Curcuma longa Linn versus omeprazole in treatment of functional dyspepsia: A randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Functional dyspepsia (FD) is a common problem in gastroenterology practice. The study aimed to compare the efficacy of Curcuma longa Linn versus omeprazole and placebo among patients diagnosed with FD. METHODS: From November 2017 to November 2018, patients diagnosed with FD according to ROME IV criteria were enrolled. Patients were randomized into curcumin, omeprazole, or placebo groups. The Severity of Dyspepsia Assessment (SODA) was used to evaluate clinical effectiveness after 2 and 4 weeks. Health-related quality of life was assessed using the EuroQol-5 Dimension questionnaire. RESULTS: A total of 132 patients were randomized. Forty-five, 43, and 44 patients were in the curcumin, omeprazole, and placebo groups, respectively. At 4 weeks, the mean SODA score change of pain and non-pain symptoms decreased in the curcumin group compared with the placebo group (pain -16.98 ± 8.09 vs -10.53 ± 4.43; P < 0.001, non-pain -7.96 ± 3.41 vs -6.05 ± 3.03; P < 0.008). No significant difference was observed between curcumin and omeprazole groups (pain -16.98 ± 8.09 vs -14.69 ± 6.41; P = 0.302, non-pain -7.96 ± 3.41 vs -7.07 ± 2.27; P = 0.486). The mean change of the SODA satisfaction score at 4 weeks was higher in the curcumin group compared with the omeprazole group but without statistical significance (9.17 ± 3.88 vs 8.63 ± 3.89, P = 1). The mean change of EQ-5D index at 4 weeks was highest in the curcumin group but not statistically different from other groups (0.12 ± 0.13 vs 0.09 ± 0.10 vs 0.07 ± 0.05; P = 0.055). CONCLUSION: Curcuma longa Linn can improve dyspeptic symptoms, improve quality of life, and provide satisfaction equivalent to omeprazole in treatment of FD.

Real-world effectiveness and safety of sofosbuvir and nonstructural protein 5A inhibitors for chronic hepatitis C genotype 1, 2, 3, 4, or 6: a multicentre cohort study.

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

Comparison of normal saline versus Lactated Ringer's solution for fluid resuscitation in patients with mild acute pancreatitis, A randomized controlled trial.

BACKGROUND/OBJECTIVES: Aggressive fluid resuscitation is recommended for initial management of acute pancreatitis. However, there are few studies which focus on types of fluid therapy. METHODS: We performed a randomized controlled trial in patients with acute pancreatitis. The patients were randomized into two groups. Each group received Normal Saline solution (NSS) or Lactated Ringer's solution (LRS) through a goal-directed fluid resuscitation protocol. Systemic inflammatory response syndrome (SIRS) at 24 and 48 h, mortality, presence of local complications and inflammatory markers were measured. RESULTS: Forty-seven patients were included. Twenty-four patients (51%) received NSS and 23 patients received LRS. There was significant reduction in SIRS after 24 h among subjects who resuscitated with LRS compared with NSS (4.2% in NSS, 26.1% in LRS, P = 0.02). However, SIRS reduction at 48 h was not different between groups (33.4% in NSS, 26.1% in LRS, P = 0.88). Mortality was not different between NSS and LRS (4.2% in NSS, 0% in LRS, P = 1.00). CRP, ESR and procalcitonin increased at 24 h and 48 h after admission with no difference between the two groups. Local complications were 29.2% in NSS and 21.7% in LRS (P = 0.74). The median length of hospital stay was not significantly different in the two groups (5.5 days in NSS, 6 days in LRS, P = 0.915). CONCLUSIONS: Lactated Ringer's solution was superior to NSS in SIRS reduction in acute pancreatitis only in the first 24 h. But SIRS at 48 h and mortality were not different between LRS and NSS.

Association of the S267F variant on NTCP gene and treatment response to pegylated interferon in patients with chronic hepatitis B: a multicentre study.

BACKGROUND: Sodium taurocholate co-transporting polypeptide (NTCP) is a cell receptor for HBV. The S267F variant on the NTCP gene is inversely associated with the chronicity of HBV infection, progression to cirrhosis and hepatocellular carcinoma in East Asian populations. The aim of this study was to determine whether the S267F variant was associated with response to pegylated interferon (PEG-IFN) in patients with chronic HBV infection. METHODS: A total of 257 patients with chronic HBV, treated with PEG-IFN for 48 weeks, were identified from 13 tertiary hospitals included in the hepatitis B database of the Thai Association for the Study of the Liver (THASL). RESULTS: Of these, 202 patients were infected with HBV genotype C (84.9%); 146 patients were hepatitis B e antigen (HBeAg)-positive (56.8%). Genotypic frequencies of the S267F polymorphism were 85.2%, 14.8% and 0% for the GG, GA and AA genotypes, respectively. S267F GA was associated with sustained alanine aminotransferase (ALT) normalization (OR = 3.25, 95% CI 1.23, 8.61; P=0.02) in HBeAg-positive patients. Patients with S267F variant tended to have more virological response, sustained response with hepatitis B surface antigen (HBsAg) loss at 24 weeks following PEG-IFN treatment. There was no association between the S267F variant and improved patient outcomes in HBeAg-negative patients. CONCLUSIONS: The S267F variant on the NTCP gene is independently associated with sustained normalization of ALT following treatment with PEG-IFN in patients with HBV infection who are HBeAg-positive. The findings of this study provide additional support for the clinical significance of the S267F variant of NTCP beyond HBV entry.

A Phase I/II Multicenter Study of Single-Agent Foretinib as First-Line Therapy in Patients with Advanced Hepatocellular Carcinoma.

Purpose: This phase I/II single-arm study evaluated the safety, pharmacokinetics, pharmacodynamics, and activity of foretinib, an oral multikinase inhibitor of MET, ROS, RON, AXL, TIE-2, and VEGFR2, in the first-line setting in advanced hepatocellular carcinoma patients.Experimental Design: In the phase I part, advanced hepatocellular carcinoma patients were dose escalated on foretinib (30-60 mg) every day using the standard 3+3 design. Once the maximum tolerated dose (MTD) was determined, an additional 32 patients were dosed at the MTD in the phase II expansion cohort for assessment of efficacy and safety. Exploratory analyses were conducted to assess potential biomarkers that might correlate with clinical efficacy and survival.Results: The MTD of foretinib was established as 30 mg every day. The most frequent adverse events were hypertension, decreased appetite, ascites, and pyrexia. When dosed at 30 mg every day in the first-line setting, foretinib demonstrated promising antitumor activity. According to the modified mRECIST, the objective response rate was 22.9%, the disease stabilization rate 82.9%, and the median duration of response 7.6 months. The median time to progression was 4.2 months and the median overall survival (OS) was 15.7 months. Fifteen candidate biomarkers whose levels in the circulation were significantly altered in response to foretinib treatment were elucidated. Multivariate analyses identified IL6 and IL8 as independent predictors of OS.Conclusions: Foretinib demonstrated promising antitumor activity and good tolerability in the first-line setting in Asian advanced hepatocellular carcinoma patients. Baseline plasma levels of IL6 or IL8 might predict the response to foretinib. Clin Cancer Res; 23(10); 2405-13. ©2016 AACR.

Treatment outcomes and validation of the stopping rule for response to peginterferon in chronic hepatitis B: A Thai nationwide cohort study.

BACKGROUND AND AIMS: Peginterferon has demonstrated effectiveness in clinical trials in patients with chronic hepatitis B (CHB). However, its efficacy in real-life settings remains unclear. We investigated the efficacy of peginterferon for CHB and validated the performance of previously identified response predictors in clinical practice. METHODS: We analyzed prospectively collected data from a Thai nationwide cohort of CHB patients treated with peginterferon alfa-2a (180 µg/week, 48 weeks). RESULTS: Among a total of 233 patients, mostly with genotype B or C, sustained response was observed in 23% of 135 hepatitis B e antigen (HBeAg)-positive patients (HBeAg seroconversion with hepatitis B virus [HBV] DNA < 2000 IU/mL) and 42% of 98 HBeAg-negative patients (HBV DNA < 2000 IU/mL with aminotransferase normalization) at 24 weeks after treatment. Age, sex, presence of cirrhosis, genotype, and pretreatment levels of aminotransferase, HBV DNA, and hepatitis B surface antigen (HBsAg) were not identified as significant predictors of sustained response. In HBeAg-positive patients, HBsAg > 20 000 IU/mL at week 12 provided a good stopping rule, with a negative predictive value of 96%. In HBeAg-negative patients, the performance of 12-week stopping rules of no decline in HBsAg with a < 2log10 decline in HBV DNA and a < 10% log10 decline in HBsAg showed modest negative predictive values of 80% and 66%, respectively, for achieving sustained response. CONCLUSION: Outcomes in CHB patients treated with peginterferon in a clinical setting are similar to those demonstrated in clinical trials. Application of the early stopping rule based on HBsAg quantification may allow individualization of therapy, particularly in HBeAg-positive patients.