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Introduction: The utility of serial procalcitonin (PCT) measurements in cirrhotic patients with systemic inflammatory response syndrome (SIRS) is not well understood. This study aimed to assess the effectiveness of serial PCT measurements for diagnosing bacterial infections and predicting 30-day mortality in this population., Methods: We prospectively studied 120 cirrhotic patients with SIRS, 64.2% of whom had bacterial infections. Serial PCT levels were measured within the first 72 hours of admission., Results: Patients with bacterial infections had significantly higher PCT levels at admission, 24 hours, and 72 hours compared to those without infections. PCT values >0.5 ng/mL within 72 hours demonstrated high sensitivity (81.8-87.5%) but moderate specificity (27.9-44.2%) for diagnosing bacterial infections. Serial PCT monitoring, including the 72-hour/baseline ratio and changes in PCT over 72 hours, provided insights into the evolution of bacterial infections and short-term mortality. Patients with a PCT 72-hour/baseline ratio >0.8 had higher 30-day mortality than those with a ratio <0.5 (50.0% vs. 25.6%; OR 3.91, 95% CI 1.40-10.97). Patients whose PCT levels decreased by >50% had lower 30-day mortality than those with increasing levels (23.3% vs. 46.7%; OR 0.25, 95% CI 0.08-0.74). Patients with MELD scores >15 and bacterial infections who experienced a PCT decrease of <50% had higher 30-day mortality than those with greater reductions (57.7% vs. 25.0%, p=0.021)., Discussion: Serial PCT measurements within 72 hours of admission are useful for determining bacterial infections and mortality in cirrhotic patients with SIRS. PCT monitoring may optimize antibiotic use and enhance early risk stratification, potentially improving patient outcomes., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background and Aim: Patients with type 2 diabetes mellitus (T2DM) face a heightened susceptibility to advanced fibrosis, a condition linked to adverse clinical outcomes. However, reported data on liver fibrosis severity among individuals with T2DM vary significantly across studies with diverse characteristics. This meta-analysis aimed to estimate the global prevalence of advanced fibrosis among T2DM patients., Methods: A comprehensive systematic search of the EMBASE and MEDLINE databases from inception to November 2022 was conducted to identify studies assessing advanced fibrosis in individuals with T2DM. Random-effects models were utilized to calculate point estimates of prevalence, accompanied by 95% confidence interval (CI). Meta-regression with subgroup analysis was employed to address heterogeneity., Results: We identified 113 eligible studies involving 244,858 individuals from 29 countries. Globally, the prevalence of advanced fibrosis among T2DM patients was 19.5% (95% CI 16.8-22.4%). Regionally, the prevalence rates were as follows: 60.5% in West Asia (95% CI 50.3-70.4%), 24.4% in South Asia (95% CI 16.2-33.7%), 20.1% in East Asia (95% CI 14.7-26.1%), 20.0% in Europe (95% CI 15.8-24.6%), 15.8% in North America (95% CI 11.0-21.3%), and 11.3% in South America (95% CI 6.2-17.5%). The prevalence of advanced fibrosis varied notably based on the study setting and diagnostic methodology employed. Meta-regression models highlighted that 45.13% of the observed heterogeneity could be attributed to combined diagnostic modality and study setting., Conclusions: Globally, approximately one fifth of the T2DM population presents advanced fibrosis, with prevalence differing across geographical regions. Our findings underscore the need for effective strategies to alleviate its global burden., (© 2024 The Author(s). Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Accurate early detection of ileocolonic lesions in patients with chronic lower gastrointestinal symptoms (LGISs) is often difficult due to the rarity of early-stage alarm signs. This study assesses the effectiveness of noninvasive blood and stool biomarkers in diagnosing ileocolonic lesions in patients with chronic LGISs undergoing colonoscopy., Methods: We conducted a prospective study between April 2020 and July 2022 involving patients with LGISs lasting a month or more. Before colonoscopy, we gathered clinical data, blood samples for C-reactive protein (CRP) and stool samples for fecal immunochemical test (FIT) and fecal calprotectin (FC) analysis., Results: Of 922 participants analyzed (average age 62 years, 37% male), 130 (14.1%) had significant colonoscopy findings, including cancer, advanced adenoma, and inflammatory conditions. Test effectiveness showed an area under the curve of 0.630 for alarm features, 0.643 for CRP, 0.781 for FIT, and 0.667 for FC. Combining stool tests with alarm features improved diagnostic precision. Those without alarm features had a high negative predictive value of 0.97 with low threshold FIT and FC, missing minimal significant lesions, and no cancer. For patients with alarm features, dual high-cutoff test positivity showed a positive predictive value of 0.67. Adding CRP to fecal tests did not enhance accuracy., Discussion: FIT and FC are valuable in evaluating LGISs. Negative results at low cutoffs can delay colonoscopy in limited resource settings while positive results at dual high cutoffs substantiate the need for the procedure., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

The systematic review aimed to assess the risks of metabolic dysfunction-associated steatotic liver disease (MASLD) on all-cause and cause-specific mortality in patients with type 2 diabetes (T2DM). EMBASE and MEDLINE were searched from inception to June 2022 for observational studies examining the relationship between MASLD and the risk of mortality among T2DM patients. Meta-analysis was conducted using random-effects models with hazard ratios (HRs) to quantify the risk of mortality. A total of 5877 articles were screened, and ultimately, 12 eligible studies encompassing 368 528 T2DM patients, with a median follow-up of 8.9 years (interquartile range, 4.7-14.5), were included. Our analysis revealed a significant association between MASLD and an increased risk of all-cause mortality in T2DM patients [HR 1.28; 95% confidence interval (CI), 1.05-1.58; I 2  = 90%]. Meta-regression analyses did not show significant effects of mean age, mean BMI, and percentage of smokers, hypertension, and hyperlipidemia on the association between MASLD and the risk of all-cause mortality. However, we found that MASLD was not significantly associated with mortality related to cardiovascular diseases (HR 1.05; 95% CI, 0.82-1.35; I2  = 0%) or cancer (HR 1.21; 95% CI, 0.41-3.51; I 2  = 79%) among patients with T2DM. No publication bias was observed. This comprehensive meta-analysis provides substantial evidence supporting a significant association between MASLD and an increased risk of all-cause mortality among the T2DM population. These findings underscore the potential benefits of screening for MASLD in T2DM patients, aiding in the early identification of high-risk individuals and enabling risk modification strategies to improve survival., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: There is an urgent need for noninvasive tests to identify patients with psoriasis at risk of significant liver fibrosis., Objectives: To externally validate the ability of the Steatosis-Associated Fibrosis Estimator (SAFE) score to detect significant liver fibrosis in patients with psoriasis using transient elastography (TE) as a reference., Methods: We analysed data from 75 patients with psoriasis, including TE, SAFE score, Fibrosis-4 Index (FIB-4) and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Significant liver fibrosis was defined as TE values ≥ 7.1 kPa. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUROC)., Results: Fifteen patients (20%) exhibited significant liver fibrosis. The AUROCs for the SAFE and FIB-4 scores were 0.82 [95% confidence interval (CI) 0.67-0.97] and 0.62 (95% CI 0.45-0.79), respectively. The SAFE score outperformed the FIB-4 Index (P = 0.01) but was comparable with the NFS (P = 0.05) in predicting significant fibrosis. Using thresholds of < 0, 0 to < 100 and ≥ 100, the SAFE score categorized 36, 24 and 15 patients into low, intermediate and high-risk groups for significant fibrosis, respectively. The negative predictive value for excluding significant fibrosis with a SAFE score of < 0 was 94.4%, and the positive predictive value for diagnosing significant fibrosis with a SAFE score of > 100 was 53.3%. The duration of psoriasis, joint involvement and methotrexate treatment did not affect the diagnostic ability of the SAFE score whereas age of the patient did., Conclusions: The SAFE score demonstrated good accuracy in assessing clinically significant fibrosis among patients with psoriasis. This score should prove valuable for risk stratification and patient management in dermatology practice., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The precise estimation of cases with significant fibrosis (SF) is an unmet goal in non-alcoholic fatty liver disease (NAFLD/MASLD)., Aims: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients., Methods: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria)., Results: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p < 0.001, each). ML models showed 7%-12% better discrimination than FIB-4 to detect SF. Optimised random forest (RF) yielded best NPV/F1 in overall set (0.947/0.754), test set (0.798/0.588) and validation set (0.852/0.559), as compared to FIB4 in overall set (0.744/0.499), test set (0.722/0.456), and validation set (0.806/0.507). Compared to FIB-4, RF could pick 10 times more patients with SF, reduce unnecessary referrals by 28%, and prevent missed referrals by 78%. Age, AST, ALT fasting plasma glucose, and platelet count were top features determining the SF. Sequential use of SAFE < 140 and FIB4 < 1.2 (when SAFE > 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set)., Conclusions: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients., (© 2024 John Wiley & Sons Ltd.)

Introduction: Previous research has examined the association between coffee and tea consumption and non-alcoholic fatty liver disease (NAFLD). Preclinical studies have indicated the potential hepatoprotective properties of cocoa/chocolate. However, clinical research on the consumption of cocoa/chocolate and soft drinks and their relation to NAFLD, particularly among individuals with metabolic syndrome, is limited. This study primarily aimed to assess the association between beverage consumption and NAFLD in these patients., Methods: This cross-sectional study enrolled adult patients with metabolic syndrome visited the Medicine Outpatient Department at Siriraj Hospital, Thailand, from November 2011 to January 2013. The exclusion criteria were secondary causes of hepatic steatosis, such as excessive alcohol use, viral hepatitis, or drug-induced hepatitis. Participants completed a 23-item self-administered questionnaire covering their beverage consumption habits, including type, frequency, volume, duration, and additives in drinks, namely, coffee, tea, cocoa/chocolate, and soft drinks. To ensure accurate responses, these questionnaires were supplemented by face-to-face interviews. Ultrasonography was employed early in the methodology to diagnose NAFLD. Univariable analyses were used to compare the beverage consumption behaviors of participants with and without NAFLD. Multivariable logistic regression was used to adjust for potential confounders, including total beverage energy intake, age, anthropometric data, laboratory results, and comorbidities., Results: This study included 505 patients with metabolic syndrome. Of these, 341 (67.5%, 95%CI: 63.2-71.6%) were diagnosed with NAFLD. The consumption rates of coffee, cocoa/chocolate, and soft drinks were similar between the two groups. However, tea consumption was significantly more common in patients with NAFLD (68.3% vs. 51.8%, p  < 0.001). The groups had no significant differences in caffeine intake or total energy intake from beverages. Notably, daily intake of three or more cups of coffee was correlated with a reduced prevalence of NAFLD, with an adjusted odds ratio of 0.35 (95%CI: 0.14-0.89)., Conclusion: This study revealed that patients with metabolic syndrome, irrespective of NAFLD status, exhibited similar patterns of beverage consumption. While no definitive associations were identified between the intake of coffee, tea, cocoa/chocolate, or soft drinks and NAFLD, a notable exception was observed. A higher consumption of coffee (≥3 cups daily) was associated with a lower prevalence of NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kositamongkol, Ngaohirunpat, Samchusri, Chaisathaphol, Srivanichakorn, Washirasaksiri, Auesomwang, Sitasuwan, Tinmanee, Sayabovorn, Charatcharoenwitthaya and Phisalprapa.)

Scoring systems for metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with prediabetes have not been extensively explored. This study aimed to investigate the prevalence of MASLD and to develop predictive tools for its detection in high cardiometabolic people with prediabetes. A cross-sectional study was conducted using baseline data from the prediabetes cohort. All participants underwent transient elastography to assess liver stiffness. MASLD was defined using a controlled attenuation parameter value > 275 dB/m and/or a liver stiffness measurement ≥ 7.0 kPa. Cases with secondary causes of hepatic steatosis were excluded. Out of 400 participants, 375 were included. The observed prevalence of MASLD in individuals with prediabetes was 35.7%. The most effective predictive model included FPG ≥ 110 mg/dL; HbA1c ≥ 6.0%; sex-specific cutoffs for HDL; ALT ≥ 30 IU/L; and BMI levels. This model demonstrated good predictive performance with an AUC of 0.80 (95% CI 0.73-0.86). At a cutoff value of 4.5, the sensitivity was 70.7%, the specificity was 72.3%, the PPV was 58.8%, and the NPV was 81.5%. Our predictive model is practical, easy to use, and relies on common parameters. The scoring system should aid clinicians in determining when further investigations of MASLD are warranted among individuals with prediabetes, especially in settings with limited resources.

Background and Aims: The heritability of nonalcoholic fatty liver disease (NAFLD) in lean individuals is undetermined. This familial aggregation study aimed to evaluate familial linkage for NAFLD and the risk of NAFLD among first-degree relatives of probands with lean NAFLD., Methods: This study prospectively recruited cohorts of probands with lean NAFLD, probands with obese NAFLD, and lean probands with non-NAFLD and their respective first-degree relatives. A total of 257 participants were evaluated for liver steatosis, defined by the controlled attenuation parameter ≥288 dB/m 2 , metabolic characteristics, and the PNPLA3, TM6SF2, and MBOAT7 polymorphisms., Results: The prevalence of NAFLD in first-degree relatives of lean NAFLD probands (39.9%) was similar to that in the obese NAFLD group (36.9%) and was significantly higher than in lean persons without NAFLD (19.1%). First-degree relatives of probands with NAFLD who were male, and had central obesity, hypertriglyceridaemia, insulin resistance, and the PNPLA3 rs738409C>G allele had a significantly higher prevalence of NAFLD. After multivariable adjustment for gender, metabolic characteristics, and the PNPLA3 rs738409C>G allele, first-degree relatives of probands with lean NAFLD (odds ratio [OR], 5.13; 95% CI, 1.77-14.86) and obese NAFLD (OR, 3.20; 95% CI, 1.14-8.99) exhibited an increased risk of NAFLD compared with those of lean controls without NAFLD., Conclusions: Our well-phenotype cohorts revealed familial clustering of NAFLD and higher risks of NAFLD in first-degree relatives of probands with lean or obese NAFLD. The findings encourage clinicians caring for NAFLD patients to be more vigilant for NAFLD in their family members., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Competing Interests: Conflicts of interest: C.E.M.G. reports research grants and/or honoraria from AbbVie, Almirall, AnaptysBio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Eli Lilly, Evelo Biosciences, GSK, Inmagene, Janssen, Kyowa Kirin, ONO Pharmaceuticals, Novartis, UCB Pharma and the LEO Foundation.

Background: Accumulating evidence suggests a potential relationship between non-alcoholic fatty liver disease (NAFLD) and fatty pancreas, as both conditions are associated with fat deposition in the liver and pancreas, respectively. The meta-analysis aimed to investigate the bidirectional association between NAFLD and fatty pancreas, as well as their respective effects on disease severity., Methods: A systematic search of the EMBASE and MEDLINE databases, from inception to August 2022, was conducted to identify observational studies examining the association between NAFLD and fatty pancreas, as well as their impact on disease severity. The pooled odds ratio (OR) with a 95% confidence interval (CI) was estimated using a random-effects model., Results: Our analysis included 26 case-control or cross-sectional studies, comprising 67,803 participants. We observed a significant association between NAFLD and an increased odds of having fatty pancreas (OR, 6.18; 95% CI, 4.49-8.51; I2 = 92%). Similarly, fatty pancreas was significantly associated with an increased odds of having NAFLD (OR, 9.56; 95% CI, 5.09-17.95; I2 = 83%). Furthermore, the presence of fatty pancreas was associated with a 1.75-fold increased risk of severe NAFLD based on ultrasonographic classification (95% CI, 1.46-2.10; I2 = 0%). Among NAFLD patients, the coexistence of fatty pancreas was associated with a trend towards increased odds of having non-alcoholic steatohepatitis (OR, 3.52; 95% CI, 0.65-18.93; I2 = 82%) and advanced fibrosis (OR, 2.47; 95% CI, 0.52-11.80; I2 = 76%)., Conclusion: This meta-analysis discloses a bidirectional association between NAFLD and fatty pancreas, emphasizing the importance of understanding the intricate relationship between these two conditions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: PC has been an editorial board member of Journal of Clinical and Translational Hepatology since 2013, the author has no other conflict of interests related to this publication.

Introduction: Cytomegalovirus (CMV) viral load detected by real-time polymerase chain reaction (PCR) in plasma or stool may facilitate detection of CMV colitis., Methods: This prospective study enrolled 117 patients with clinically suspected CMV colitis. Patients presenting with gastrointestinal symptoms and having increased risk of CMV infection were eligible. All participants underwent colonoscopy with tissue biopsy. Five patients underwent colonoscopy twice because of clinical recurrence, resulting in a total of 122 colonoscopies. Stool CMV-PCR and plasma CMV-PCR were performed within 7 days before/after colonoscopy. Twenty asymptomatic volunteers also underwent the same protocol., Results: Twenty-seven (23.1%) of 122 colonoscopies yielded positive for CMV colitis. The sensitivity and specificity was 70.4% and 91.6% for stool CMV-PCR and 66.7% and 94.7% for plasma CMV-PCR, respectively. The sensitivity of either positive plasma or positive stool CMV-PCR was 81.5%, which is significantly higher than that of plasma CMV-PCR alone ( P = 0.045). However, positive results from both tests yielded a specificity of 95.8%, which is significantly higher than that of stool CMV-PCR alone ( P = 0.045). There was a good and significant correlation between stool CMV-PCR and plasma CMV-PCR ( r = 0.71, P < 0.01), and both tests significantly correlated with the cytomegalic cell count ( r = 0.62, P < 0.01 for stool and r = 0.64, P < 0.01 for plasma). There were no positive stool or plasma CMV-PCR assays among volunteers., Discussion: The results of this study strongly suggest that the combination of stool CMV-PCR and plasma CMV-PCR can be used to confidently rule in (both positive) or rule out (both negative) a diagnosis of CMV colitis., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: International guidelines for hepatitis B infection (HBV) recommend initiating antiviral treatment based on viral replication with inflammation or fibrosis. HBV viral loads and liver fibrosis measurements are not widely available in resource-limited countries. Aim: To develop a novel scoring system for the initiation of antiviral treatment in HBV-infected patients. Methods: We examined 602 and 420 treatment-naïve, HBV mono-infected patients for derivation and validation cohorts. We performed regression analysis to identify parameters associated with the initiation of antiviral treatment based on the European Association for the Study of the Liver (EASL) guidelines. The novel score was developed based on these parameters. Results: The novel score (HePAA) was based on HBeAg (hepatitis B e-antigen), the platelet count, alanine transaminase, and albumin. The HePAA score showed excellent performance, with AUROC values of 0.926 (95% CI, 0.901-0.950) for the derivation cohort and 0.872 (95% CI, 0.833-0.910) for the validation cohort. The optimal cutoff was ≥3 points (sensitivity, 84.9%; specificity, 92.6%). The HePAA score performed better than the World Health Organization (WHO) criteria and the Risk Estimation for HCC in Chronic Hepatitis B (REACH-B) score, and it performed similarly to the Treatment Eligibility in Africa for HBV (TREAT-B) score. Conclusions: The HePAA scoring system is simple and accurate for chronic hepatitis B treatment eligibility in resource-limited countries.

Background and Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is prevalent in patients with chronic hepatitis B (CHB). The effect of the histologic MAFLD phenotype on long-term CHB outcomes is unknown. We performed a longitudinal study to determine the prognostic relevance of biopsy-proven hepatic steatosis and steatohepatitis for CHB patients., Methods: Clinical and laboratory data were obtained from CHB patients who underwent liver biopsy during 2002-2008 and were treated with antiviral drugs. A hepatopathologist reviewed the biopsy specimens. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (aHR) of outcomes, including all-cause mortality, liver transplantation, and liver-related events., Results: In accordance with Brunt's classification, 408 patients had steatohepatitis ( n =34), "steatosis but not steatohepatitis" ( n =118), or "non-steatosis" ( n =256). All steatohepatitis patients had features of metabolic dysfunction. Over a mean follow-up of 13.8±3.1 years, 18 patients died or underwent liver transplantation. In multivariate-adjusted analysis, steatohepatitis (aHR, 6.37; 95% confidence interval [CI]: 1.59-25.5) compared with non-steatosis and advanced fibrosis (aHR, 11.3; 95% CI: 1.32-96.3) compared with no fibrosis were associated with overall mortality/liver transplantation. Thirty-five patients developed 43 liver-related events, among which 32 were hepatocellular carcinoma. These events were associated with steatohepatitis (aHR, 5.55; 95% CI: 2.01-15.3) compared with non-steatosis and advanced fibrosis (aHR, 6.23; 95% CI: 1.75-22.2) compared with no fibrosis. The steatosis but not steatohepatitis group had a non-significantly higher risk of overall mortality and liver-related events., Conclusions: Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in CHB patients., Competing Interests: PC has been an editorial board member of Journal of Clinical and Translational Hepatology since 2013, TT has been an associate editor of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflicts of interest related to this publication., (© 2023 Authors.)

Currently, scientific interest has focused on fat accumulation outside of subcutaneous adipose tissue. As various imaging modalities are available to quantify fat accumulation in particular organs, fatty pancreas has become an important area of research over the last decade. The pancreas has an essential role in regulating glucose metabolism and insulin secretion by responding to changes in nutrients under various metabolic circumstances. Mounting evidence has revealed that fatty pancreas is linked to impaired β-cell function and affects insulin secretion with metabolic consequences of impaired glucose metabolism, type 2 diabetes, and metabolic syndrome. It has been shown that there is a connection between fatty pancreas and the presence and severity of nonalcoholic fatty liver disease (NAFLD), which has become the predominant cause of chronic liver disease worldwide. Therefore, it is necessary to better understand the pathogenic mechanisms of fat accumulation in the pancreas and its relationship with NAFLD. This review summarizes the epidemiology, diagnosis, risk factors, and metabolic consequences of fatty pancreas and discusses its pathophysiology links to NAFLD., Competing Interests: PC has been an editorial board member of Journal of Clinical and Translational Hepatology since 2013. The other authors have no conflict of interests related to this publication., (© 2022 Authors.)

Background: Palliative endobiliary drainage is the mainstay treatment for unresectable malignant biliary obstruction (MBO). Despite optimal drainage, the survival benefit is arguable. This study aimed to identify factors predicting post-endoscopic drainage mortality and develop and validate a mortality prediction model., Methods: We retrospectively analyzed data for 451 patients with unresectable pancreatobiliary cancers undergoing first endoscopic retrograde cholangiopancreatography (ERCP)-guided endobiliary stent placement between 2007 and 2017. We randomly assigned patients in a 3:1 fashion into a derivation cohort (n=339) and validation cohort (n=112). Predictors for 90-day mortality post-stenting were identified from the derivation cohort. A prediction model was subsequently developed and verified with the validation cohort., Results: The overall 90-day mortality rate of the derivation cohort was 46.9%, and the mean age was 64.2 years. The 2 most common diagnoses were cholangiocarcinoma (53.4%) and pancreatic cancer (35.4%). In all, 34.2% had liver metastasis. The median total bilirubin (TB) level was 19.2 mg/dL, and the mean serum albumin was 3.2 g/dL. A metallic stent was used for 64.6% of the patients, and the median stent patency time was 63 days. A total of 70.8% had TB improvement of more than 50% within 2 weeks after stenting, and 14.5% were eligible for chemotherapy. Intrahepatic obstruction (OR=5.69; P =0.023), stage IV cancer (OR=3.01; P =0.001), pre-endoscopic serum albumin (OR=0.48; P =0.001), TB improvement within 2 weeks after stenting (OR=0.57; P =0.036), and chemotherapy after ERCP (OR=0.11; P <0.001) were associated with 90-day mortality after stenting. The prediction model was developed to identify the risk of death within 90 days post-stent placement. The AUROC was 0.76 and 0.75 in derivation and validation cohorts. Patients with a score ≥ 1.40 had a high likelihood of death, whereas those scoring < -1.50 had a low likelihood of death. Additionally, a score ≥ 0.58 provided a 75.2% probability of death, which highlights the usability of the model., Conclusions: This study proposes a useful validated prediction model to forecast the 90-day mortality of unresectable MBO patients after stenting. The model permits physicians to stratify the death risk and may be helpful to provide a proper palliative strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Termsinsuk, Charatcharoenwitthaya and Pausawasdi.)

Background: Endoscopic drainage is the primary treatment for unresectable malignant biliary obstruction (MBO). This study developed and validated a pre-endoscopic predictive score for clinical success after stent placement., Methods: Patients with unresectable MBO undergoing ERCP-guided endobiliary stent placement between 2007 and 2017 were randomly divided into derivation (n = 383) and validation (n = 128) cohorts. To develop the risk score, clinical parameters were built by logistic regression to predict (1) ≥ 50% total bilirubin (TB) resolution within 2 weeks and (2) bilirubin normalization (TB level <1.2 mg/dL) within 6 weeks following stenting. The scoring scheme was applied to the validation cohort to test its performance., Results: A ≥ 50% TB resolution within 2 weeks was shown in 70.5% of cases. The risk scoring scheme had areas under the receiver operating characteristic curve (AUROC) of 0.70 (95% CI, 0.64-0.76) and 0.67 (95% CI, 0.57-0.77) in the derivation and validation cohorts, respectively. Thirty-one percent had TB normalization within 6 weeks after stenting. Significant predictors for TB normalization were extrahepatic biliary obstruction (odds ratio [OR] = 2.35), pre-endoscopic TB level (OR = 0.88), and stent type (OR = 0.42). The AUROC of a risk score for predicting TB normalization within 6 weeks was 0.78 (95% CI, 0.72-0.83) and 0.76 (95% CI, 0.67-0.86) in the derivation and validation cohorts, respectively. A score > 1.30 yielded a specificity of 98% and a positive predictive value of 84% for predicting TB normalization. A score of < -4.18 provided a sensitivity of 80%-90% and a negative predictive value of 90%-93% for predicting the absence of TB normalization., Conclusions: The pre-endoscopic scoring system comprising biliary obstruction level, liver biochemistry, and type of stent provides prediction indices for TB normalization within 6 weeks after stenting. This scheme may help endoscopists identify patients with unresectable MBO suited for palliative stenting., Competing Interests: The authors have declared that no competing interests exist.

Metabolic syndrome (MetS) patients are at higher risk for nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular diseases (ASCVD), and death. Given a lack of longitudinal data on patients with MetS in Southeast Asia, this study investigated the incidence of NAFLD and ASCVD and the all-cause mortality rate during a 10-year follow-up of Thai patients with MetS. Retrospective data were collected on 496 MetS patients with ultrasonography or transient elastography results. The patients had been followed up continuously by a university hospital between October 2011 and November 2021, and their mean age was 61.0 ± 10.9 years. Patients with secondary causes of hepatic steatosis were excluded. Cox proportional hazards regression models with time-varying covariates were adopted. During the 10-year follow-up, 17 patients (11.2%) developed NAFLD, and 27 (6.4%) developed ASCVD. The NAFLD and ASCVD incidence rates were 21.7 and 10.9 events per 1000 person years, respectively. The mortality rate was 14.2 deaths per 1000 person years. The prevalence of hypertension, dyslipidemia, ASCVD, NAFLD, advanced fibrosis, and cirrhosis at baseline was significantly higher in the nonsurvival group. The NAFLD incidence and mortality rate of patients with MetS were lower than those in previous studies. Intensive, holistic, and continuous care should be considered for better outcomes.

Background: Colorectal cancer (CRC) screening uptake is generally low in the Asia Pacific and physicians' recommendations affect the screening participation., Objective: The study aimed to assess Thai physicians' recommendations for CRC screening, and the awareness of and adherence to international guidelines., Methods: A survey containing questions assessing physicians' demographic data, screening recommendations, and awareness of the international CRC screening guidelines assessed by clinical vignettes. Independent predictors of physicians' recommendations for CRC screening were determined by logistic regression analysis., Results: Five hundred and eighty-sixth of 1,286 (46%) physicians completed the survey, and 58% of them offered CRC screening. The majority of colorectal surgeons (91%) and gastroenterologists (86%) endorsed screening, whereas 35% of primary care physicians recommended screening. The patient's age was the only factor influencing the physician's decision to offer CRC screening (OR, 2.75: 95% CI, 1.61-4.67). Colonoscopy was the most recommended modality among specialists, whereas 60% of primary care physicians offered fecal occult blood tests (FOBTs). The guidelines awareness was noted in 81% of participants, with the highest rates among gastroenterologists and colorectal surgeons. Gastroenterologists were more likely to adhere to the guidelines than surgeons, but both recommended shorter interval surveillance colonoscopy than guidelines recommendations in cases of small hyperplastic rectosigmoid polyps., Conclusions: Recommendations for CRC screening and awareness of guidelines vary among different specialties. A low proportion of primary care physicians recommended screening and colorectal surgeons and gastroenterologists recommended shorter intervals for surveillance of small hyperplastic polyp than suggested by guidelines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pausawasdi, Tongpong, Geeratragool and Charatcharoenwitthaya.)

This study aims to investigate the effects of COVID-19 on clinical outcomes of non-COVID-19 patients hospitalized for upper gastrointestinal bleeding (UGIB) during the pandemic. A retrospective review is conducted. We recruited patients with UGIB admitted during the pandemic’s first wave (April 2020 to June 2020), and the year before the pandemic. The outcomes between the two groups were compared using propensity score matching (PSM). In total, 60 patients (pandemic group) and 460 patients (prepandemic group) are included. Patients admitted during the pandemic (mean age of 67 ± 14 years) had a mean Glasgow−Blatchford score of 10.8 ± 3.9. They were older (p = 0.045) with more underlying malignancies (p = 0.028), had less history of NSAID use (p = 0.010), had a lower platelet count (p = 0.007), and had lower serum albumin levels (p = 0.047) compared to those admitted before the pandemic. Esophagogastroduodenoscopy (EGD) was performed less frequently during the pandemic (43.3% vs. 95.4%, p < 0.001). Furthermore, the procedure was less likely to be performed within 24 h after admission (p < 0.001). After PSM, admissions during the pandemic were significantly associated with decreased chances of receiving an endoscopy (adjusted odds Ratio (OR), 0.02; 95% CI, 0.003−0.06, p < 0.001) and longer hospital stay (adjusted OR, 2.17; 95% CI, 1.13−3.20, p < 0.001). Additionally, there was a slight increase in 30-day mortality without statistical significance (adjusted OR, 1.92; 95% CI, 0.71−5.19, p = 0.199) and a marginally higher rebleeding rate (adjusted OR, 1.34; 95% CI, 0.44−4.03, p = 0.605). During the pandemic, the number of EGDs performed in non-COVID-19 patients with UGIB decreased with a subsequent prolonged hospitalization and potentially increased 30-day mortality and rebleeding rate.

This study investigated differences in the clinical data and prevalence of lean and non-lean patients with non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). Data on patients with MetS who had results of ultrasonography or transient elastography were collected from a Thai university hospital database. Patients with exclusion criteria for NAFLD diagnosis were excluded. Patients' clinical characteristic and the performances of three non-invasive scoring systems (fatty liver index [FLI], fibrosis-4 [FIB-4] index, and NAFLD fibrosis score [NFS]) were evaluated. The 743 subjects were classified into two groups: lean MetS (131 patients) and non-lean MetS (612 patients). The NAFLD prevalence in the non-lean group (62.6%) was higher than that in the lean group (31.3%). The age-adjusted odds ratio was 3.43. Advanced fibrosis was detected in 7.6% of lean patients and 10.8% of non-lean patients. FLI was not sensitive enough to detect NAFLD in the lean group at a high cutoff, but it performed acceptably at a low cutoff. FIB-4 performed better than NFS in determining advanced fibrosis. NAFLD was more common in non-lean than lean patients. Lean patients with MetS had a relatively higher risk of NAFLD than the general population. FLI and FIB-4 index performed acceptably in both groups.

Background/aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a standard procedure for obtaining tissue from lesions near the gastrointestinal lumen. However, there is a scarcity of information on the diagnostic performance of EUS-FNA for abdominal lymphadenopathy of unknown causes. To assess the accuracy of EUS-FNA in diagnosing abdominal lymphadenopathy of unknown etiology., Methods: The EUS records of patients with undiagnosed abdominal lymphadenopathy between 2010 and 2015 were reviewed., Results: A total of 42 patients were included in this study. Adequate specimens were obtained from 40 patients (95%). The final diagnoses were metastatic cancer (n=16), lymphoma (n=9), tuberculosis (n=8), inflammatory changes (n=6), and amyloidosis (n=1). For diagnosing malignancy, EUS-FNA had a sensitivity of 84.6%, specificity of 95.7%, positive predictive value of 91.7%, negative predictive value of 91.7%, and area under the receiver operating characteristic curve (AUROC) of 0.901. For the diagnosis of lymphoma, EUS-FNA was 100% accurate when combined with cytologic evaluation and immunohistochemical staining. The diagnostic sensitivity decreased to 75%, whereas the specificity remained 100%, for tuberculosis. The overall AUROC was 0.850. No procedure-related complications occurred., Conclusion: EUS-FNA showed high diagnostic performance for abdominal lymphadenopathy of unknown causes, especially malignancy, lymphoma, and tuberculosis. Therefore, it is a crucial diagnostic tool for this patient population.

Background: The impact of rapid on-site cytologic evaluation (ROSE) on endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is widely debated. This study aims to assess the diagnostic performance of EUS-FNB in the absence of ROSE in abdominal masses., Methods: Patients with abdominal masses undergoing EUS-FNB using 22-gauge Franseen needles and the slow-pull technique were prospectively enrolled in this study. Macroscopic on-site evaluation (MOSE) was performed without ROSE., Results: 100 patients were recruited between 2018 and 2020. Seventy-eight patients had neoplasms, and twenty-two patients had benign diseases. Common diagnoses included pancreatic cancer ( n = 27), mesenchymal tumors ( n = 17), and metastatic tumors ( n = 14). The mean mass size was 3.9 ± 2.6 cm. The median pass number was three. Eighty-nine percent had adequate specimens for histologic evaluation. Malignancy increased the odds of obtaining adequate tissue (OR 5.53, 95% CI, 1.36-22.5). For pancreatic cancer, FNB had a sensitivity of 92.3%, a specificity of 100%, a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of 97%, and an AUROC of 0.96. The sensitivity, specificity, PPV, NPV, and AUROC for mesenchymal cell tumors were 100%, 95.9%, 84.2%, 100%, and 0.98, respectively. For metastatic tumors, FNB was 100% sensitive and specific, with an AUROC of 1.00. There were no procedure-related complications., Conclusions: 22-gauge Franseen needles with the slow-pull technique and MOSE without ROSE provide excellent diagnostic performances for malignant lesions. Thus, MOSE should be implemented in real-world practice, and ROSE can be obviated when EUS-FNB is employed.

Background/aims: Endoscopic ultrasonography (EUS) is warranted when cross-sectional imaging demonstrates common bile duct (CBD) dilatation without identifiable causes. This study aimed to assess the diagnostic performance of EUS in CBD dilatation of unknown etiology., Methods: Retrospective review of patients with dilated CBD without definite causes undergoing EUS between 2012 and 2017., Results: A total of 131 patients were recruited. The mean age was 63.2±14.1 years. The most common manifestation was abnormal liver chemistry (85.5%). The mean CBD diameter was 12.2±4.1 mm. The area under the receiver operating characteristic curve (AUROC) of EUS-identified pathologies, including malignancy, choledocholithiasis, and benign biliary stricture (BBS), was 0.98 (95% confidence interval [CI], 0.95-1.00). The AUROC of EUS for detecting malignancy, choledocholithiasis, and BBS was 0.91 (95% CI, 0.85-0.97), 1.00 (95% CI, 1.00-1.00), and 0.93 (95% CI, 0.87-0.99), respectively. Male sex, alanine aminotransferase ≥3× the upper limit of normal (ULN), alkaline phosphatase ≥3× the ULN, and intrahepatic duct dilatation were predictors for pathological obstruction, with odds ratios of 5.46 (95%CI, 1.74-17.1), 5.02 (95% CI, 1.48-17.0), 4.63 (95% CI, 1.1-19.6), and 4.03 (95% CI, 1.37-11.8), respectively., Conclusion: EUS provides excellent diagnostic value in identifying the etiology of CBD dilatation detected by cross-sectional imaging.

Dietary modification is essential for treating nonalcoholic fatty liver disease (NAFLD); however, the dietary components are less well defined. We enrolled 252 adults with no history of liver disease and excessive alcohol use to evaluate the relationship between macronutrients and NAFLD and insulin resistance. Participants took photographs of their meals and documented their food intake in a food diary for seven consecutive days. A dietitian estimated the type and portion size of food items and analyzed nutrients with INMUCAL-Nutrients software. Later, participants underwent transient elastography to diagnose NAFLD and blood tests to measure insulin resistance using the homeostasis model. Total energy intake and the proportion of carbohydrate, fat, and protein consumption did not differ between participants with NAFLD ( n = 41) and those without NAFLD ( n = 211). Using multiple logistic regression analysis, daily intake of protein < 1.0 g/kg (OR: 3.66, 95% CI: 1.41-9.52) and full-fat dairy product ≥ 50 g (OR: 0.42, 95% CI: 0.18-0.99) were associated with NAFLD. Insulin resistance was associated with a daily intake of protein < 1.0 g/kg (OR: 3.09, 95% CI: 1.59-6.05), full-fat dairy product ≥ 50 g (OR: 0.46, 95% CI: 0.25-0.82), and dietary fiber ≥ 8 g (OR: 0.41, 95% CI: 0.22-0.74). Our data show that a low protein intake increases the odds for NAFLD and insulin resistance. Contrarily, a high intake of full-fat dairy products and dietary fiber has been associated with a potential protective effect against NAFLD and insulin resistance.

Objective: Age and alarm features are commonly used as indicators for endoscopy in dyspeptic patients; however, the age cut-off and the predictive value of these parameters for identifying upper gastrointestinal (UGI) malignancies are uncertain., Design: Cross-sectional study., Setting: Data were extracted from the Gastrointestinal Endoscopy Centre of Siriraj Hospital, Thailand, during 2005-2011., Participants: Consecutive patients underwent a first-time upper endoscopy for dyspepsia. Patients with previous surgery, suspected UGI malignancy by imaging, or indefinite biopsy results on prior examination were excluded., Main Outcome Measures: Alarm features included dysphagia, unintentional weight loss, GI bleeding/anaemia, and persistent vomiting. The diagnostic performance of each alarm feature and different age cut-off values were evaluated., Results: A total of 4664 patients (mean age: 52.0±14.4 years, 66% female) were included. Alarm symptoms were presented in 21.6%. The prevalence of active Helicobacter pylori infection was 26.3%. Fifty-eight (1.2%) patients had UGI malignancy. The prevalence of malignancy significantly increased with increasing age (0.6% in patients aged <50 years, and 1.8% in patients aged >60 years (p<0.001)). Cancer was found in two patients aged <50 years who did not have alarm features. Patients with alarm features had a higher prevalence of malignancy (OR 22.3, 95% CI 10.5 to 47.4; p<0.001) than those without. The pooled sensitivity, specificity, positive predictive value and negative predictive value of alarm features for UGI malignancy were 87.0%, 79.1%, 4.7% and 99.8%, respectively. Among all age groups, persistent vomiting had a positive likelihood ratio (PLR) >10, while dysphagia and GI bleeding/anaemia had a PLR >10 in patients <50 years old., Conclusion: Despite the overall limited value of age and alarm features, persistent vomiting, dysphagia, and GI bleeding/anaemia are strong predictors for malignancy in patients aged <50 years. Without these symptoms, cancer prevalence is negligible; thus, they are worthy guidance for endoscopic evaluation in this age group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The decision regarding whether to perform a liver biopsy in patients with cirrhosis and clinically suspected autoimmune hepatitis (AIH) remains a challenge. This study aimed to assess the utility and complications of percutaneous liver biopsy in cirrhosis for differentiating AIH from other liver conditions., Methods: A clinicopathological database of patients undergoing percutaneous liver biopsies for suspected AIH (unexplained hepatitis with elevated γ-globulin and autoantibody seropositivity) was reviewed to identify patients presenting with cirrhosis. Biopsy slides were reviewed by an experienced hepatopathologist who was blinded to clinical data., Results: In 207 patients who underwent liver biopsy for suspected AIH, 59 patients (mean age: 59.0±12.0 years, 83.1% female) had clinically diagnosis of cirrhosis. Mean Child-Turcotte-Pugh score was 6.6±1.6, and 44% of patients had a Child-Turcotte-Pugh score≥7. According to the revised International AIH Group (IAIHG) criteria, histology assessment combined with clinical information facilitated a diagnosis of AIH or overlap syndrome of AIH and primary biliary cholangitis (PBC) in 81.4% of cases. Liver biopsy identified other aetiologies, including PBC (n=2), non-alcoholic steatohepatitis (n=6) and cryptogenic cirrhosis (n=3). A reliable diagnosis of AIH could be made using histological category of the simplified criteria in 69.2% and 81.8% of cases using IAIHG scores before biopsy of <10 and 10-15, respectively. Three patients with cirrhosis (5.1%) experienced bleeding following biopsy, but none of 148 patients with non-cirrhosis had bleeding complication (p=0.022)., Conclusion: Liver biopsy provides important diagnostic information for the management of patients with cirrhosis and suspected AIH, but the procedure is associated with significant risk., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Type 1 hepatorenal syndrome (type 1 HRS) or hepatorenal syndrome-acute renal injury (HRS-AKI) leads to high short-term mortality rates in patients with cirrhosis. Vasoconstrictor therapy effectively improves survival of these patients and has been a bridge to liver transplantation. The aim of this study was to assess the cost-utility of terlipressin plus albumin (T+A) and noradrenaline plus albumin (N+A) compared to best supportive care (BSC) for treating type 1 HRS patients in Thailand., Methods: A cost-utility analysis using a six-state Markov model was performed from societal and payer perspectives over a lifetime horizon. The clinical outcomes, costs, and utility parameters were obtained from literature, network meta-analyses, and expert opinion. One-way and probabilistic sensitivity analyses were conducted to account for uncertainty., Results: The T+A yielded the highest cost (848,325 Thai Baht (THB)) and health outcomes (2.82 life-years (LY) and 2.27 quality-adjusted life-years (QALY)). Compared to BSC, incremental cost-effectiveness ratios (ICERs) of the T+A and N+A were 377,566 and 412,979 THB per QALY gained, respectively. If N+A is administered outside the intensive care unit, the ICER was 308,964 THB per QALY. The treatment cost after liver transplantation from year 3 onwards was the most influential factor for ICERs, followed by the cost of terlipressin, duration of noradrenaline treatment, and cost of albumin. At the Thai societal willingness-to-pay threshold of 160,000 THB per QALY gained, the probabilities of being cost-effective for T+A, N+A, and BSC were 11%, 20%, and 69%, respectively., Conclusion: The T+A and N+A treatments would not be cost-effective compared to BSC in the Thai setting., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Sangroongruangsri et al.)

Background: Accurate noninvasive methods for the assessment of liver fibrosis are urgently needed. This prospective study evaluated the diagnostic accuracy of diffusion-weighted magnetic resonance imaging (DWI) for the staging of liver fibrosis and proposed a diagnostic algorithm using DWI to identify cirrhosis in patients with chronic viral hepatitis., Methods: One hundred twenty-one treatment-naïve patients with chronic hepatitis B or C were evaluated with DWI followed by liver biopsy on the same day. Breath-hold single-shot echo-planar DWI was performed to measure the apparent diffusion coefficient (ADC) of the liver and spleen. Normalized liver ADC was calculated as the ratio of liver ADC to spleen ADC., Results: There was an inverse correlation between fibrosis stage and normalized liver ADC (p<0.05). For the prediction of fibrosis stage ≥2, stage ≥3, and cirrhosis, the area under the receiver-operating curve of normalized liver ADC was 0.603, 0.704, and 0.847, respectively. The normalized liver ADC value ≤1.02×10-3 mm2/s had 88% sensitivity, 81% specificity, 25% positive predictive value (PPV), and 99% negative predictive value (NPV) for the diagnosis of cirrhosis. Using a sequential approach with the Fibrosis-4 index followed by DWI, normalized liver ADC ≤1.02×10-3 mm2/s in patients with Fibrosis-4 >3.25 yielded an 80% PPV for cirrhosis, and a 100% NPV to exclude cirrhosis in patients with Fibrosis-4 between 1.45 and 3.25. Only 15.7% of patients would require a liver biopsy. This sequential strategy can reduce DWI examinations by 53.7%., Conclusion: Normalized liver ADC measurement on DWI is an accurate and noninvasive tool for the diagnosis of cirrhosis in patients with chronic viral hepatitis., Competing Interests: The authors have declared that no competing interests exist.

Introduction: This randomized trial aimed to compare the effects of moderate-intensity aerobic vs resistance exercise with dietary modification in patients with nonalcoholic fatty liver disease (NAFLD)., Methods: Patients with NAFLD were randomly assigned (1:1) to a 12-week supervised training program of moderate-intensity aerobic or resistance exercise with dietary intervention consisting of monthly individual nutritional counseling by a dietician. Transient elastography, anthropometry, body composition, cardiorespiratory fitness, biochemistries, and glucose tolerance were measured at baseline and 12 weeks., Results: Eighteen subjects exercised for an average of 3.35 ± 0.30 sessions a week in the aerobic group, and 17 subjects exercised an average of 3.39 ± 0.28 sessions a week in the resistance group. After completion of the training program, hepatic fat content was similarly reduced in both groups (P < 0.001). The mean relative reduction from baseline in the aerobic group was -10.3% (95% confidence interval -18.2 to -2.40) and the resistance group was -12.6% (-20.5 to -4.69). Liver steatosis (defined as controlled attenuation parameter >248 dB/m) disappeared in 9 (50%) of the aerobic group and in 9 (53%) of the resistance group. Whole-body and muscle insulin sensitivity indexes were improved, and waist circumference was reduced comparably in both exercise groups. The number of exercise sessions per week was correlated with the absolute reduction in hepatic fat content (r = 0.52; P = 0.001). Weekly exercise training ≥3 sessions substantially attenuates liver fat accumulation independent of weight loss., Discussion: Moderate-intensity aerobic training and resistance training with dietary modification are equally effective for reducing intrahepatic fat and improving underlying insulin resistance among patients with NAFLD.

Nontumoral portal vein thrombosis (PVT) is an increasingly recognized complication in patients with cirrhosis. Substantial evidence shows that portal flow stasis, complex thrombophilic disorders, and exogenous factors leading to endothelial dysfunction have emerged as key factors in the pathogenesis of PVT. The contribution of PVT to hepatic decompensation and mortality in cirrhosis is debatable; however, the presence of an advanced PVT increases operative complexity and decreases survival after transplantation. The therapeutic decision for PVT is often determined by the duration and extent of thrombosis, the presence of symptoms, and liver transplant eligibility. Evidence from several cohorts has demonstrated that anticoagulation treatment with vitamin K antagonist or low molecular weight heparin can achieve recanalization of the portal vein, which is associated with a reduction in portal hypertension-related events and improved survival in cirrhotic patients with PVT. Consequently, interest in direct oral anticoagulants for PVT is increasing, but clinical data in cirrhosis are limited. Although the most feared consequence of anticoagulation is bleeding, most studies indicate that anticoagulation therapy for PVT in cirrhosis appears relatively safe. Interestingly, the data showed that transjugular intrahepatic portosystemic shunt represents an effective adjunctive therapy for PVT in cirrhotic patients with symptomatic portal hypertension if anticoagulation is ineffective. Insufficient evidence regarding the optimal timing, modality, and duration of therapy makes nontumoral PVT a challenging consequence of cirrhosis. In this review, we summarize the current literature and provide a potential algorithm for the management of PVT in patients with cirrhosis., Competing Interests: The authors have no conflict of interests related to this publication., (© 2020 Authors.)

Over half of metabolic syndrome (MetS) patients have nonalcoholic fatty liver disease (NAFLD). To prevent its complications, standard routine screening is required, but the human-resource and budgetary implications need to be taken into consideration. This study compared the performances of 4 noninvasive scoring systems in predicting NAFLD in MetS patients. They were the fatty liver index, hepatic steatosis index, lipid accumulation product index, and nonalcoholic fatty liver disease in metabolic syndrome patients scoring system (NAFLD-MS).Scores were determined for 499 MetS patients, including 249 patients in a type 2 diabetes mellitus (T2DM) subgroup. Ultrasonography was used to diagnose NAFLD. The accuracies and performance of the scoring systems were analyzed using published cutoff values, and comparisons were made of their areas under receiver operating characteristic curves, sensitivities, specificities, positive and negative predictive values, and likelihood ratios.NAFLD was detected in 68% of the MetS patients and 77% of the MetS patients with T2DM. According to the areas under receiver operating characteristic curves, fatty liver index and hepatic steatosis index provided better performances in predicting NAFLD. NAFLD-MS provided the highest specificity of 99% among the MetS patients as a whole, and it provided even better accuracy with similar performance when applied to the subgroup of MetS patients with T2DM. The maximum cost avoidance from unnecessary ultrasonography was also reported by using NAFLD-MS. In terms of simplicity and ease of calculation, the lipid accumulation product index and NAFLD-MS are preferred.All 4 scoring systems proved to be acceptable for predicting NAFLD among MetS and T2DM patients in settings where the availability of ultrasonography is limited. NAFLD-MS provided the highest specificity and cost avoidance, and it is simple to use. All 4 systems can help clinicians decide further investigations.

Background: The evidence suggests a detrimental effect of cigarette smoking on the progression of chronic liver disease. However, the impact of cigarette smoking on mortality among patients with non-alcoholic fatty liver disease (NAFLD) remain unclear. Methods: We used the National Health Examination Survey data collected during 2008-2009 to link the National Death Index to follow-up respondent survival. Diagnosis of NAFLD was based on a lipid accumulation product in participants without significant alcohol use or other liver diseases. Results: During 64,116 person-years of follow-up, 928 of 7,529 participants with NAFLD died, and the cumulative all-cause mortality was 14.5 per 1,000 person-years. In a Cox regression model adjusted for age, body mass index, alcohol intake, exercise, comorbidities, lipid profiles, and handgrip strength, current smoking increased the risk of mortality by 109% (adjusted hazard ratio (aHR): 2.09, 95% confidence interval [CI]: 1.18-3.71) compared with never smoker status in women, but showed only a trend toward harm among men (aHR: 1.41, 95% CI: 0.96-2.08). After controlling for potential confounders, smoking ≥10 pack-years continued to show a significant harmful effect on all-cause mortality among women (aHR: 5.40, 95% CI: 2.19-13.4), but not in men. Among women who drink alcohol ≥10 grams per day, current smoking (aHR: 13.8, 95% CI: 1.66-145) and smoking ≥10 pack-years (aHR: 310, 95% CI: 78-1,296) also significantly increased risk of death. Conclusion: This nationwide population-based study highlight a detrimental effect of cigarette smoking on mortality, with a similar but more definite association in women than in men with NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Charatcharoenwitthaya, Karaketklang and Aekplakorn.)

Background: Data on external validation of models developed to distinguish Crohn's disease (CD) from intestinal tuberculosis (ITB) are limited. This study aimed to validate and compare models using clinical, endoscopic, and/or pathology findings to differentiate CD from ITB., Methods: Data from newly diagnosed ITB and CD patients were retrospectively collected from 5 centers located in Thailand or Hong Kong. The data was applied to Lee, et al., Makharia, et al., Jung, et al., and Limsrivilai, et al. model., Results: Five hundred and thirty patients (383 CD, 147 ITB) with clinical and endoscopic data were included. The area under the receiver operating characteristic curve (AUROC) of Limsrivilai's clinical-endoscopy (CE) model was 0.853, which was comparable to the value of 0.862 in Jung's model (p = 0.52). Both models performed significantly better than Lee's endoscopy model (AUROC: 0.713, p<0.01). Pathology was available for review in 199 patients (116 CD, 83 ITB). When 3 modalities were combined, Limsrivilai's clinical-endoscopy-pathology (CEP) model performed significantly better (AUROC: 0.887) than Limsrivilai's CE model (AUROC: 0.824, p = 0.01), Jung's model (AUROC: 0.798, p = 0.005) and Makharia's model (AUROC: 0.637, p<0.01). In 83 ITB patients, the rate of misdiagnosis with CD when used the proposed cutoff values in each original study was 9.6% for Limsrivilai's CEP, 15.7% for Jung's, and 66.3% for Makharia's model., Conclusions: Scoring systems with more parameters and diagnostic modalities performed better; however, application to clinical practice is still limited owing to high rate of misdiagnosis of ITB as CD. Models integrating more modalities such as imaging and serological tests are needed., Competing Interests: The authors have declared that no competing interests exist.

The prevalence of Crohn disease (CD) is increasing in Asia, but data from Southeast Asian population are scarce.The databases of 2 university-based national tertiary referral centers located in Bangkok, Thailand, were retrospectively reviewed for adult patients diagnosed with CD during January 2000 to December 2017. Disease characteristics, diagnosis, treatment, and outcomes were described and compared between the 2000 to 2009 cohort (cohort A) and the 2010 to 2017 cohort (cohort B).One hundred eighty-two patients (mean age: 46.4 years, 50% male) with 993 patient-years of follow-up were included. Thirteen percent had a history of intestinal resection, but were not diagnosed until disease recurrence. Another 6% were diagnosed at the time of first surgery. There was no improvement in diagnostic proficiency between cohorts. Mesalamine, corticosteroids, thiopurines, and biologics were prescribed in 75.8%, 81.3%, 84.6%, and 13.7% of patients, respectively (P > .05 between cohorts). Notably, thiopurines were started earlier in cohort B. Median time to the start of thiopurines was 6.2 and 1.65 months in cohort A and B, respectively (P < .01). However, the cumulative 5-year rates of disease behavior progression (P = .43), hospitalization (P = .14), and bowel surgery (P = .29) were not significantly different between cohorts. Subgroup analysis including only patients who required thiopurines showed the early use of thiopurines to be associated with lower risk of intestinal surgery after diagnosis (hazard ratio: 0.30, 95% confidence interval: 0.11-0.85).Early disease recognition and early introduction of immunomodulators may prevent long-term complications and reduce unnecessary surgery in CD.

Background: Gamma-glutamyl transferase (GGT) is associated with the risk of cardiovascular disease (CVD) in the general population., Aim: To identify the association of baseline GGT level and QRISK2 score among patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD)., Methods: This was a retrospective study involving 1535 biopsy-proven NAFLD patients from 10 Asian centers in 8 countries using data collected by the Gut and Obesity in Asia (referred to as "GO ASIA") workgroup. All patients with available baseline GGT levels and all 16 variables for the QRISK2 calculation (QRISK2-2017; developed by researchers at the United Kingdom National Health Service; https://qrisk.org/2017/; 10-year cardiovascular risk estimation) were included and compared to healthy controls with the same age, sex, and ethnicity. Relative risk was reported. QRISK2 score > 10% was defined as the high-CVD-risk group. Fibrosis stages 3 and 4 (F3 and F4) were considered advanced fibrosis., Results: A total of 1122 patients (73%) had complete data and were included in the final analysis; 314 (28%) had advanced fibrosis. The median age (interquartile range [IQR]) of the study population was 53 (44-60) years, 532 (47.4%) were females, and 492 (43.9%) were of Chinese ethnicity. The median 10-year CVD risk (IQR) was 5.9% (2.6-10.9), and the median relative risk of CVD over 10 years (IQR) was 1.65 (1.13-2.2) compared to healthy individuals with the same age, sex, and ethnicity. The high-CVD-risk group was significantly older than the low-risk group (median [IQR]: 63 [59-67] vs 49 [41-55] years; P < 0.001). Higher fibrosis stages in biopsy-proven NAFLD patients brought a significantly higher CVD risk ( P < 0.001). Median GGT level was not different between the two groups (GGT [U/L]: Median [IQR], high risk 60 [37-113] vs low risk 66 [38-103], P = 0.56). There was no correlation between baseline GGT level and 10-year CVD risk based on the QRISK2 score (r = 0.02)., Conclusion: The CVD risk of NAFLD patients is higher than that of healthy individuals. Baseline GGT level cannot predict CVD risk in NAFLD patients. However, advanced fibrosis is a predictor of a high CVD risk., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ultrasound-based elastography and serum indexes have been individually validated as noninvasive methods for staging liver fibrosis in chronic viral hepatitis. We aimed to compare the accuracy of transient elastography (TE), shear wave elastography (SWE), aspartate aminotransferase to platelet index (APRI) and Fibrosis-4 index (FIB-4) with the METAVIR liver fibrosis staging in viral hepatitis patients. We enrolled 121 treatment-naïve chronic hepatitis B and C monoinfected patients. All underwent liver biopsy had biochemistry tests and liver stiffness measurements by TE using M and XL probes followed by point SWE performed on the same day. The accuracy of each method for predicting different fibrosis stages was demonstrated as an area under the receiver operating characteristic (AUROC) curves. The AUROCs of TE using M and XL probes, SWE, APRI and FIB-4 were 0.771, 0.761, 0.700, 0.698 and 0.697, respectively, for significant fibrosis; 0.974, 0.973, 0.929, 0.738 and 0.859, respectively, for advanced fibrosis; and 0.954, 0.949, 0.962, 0.765 and 0.962, respectively, for cirrhosis. TE using the M probe was comparable to the XL probe in detecting all fibrosis stages. TE was superior to SWE for assessing significant fibrosis and advanced fibrosis. For cirrhosis, the performances of TE, SWE and FIB-4 were similar. APRI was least accurate in liver fibrosis staging. To conclude, for patients with viral hepatitis, TE using either M or XL probe is an effective noninvasive test for assessing liver fibrosis, particularly advanced fibrosis and cirrhosis, while SWE and FIB-4 possess an excellent accuracy in predicting cirrhosis., (© 2019 John Wiley & Sons Ltd.)

Background: We investigated real-world effectiveness and safety of sofosbuvir and the nonstructural protein 5A inhibitors in the treatment of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, 4, or 6., Methods: We analyzed data from 1021 patients with HCV infection (506 with genotype 1; 16 with genotype 2; 314 with genotype 3; 13 with genotype 4; 166 with genotype 6) who received 12 to 24 weeks of daclatasvir plus sofosbuvir (n = 767), ledipasvir/sofosbuvir (n = 197), or sofosbuvir/velpatasvir (n = 57), with or without ribavirin in 12 centers across Thailand to estimate sustained virologic response at post-treatment week 12 (SVR12)., Results: Overall, SVR12 rate was 98.0% (95% confidence interval [CI], 96.7-98.8%) with daclatasvir plus sofosbuvir, 97.9% (95% CI, 94.8-99.2%) with ledipasvir/sofosbuvir, and 96.5% (95% CI, 88.1-99.0%) with sofosbuvir/velpatasvir. SVR12 was achieved by 99.2% (95% CI, 97.9-99.7%) of subjects with genotype 1 infection, 100% (95% CI, 78.5-100%) of those with genotype 2 infection, 96.7% (95% CI, 94.0-98.2%) of those with genotype 3 infection, 90.9% (95% CI, 62.3-98.4%) of those with genotype 4 infection, and 96.7% (95% CI 92.5-98.6%) of those with genotype 6 infection. Patients with advanced liver disease were at risk of treatment failure. Only four patients discontinued treatment before week 4 due to non-hepatic adverse events., Conclusions: In this large cohort of patients with various HCV genotypes managed in the real-world practice setting, daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir achieved high SVR rates with good safety profile, comparable to those observed in clinical trials.