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.

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.

Real world for management of hepatocellular carcinoma: a large population-based study.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. This study investigated the risk factors, treatment responses and survival outcomes in real-world patients with HCC. MATERIALS AND METHODS: This was a large, retrospective cohort study of patients newly diagnosed with HCC at tertiary referral centers in Thailand between 2011 and 2020. Survival time was defined as the time from the date of HCC diagnosis to the date of death or last follow-up. RESULTS: A total of 1145 patients with a mean age of 61.4 ± 11.7 years were included. Next, 568 (48.7%), 401 (34.4%) and 167 (15.1%) patients were classified as Child-Pugh score A, B and C, respectively. Over half of the patients (59.0%) were diagnosed with noncurative-stage HCC (BCLC B-D). Patients with Child-Pugh A scores were more likely to be diagnosed with curative-stage HCC (BCLC 0-A) than noncurative stage (67.4% vs. 37.2%, p < .001). Patients with curative-stage HCC and Child-Pugh A cirrhosis underwent more liver resections than radiofrequency ablation (RFA) (91.8% vs. 69.7%, p < .001). For BCLC 0-A patients with portal hypertension, RFA was selected more frequently than liver resection (52.1% vs. 28.6%, p < .001). Patients who received RFA monotherapy tended to experience increased median survival times compared to those who underwent resection (55 vs. 36 months; p = .058). CONCLUSIONS: Surveillance programs should be encouraged to detect early-stage HCC, which is suitable for curative treatment improving survival outcomes. RFA may be an appropriate first-line treatment for curative-stage HCC. Sequential multi-modality treatment in the curative stage can achieve favorable 5-year survival.

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.

Antiviral treatment could not provide clinical benefit in management of mild COVID-19: A Retrospective Experience from Field hospital.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected over 145 million infected people and 3 million deaths worldwide. There has been limited data to recommend either for or against use of antiviral regimens in mild COVID-19 patients. This study aimed to compare clinical outcomes between mild COVID-19 patients receiving antiviral drugs and those without. METHOD: Thai patients diagnosed with COVID-19 at field hospital affiliated to Thammasat University Hospital, Thailand were evaluated between January 1, 2020 and April 13, 2021. Patients' data, clinical presentation, past medical history, laboratory results, and treatment outcomes were extensively reviewed. RESULTS: Five hundred patients with positive tests were included in the study. The mean age was 35.9 years; 46% males. There were 225 (45%), 207 (41.4%), 44 (8.8%), 18 (3.6%), 6 (1.2%) patients with asymptomatic, mild, moderate, severe, and critical COVID-19, respectively. Of 207 mild COVID-19 patients, 9 (4.3%) received lopinavir/ritonavir or darunavir/ritonavir, 17 (8.2%) received favipiravir, while 175 (84.5%) had only supportive care. Mild COVID-19 patients receiving antiviral treatment had longer median length of hospital stay [13 days (IQR 11-14) vs. 10 days (IQR 8-12), p < 0.001] than patients having only supportive treatment. Antiviral drug use was significantly associated with longer hospital stay (>10 days) in mild COVID-19 patients (OR 5.52; 95%CI 2.12-14.40, p < 0.001). Adverse drug reactions such as diarrhea, abdominal pain, and hepatitis were also demonstrated in our COVID-19 patients with antiviral treatments. Majority of patients (97.6%) recovered without any complications and were discharged home. Two deaths were caused by acute respiratory distress syndrome from severe COVID-19 pneumonia. CONCLUSION: Antiviral treatment could not provide superior clinical outcomes to supportive care in mild COVID-19 patients. Mild COVID-19 patients receiving antiviral medication had longer length of hospital stay than those without. Standard supportive care and regular monitoring of disease progression might be keys for successful management of mild COVID-19.

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.