Cost-utility analysis of non-contrast abbreviated magnetic resonance imaging for hepatocellular carcinoma surveillance in cirrhosis

Background/Aims: Ultrasonography has a low sensitivity for detecting early-stage hepatocellu- lar carcinoma (HCC) in cirrhotic patients. Non-contrast abbreviated magnetic resonance imaging (aMRI) demonstrated a comparable performance to that of magnetic resonance imaging without the risk of contrast media exposure and at a lower cost than that of full diagnostic MRI. We aimed to investigate the cost-effectiveness of non-contrast aMRI for HCC surveillance in cirrhotic pa- tients, using ultrasonography with alpha-fetoprotein (AFP) as a reference. Methods: Cost-utility analysis was performed using a Markov model in Thailand and the United States. Incremental cost-effectiveness ratios were calculated using the total costs and quality- adjusted life years (QALYs) gained in each strategy. Surveillance protocols were considered cost-effective based on a willingness-to-pay value of USD 4,665 (160,000 Thai Baht) in Thailand and USD 50,000 in the United States. Results: aMRI was cost-effective in both countries with incremental cost-effectiveness ratios of USD 3,667/QALY in Thailand and USD 37,062/QALY in the United States. Patient-level microsimulations showed consistent findings that aMRI was cost-effective in both countries. By probabilistic sen- sitivity analysis, aMRI was found to be more cost-effective than combined ultrasonography and AFP with a probability of 0.77 in Thailand and 0.98 in the United States. By sensitivity analyses, annual HCC incidence was revealed as the most influential factor affecting cost-effectiveness. The cost-effectiveness of aMRI increased in settings with a higher HCC incidence. At a higher HCC incidence, aMRI would remain cost-effective at a higher aMRI-to-ultrasonography with AFP cost ratio. Conclusions: Compared to ultrasonography with AFP, non-contrast aMRI is a cost-effective strategy for HCC surveillance and may be useful for such surveillance in cirrhotic patients, espe- cially in those with high HCC risks

Regional differences in admissions and treatment outcomes for hepatocellular carcinoma patients in Thailand

Background: Hepatocellular carcinoma (HCC) is one of the commonest cancers in Thailand. We report the stage and survival of patients who were admitted under the public universal health fund (NHSO) covering 47 million people to determine if there were regional disparities in the treatment outcomes in the country. Method: We used the 2009-2013 Nationwide Hospital Admission Data, Thailand. Patients with hepatocellular carcinoma (HCC) were identified by the ICD10 code C22.0. Procedures were identified by ICD9-CM codes, and deaths were confirmed from the NHSO database and the national citizen registry. Thailand is divided into 6 regions and Bangkok. Hospitals were identified according to their specific reimbursement codes. Survival time started from the day of first admission and was estimated using the Kaplan-Meier method. The statistical method used to compare regions was Chi-squared tests (Pearson, likelihood ratio, linear-by linear association and Mantel-cox). Results: There were 36,956 HCC patients admitted during the study period. The overall median survival was 36 days. 1.63% of the patients had surgery, 0.96% had radiofrequency ablation (RFA), and 5.24% had trans-arterial chemoembolization (TACE). 90.24% did not have any tumor-specific therapy. The proportion of patients admitted for tumor-specific therapy vs. no tumor-specific therapy was significantly different between regions in all treatment modalities (p<0.01). Each treatment modality showed a wide range of median survival values across the regions (p<0.01). The best survival was seen in Bangkok, the South and the North (for surgery, RFA and TACE) and was often more than twice as long as the regions with the lowest survival, Central, East and West. Conclusions: There was a large previously-unreported disparity in admissions and outcomes in Thailand for different treatment modalities for HCC. Bangkok and the South had the best treatment outcomes and often had median survivals more than twice as long as those in the West and East. Public policy to reduce this disparity will need to be implemented in the future

Urine Liver-Type Fatty Acid Binding Protein; Biomarker for Diagnosing Acute Kidney Injury and Predicting Mortality in Cirrhotic Patients

Objective: To determine impact of urine liver-type fatty acid binding protein (uL-FABP) and urine neutrophil gelatinase-associated lipocalin (uNGAL), which were biomarkers linked to acute kidney injury (AKI), in AKI diagnosis and prediction of 28-day mortality among hospitalized cirrhotic patients. Materials and Methods: We prospectively enrolled hospitalized cirrhotic patients at a tertiary care university hospital between June 2018 and November 2019. The uL-FABP, uNGAL, and plasma NGAL (pNGAL) were collected within 48 hours of admission. Cutoff values of biomarkers for diagnosing AKI derived from receiver operating characteristic (ROC) curve. Logistic regression analysis was used to identify independent factors for 28-day mortality. Results: We enrolled 109 cirrhotic patients in derivative cohort, 41.3% had AKI. Median uL-FABP, uNGAL, and pNGAL levels in AKI group were higher than non-AKI group: 8.1 vs. 2.8 ng/mL (p=0.002), 40.5 vs. 10.1 ng/mL (p<0.001), and 195.7 vs 81.4 ng/mL (p=0.001), respectively. Areas under the ROC curve of uL-FABP, uNGAL, and pNGAL for AKI diagnosis were 0.68, 0.73 and 0.68, respectively. Also, all biomarkers were significantly higher in mortality group. Multivariate analysis showed that the only independent predictor for 28-day mortality was uL-FABP ≥ 4.68 ng/mL (odd ratio 4.15, p=0.02). Conclusion: UL-FABP, uNGAL, and pNGAL are associated with AKI in hospitalized cirrhotic patients. Moreover, uL-FABP ≥ 4.68 ng/mL was a significant independent predictor for 28-day mortality

A randomized controlled trial of comparative effectiveness between the 2 dose and 3 dose regimens of hepatitis a vaccine in kidney transplant recipients.

Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients

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