Search

Abstract Liver fibrosis is a pathological condition characterized by the abnormal proliferation of liver tissue, subsequently able to progress to cirrhosis or possibly hepatocellular carcinoma. The development of artificial intelligence and deep learning have begun to play a significant role in fibrosis detection. This study aimed to develop SMART AI‐PATHO, a fully automated assessment method combining quantification of histopathological architectural features, to analyze steatosis and fibrosis in nonalcoholic fatty liver disease (NAFLD) core biopsies and employ Metavir fibrosis staging as standard references and fat assessment grading measurement for comparison with the pathologist interpretations. There were 146 participants enrolled in our study. The correlation of Metavir scoring system interpretation between pathologists and SMART AI‐PATHO was significantly correlated (Agreement = 68%, Kappa = 0.59, p‐value

Summary: Background: Obesity represents a major global health challenge with important clinical implications. Despite its recognized importance, the global disease burden attributable to high body mass index (BMI) remains less well understood. Methods: We systematically analyzed global deaths and disability-adjusted life years (DALYs) attributable to high BMI using the methodology and analytical approaches of the Global Burden of Disease Study (GBD) 2021. High BMI was defined as a BMI over 25 kg/m2 for individuals aged ≥20 years. The Socio-Demographic Index (SDI) was used as a composite measure to assess the level of socio-economic development across different regions. Subgroup analyses considered age, sex, year, geographical location, and SDI. Findings: From 1990 to 2021, the global deaths and DALYs attributable to high BMI increased more than 2.5-fold for females and males. However, the age-standardized death rates remained stable for females and increased by 15.0% for males. Similarly, the age-standardized DALY rates increased by 21.7% for females and 31.2% for males. In 2021, the six leading causes of high BMI-attributable DALYs were diabetes mellitus, ischemic heart disease, hypertensive heart disease, chronic kidney disease, low back pain and stroke. From 1990 to 2021, low-middle SDI countries exhibited the highest annual percentage changes in age-standardized DALY rates, whereas high SDI countries showed the lowest. Interpretation: The worldwide health burden attributable to high BMI has grown significantly between 1990 and 2021. The increasing global rates of high BMI and the associated disease burden highlight the urgent need for regular surveillance and monitoring of BMI. Funding: National Natural Science Foundation of China and National Key R&D Program of China.

Abstract The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p

Background/Aims: Ultrasonography has a low sensitivity for detecting early-stage hepatocellular carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic patients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Methods: Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality-adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of $4,665 (160,000 Thai Baht) in Thailand and $50,000 in the United States. Results: aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of $3,667/QALY in Thailand and $37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sensitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Conclusions: Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, especially in those with high HCC risks.

Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients. Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality. Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p

Abstract Aims Nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are common diseases worldwide. Reports of a high prevalence of CKD in NAFLD patients have been documented. Urinary neutrophil gelatinase‐associated lipocalin (NGAL) is a reliable biomarker for renal dysfunction, and it is recommended for early detection of acute kidney injury (AKI) in cirrhotic patients. Currently, there is no evidence for using urine NGAL to predict CKD in NAFLD patients. We aim to determine the proportion of CKD and identify the predictive value of NGAL and other factors associated with CKD in these patients. Methods A single‐center, cross‐sectional study was conducted between July 2018 and December 2019 in consecutive NAFLD patients diagnosed by transient elastography (TE) or liver biopsy at a tertiary care university hospital in Bangkok, Thailand. Advanced liver fibrosis is defined as fibrosis stages 3–4. The definition of CKD is estimated glomerular filtration rate (eGFR)

Abstract Nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease, and its prevalence is expected to increase in the future due to the increasing prevalence of obesity and an increasing aging population. With increases in longevity, NAFLD has emerged as a growing public health concern worldwide. NAFLD is a multisystem disease that has a strong association with metabolic risk factors. The presence of NAFLD increases the risks of liver‐ and cardiovascular‐related mortality. Many studies have found age to be an additional risk factor for advanced fibrosis, which is associated with adverse outcomes. The identification of high‐risk older persons using noninvasive methods is a key step in community management. Limitations in the diagnostic performance of current assessment methods have been encountered. This review provides an update on the new terminology that has changed from NAFLD to metabolic‐associated fatty liver disease (MAFLD), and the epidemiology, clinical characteristics, noninvasive assessment, and prognosis of older persons with NAFLD.

Abstract Circulating tumor cells (CTCs) have been shown as a surrogate for cancer progression and prognostication. We aimed to determine an association between CTCs and survival of hepatocellular carcinoma (HCC) patients. Peripheral blood was obtained from 73 HCC patients to enumerate for epithelial CTCs/8 mL blood. CTCs were detected by immunoaffinity-based method using epithelial cell adhesion molecule (EpCAM) and mucin1 (MUC1). The CTCs detection rates of BCLC stages A, B, and C patients were 65.4% (17/26), 77.3% (17/22), and 96% (24/25), respectively, p = 0.018. Patients with CTCs 36 vs. 4.6 months, p

Abstract Background and Aim Acute‐on‐chronic liver failure (ACLF) leads to multi‐organ failure related to high mortality rates. This study aimed to gather epidemiological data and validate a scoring system to predict mortality in ACLF. Methods This retrospective cohort study collected data from multicenter tertiary care hospitals in Thailand. A total of 638 hospitalized patients (acute decompensated liver disease [ADLD], 292 patients; ACLF, 346 patients) from January 2019 to June 2020 were enrolled in this study. We compared the mortality rate at days 30 and 90 between patients with ADLD and ACLF. Areas under the receiver operating characteristic (AUROC) curves of chronic liver failure–sequential organ failure assessment (CLIF‐SOFA) and other existing scoring systems were compared among patients with ACLF. Results The incidence of patients with ACLF was 54%. The main cause of chronic liver disease was alcohol (38%), with sepsis (50%) as the most common precipitating factor. ACLF with coagulopathy (AUROC 0.58, 95% confidence interval [CI]: 0.52–0.64), metabolic acidosis (AUROC 0.58, 95% CI: 0.52–0.64), and high aspartate aminotransferase (AST) (AUROC 0.59, 95% CI: 0.53–0.66) were associated with high 30‐day mortality. The 30‐day mortality rate of patients with acute decompensation and patients with ACLF was 46 and 58%, respectively. Respiratory system (P = 0.001) failure was the major end result in ACLF and constituted a significant factor to predict mortality. The AUROC of CLIF‐SOFA score was superior to that of the other predicted score (AUROC 0.64, 95% CI: 0.585–0.704). Conclusion Patients with ACLF with more organ failure and high CLIF‐SOFA score were associated with high short‐term mortality. Future studies should include an ACLF prospective registry to confirm these finding.

Abstract There is an urgent need of non-invasive tests (NITs) for monitoring treatment response and disease progression in chronic liver disease. Liver stiffness (LS) evaluated by transient elastography (TE), shear wave elastography (SWE), and magnetic resonance elastography (MRE) and serum markers e.g. APRI and FIB-4 scores were assessed at baseline and the 1-year follow-up. In all, 89 chronic hepatitis C virus (HCV) patients with sustained virological response and 93 non-alcoholic fatty liver disease (NAFLD) patients were included. There was a significantly strong correlation among imaging techniques. Using MRE as the reference standard, the area under the receiver operating characteristics curves for TE, SWE, APRI, and FIB-4 in detecting stage1–4 fibrosis were 0.88–0.95, 0.87–0.96, 0.83–0.89, and 0.79–0.92, respectively. In chronic HCV patients, the values of TE, SWE, MRE, APRI and FIB-4 significantly decreased from baseline to the 1-year follow-up. Liver steatosis did not significantly change over time. In NAFLD, compared to obese patients, non-obese patients had less LS and steatosis at baseline, and these values did not show significant changes at the 1-year follow-up. Our study suggests that the current NITs have a good correlation and accuracy in monitoring the treatment outcomes in patients with chronic liver diseases.

Abstract Background Accurate population-based data are required concerning the rate, economic impact, and long-term outcome from acute on chronic liver failures (ACLF) in hospitalized patients with cirrhosis. We aimed to discover time trends for the epidemiology, economic burden, and mortality of ACLF in Thailand. Methods We conducted a nationwide, population-based, cohort study which involved all hospitalized patients with cirrhosis in Thailand during the period between 2009 and 2013, with data from the National Health Security Office. ACLF was defined by two or more extrahepatic organ failures in patients with cirrhosis. Primary outcomes were trends in hospitalizations, hospital costs, together with inpatient mortality. Results The number of ACLF hospitalizations in Thailand doubled between 3185 in 2009 and 7666 in 2013. The average cost of each ACLF hospitalization was 3.5-fold higher than for cirrhosis ($ 1893 versus $ 519). The hospital is paid using a diagnosis-related group (DRG) payment system that is only 15% of the average treatment costs ($ 286 from $ 1893). The in-hospital fatality rate was 51% for ACLF while the additional fatality rate was 85% up to 1 year. The ACLF organ failure trends indicated sepsis with septic shock and renal failure as the majority proportion. Age, the number and types of organ failure and male sex were predictors of ACLF death. Conclusions and relevance Cirrhosis and ACLF both represent substantial and increasing health and economic burdens for Thailand. These data can assist national health care policy stakeholders to target high-risk patients with cirrhosis for care.

Background and aimsAccess to Hepatitis B virus (HBV) DNA testing to determine treatment eligibility is limited in low-income countries. Therefore, this study aimed to assess and validate the TREAT-B score proposed as the treatment threshold in an Asian cohort in determining the HBV treatment eligibility.MethodsA retrospective analysis was conducted on consecutive patients with treatment-naïve chronic HBV mono-infection who visited the liver clinic at Chulalongkorn University Hospital, Bangkok, Thailand, from 2016 to 2020. The 2018 American Association for the Study of Liver Diseases guideline was the reference standard.ResultsOverall, 825 patients with chronic HBV infection were enrolled, comprising 409 (50.4%) males, with a median age of 50 (38–58) years. Of these, 216 (26.2%), 565 (68.5%), and 377 (45.7%) were eligible for treatment based on the AASLD, TREAT-B score, and simplified WHO criteria, respectively. The area under the receiver operating characteristics curve (AUROC) of the TREAT-B ≥ 2 was better than the simplified WHO criteria (0.69 vs. 0.62, p = 0.006) for selecting patients eligible for antiviral therapy. The sensitivity and specificity of the TREAT-B ≥ 2 were 96.3% and 41.4%, respectively. Applying the TREAT-B ≥ 3 improved the specificity (89.0%) and AUROC (0.80, 95% CI 0.76–0.84, but reduced the sensitivity (70.8%) for selecting eligible patients for HBV therapy.ConclusionsIn resource-constrained countries where HBV DNA is unavailable, the TREAT-B score is an alternative criteria for indicating treatment eligibility. The TREAT-B score of ≥3 is highly accurate and may minimize the number of patients unnecessarily treated in Asian HBV patients.

Abstract Background Non-alcoholic steatohepatitis (NASH) has been recognised as a significant form of chronic liver disease and a common cause of cirrhosis and hepatocellular carcinoma, resulting in a considerable financial burden on healthcare resources. Currently, there is no information regarding the economic burden of NASH in low- and middle-income countries (LMICs). The aim of this study was to estimate the economic burden of NASH in Thailand as a lesson learned for LMICs. Methods To estimate the healthcare costs and prevalence of NASH with significant fibrosis (fibrosis stage ≥ 2) in the general Thai population, an eleven-state lifetime horizon Markov model with 1-year cycle length was performed. The model comprised Thai population aged 18 years and older. The cohort size was based on Thailand Official Statistic Registration Systems. The incidence of NASH, transitional probabilities, and costs-of-illness were based on previously published literature, including systematic reviews and meta-analyses. The age-specific prevalence of NASH was based on Thai NASH registry data. Costs were expressed in 2019 US Dollars ($). As we undertook analysis from the payer perspective, only direct medical costs were included. All future costs were discounted at an annual rate of 3%. A series of sensitivity analyses were performed. Results The estimated total number of patients with significant NASH was 2.9 million cases in 2019, based on a NASH prevalence of 5.74%. The total lifetime cost of significant NASH was $15.2 billion ($5,147 per case), representing approximately 3% of the 2019 GDP of Thailand. The probabilistic sensitivity analysis showed that the lifetime costs of significant NASH varied from $11.4 billion to $18.2 billion. Conclusions The economic burden associated with NASH is substantial in Thailand. This prompts clinicians and policy makers to consider strategies for NASH prevention and management.

Abstract Background The gold standard for the diagnosis of liver fibrosis and nonalcoholic fatty liver disease (NAFLD) is liver biopsy. Various noninvasive modalities, e.g., ultrasonography, elastography and clinical predictive scores, have been used as alternatives to liver biopsy, with limited performance. Recently, artificial intelligence (AI) models have been developed and integrated into noninvasive diagnostic tools to improve their performance. Methods We systematically searched for studies on AI-assisted diagnosis of liver fibrosis and NAFLD on MEDLINE, Scopus, Web of Science and Google Scholar. The pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic odds ratio (DOR) with their 95% confidence intervals (95% CIs) were calculated using a random effects model. A summary receiver operating characteristic curve and the area under the curve was generated to determine the diagnostic accuracy of the AI-assisted system. Subgroup analyses by diagnostic modalities, population and AI classifiers were performed. Results We included 19 studies reporting the performances of AI-assisted ultrasonography, elastrography, computed tomography, magnetic resonance imaging and clinical parameters for the diagnosis of liver fibrosis and steatosis. For the diagnosis of liver fibrosis, the pooled sensitivity, specificity, PPV, NPV and DOR were 0.78 (0.71–0.85), 0.89 (0.81–0.94), 0.72 (0.58–0.83), 0.92 (0.88–0.94) and 31.58 (11.84–84.25), respectively, for cirrhosis; 0.86 (0.80–0.90), 0.87 (0.80–0.92), 0.85 (0.75–0.91), 0.88 (0.82–0.92) and 37.79 (16.01–89.19), respectively; for advanced fibrosis; and 0.86 (0.78–0.92), 0.81 (0.77–0.84), 0.88 (0.80–0.93), 0.77 (0.58–0.89) and 26.79 (14.47–49.62), respectively, for significant fibrosis. Subgroup analyses showed significant differences in performance for the diagnosis of fibrosis among different modalities. The pooled sensitivity, specificity, PPV, NPV and DOR were 0.97 (0.76–1.00), 0.91 (0.78–0.97), 0.95 (0.87–0.98), 0.93 (0.80–0.98) and 191.52 (38.82–944.81), respectively, for the diagnosis of liver steatosis. Conclusions AI-assisted systems have promising potential for the diagnosis of liver fibrosis and NAFLD. Validations of their performances are warranted before implementing these AI-assisted systems in clinical practice. Trial registration: The protocol was registered with PROSPERO (CRD42020183295).

Abstract Background Vitamin D (VD) is important in hepatic fibrogenesis in animal models and human studies. VD deficiency is associated with liver fibrosis progression. Metabolic dysfunction of the liver, as an intermediate organ for VD metabolism, contributes partly to this deficiency. We hypothesized that improving hepatic fibrosis and inflammation in chronic hepatitis C (CHC) patients after eradication with direct-acting antivirals (DAA) would increase 25-hydroxyVD [25(OH)VD] levels. Methods Eighty CHC patients (17 chronic hepatitis, and 63 cirrhosis) were enrolled. Baseline characteristics, hepatitis C viral load (VL), genotypes, liver enzymes and liver stiffness measurements (LSM) were assessed at baseline. Blood samples for 25(OH)VD and the procollagen type III N-terminal peptide (P3NP) were collected at baseline, 24 and 48 weeks. LSMs were re-evaluated at 48 weeks. Serum 25(OH)VD levels

Background/Aim The global problems of chronic liver disease and non‐alcoholic fatty liver disease (NAFLD) are increasing. We examined the prevalence of NAFLD and significant liver stiffness in an asymptomatic population and identified the predictors of significant fibrosis in NAFLD. Method We prospectively enrolled Thai subjects, aged 18–80 years, from four regions (Bangkok, Central, North, South) of Thailand from March 2013 to November 2016. All participants underwent controlled attenuation parameter (CAP) measurement for liver fat quantification and transient elastography (TE) for liver stiffness measurement (LSM). NAFLD was defined as liver fat ≥10% (CAP ≥ 306 dB/m). Of 1145 participants, 782 (68.3%) were eligible for analysis. Result The mean age ± standard deviation (SD) was 53.1 ± 4.6 years, and 71.6% were female. The mean ± SD values of CAP and LSM of the overall cohort were 241.9 ± 61.4 dB/m and 5.5 ± 3.8 kPa, respectively. The prevalence of NAFLD was 18.0%, whereas 5.4% of the cohort had nonobese NAFLD (BMI

Abstract Background The Gut and Obesity in Asia (GOASIA) Workgroup was formed to study obesity and gastrointestinal diseases in the Asia Pacific region. We aimed to 1) compare the characteristics of elderly (i.e. age ≥ 60) vs. non-elderly patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD); 2) identify predictors of advanced fibrosis in elderly patients with NAFLD; and 3) assess the performance of non-invasive fibrosis scores in the prediction of advance fibrosis in the elderly population. Methods We abstracted the data of 1008 patients with NAFLD from nine centers across eight countries. Characteristics of elderly and non-elderly patients with NAFLD were compared using 1:3 sex-matched analysis. Results Of the 1008 patients, 175 were elderly [age 64 (62–67) years], who were matched with 525 non-elderly patients [46 (36–54) years]. Elderly patients were more likely to have advanced fibrosis (35.4% vs. 13.3%; p

Accurate population‐based data are needed on the rate, economic impact, and the long‐term outcomes of readmission among patients with cirrhosis. To examine the rates, costs, and 1‐year outcomes of patients readmitted within 30 days following their index hospitalization for complications of cirrhosis, we conducted a nationwide, population‐based cohort study involving all patients with cirrhosis in Thailand from 2009 through 2013, using data from the National Health Security Office databases, which included those from nationwide hospitalizations. Readmission was captured from hospitals at all health care levels across the country within the Universal Coverage Scheme. For the 134,038 patients hospitalized with cirrhosis, the overall 30‐day readmission rate was 17%. Common causes of readmission consisted of complications of portal hypertension (47%) and infections (17%). After adjusting for multiple covariates, predictors of 30‐day readmission included hepatocellular carcinoma (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.84‐2.06), human immunodeficiency virus–related admission (OR 1.81, 95% CI 1.51‐2.17) and cholangiocarcinoma (OR 1.64, 95% CI 1.3‐2.05). In all, 2,936 deaths (13%) occurred during readmission, and an additional 14,425 deaths up to 1 year (63.5% total mortality among readmitted patients). Causes of death were mostly from liver‐related mortality. Average cost at index admission for those with a 30‐day readmission were significantly higher than those readmitted beyond 30 days or not readmitted. Conclusions: Patients hospitalized with cirrhosis complications had high rates of unscheduled 30‐day readmission. Average hospitalization costs were high, and only 36.5% of patients readmitted within 30 days survived at 1 year.

Background and Aim Fibrotic stage (FS) assessment is essential in chronic hepatitis C treatment cascade. Liver stiffness measurement (LSM) using transient elastography (TE) is reliable and correlated with liver biopsy. However, TE may not be widely available. This study aimed to evaluate the diagnostic performances of aspartate aminotransferase to platelet ratio index (APRI) and fibrosis 4 (FIB‐4) scores compared with TE. Methods We conducted a multicenter, cross‐sectional study, including all chronic hepatitis C virus (HCV) monoinfection patients with successful and reliable LSM, at 10 centers in Thailand from 2012 to 2017. Characteristics and laboratory data within 3 months of TE were retrospectively reviewed. Using TE as a reference standard, the diagnostic performances of APRI and FIB‐4 were evaluated. TE cut‐off levels of 7.1 and 12.5 kPa represented significant fibrosis (SF) and cirrhosis, respectively. Results The distribution of FS by TE in 2000 eligible patients was as follows: no SF 28.3%, SF 31.4%, and cirrhosis 40.3%. APRI ≥ 1 provided 70.1% sensitivity and 80.6% specificity, with an area under the receiver operator characteristics curve (AUROC) of 0.834 for cirrhosis. The specificity increased to 96.3% when using a cut‐off level of APRI ≥ 2. FIB‐4 ≥ 1.45 provided a sensitivity, specificity, and AUROC of 52.4%, 91.0%, and 0.829 for cirrhosis, respectively. For SF, APRI performed better than FIB‐4, with an AUROC of 0.84 versus 0.80 (P 1.45 yielded sensitivities of 82.3% and 74.4% and specificities of 65.4% and 69.8%, respectively. Conclusions APRI and FIB‐4 scores had good diagnostic performances for FS assessment compared with TE, especially for cirrhosis. APRI may be used as the noninvasive assessment in resource‐limited settings for HCV patients’ management.

Background & objectivesCirrhosis patients with worsening of the liver function are defined as acute decompensation (AD) and those who develop extrahepatic organ failure are defined as acute-on-chronic liver failure (ACLF). Both AD and ACLF have an extremely poor prognosis. However, information regarding prognostic predictors is still lacking in Asian populations. We aimed to identify prognostic factors for 30-day and 90-day mortality in cirrhosis patients who develop AD with or without ACLF.MethodsWe included 9 tertiary hospitals from Thailand in a retrospective observational study enrolling hospitalized cirrhosis patients with AD. ACLF was diagnosed according to the EASL-CLIF criteria, which defined as AD patients who have kidney failure or a combination of at least two non-kidney organ failure. Outcomes were clinical parameters and prognostic scores associated with mortality evaluated at 30 days and 90 days.ResultsBetween 2015 and 2020, 602 patients (301 for each group) were included. The 30-day and 90-day mortality rates of ACLF vs. AD were 57.48% vs. 25.50% (pConclusionsRegarding Thai patients, the CLIF-C OF score was the best predictor for 30-day and 90-day mortalities in ACLF patients, while appropriate prognostic factors for AD patients remained inconclusive.

Lenvatinib, an oral small-molecule multiple tyrosine kinase inhibitor (TKI), has been approved for first-line therapy for unresectable hepatocellular carcinoma (HCC). Proteinuria is one of the most common adverse events associated with lenvatinib treatment. We reported a 67-year-old Thai female was diagnosed with NASH cirrhosis and HCC BCLC B with TACE refractoriness. She received 8 mg of lenvatinib for 2 weeks and began to experience worsening hypertension, bilateral pleural effusion, pedal edema, hypoalbuminemia, hypercholesterolemia, and proteinuria. After exclusion of all possible causes, lenvatinib-induced nephrotic syndrome (NS) was diagnosed. One week after discontinuing the drug, her symptoms gradually improved. To date, there have been only a handful of reported cases of lenvatinib-induced nephrotoxicity. We report herein the case of lenvatinib-induced NS in a cirrhotic patient with HCC with resolution of symptoms in a short period after drug discontinuation. In addition, we reviewed all reported cases of lenvatinib-induced nephrotoxicity.

Background: The global prevalence of non-alcoholic fatty liver disease (NAFLD) continues to rise. Non-invasive diagnostic modalities including ultrasonography and clinical scoring systems have been proposed as alternatives to liver biopsy but with limited performance. Artificial intelligence (AI) is currently being integrated with conventional diagnostic methods in the hopes of performance improvements. We aimed to estimate the performance of AI-assisted systems for diagnosing NAFLD, non-alcoholic steatohepatitis (NASH), and liver fibrosis. Methods: A systematic review was performed to identify studies integrating AI in the diagnosis of NAFLD, NASH, and liver fibrosis. Pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and summary receiver operating characteristic curves were calculated. Results: Twenty-five studies were included in the systematic review. Meta-analysis of 13 studies showed that AI significantly improved the diagnosis of NAFLD, NASH and liver fibrosis. AI-assisted ultrasonography had excellent performance for diagnosing NAFLD, with a sensitivity, specificity, PPV, NPV of 0.97 (95% confidence interval (CI): 0.91–0.99), 0.98 (95% CI: 0.89–1.00), 0.98 (95% CI: 0.93–1.00), and 0.95 (95% CI: 0.88–0.98), respectively. The performance of AI-assisted ultrasonography was better than AI-assisted clinical data sets for the identification of NAFLD, which provided a sensitivity, specificity, PPV, NPV of 0.75 (95% CI: 0.66–0.82), 0.82 (95% CI: 0.74–0.88), 0.75 (95% CI: 0.60–0.86), and 0.82 (0.74–0.87), respectively. The area under the curves were 0.98 and 0.85 for AI-assisted ultrasonography and AI-assisted clinical data sets, respectively. AI-integrated clinical data sets had a pooled sensitivity, specificity of 0.80 (95%CI: 0.75–0.85), 0.69 (95%CI: 0.53–0.82) for identifying NASH, as well as 0.99–1.00 and 0.76–1.00 for diagnosing liver fibrosis stage F1–F4, respectively. Conclusion: AI-supported systems provide promising performance improvements for diagnosing NAFLD, NASH, and identifying liver fibrosis among NAFLD patients. Prospective trials with direct comparisons between AI-assisted modalities and conventional methods are warranted before real-world implementation. Protocol registration: PROSPERO (CRD42021230391)

Abstract Background Acute liver failure (ALF) is uncommon but progresses rapidly with high mortality. We investigated the incidence, etiologies, outcomes, and predictive factors for 30-day mortality in patients with ALF. Methods We conducted a population-based study of ALF patients hospitalized between 2009 and 2013 from the Thai Nationwide Hospital Admission database, which comprises 76% of all admissions from 858 hospitals across 77 provinces in Thailand. ALF was diagnosed using ICD-10 codes K72.0 and K71.11. Patients with liver cirrhosis were excluded. Results There were 20,589 patients diagnosed with ALF during the study period with 12,277 (59.6%) males and mean age of 46.6 ± 20.7 years. The incidence of ALF was 62.9 per million population per year. The most frequent causes of ALF were indeterminate (69.4%), non-acetaminophen drug-induced (26.1%), and viral hepatitis (2.5%). Acetaminophen was the presumptive cause in 1.7% of patients. There were 5502 patients (26.7%) who died within 30 days after admission. One patient (0.005%) underwent liver transplantation. The average hospital stay was 8.7 ± 13.9 days, and the total cost of management was 1075.2 ± 2718.9 USD per admission. The most prevalent complications were acute renal failure (ARF)(24.2%), septicemia (18.2%), and pneumonia (12.3%). The most influential predictive factors for 30-day mortality were ARF (HR = 3.64, 95% CI: 3.43–3.87, p

Background Replacement of vitamin D (VD) among patients with chronic hepatitis C (CHC) before viral eradication has demonstrated a protective effect on serum markers associated with hepatic fibrogenesis. We therefore hypothesized that VD may facilitate further fibrosis amelioration following curative treatment with direct-acting antivirals (DAA). Methods This study was a randomized, double-blind, placebo-controlled trial conducted between February 2018 and August 2018. Patients with CHC and VD deficiency were randomized in a 1:1 ratio to either receive ergicalciferol or placebo over 6 weeks. Biochemical analysis indicators, including 25-hydroxyvitamin D (25(OH)D), fibrogenic markers [(transforming growth factor beta 1 (TGF-β1) and tissue inhibitors of matrix metalloproteinases 1 (TIMP-1)], and fibrolytic markers [matrix metalloproteinase 9 (MMP-9) and amino terminal type III procollagen peptide (P3NP)], were assessed at baseline and at 6 weeks. Serum 25(OH)D was analyzed by a chemiluminescence immunoassay. Serum hepatic fibrogenesis markers were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Results Seventy-five patients with CHC and VD deficiency were randomly assigned to VD (n = 37) and placebo (n = 38) groups. At the end of the study, the mean serum 25(OH)D level had risen to a normal level in the VD group, but was still deficient in the placebo group (41.8 ± 9.1 vs. 18.1 ± 4.6 ng/mL, p < 0.001). Upon restoration of the VD level, there were no significant mean differences in the change from baseline for TGF-β1 (−0.6 ng/mL (95% confidence interval (95% CI) [−2.8–1.7]), p = 0.63), TIMP-1 (−5.5 ng/mL (95% CI [−26.4 –15.3]), p = 0.60), MMP-9 (122.9 ng/mL (95% CI [−69.0 –314.8]), p = 0.21), and P3NP (−0.1 ng/mL (95% CI [−2.4 –2.2]), p = 0.92) between the VD and placebo groups. Conclusion Short-term VD supplementation after DAA treatment in patients with CHC does not improve serum fibrogenesis markers and may not expedite the residual liver fibrosis healing process. Future studies are warranted to evaluate the long-term effect of VD supplementation on hepatic fibrosis regression.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA). Methods A search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics. Results Seven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36–2.79, I 2 =76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52–3.24, I 2 =67%) and 1.55 (95%CI: 1.03–2.33, I 2 =69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41–2.75, I 2 =71%), 2.09 (95%CI, 1.49–2.91, I 2 =42%) and 2.05 (95%CI, 1.59–2.64, I 2 =0%) for all CCAs, iCCA, and eCCA, respectively. Conclusions This meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted. Trial registration The protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573).

Abstract Background Patients with chronic hepatitis C (HCV) infection have high prevalence of vitamin D deficiency. Genome-wide association study data has showed that several genetic variants within vitamin D cascade affect vitamin D function. This study aimed to determine whether genetic polymorphisms of genes in the vitamin D pathway are associated with treatment responses to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. Methods The study included 623 Thai patients from 2 university hospitals diagnosed with chronic HCV infection who were treated with a PEG-IFN and ribavirin. Patients were genotyped for functional variants on vitamin D synthetic pathway including GC (rs4588, rs7041, rs22020, rs2282679), CYP2R1 (rs2060793, rs12794714), CYP27B1 (rs10877012), and DHCR7 (rs12785878). Pre-treatment predictors of sustained virologic response (SVR) at 24 weeks following discontinuation of therapy were identified using a logistic regression analysis. Results SVR was achieved by 60.5% of patients (52.9% with HCV genotype 1; 66.7% with HCV non-genotype 1). In 44.6% of HCV genotype 1-infected patients, only the variant rs12785878 in the DHCR7 locus was significantly associated with an SVR. HCV genotype 1 patients who had DHCR7 rs12785878 GT/TT had a higher rate of SVR than those with the GG allele (59.7% vs. 43.4%, P = 0.03), but in HCV non-genotype 1-infected patients, the SVR rate did not differ between the two groups (63.3% and 59.1% for GT/TT and GG allele, P = 0.54). By multivariate analysis, liver fibrosis stage 0–1 (OR = 5.00; 95% CI, 2.02–12.37; P

Background/Aim: The risk of upper gastrointestinal bleeding (UGIB) increases in patients with coronary artery disease (CAD) due to the frequent use of antiplatelets. There is some data reporting on treatment outcomes in CAD patients presenting with UGIB. We aim to determine the clinical characteristics and outcomes of UGIB in patients with CAD, compared with non-CAD patients. Patients and Methods: We conducted a prospective multi-center cohort study (THAI UGIB-2010) that enrolled 981 consecutive hospitalized patients with acute UGIB. A matched case–control analysis using this database, which was collected from 11 tertiary referral hospitals in Thailand between January 2010 and September 2011, was performed. Result: Of 981 hospitalized patients with UGIB, there were 61 CAD patients and 244 gender-matched non-CAD patients (ratio 1:4). UGIB patients with CAD were significantly older, and had more frequently used antiplatelets and warfarin than in non-CAD patients. Compared with non-CAD, the CAD patients had significantly higher Glasgow–Blatchford score, full and pre-endoscopic Rockall score and full. Peptic ulcer in CAD patients was identified more often than in non-CAD patients. UGIB patients with CAD and non-CAD had similar outcomes with regard to mortality rate, re-bleeding, surgery, embolization, and packed erythrocyte transfusion. However, CAD patients had longer duration of hospital stays than non-CAD patients. Two CAD patients died from cardiac arrest after endoscopy, whereas three non-CAD patients died from pneumonia and acute renal failure during their hospitalization. Conclusion: In Thailand, patients presenting with UGIB, concomitant CAD did not affect clinical outcome of treatment, compared with non-CAD patients, except for longer hospital stay.

Background and rationale. Cirrhosis is responsible for significant health-care costs and morbidity. This study aims to evaluate the burden of illness associated with cirrhosis, its impact on the universal coverage public health care system in Thailand.Material and methods. We used data from the 2010 Nationwide Hospital Admission Data, the National Health Security Office (NHSO), Thailand. Their baseline characteristics, hospital costs, and outcomes were analyzed according to national health insurance categories including medical welfare scheme (MWFS), social security scheme (SSS) and civil servant medical benefit scheme (CSMBS).Results. 92,301 admissions were eligible for analysis. The mean age was 55 ± 12.8 years, and 63.3% of patients were above 50 years old. The majority of patients (79%) belonged to the MWFS group. The MWFS group incurred the lowest medical expense and had the shortest hospital stay compared to the SSS and CSMBS groups. Overall in-hospital mortality was 10.7%. Cirrhosis complications include bleeding esophageal varices, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, and hepatocellular carcinoma. These complications significantly increased mortality rates compared to patients without complications (26 vs. 8.9%, p < 0.001). In-hospital mortality of patients with cirrhosis complications did not differ among the three national health insurance groups. Respiratory failure and septicemia were associated with the highest risk of death (HR 5.4; 95% CI: 4.8-5.9 and HR 5.2; 95% CI: 4.9-5.6 respectively; P < 0.001).Conclusions. Illness associated with cirrhosis is a significant public health problem in Thailand. Outcomes of cirrhosis complications did not differ between universal public health care coverage systems in Thailand.

Background and study aims: Endoscopic ultrasound-guided needle-based confocal laser endomicroscopy (EUS-nCLE) has been shown to aid in the diagnosis of cystic pancreatic lesions. This is a pilot project to study its findings in patients with solid pancreatic lesions (SPLs) with a prospective single-blinded study design. Methods: Patients with SPLs undergoing trans-gastric EUS fine needle aspiration (EUS-FNA) from July 2013 to March 2014 were prospectively enrolled. The nCLE diagnoses were compared with the final diagnoses. Researchers learned about the EUS-nCLE findings from previously published studies and applied it to diagnose SPLs. In the meantime, the findings were recorded. Results: In total, 22 patients were recruited (mean age 62.7 years, SD 13.8 years; 14 men and eight women). The mean maximal tumor diameter was 36.0 mm (SD 10.9 mm). EUS-nCLE yielded satisfactory images in all patients during the first EUS procedure and diagnosed benign and malignant SPLs in 3 and 19 patients, respectively. Final diagnoses of malignant SPLs were made in 19 patients. Benign SPLs were eventually diagnosed in three patients, with confirmed the cytology and disease stability during the 12-month follow-up period. At the end of the project, based on the results of this current study, EUS-nCLE findings for malignant SPLs were dark clumping with or without dilated vessels (> 40 μm). There were two criteria for diagnosing benign lesions which were white fibrous bands and normal acini cells. The accuracy rate of EUS-nCLE was 90.9 % (20/22). One falsely diagnosed malignant SPL was an inflammatory mass from a recent acute pancreatitis. Another one with a pancreatic neuroendocrine tumor presenting with a symptomatic pseudocyst was incorrectly diagnosed as an inflammatory mass. This was likely from sampling error of the EUS-nCLE probe in an inflammatory area. Only one patient had post EUS-FNA bleeding but did not require a blood transfusion. The inter-observer agreement among three blinded endoscopists was almost perfect (Kappa 0.82). Conclusion: EUS-nCLE is a promising technique for the diagnosis of SPLs with good inter-observer agreement. Study registration‎: TCTR20140402001

Pretreatment serum levels of interferon-γ-inducible protein-10 (IP-10, CXCL10) and dipeptidyl peptidase-4 (DPP IV) predict treatment response in chronic hepatitis C (CHC). The association between functional genetic polymorphisms of CXCL10 and DPP4 and treatment outcome has not previously been studied. This study aimed to determine the association between genetic variations of CXCL10 and DPP4 and the outcome of treatment with pegylated interferon-α (PEG-IFN-α) based therapy in Thai patients with CHC. 602 Thai patients with CHC treated using a PEG-IFN-α based regimen were genotyped for CXCL10 rs56061981 G>A and IL28B rs12979860 C>T. In addition, in patients infected with CHC genotype 1, DPP4 (rs13015258 A>C, rs17848916 T>C, rs41268649 G>A, and rs 17574 T>C) were genotyped. Correlations between single nucleotide polymorphisms, genotype, and treatment response were analyzed. The rate of sustained virologic response (SVR) was higher for the CC genotype of IL28B rs12979860 polymorphisms than for non-CC in both genotype 1 (60.6% vs. 29.4%, P < 0.001) and non-genotype 1 (69.4% vs. 49.1%, P < 0.05) CHC. SVR was not associated with the CXCL10 gene variant in all viral genotypes or DPP4 gene polymorphisms in viral genotype1. Multivariate analysis revealed IL28B rs12979860 CC genotype (OR = 3.12; 95% CI, 1.72-5.67; P < 0.001), hepatitis C virus RNA < 400,000 IU/ml (OR = 2.21; 95% CI, 1.22-3.99, P < 0.05), age < 45 years (OR = 2.03; 95% CI, 1.11-3.68; P < 0.05), and liver fibrosis stage 0-1 (OR = 1.64; 95% CI, 1.01-2.65, P < 0.05) were independent factors for SVR. Unfavorable IL28B rs12979860 CT or TT genotypes with the CXCL10 rs56061981 non-GG genotype were associated with a higher SVR than GG genotype (66.7% vs. 33.0%, P = 0.004) in viral genotype 1. In Thai CHC genotype 1 infected patients with an unfavorable IL28B rs12979860 CT/TT genotype, the complementary CXCL10 polymorphism strongly enhances prediction of treatment response.

Background and study aims: In overt obscure gastrointestinal bleeding (OV), double balloon endoscopy (DBE) is recommended as one of the most important investigations as it can provide both diagnosis and treatment. However, there is no set standard on the timing of DBE in OV. The aim of this study was to compare the diagnostic and therapeutic yields between urgent and non-urgent DBE in patients with OV. Patients and methods: Between January 2006 and February 2013, 120 patients with OV who underwent DBE were retrospectively reviewed. An urgent DBE was defined as DBE performed within 72 h from the last visible gastrointestinal bleeding (n = 74) whereas a non-urgent DBE was defined as DBE performed after 72 h (n = 46). Diagnostic yields, therapeutic impact and clinical outcomes were evaluated. Results: Diagnostic yield in urgent DBE was significantly higher than that in non-urgent DBE (70 % versus 30 %; P