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.

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.

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/# ).

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.

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.

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.

N-Acetylcysteine Prevents Post-embolization Syndrome in Patients with Hepatocellular Carcinoma Following Transarterial Chemoembolization.

BACKGROUND: Post-embolization syndrome is a common complication after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). N-acetylcysteine (NAC) is known to ameliorate liver damage from several causes. AIM: To determine the efficacy of intravenous NAC in the prevention of post-embolization syndrome in HCC patients following TACE. METHODS: In this study, patients with HCC admitted for TACE were prospectively enrolled. All patients were randomized stratified by Child A or B to receive NAC or placebo. The NAC group received intravenous NAC 24 h prior to TACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h, then continuous infusion 6.25 mg/h for 48 h after the procedure). The placebo group received an infusion of 5% glucose solution until 48 h after procedure. The post-embolization syndrome was defined as: T ≥ 38.5 c and serum ALT > 3 times of pretreatment value. RESULTS: In total, 111 HCC patients were enrolled; 57 were randomly assigned to NAC group and 54 to placebo group. The incidence of post-embolization syndrome was lower in NAC group (24.6%) compared to placebo group (48.2%); P = 0.01. On multivariate analysis, receiving IV NAC (P = 0.03) and HCC diameter (P < 0.01) were associated with developing post-embolization syndrome. Post-TACE liver decompensation was documented in 26/111 (23.4%) patients. There was no difference in the incidence of post-TACE liver decompensation between NAC and placebo group. CONCLUSIONS: In this study, intravenous NAC administration reduces the incidence of post-embolization syndrome after TACE in patients with HCC. However, it does not prevent post-TACE liver decompensation. TRIAL REGISTRATION NUMBER: This study was registered with Thai Clinical Trial Registry (TCTR20150313002).

Clinical and histologic features of Azathioprine-induced hepatotoxicity.

BACKGROUND: Hepatoxicity is a relative uncommon complication related with Azathioprine, however most studies were performed in inflammatory bowel diseases patients. The aim of this study is to report the clinical profile of patients with Azathioprine-induced hepatotoxicity. METHODS: All medical records of patients received Azathioprine from 2010 to 2015 were retrospectively reviewed. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) or aspatate aminotransferase (AST) or total bilirubin >2 times upper limit normal. Other causes of liver diseases were excluded. All subjects were followed until the resolution of liver injury. RESULTS: Two-hundred and ninety-three patients receiving Azathioprine were retrospectively reviewed. Eight patients (2.7%) were diagnosed with Azathioprine-induced hepatotoxicity. The median age was 45 year with female preponderance. The latency to onset of liver injury ranged from 7 to 236 d, and 4 patients were symptomatic. Median peak levels were ALT 295 U/L, alkaline phosphatase 169 U/L, and total bilirubin 1 mg/dl. According to R-ratio, mixed pattern (50%) was more frequent than cholestatic (37.5%) and hepatocellular pattern (12.5%). Liver biopsies were performed in 2 patients, and showed hepatocellular and canalicular cholestasis with mild portal and peri-portal inflammation. All patients recovered fully with a median time of 41.3 days. Two patients developed prolonged cholestasis >2 months, hence none had liver failure or required liver transplantation. CONCLUSION: Hepatotoxicity is relative uncommon in patients receiving Azathioprine, and predominantly is mixed hepatocellular and cholestatic in nature. Even though all patients recover fully after drug withdrawal, severe cholestasis can occur.

Improved participants' understanding of research information in real settings using the SIDCER informed consent form: a randomized-controlled informed consent study nested with eight clinical trials.

PURPOSE: This study aimed to test the applicability and effectiveness of the principles and informed consent form (ICF) template proposed by the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) across multiple clinical trials involving Thai research participants with various conditions. METHODS: A single-center, randomized-controlled study nested with eight clinical trials was conducted at Thammasat University Hospital, Thailand. A total of 258 participants from any of the eight clinical trials were enrolled and randomly assigned to read either the SIDCER ICF (n = 130) or the conventional ICF (n = 128) of the respective trial. Their understanding of necessary information was assessed using the post-test questionnaire; they were allowed to consult a given ICF while completing the questionnaire. The primary endpoint was the proportion of the participants who had the post-test score of ≥80%, and the secondary endpoint was the total score of the post-test. RESULTS: The proportion of the participants in the SIDCER ICF group who achieved the primary endpoint was significantly higher than that of the conventional ICF group (60.8 vs. 41.4%, p = 0.002). The total score of the post-test was also significantly higher among the participants who read the SIDCER ICF than those who read the conventional ICF (83.3 vs. 76.0%, p < 0.001). CONCLUSIONS: The present study demonstrated that the SIDCER ICF was applicable and effective to improve Thai research participants' understanding of research information in diverse clinical trials. Using the SIDCER ICF methodology, clinical researchers can improve the quality of ICFs for their trials.

Feasibility of the unilateral-flange stent for the treatment of benign pancreatic duct stricture: a pilot study.

Endoscopic placement of the plastic stent has been adopted as an initial treatment for chronic pancreatitis with pancreatic duct stricture. Stent fracture while attempting removal is one of the complications of stent exchange. The use of the unilateral-flange stent in these patients has never been reported. We investigated the outcomes associated with the use of this stent with regard to stent exchange and stent-related adverse events. From 2011 to 2015, 9 patients with chronic pancreatitis and main pancreatic duct (MPD) stricture treated with the unilateral-flange stent were included. Eleven endoscopic treatment sessions, 53 endoscopic stent deployments or exchange procedures were analyzed. Technical success rate was 100%. Forty-eight stents were exchanged on a regular basis in 1 to 6-month intervals. Another 5 stent exchange procedures were urgently performed due to stent obstruction and caused pancreatitis (n=2), symptomatic external stent migration (n=2), and concurrent cholangitis (n=1). The rate of symptomatic migration was 3.7%. The mean duration for stent exchange was 29 minutes and no stent fracture occurred during the procedure. Of 11 endoscopic treatment sessions, 7 were successful, 3 were changed to the metallic stents, and 1 was lost to follow-up. According to this study, unilateral-flange stent placement for benign MPD stricture is technically feasible and effective. Stent removal during the exchange period is unchallenging and without stent fracture.

Idiopathic portal hypertension: natural history and long-term outcome.

UNLABELLED: Idiopathic portal hypertension (IPH) is a rare cause of intrahepatic portal hypertension. Data on natural history and prognosis of IPH are limited. We sought to describe the complications and long-tem outcome of IPH by retrospectively studying 69 biopsy-proven cases of IPH. Mean duration of follow-up was 6.7 ± 4.6 years. All patients had evidence of portal hypertension (PH) at diagnosis, and 42% were symptomatic. Variceal bleeding (VB) was the most common manifestation. In those without bleeding at diagnosis, 74% had varices at first endoscopy. In those with large varices, the 1-year probability of first bleeding despite primary prophylaxis was 9%. The 1-year probability of rebleeding was 22%. Ascites and hepatic encephalopathy was documented in 26% and 7% of patients, respectively, at least once during the clinical course. The 1-year probability of developing portal vein thrombosis (PVT) was 9%, and 53% of patients receiving anticoagulation achieved recanalization. Human immunodeficiency virus (HIV) infection and VB at diagnosis were the independent predictors of PVT. Seven patients died (6 as a result of an IPH-related cause) and 2 were transplanted. Probability of liver transplantation-free survival was 82% at 10 years. Presence of a severe associated disorder and ascites as a presenting symptom were associated with poor survival. CONCLUSION: Variceal bleeding is a major complication of IPH. Using, in IPH patients, the same management approach for PH as in cirrhosis is safe and maintains a low incidence of first bleeding and rebleeding in IPH patients. PVT is a frequent complication, particularly in those with HIV infection. Despite several complications, overall survival of patients with IPH is considerably good.

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.

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.

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.

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.

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.

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.

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.

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.

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.