The incidence, etiologies, outcomes, and predictors of mortality of acute liver failure in Thailand: a population-base study

Background: Acute liver failure (ALF) is uncommon but progresses rapidly with high mortality. We investigated the incidence, etiologies, outcomes, and predictive factors for 30-day mortality in patients with ALF. Methods: We conducted a population-based study of ALF patients hospitalized between 2009 and 2013 from the Thai Nationwide Hospital Admission database, which comprises 76% of all admissions from 858 hospitals across 77 provinces in Thailand. ALF was diagnosed using ICD-10 codes K72.0 and K71.11. Patients with liver cirrhosis were excluded. Results: There were 20,589 patients diagnosed with ALF during the study period with 12,277 (59.6%) males and mean age of 46.6 ± 20.7 years. The incidence of ALF was 62.9 per million population per year. The most frequent causes of ALF were indeterminate (69.4%), non-acetaminophen drug-induced (26.1%), and viral hepatitis (2.5%). Acetaminophen was the presumptive cause in 1.7% of patients. There were 5502 patients (26.7%) who died within 30 days after admission. One patient (0.005%) underwent liver transplantation. The average hospital stay was 8.7 ± 13.9 days, and the total cost of management was 1075.2 ± 2718.9 USD per admission. The most prevalent complications were acute renal failure (ARF)(24.2%), septicemia (18.2%), and pneumonia (12.3%). The most influential predictive factors for 30-day mortality were ARF (HR = 3.64, 95% CI: 3.43–3.87, p < 0.001), malignant infiltration of the liver (HR = 3.37, 95% CI: 2.94–3.85, p < 0.001), and septicemia (HR = 1.96, 95%CI: 1.84–2.08, p < 0.001). Conclusions: ALF patients have poor outcomes with 30-day mortality of 26.7% and high economic burden. Indeterminate etiology is the most frequent cause. ARF, malignant infiltration of the liver, and septicemia are main predictors of 30-day mortality

Metformin as an Adjunctive Therapy for Pancreatic Cancer: A Review of the Literature on Its Potential Therapeutic Use

Pancreatic ductal adenocarcinoma has the worst prognosis of any cancer. New adjuvant chemotherapies are urgently required, which are well tolerated by patients with unresectable cancers. This paper reviews the existing proof of concept data, namely laboratory, pharmacoepidemiological, experimental medicine and clinical trial evidence for investigating metformin in patients with pancreatic ductal adenocarcinoma. Laboratory evidence shows metformin inhibits mitochondrial ATP synthesis which directly and indirectly inhibits carcinogenesis. Drug–drug interactions of metformin with proton pump inhibitors and histamine H2-receptor antagonists may be of clinical relevance and pertinent to future research of metformin in pancreatic ductal adenocarcinoma. To date, most cohort studies have demonstrated a positive association with metformin on survival in pancreatic ductal adenocarcinoma, although there are many methodological limitations with such study designs. From experimental medicine studies, there are sparse data in humans. The current trials of metformin have methodological limitations. Two small randomized controlled trials (RCTs) reported null findings, but there were potential inequalities in cancer staging between groups and poor compliance with the intervention. Proof of concept data, predominantly from laboratory work, supports assessing metformin as an adjunct for pancreatic ductal adenocarcinoma in RCTs. Ideally, more experimental medicine studies are needed for proof of concept. However, many feasibility criteria need to be answered before such trials can progress

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

Characteristics and outcomes of cholangiocarcinoma by region in Thailand: A nationwide study

Aim To identify the potential risk factors of cholangiocarcinoma, we determined the characteristics of cholangiocarcinoma patients among 5 different regions of Thailand. Methods All patients diagnosed with cholangiocarcinoma between 2008 and 2013 were identified using the Nationwide Hospital Admission Data registry (n = 39421). Baseline characteristics, comorbidities and survival were abstracted. Results The annual incidence during the study period was stable in all regions. Most patients lived in the Northeast (62.8%), followed by the North (16.9%), Central (12.3%), Bangkok (5.4%), and South (n = 2.6%) regions (p Conclusions Diabetes and chronic liver diseases may be associated with cholangiocarcinoma in the Thai population.</p

Characteristics and outcomes of cholangiocarcinoma by region in Thailand: A nationwide study

Aim To identify the potential risk factors of cholangiocarcinoma, we determined the characteristics of cholangiocarcinoma patients among 5 different regions of Thailand. Methods All patients diagnosed with cholangiocarcinoma between 2008 and 2013 were identified using the Nationwide Hospital Admission Data registry (n = 39421). Baseline characteristics, comorbidities and survival were abstracted. Results The annual incidence during the study period was stable in all regions. Most patients lived in the Northeast (62.8%), followed by the North (16.9%), Central (12.3%), Bangkok (5.4%), and South (n = 2.6%) regions (p &lt; 0.0001). Significantly more cholangiocarcinoma patients had diabetes, cirrhosis, and chronic viral hepatitis B/C infection than noncholangiocarcinoma participants (diabetes: 11.42% vs 5.28%; cirrhosis: 4.81% vs 0.92%; hepatitis B: 0.74% vs 0.12%; and hepatitis C: 0.50% vs 0.10%, p &lt; 0.0001 for all, respectively). The overall 1-year mortality rate was 81.7%, with a stable trend over time. Conclusions Diabetes and chronic liver diseases may be associated with cholangiocarcinoma in the Thai population.</p