Liver disease remains a major critical challenge in Thailand due to viral hepatitis. Clinical management requires close monitoring of liver fibrosis severity. Non-invasive testing is an attractive ...method for probing of disease progression. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel serum marker for fibrosis staging. The current study evaluates the marker among healthy donors and hepatitis C (HCV) patients. 100 HCV subjects were evaluated by liver biopsy. These patients had varying fibrosis severity based on METAVIR scores. Healthy donors were confirmed based on normal liver functions tests. Comparisons of M2BPGi levels among different study groups were performed and the effectiveness was evaluated using receiver operating characteristics (ROC) curves. Using liver biopsy as the reference standard, median M2BPGi levels in HCV cases were 0.74, 1.38 and 2.88 COI for F0-1, F2 and > F3 cases respectively. In healthy donors, the baseline values ranged 0.1-0.24 COI and statistically lower than liver disease cases profiled using M2BPGi. ROC analysis demonstrated superior results for M2BPGi levels among diseased populations and healthy controls. AUROC was determined at 0.983. Comparing with other non-invasive tests, M2BPGi showed a positive linear trend that indicated a strong match to existing methodologies. M2BPGi addresses a critical need in the management of liver disease by providing straightforward means to probe fibrosis severity. In this study, we found significant differences between hepatitis C and healthy subjects and established the background level in healthy donors.
Clinical trials have proven the efficacy and safety of atezolizumab combined with bevacizumab (A+B) in treating unresectable hepatocellular carcinoma (uHCC). This study aimed to assess the ...cost-utility of A+B compared to best supportive care (BSC) among uHCC patients in Thailand.
We conducted a cost-utility analysis from a societal perspective. We used a three-state Markov model to estimate relevant costs and health outcomes over the lifetime horizon. Local cost and utility data from Thai patients were applied. All costs were adjusted to 2023 values using the consumer price index. We reported results as incremental cost-effectiveness ratios (ICERs) in United States dollars ($) per quality-adjusted life year (QALY) gained. We discounted future costs and outcomes at 3% per annum. We then performed one-way sensitivity analysis and probabilistic sensitivity analysis to assess parameter uncertainty. The budget impact was conducted to estimate the financial burden from the governmental perspective over a five-year period.
Compared to BSC, A+B provided a better health benefit with 0.8309 QALY gained at an incremental lifetime cost of $45,357. The ICER was $54,589 per QALY gained. The result was sensitive to the hazard ratios for the overall survival and progression-free survival of A+B. At the current Thai willingness-to-pay (WTP) threshold of $4,678 per QALY gained, the ICER of A+B remained above the threshold. The projected budgetary requirements for implementing A+B in the respective first and fifth years would range from 8.2 to 27.9 million USD.
Although A+B yielded the highest clinical benefit compared with BSC for the treatment of uHCC patients, A+B is not cost-effective in Thailand at the current price and poses budgetary challenges.
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.
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.
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.
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.
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.
Abstract
Background
Hypertensive crisis is an urgent/emergency condition. Although obstructive sleep apnea (OSA) in resistant hypertension has been thoroughly examined, information regarding the risk ...factors and prevalence of hypertensive crisis in co-existing OSA and hypertension is limited. This study thus aimed to determine prevalence of and risk factors for hypertensive crisis in patients with hypertension caused by OSA.
Methods
The inclusion criteria were age of 18 years or over and diagnosis of co-existing OSA and hypertension. Those patients with other causes of secondary hypertension were excluded. Patients were categorized by occurrence of hypertensive crisis. Factors associated with hypertensive crisis were calculated using multivariate logistic regression analysis.
Results
There were 121 patients met the study criteria. Of those, 19 patients (15.70%) had history of hypertensive crisis. Those patients in hypertensive crisis group had significant higher systolic and diastolic blood pressure at regular follow-ups than those without hypertensive crisis patients (177 vs. 141 mmHg and 108 vs. 85 mmHg;
p
value < 0.001 for both factors). After adjusted for age, sex, and Mallampati classification, only systolic blood pressure was independently associated with hypertensive crisis with adjusted odds ratio (95% CI) of 1.046 (1.012, 1.080).
Conclusions
The prevalence of hypertensive crisis in co-existing OSA and hypertension was 15.70% and high systolic blood pressure or uncontrolled blood pressure associated with hypertensive crisis in patients with OSA-associated hypertension.
Background:
The objectives of this phase II study were to determine the clinical activity of the MET tyrosine kinase inhibitor capmatinib (INC280) in patients with MET-dysregulated advanced ...hepatocellular carcinoma (HCC) and to assess the safety, pharmacokinetics, and correlation of biomarkers with the response.
Methods:
This phase II, open-label, single-arm study evaluated twice daily (BID) oral capmatinib in a dose-determining stage, utilizing a Bayesian Logistic Regression Model (BLRM) subject to Escalation with Overdose Control criteria, safety, pharmacokinetics, and pharmacodynamic information to determine a recommended dose for expansion (RDE) evaluating efficacy in patients with MET-dysregulated HCC.
Results:
A total of 38 patients received treatment. In the dose-determining stage, patients received capmatinib 300 mg BID capsules (n = 8), and in the expansion, patients received 600 mg BID capsules (n = 28) or 400 mg BID tablets (n = 2) based on the BLRM and other relevant clinical data. No predefined qualifying adverse events (AEs) were observed during the first 28 days of treatment, and the RDE was 600 mg BID capsules (equivalent pharmacokinetics to 400 mg BID tablets). The most common any causality AEs were nausea (42%), vomiting (37%), and diarrhea (34%). In the expansion stage, in a subgroup of 10 patients with MET-high HCC, the overall response rate was 30%, including 1 durable complete response (>600 days) and 2 partial responses 1 durable (>600 days).
Conclusions:
Single agent capmatinib at the RDE is tolerable with a manageable safety profile. Antitumor activity was seen in a subset of patients with MET-dysregulated (MET-high) HCC.
Trial registration:
ClinicalTrials.gov: NCT01737827. https://clinicaltrials.gov/ct2/show/NCT01737827
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.
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.
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.
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.
.
Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as ...entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.
Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. The appropriate treatment according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) ...guideline was 19-60%. However, there are limited data on predictors of appropriate treatment in patients with COPD. This study aimed to evaluate risk factors of appropriate treatment in patients with COPD according to the GOLD guideline in a real-world community setting.
Methods: This is a retrospective study conducted at a community hospital. Inclusion criteria were adult patients diagnosed as COPD treated at a COPD clinic. The primary outcome was the appropriate treatment, defined by correct pharmacological treatment by the GOLD guideline according to the ABCD severity assessment. Clinical predictors of appropriate treatment were executed by stepwise multivariate logistic regression analysis.
Results: 136 patients with COPD met the study criteria. Of those, 100 patients had inappropriate treatment according to the GOLD guideline. Three factors were independently associated with the appropriate treatment including number of admissions, modified Medical Research Council (mMRC) score, and CAT score. These factors had adjusted odds ratio of 3.11, 2.86, and 1.26, respectively. Causes of inappropriate treatment were unavailability of long-acting muscarinic antagonist (LAMA) (51 patients; 79.69%), treated by inhaled corticosteroid (ICS) alone (12 patients; 18.75%), and treated with only bronchodilator (1 patient; 1.56%).
Conclusions: Appropriate COPD patients’ treatment according to the GOLD guideline was 26.47% in community setting. Factors associated with severity of COPD were associated with prescribing appropriate treatments.
Hypertension is a common disease in clinical practice. Calcium channel blocker (CCB) is an effective antihypertensive agent. There is inconsistent data of an association of CCB and breast cancer in ...literatures particularly in breast cancer cytology. This study aimed to evaluate this association by a case-control design. The inclusion criteria were adult patients with an age of 18 years or over, diagnosed as hypertension, with a result of mammogram. Those who were pregnant, had no pathological results, or had breast mass prior to diagnosis of hypertension were excluded. Cases defined if the pathological report of any types of breast cancer, while controls were those with benign breast mass. Factors associated with breast cancer were calculated by logistic regression analysis. There were 299 patients met the study criteria. Of those, 100 patients (33.4 %) were in the case group or breast cancer group. There were three factors independently associated with breast cancer. CCB treatment had adjusted odds ratio of 2.25 (95 % confidence interval of 1.36, 3.77), while age of 50 years old or over and hormonal therapy also independently associated with breast cancer with adjusted odds ratios of 3.41 and 2.91, respectively. The CCB group had significantly higher proportion of ductal breast cancer than those who did not take CCB (42.5 % vs 23.8 %, p < 0.001). CCB treatment may be associated with breast cancer especially ductal carcinoma in this study population.
PDF
