Fourteen-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication in an area with high clarithromycin and levofloxacin resistance: a prospective randomized study (VQ-HP trial).

Potassium-competitive acid blockers (P-CABs) provide potent acid inhibition, yet studies on P-CAB-based quadruple therapy for H. pylori eradication are limited. We theorized that integrating bismuth subsalicylate into a quadruple therapy regimen could enhance eradication rates. However, data on the efficacy of vonoprazan bismuth quadruple therapy are notably scarce. Therefore, the aim of this study was to evaluate the efficacy of vonoprazan-based bismuth quadruple therapy in areas with high clarithromycin and levofloxacin resistance. This was a prospective, single-center, randomized trial conducted to compare the efficacy of 7-day and 14-day vonoprazan-based bismuth quadruple therapy for H. pylori eradication between June 1, 2021, and March 31, 2022. Qualified patients were randomly assigned to the 7-day or 14-day regimen (1:1 ratio by computer-generated randomized list as follows: 51 patients for the 7-day regimen and 50 patients for the 14-day regimen). The regimens consisted of vonoprazan (20 mg) twice daily, bismuth subsalicylate (1024 mg) twice daily, metronidazole (400 mg) three times daily, and tetracycline (500 mg) four times daily. CYP3A4/5 genotyping and antibiotic susceptibility tests were also performed. Successful eradication was defined as 13negative C-UBTs 4 weeks after treatment. The primary endpoint was to compare the efficacy of 7-day and 14-day regimens as first-line treatments, which were assessed by intention-to-treat (ITT) and per-protocol (PP) analyses. The secondary endpoints included adverse effects. A total of 337 dyspeptic patients who underwent gastroscopy were included; 105 patients (31.1%) were diagnosed with H. pylori infection, and 101 patients were randomly assigned to each regimen. No dropouts were detected. The antibiotic resistance rate was 33.3% for clarithromycin, 29.4% for metronidazole, and 27.7% for levofloxacin. The CYP3A4 genotype was associated with 100% rapid metabolism. The H. pylori eradication rates for the 7-day and 14-day regimens were 84.4%, 95% CI 74.3-94.2 and 94%, 95% CI 87.4-100, respectively (RR difference 0.25, 95% CI 0.03-0.53, p value = 0.11). Interestingly, the 14-day regimen led to 100% eradication in the clarithromycin-resistant group. Among the patients in the 7-day regimen group, only two exhibited resistance to clarithromycin; unfortunately, neither of them achieved a cure from H. pylori infection. The incidence of adverse events was similar in both treatment groups, occurring in 29.4% (15/51) and 28% (14/50) of patients in the 7-day and 14-day regimens, respectively. No serious adverse reactions were reported. In conclusion, 14 days of vonoprazan-based bismuth quadruple therapy is highly effective for H. pylori eradication in areas with high levels of dual clarithromycin and levofloxacin resistance.

Predictive Factors Associated with Survival in Female Gastric Cancer Patients in Southeast Asia.

Introduction: Association of Southeast Asian Nations (ASEAN) countries have high Helicobacter pylori infections, and gastric cancer (GC) is a leading fatal cancer in this region, especially in female patients. This study aimed to compare clinical manifestations, histopathological subtypes, and prognostic factors associated with the overall survival rate of female GC patients in this important region. Methods: This retrospective cohort study was conducted between 2007 and 2022 at a tertiary care center in Thailand. All clinical information, endoscopic findings, and histological types were extensively reviewed. Furthermore, all qualified studies in ASEAN published in PubMed and Scopus between 2000 and 2022 were extracted and thoroughly analyzed. Young female GC patients are defined as those ≤50 years of age. Results: A total of 98 Thai female GC patients were included, with a mean age of 58.99 ± 14 years; 70.4% were elderly women. The common presenting symptoms were weight loss (69.4%) and dyspepsia (68.4%). Younger female GC patients had significantly more common diffuse-type GC than elderly female GC patients (82.8% vs. 53.6%, p-value = 0.007). Moreover, elderly female GC patients demonstrated significantly better survival than younger female GC patients (44.8% vs. 20.7%, odds ratio = 3.49; 95% confidence interval: 1.20-10.14, p-value = 0.022). Furthermore, a total of 1,491 female GC patients from ASEAN were reviewed and included in this study, aged 15 to 93 years. The top three countries with the highest proportion of female GC from ASEAN were Indonesia (66.7%), Thailand (44.9%), and Singapore (38.4%). Conclusion: GC in women is not uncommon in ASEAN and presents at an advanced stage with a grave prognosis. This study showed that ASEAN countries with the highest disease burden were Indonesia, Thailand, and Singapore. Overall, survival rates for female GC patients in ASEAN countries were relatively low, highlighting the need for proactive measures such as intensive H. pylori eradication and the development of early detection methods for GC.

Simultaneous detection of Helicobacter pylori infection comparing between white light and image-enhanced endoscopy.

BACKGROUND: Helicobacter pylori (H. pylori) is associated with gastric cancer. Early and accurate diagnosis of H. pylori infection can reduce risk of gastric cancer. Conventional white light imaging (WLI) and image-enhanced endoscopic (IEE) techniques such as narrow-band imaging (NBI), linked color imaging (LCI) and blue laser imaging (BLI) plays pivotal role in H. pylori diagnosis. This study aimed to determine diagnostic performance of real-time endoscopy between WLI and other IEE techniques for diagnosis of H. pylori infection. METHODS: This prospective study compared endoscopic images by gastroscopy using WLI and IEE techniques (LCI, Magnifying-BLI, and Magnifying-NBI) at Thammasat University Hospital, Thailand between January 2020, and July 2021. All participants underwent gastroscopy. Three biopsies at gastric antrum and two biopsies at body were obtained for H.pylori diagnosis. H. pylori infection was defined as a positive test of either one of the following tests: rapid urease test, histopathology, H. pylori culture. RESULTS: Of 167 dyspeptic patients undergoing gastroscopy, 100 were enrolled in this study. Overall H. pylori infection was 40%. Patients had the mean age of 59.1 years and 53% were males. Enlarged gastric folds and antral nodularity can predict H. pylori infection with 100% PPV, while fundic gland polyps and red streak provided 100% PPV for exclusion of H. pylori infection on WLI. Sensitivity, specificity, PPV, NPV and accuracy for diagnosis of H. pylori infection for WLI were 80%, 71.7%, 65.3%, 84.3% and 75% respectively, while those for LCI were 90%, 70%, 66.7%, 91.3% and 78% respectively. M-NBI and M-BLI endoscopy demonstrated elongated pits in H. pylori-positive patients. Sensitivity, specificity, PPV, NPV and accuracy for M-BLI were 95%, 80%, 76%, 96% and 86% respectively, whereas those for M-NBI were 92.5%, 86.7%, 82.2%, 94.6% and 89% respectively. Sensitivity of M-BLI was better than WLI, while sensitivities of LCI and M-NBI were also numerically higher than WLI without statistical difference (M-BLI 95%vs.WLI 80%, p = 0.03; M-NBI 92.5%vs.WLI 80%, p = 0.13; LCI 90%vs.WLI 80%, p = 0.22). Sensitivities of all IEE modes were not different from one another (LCI 90%vs.M-BLI 95%, p = 0.50; LCI 90%vs.M-NBI 92.5%, p = 1.00, M-BLI 95%vs.M-NBI 92.5%, p = 1.00). CONCLUSIONS: M-BLI significantly improved sensitivity of real-time endoscopic diagnosis of H. pylori infection compared with WLI. Enlarged gastric folds and antral nodularity could be reliable predictors for H. pylori infection, while fundic gland polyps and red streak could be important endoscopic findings for H. pylori-negative mucosa.

Diabetes Mellitus and Poor Glycemic Control Negatively Impact Clinical Outcomes and Survival in Patients with Compensated Cirrhosis.

Background and objectives: Diabetes mellitus (DM) increases morbidity and mortality in advanced cirrhosis. Information on the prognostic impact of DM in compensated cirrhosis is scarce. We aimed to explore the effect of DM and glycemic control on the natural history of compensated cirrhotic patients. Methods: This retrospective longitudinal cohort study included Child A/B cirrhosis without or free from decompensation or hospitalization > 1 year. Data on survival, unplanned hospitalization, hepatic decompensation (ascites, portal hypertension-related bleeding, hepatic encephalopathy, acute kidney injury), new infection, and hepatocellular carcinoma (HCC) were collected. Results: 457 patients were included (71.3% Child A, model for end-stage liver disease [MELD] 9.9 ± 3.1, alcohol/hepatitis B virus/hepatitis C virus 39.2%/21.7%/15.1%, 34.4% had DM). The cumulative overall survival was lower in DM group (75.7% vs. 86.5% at 10 yrs, P = 0.01). By multivariable Cox regression models adjusted with Child-Pugh and MELD score, DM was associated with higher mortality (hazards ratio [HR] 2.4, P = 0.014, and HR 2.03, P = 0.04, respectively). The cumulative incidences of unplanned hospitalizations (46.3% vs. 24.8% at 5 yrs, P < 0.001), hepatic decompensation (45% vs. 20.8% at 5 yrs, P < 0.001), new infection (47.2% vs. 20.2% at 5 yrs, P < 0.001), and HCC (29.3% vs. 16.8% at 10 yrs, P = 0.03) were higher in DM group. In patients with DM, 27.4% patients had poor glycemic control (HbA1c ≥7.0% for ≥80% of the study period). The cumulative overall survival was lower in poor glycemic control group (52.3% vs. 85.2% at 10 yrs, P = 0.02). By univariable Cox regression model, poor glycemic control was associated with higher mortality (HR 2.67, P = 0.025). Conclusions: In compensated cirrhosis, when coexisting with DM, the complications and mortality rates magnify. Poor glycemic control reduces survival in cirrhotic patients with DM. Proper diabetic screening and management should be emphasized in the care of these patients.

Pilot studies of vonoprazan-containing Helicobacter pylori eradication therapy suggest Thailand may be more similar to the US than Japan.

BACKGROUND: Vonoprazan-containing Helicobacter pylori eradication is reliably effective in Japan. Its effectiveness in other countries remains unclear. Here, we examined vonoprazan-H. pylori therapies in Thailand. MATERIALS AND METHODS: This was pilot study of four different vonoprazan containing therapies. Subjects were randomized to: 14-day dual therapy (500 mg amoxicillin q.i.d. plus 20 mg vonoprazan b.i.d.), 14-day triple therapy (amoxicillin 1 g b.i.d., slow release clarithromycin-MR, 1 g daily plus vonoprazan 20 mg b.i.d.), 7-day high-dose vonoprazan triple therapy (amoxicillin 1 g b.i.d., clarithromycin-MR 1 g daily and 60 mg vonoprazan once daily), and 14-day vonoprazan triple therapy plus bismuth (amoxicillin 1 g b.i.d., clarithromycin-MR 1 g daily, vonoprazan 20 mg b.i.d., and bismuth subsalicylate 1048 mg b.i.d.). Eradication was confirmed 4 weeks after therapy. Antimicrobial susceptibility and CYP3A4/5 genotyping were performed. RESULTS: One hundred H. pylori-infected patients (mean age 54.3 ± 13 years, 51% men) were randomized. All were CYP3A4 extensive metabolizers. Cure rates with both 14-day vonoprazan dual therapy and 14-day triple therapy were low: 66.7%; 95% CI = 43-85% (14/21), and 59.3%; 95% CI = 39-78%) (16/27), respectively. In contrast, 7-day high-dose vonoprazan triple therapy and 14-day vonoprazan triple plus bismuth proved effective 92.3%; 95% CI = 75%-99% (24/26) and 96.2%; 95% CI = 80%-100% (25/26), respectively. CONCLUSION: Both 14-day vonoprazan dual and triple therapy were ineffective for H. pylori eradication in Thailand. Higher dosage of vonoprazan, and/or the addition of bismuth may be required to achieve high H. pylori eradication rates. High-dose vonoprazan triple therapy and vonoprazan triple therapy adding bismuth might be used as first-line treatments in some regions with high efficacy irrespective of CYP3A4/5 genotype and clarithromycin resistance.

Correlation between Cumulative Methotrexate Dose, Metabolic Syndrome and Hepatic Fibrosis Detected by FibroScan in Rheumatoid Arthritis Patients.

Background and Objectives: Methotrexate (MTX) is routinely prescribed for rheumatoid arthritis (RA) patients, but high cumulative doses may lead to hepatic fibrosis. Additionally, a high proportion of RA patients suffer from metabolic syndrome, which also increases the risk of hepatic fibrosis. This cross-sectional study aimed to explore the association between a cumulative MTX dose, metabolic syndrome, and hepatic fibrosis in patients diagnosed with RA. Materials and Methods: RA patients undergoing treatment with MTX were examined using transient elastography (TE). All patients, regardless of having hepatic fibrosis, were compared to identify the risk factors. Results: Two hundred and ninety-five rheumatoid arthritis patients were examined using FibroScan. One hundred and seven patients (36.27%) were found to have hepatic fibrosis (TE > 7 kPa). After multivariate analysis, only BMI (OR = 14.73; 95% CI 2.90-74.79; p = 0.001), insulin resistance (OR = 312.07; 95% CI 6.19-15732.13; p = 0.04), and cumulative MTX dosage (OR 1.03; 95% CI 1.01-1.10; p = 0.002) were associated with hepatic fibrosis. Conclusions: While the cumulative MTX dose and metabolic syndrome are both the risk factors of hepatic fibrosis, metabolic syndrome, including a high BMI and insulin resistance, poses a greater risk. Therefore, MTX-prescribed RA patients with metabolic syndrome factors should be attentively monitored for signs of liver fibrosis.

Branched-chain amino acids supplementation improves liver frailty index in frail compensated cirrhotic patients: a randomized controlled trial.

BACKGROUND: Physical frailty is related with morbidity and mortality in patients with cirrhosis. Currently, there is no approved treatment of frailty in these patients. Here, we evaluated the efficacy of 16 weeks branched-chain amino acids (BCAA) supplementation on frailty in frail compensated cirrhotic patients. METHODS: After a 4-week run-in period consisted of dietary and exercise counseling, compensated cirrhotic patients with frailty, defined by liver frailty index (LFI)≥4.5, were randomly assigned (1:1) to BCAA or control group. The BCAA group received twice daily BCAAs supplementation (210 kcal, protein 13.5 g, BCAA 2.03 g) for 16 weeks. The primary outcome was frailty reversion. The secondary outcomes were changes in biochemistries, body composition evaluated by bioelectrical impedance analysis, and quality of life (QoL). RESULTS: 54 patients were prospectively enrolled (age 65.5 ± 9.9 years, 51.9% female, Child-Pugh A/B 68.5%/31.5%, MELD 10.3 ± 3.1). Baseline characteristics were similar between both groups. At week 16, BCAA group had a significant improvement in LFI (-0.36 ± 0.3 vs. -0.15 ± 0.28, P = 0.01), BMI (+ 0.51 ± 1.19 vs. -0.49 ± 1.89 kg/m2, P = 0.03), and serum albumin (+ 0.26 ± 0.27 vs. +0.06 ± 0.3 g/dl, P = 0.01). The proportion of frailty reversion at week 16 was significantly higher in BCAA group (36% vs. 0%, P < 0.001). Compared with baseline, BCAA group had a significant increase in skeletal muscle index (7.5 ± 1.6 to 7.8 ± 1.5 kg/m2, P = 0.03). Regarding the QoL, only the BCAA group had a significant improvement in all 4 domains of physical component score of the SF-36 questionnaire. CONCLUSIONS: A 16-week BCAA supplementation improved frailty in frail compensated cirrhotic patients. In addition, this intervention resulted in an improvement of muscle mass and physical domain of QoL in these patients. TRIAL REGISTRATION: This study was registered with Thai Clinical Trial Registry (TCTR20210928001; https://www.thaiclinicaltrials.org/# ).

Characteristics of Drug-induced Liver Injury in Chronic Liver Disease: Results from the Thai Association for the Study of the Liver (THASL) DILI Registry.

Background and Aims: The impact of drug-induced liver injury (DILI) on patients with chronic liver disease (CLD) is unclear. There are few reports comparing DILI in CLD and non-CLD patients. In this study, we aimed to determine the incidence and outcomes of DILI in patients with and without CLD. Methods: We collected data on eligible individuals with suspected DILI between 2018 and 2020 who were evaluated systematically for other etiologies, causes, and the severity of DILI. We compared the causative agents, clinical features, and outcomes of DILI among subjects with and without CLD who were enrolled in the Thai Association for the Study of the Liver DILI registry. Subjects with definite, or highly likely DILI were included in the analysis. Results: A total of 200 subjects diagnosed with DILI were found in the registry. Of those, 41 had CLD and 159 had no evidence of CLD in their background. Complementary and alternative medicine (CAM) products were identified as the most common class of DILI agents. Approximately 59% of DILI in the CLD and 40% in non-CLD group were associated with CAM use. Individuals with pre-existing CLD had similar severity including mortality. Twelve patients (6%) developed adverse outcomes related to DILI including seven (3.5%) deaths and five (2.5%) with liver failure. Mortality was 4.88% in CLD and 3.14% in non-CLD subjects over median periods of 58 (8-106) days and 22 (1-65) days, respectively. Conclusions: In this liver disease registry, the causes, clinical presentation, and outcomes of DILI in subjects with CLD and without CLD patients were not different. Further study is required to confirm our findings.

Validation of prognostic scores predicting mortality in acute liver decompensation or acute-on-chronic liver failure: A Thailand multicenter study.

BACKGROUND & OBJECTIVES: Cirrhosis 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. METHODS: We 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. RESULTS: Between 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% (p<0.001) and 67.44% vs. 32.78% (p<0.001), respectively. For ACLF patients, logistic regression analysis adjusted for demographic data, and clinical information showed that increasing creatinine was a predictor for 30-day mortality (p = 0.038), while the CLIF-C OF score predicted both 30-day (p = 0.018) and 90-day (p = 0.037) mortalities, achieving the best discriminatory power with AUROCs of 0.705 and 0.709, respectively. For AD patients, none of the parameters was found to be significantly associated with 30-day mortality, while bacterial infection, CLIF-AD score and Child-Turcotte-Pugh score were independent parameters associated with 90-day mortality, with p values of 0.041, 0.024 and 0.024. However, their predictive performance became nonsignificant after adjustment by multivariate regression analysis. CONCLUSIONS: Regarding 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.

Acute-on-chronic liver failure: Epidemiology, prognosis, and outcome of a multicenter study in Thai population.

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.

Hemostatic parameters predict 90-day mortality in hospitalized cirrhotic patients with acute decompensation: a prospective cohort study.

Hemostatic disturbances are common in patients with cirrhosis. Few studies have evaluated the prognostic role of hemostatic parameters in cirrhosis with acute decompensation. This study aims to determine the prognostic ability of standard hemostatic parameters in hospitalized cirrhotic patients with acute decompensation. Cirrhotic patients admitted with acute decompensation were prospectively enrolled. Hemostatic parameters were determined within 24 h, and the DIC (disseminated intravascular coagulation) score was calculated based on platelet count, prothrombin time (PT), fibrinogen, and D- dimer. New onset of in-hospital major bleeding and 90-day mortality were assessed. Eighty-nine patients were included (MELD 13.6 ±â€Š5.7). The indications of admission were infection (38.2%), and portal hypertension-related bleeding (31.5%). 14.6% developed in-hospital major bleeding, and 90-day mortality rate was 21.3%. Major bleeding group and 90-day nonsurvivors had significantly higher activated partial thromboplastin time (aPTT), PT, and DIC score. The 90-day mortality rate was higher in major bleeding group (46.2 vs. 17.1%, P = 0.029). By multivariate logistic regression analysis, DIC score was associated with 90-day mortality. The AUROC of DIC score for 90-day mortality prediction was significantly higher than of MELD score (0.78 vs. 0.59, P = 0.04). DIC score at least 4 predicted 90-day mortality with a sensitivity of 88.9%. The cumulative 90-day survival was significantly lower in patients with DIC score at least 4 (57.2 vs. 93.6%, P = 0.0003). The development of in-hospital major bleeding significantly increases mortality in cirrhotic patients with acute decompensation. The DIC score within 24 h can be used as a simple and reliable predictor for 90-day mortality in these patients.

Plasma Cystatin C Level is a Prognostic Marker of Morbidity and Mortality in Hospitalized Decompensated Cirrhotic Patients.

Introduction : Cystatin C (CysC) is biomarker for early detection of acute kidney injury (AKI). However, there is limited evidence in decompensated cirrhotic patients without AKI at admission. This study aimed to assess CysC as a predictor of 90-day mortality. Methods : Decompensated cirrhotic patients without AKI were prospectively enrolled. CysC and creatinine were measured within 24 hours of admission and compared between patients with in-hospital complications (AKI, hepatorenal syndrome (HRS), acute-on-chronic liver failure (ACLF)) vs. those without, and survivors vs. non-survivors. The AUROC and cut-off point of CysC in predicting 90-day mortality were determined. Results : Of 137 decompensated cirrhotic patients, 46 without AKI at admission were included (58.7% male, age 60.8 ±â€†11.2years, MELD 13.1 ±â€†5.1, ChildA / B / C 43.5% / 39.1% / 17.4%). The mean CysC level tended to be higher in patients with ACLF (1.52 ±â€†0.60 vs. 1.11 ±â€†0.28, p = 0.05), and significantly higher in non-survivors than survivors (1.61 ±â€†0.53 vs. 1.08 ±â€†0.28, p = 0.013). The 90-day mortality rate was 21.7%. After adjusting with age and bacterial infection on admission, CysC level  ≥ 1.25 mg / L was significantly associated with 90-day mortality. The CysC cut-off level  ≥ 1.25 mg / L provided 80% sensitivity and 75% specificity for predicting 90-day mortality. Conclusion : Plasma CysC within 24 hours could be used as a predictor for 90-day mortality and development of ACLF in decompensated cirrhotic patients. J. Med. Invest. 68 : 302-308, August, 2021.

Passage of intestinal casts-An unusual presentation of Cytomegalovirus enterocolitis.

Cytomegalovirus (CMV) is one of the leading opportunistic pathogens affecting immunocompromised patients. We report a case of histologically-confirmed extensive CMV enterocolitis in a young woman after receiving rituximab and tocilizumab for the treatment of autoimmune encephalitis. During the antiviral treatment, she spontaneously excreted small intestinal casts per oral and colonic casts per anus. Even though intestinal cast is an extremely unusual condition, CMV infection should be included in the differential diagnosis.

Frailty as tested by the Liver Frailty Index is associated with decompensation and unplanned hospitalization in patients with compensated cirrhosis.

BACKGROUND AND AIMS: Frailty is associated with morbidity and mortality in advanced cirrhosis. However, the information on the association between frailty and outcome in compensated cirrhosis is scarce. We aimed to explore the prognostic impact of frailty in compensated cirrhosis. METHODS: Compensated cirrhotic patients were prospectively enrolled. Frailty was defined by the Liver Frailty Index (LFI). Development of new hepatic decompensation (worsening ascites, portal hypertension-related bleeding, hepatic encephalopathy, or acute kidney injury), unplanned hospitalization, and decompensation-free survival were recorded. Quality of life (QoL) was assessed by SF-36 questionnaire. RESULTS: 152 patients were included (MELD 9.2 ± 3.4, Child-Pugh A/B 84.9%/15.1%), and 24.3% were frail. By multivariable logistic regression analysis, age > 65 years, MELD score > 10, and Child-Pugh B were associated with frailty. Compared to the robust group, pre-frail and frail patients had significantly higher cumulative 1-year probabilities of developing decompensation (0% vs. 8.5% vs. 18.4%, p = .009), and unplanned hospitalization (0% vs. 13.5% vs. 34.2%, p < .001), and lower 1-year decompensation-free survival (100% vs. 90.8% vs. 80.4%, p = .014). Two models of multivariable Cox regression analysis were done adjusted with MELD-Na and Child-Pugh B, frailty was associated with developing decompensation (HR 3.01, p = .04; and 2.98, p = .04, respectively) and unplanned hospitalization (HR 2.46, p = .02; and 2.39, p = .03, respectively), but not the decompensation-free survival. By multivariable linear regression analysis, Child-Pugh B and frailty significantly decreased both physical and mental component scores of the SF-36 questionnaire. CONCLUSION: Frailty is prevalent in compensated cirrhosis. The LFI provides additional prognostic values to recognized risk scores regarding the development of decompensation, hospitalization, and impaired QoL.

Predictors for regression and progression of intestinal metaplasia (IM): A large population-based study from low prevalence area of gastric cancer (IM-predictor trial).

BACKGROUND: Gastric intestinal metaplasia (IM) can lead to gastric cancer. Until now, there have been limited studies of predictors for regression and progression of IM. This study aimed to determine risk factors associated with regression or progression of IM for guiding proper management and prevention of gastric cancer. METHODS: 2,025 patients undergoing gastroscopy in Thammasat University Hospital, Thailand were enrolled during September 2017-August 2019. Patients' data including baseline characteristics, laboratory results, and histopathology of gastric biopsies from University medical database were extensively reviewed. RESULTS: 2,025 patients had mean age of 61.3 years and 44.2% were males. Overall H. pylori prevalence was 47.5%. There were 1,551(76.6%) patients with chronic gastritis and 361(17.8%) with IM. Of 400 patients with chronic gastritis having follow-up endoscopy and repeated gastric biopsies, 104(26%) had persistent H. pylori infection and 27(26%) developed IM during mean follow-up time of 24 months. Persistent H. pylori infection was significantly associated with development of IM (OR 3.16, 95%CI 1.56-6.39, p = 0.001). Regression, persistence, and progression of IM were demonstrated in 57.3%, 39.2%, and 3.5% of patients, respectively. Age >65 years, persistent H. pylori infection, and diabetes mellitus were significantly associated with persistent IM or progression to dysplasia with OR 2.47(95%CI 1.33-4.61, p = 0.004), OR 2.64(95%CI 1.13-6.18, p = 0.025), and OR 2.54(95%CI 1.16-5.54, p = 0.019), respectively. Patients without H. pylori infection had more IM regression than patients with persistent infection (60.4%vs.39.4%, p = 0.035). Patients with persistent H. pylori infection significantly had higher IM progression to dysplasia (15.2%vs.2.1%; OR 11.15, 95%CI 1.18-105.24, p = 0.035) than noninfected. During 24 months of study, 30 patients (1.5%) were diagnosed with gastric cancer. CONCLUSION: Regression of IM could be achieved by successful H. pylori eradication. Persistent H. pylori infection was significantly associated with development and progression of IM to dysplasia. Age >65 years and diabetes mellitus were also significant predictors for IM progression.

Clinical Features and Overall Survival of Females with Hepatocellular Carcinoma: A Retrospective Study and Review of the Literature in the Association of Southeast Asian Nations.

INTRODUCTION: Hepatocellular carcinoma (HCC) causes more than 200,000 women deaths annually. This study aimed to investigate the clinical features, provide prognostic factors for female patients with HCC, and performed a literature review on them in the Association of Southeast Asian Nations (ASEAN). MATERIALS AND METHODS: We conducted a retrospective cohort study of female patients with HCC at Thammasat University Hospital, Thailand between January 2009 and January 2019. Furthermore, important aspects of female patients with HCC in the ASEAN published in PubMed and Scopus up to October 2020 were extensively reviewed. RESULTS: A total of 187 female patients with HCC were included (mean age 65.7±11.9 years). Elderly females were diagnosed with HCC at a more advanced stage than younger individuals (37.0% vs 23.2%, p=0.049, OR 1.94, 95% CI 1.00-3.78) and the younger group had a significantly higher overall 2-year survival rate than the elderly group (65.0% vs 45.5%, p=0.03, OR 2.23, 95% CI 1.09-4.57). Abdominal pain (HR 9.89, 95% CI 2.85-34.38, p<0.001), ascites at presentation (HR 2.77, 95% CI 1.11-6.92, p=0.03), ruptured hepatoma (HR 14.68, 95% CI 12.60-83.09, p=0.002), advanced-stage HCC (HR 9.74, 95% CI 1.89-50.26; p=0.007), and serum hypoalbuminemia (HR 4.67, 95% CI 1.62-13.50, p=0.004) were significantly associated with poor survival rate. From the ASEAN, a total of 543 females HCC patients from 6 studies were extensively reviewed. Chronic hepatitis B infection was among the pre-existing liver disease leading to HCC in ASEAN. HCC in females of the ASEAN occurred most often at an advanced age and had a grave prognosis. CONCLUSION: HCC affects a large number of females, especially in Thailand and the ASEAN, is diagnosed at an advanced stage and had a grave prognosis. Abdominal pain, ascites, ruptured HCC, advanced-stage HCC, and serum hypoalbuminemia are associated with poor prognosis. Early detection of HCC and prompt treatment in patients at risk could result in better survival outcomes.

An impact of relative adrenal insufficiency on short-term outcomes in non-critically ill cirrhotic patients: A prospective cohort study.

BACKGROUND: Relative adrenal insufficiency (RAI) is frequently found in patients with liver cirrhosis, especially in critically ill conditions. However, the prognostic impact of RAI in non-critically ill cirrhosis remains controversial. The aim of the present study was to assess the prevalence of RAI and its prognostic implication in non-critically ill cirrhotic patients. METHODS: From December 2015 to November 2017, hospitalised non-critically ill cirrhotic patients admitted with hepatic decompensation were prospectively enrolled in this study. Within 24 hours after admission, 250 mcg ACTH stimulation test was performed. RAI was defined as an increase in serum cortisol <9 mcg/dL in patients with basal serum cortisol <35 mcg/dL. Clinical outcomes were evaluated during admission and at 30-, 90-day visits. RESULTS: One hundred and fifteen patients were included (66% male, mean age 59.9 ± 16 years, mean MELD 16.1 ± 6.8, Child A/B/C 15.7%/53.9%/30.4%). The main indications for admission were bacterial infection (44.6%) and portal hypertension-related bleeding (19.1%). RAI was detected in 35 patients (30.4%). Patients with RAI had higher Child-Pugh score (9.4 ± 1.9 vs 8.0 ± 1.7, P < .01), and MELD scores (18.3 ± 5.9 vs 15.1 ± 6.9, P = .02). The in-hospital, 30-, and 90-day mortality rates were 9.6%, 20.9%, and 26.1%, respectively. There was no significant difference in the incidence of nosocomial infection, severe sepsis, septic shock, HRS, and mortality rates between patients with and without RAI. By multivariate analysis, bacterial infection on admission (HR 3.13, P < .01) and acute-on-chronic liver failure (HR 4.98, P < .001) were independent predictors of 90-day survival. CONCLUSIONS: RAI is found in about one-third of hospitalised non-critically ill cirrhotic patients and is associated with the severity of cirrhosis. However, the presence of RAI has no influence on short-term outcomes.

Predictors for development of complete and incomplete intestinal metaplasia (IM) associated with H. pylori infection: A large-scale study from low prevalence area of gastric cancer (IM-HP trial).

BACKGROUND: Gastric intestinal metaplasia (IM) is precancerous lesion of gastric cancer related to H. pylori infection. There has been limited data about IM and associated risk factors. This study aimed to determine risk factors related to development of IM to guide proper management. METHODS: 1,370 patients undergoing UGI endoscopy at Thammasat University Hospital, Thailand were included between January 2018-August 2019. Patients' data including baseline characteristics, laboratory results, and histopathology from medical database were extensively reviewed. Immunohistochemical staining for p53 expression from gastric biopsies was also performed. RESULTS: Overall H. pylori prevalence was 43.8%. Mean age was 60.7 years and 45% of whom were males. Chronic gastritis was observed in 1,064(77.7%) patients, while 223(16.3%) had IM. Of 223 patients with IM, 194(87%) patients had complete IM, while 29 (13%) had incomplete IM. In groups of complete and incomplete IM, current H. pylori infection rates were 66.5% and 58.6%, respectively. The BMI of incomplete IM group(27.4) was significantly higher than BMI of complete IM group (23.6). Overweight and obese patients (BMI ≥23 kg/m2) were significantly associated with higher risk for the development of incomplete IM (OR 3.25; 95%CI 1.14-9.27, p = 0.027). Males, age >50 years, and current H. pylori infection were significantly higher in IM than chronic gastritis group with OR 1.43 (95%CI 1.01-2.03, p = 0.048), OR 1.67 (95% CI 1.08-2.57, p = 0.021), and OR 3.14 (95% CI 2.29-4.30, p<0.001), respectively. During 20 months of study, there were 15 patients (1.1%) diagnosed with gastric cancer and 1-year survival rate was only 60%. CONCLUSIONS: Males, age >50 years, and current H. pylori infection are significant predictors for the presence of intestinal metaplasia. BMI might be beneficial for using as a predictive risk factor to reduce the development of incomplete intestinal metaplasia. H. pylori eradication could be an effective way to prevent the development of gastric precancerous lesions.

Evaluation of aspartate aminotransferase to platelet ratio index and fibrosis 4 scores for hepatic fibrosis assessment compared with transient elastography in chronic hepatitis C patients.

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 < 0.001). APRI score < 0.5 and FIB-4 score > 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.

High Efficacy of Rapid Urine Test for Diagnosis of Helicobacter pylori Infection in Thai People

Background: Accurate diagnosis of Helicobacter pylori (H. pylori) infection plays an important role in further effective treatment. Rapid urine test (RAPIRUN) is a test developed for qualitative detection of urine H. Pylori antibody and use for determine the sensitivity, specificity and accuracy. However, the test needs validation in Thai population before using in clinical practice. Objective: This study aimed to compare performance of different diagnostic tests on H. pylori detection in Thai population. Methods: Total of 94 patients with dyspepsia who referred to Thammasat University Hospital, Pathumthani, Thailand, between December 2012 and April 2013 were enrolled in this study. All patients underwent gastroscopy. Then, 3 biopsies at antrum were taken for H. pylori diagnosis. including rapid urease test (Pronto Dry, Eisai, Thailand), H. pylori culture, and histopathology. Urine samples were also collected at the same time for rapid urine test (RAPIRUN H. pylori Antibody, Otsuka Pharmaceutical Co., Ltd.). Patients were diagnosed with H. pylori-positive if their culture or rapid urease tests plus histopathology yielded positive results. Results: Total of 29 patients (30.9%) were infected with H. pylori. Prevalence of H. pylori infection by rapid urease test, histopathology, culture and rapid urine test were 25.5%, 28.7%, 29.8%, and 32.9% respectively. We observed that rapid urease test, histopathology, culture, and rapid urine test had sensitivity of 82.8%, 93.1%, 93.1% and 86.2%; specificity of 100%, 100%, 100%, and 90.8%; and accuracy of 95.7%, 97.9%, 97.9%, and 89.4%, respectively. Conclusion: Rapid urine test (RAPIRUN) provided a reliable result for diagnosis of H. pylori infection. Furthermore, this rapid urine test demonstrated high accuracy, reliable, safe handle and easy to use. We suggested rapid urine test for diagnosis of H. pylori infection in Thai population since we found it less invasive and with higher reliable efficacy.