver Int, 2019 10;39(10):1818-1836.
    PMID: 31433902 DOI: 10.1111/liv.14222
    Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints.
  5. Saokaew S, Kanchanasuwan S, Apisarnthanarak P, Charoensak A, Charatcharoenwitthaya P, Phisalprapa P, et al.
    Liver Int, 2017 Oct;37(10):1535-1543.
    PMID: 28294515 DOI: 10.1111/liv.13413
    BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) can progress from simple steatosis to hepatocellular carcinoma. None of tools have been developed specifically for high-risk patients. This study aimed to develop a simple risk scoring to predict NAFLD in patients with metabolic syndrome (MetS).

    METHODS: A total of 509 patients with MetS were recruited. All were diagnosed by clinicians with ultrasonography-confirmed whether they were patients with NAFLD. Patients were randomly divided into derivation (n=400) and validation (n=109) cohort. To develop the risk score, clinical risk indicators measured at the time of recruitment were built by logistic regression. Regression coefficients were transformed into item scores and added up to a total score. A risk scoring scheme was developed from clinical predictors: BMI ≥25, AST/ALT ≥1, ALT ≥40, type 2 diabetes mellitus and central obesity. The scoring scheme was applied in validation cohort to test the performance.

    RESULTS: The scheme explained, by area under the receiver operating characteristic curve (AuROC), 76.8% of being NAFLD with good calibration (Hosmer-Lemeshow χ2 =4.35; P=.629). The positive likelihood ratio of NAFLD in patients with low risk (scores below 3) and high risk (scores 5 and over) were 2.32 (95% CI: 1.90-2.82) and 7.77 (95% CI: 2.47-24.47) respectively. When applied in validation cohort, the score showed good performance with AuROC 76.7%, and illustrated 84%, and 100% certainty in low- and high-risk groups respectively.

    CONCLUSIONS: A simple and non-invasive scoring scheme of five predictors provides good prediction indices for NAFLD in MetS patients. This scheme may help clinicians in order to take further appropriate action.

  6. Maiwall R, Sarin SK, Kumar S, Jain P, Kumar G, Bhadoria AS, et al.
    Liver Int, 2017 Oct;37(10):1497-1507.
    PMID: 28393476 DOI: 10.1111/liv.13443
    BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients.

    PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997).

    RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P

  7. Duseja A, De A, Taneja S, Choudhury AK, Devarbhavi H, Hu J, et al.
    Liver Int, 2021 01;41(1):150-157.
    PMID: 32970356 DOI: 10.1111/liv.14671
    BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF).

    METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively.

    RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P 

  8. Chuah KH, Wan Yusoff WNI, Sthaneshwar P, Nik Mustapha NR, Mahadeva S, Chan WK
    Liver Int, 2019 07;39(7):1315-1324.
    PMID: 30825254 DOI: 10.1111/liv.14084
    INTRODUCTION: MACK-3 (combination of hoMa, Ast and CK18) was reported to be a good biomarker for the diagnosis of fibrotic non-alcoholic steatohepatitis (NASH). However, there is no external validation to date.

    AIM: To evaluate the accuracy of MACK-3 for the diagnosis of fibrotic NASH.

    METHODOLOGY: Consecutive adult non-alcoholic fatty liver disease (NAFLD) patients who had liver biopsy in a university hospital were included. MACK-3 was calculated using the online calculator using the following variables: fasting glucose, fasting insulin, aspartate aminotransferase (AST) and cytokeratin 18 (CK18). MACK-3 cut-offs ≤0.134 and ≥0.550 were used to predict absence and presence of fibrotic NASH, respectively. Histopathological examination of liver biopsy specimen was reported according to the NASH Clinical Research Network Scoring System.

    RESULTS: Data for 196 subjects were analysed. MACK-3 was good for diagnosis of fibrotic NASH (area under receiver-operating characteristics curve [AUROC] 0.80), comparable to the Fibrosis-4 index (FIB4) and the NAFLD fibrosis score (NFS) and superior to the BARD score and CK18. MACK-3 was good for diagnosis of active NASH (AUROC 0.81) and was superior to other blood fibrosis tests. The overall accuracy, percentage of subjects in grey zone, sensitivity, specificity, positive predictive value and negative predictive value of MACK-3 for diagnosis of fibrotic NASH was 79.1%, 46.9%, 100%, 43.8%, 43.1% and 100%, respectively, while for diagnosis of active NASH was 90.0%, 39.3%, 84.2%, 81.4%, 88.9% and 74.5%, respectively.

    CONCLUSION: MACK-3 is promising as a non-invasive test for active NASH and fibrotic NASH and may be useful to identify patients who need more aggressive intervention.

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