Pungpapong, Surakit

Background: Coronary artery disease (CAD) is common among liver transplantation (LT) candidates, yet whether pre-transplant percutaneous coronary intervention (PCI) improves post-LT outcomes remains uncertain. Methods: We conducted a single-center, Institutional Review Board-approved cohort study of adults undergoing LT from 2005 to 2025. Asymptomatic candidates with significant stenosis on invasive angiography were included; prior coronary artery bypass grafting was excluded. The primary endpoint was major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke/transient ischemic attack, new systolic dysfunction, post-LT coronary revascularization, or all-cause death). Results: Among 111 patients (median age 65 years; 84% male), 66 (59%) underwent PCI and 45 (41%) were managed medically. Over a median 32 months of follow-up, 61 patients (55%) experienced MACE. Composite MACE did not differ between PCI and non-PCI groups (52% vs. 60%, p = 0.40; log-rank p = 0.59). Fine–Gray modeling showed no association of PCI with MACE; independent predictors were prior MI (HR 1.81, 95% CI 1.01–3.24) and pre-transplant dialysis (HR 2.13, 95% CI 1.07–4.24). Major bleeding occurred in 7%. Matched and era-stratified analyses were concordant. Conclusions: In asymptomatic LT candidates with angiographically severe CAD, pre-LT PCI was not associated with a lower incidence of post-LT MACE.

Abstract Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma. We studied the safety and immunogenicity of a novel therapeutic hepatitis C virus (HCV) genotype 1a/1b consensus DNA vaccine, INO-8000, encoding HCV NS3, NS4A, NS4B, and NS5A proteins alone or co-administered with DNA-encoding IL12 (INO-9012), a human cytokine that stimulates cellular immune function, in individuals with chronic hepatitis C. This was a phase I, multisite dose-escalation trial with an expansion cohort evaluating doses of 0, 0.3, 1.0, and 3.0 mg of INO-9012 (IL12 DNA) as an addition to 6.0 mg of (INO-8000; HCV DNA vaccine). Vaccines were administered by intramuscular injection followed by electroporation at study entry and at weeks 4, 12, and 24. HCV-specific CD4+ and CD8+ T-cell immune responses were measured by IFNγ ELISpot and flow cytometry–based assays. Transient, mild-to-moderate injection site reactions unrelated to IL12 DNA dose were common. Increases in HCV-specific IFNγ production occurred in 15/20 (75%) participants. Increases in the frequency of HCV-specific CD4+ and CD8+ T cells occurred at all dose levels, with the greatest increases seen at 1.0 mg of INO-9012. HCV-specific CD8+ and CD4+ T-cell activities increased in 16/18 (89%) and 14/17 (82%) participants with available data, respectively. The vaccine regimen was safe and induced HCV-specific CD4+ and CD8+ cellular immune responses of modest magnitude in most HCV-infected participants. The addition of 1.0 mg of IL12 DNA provided the best enhancement of immune responses. The vaccine regimen had little effect on controlling HCV viremia. Prevention Relevance: The administration of IL12 DNA along with a hepatitis C viral antigen DNA vaccine enhanced the HCV-specific immune responses induced by the vaccine in individuals with chronic hepatitis C, an important cause of hepatocellular carcinoma. IL12 could be an effective adjuvant in vaccines targeting HCV and other oncogenic viruses.

Background: Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC). Methods: We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models. Results: A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower (P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time. Conclusions: Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.

AbstractBackgroundCompare the cost-effectiveness of 2 recombinant hepatitis B virus (HBV) vaccines in patients with inflammatory bowel disease (IBD).MethodsMarkov models were developed for 2 IBD cohorts: (1) 40-year-old patients prior to starting IBD treatment and (2) 40-year-old patients already receiving therapy. Cohort A received full vaccination series, cohort B had primary vaccine failure and received a vaccine booster. Two vaccines were compared: adjuvanted HEPLISAV-B and nonadjuvanted Engerix-B. Clinical probabilities of acute hepatitis, chronic hepatitis, cirrhosis, fulminant hepatic failure and death, treatment costs, and effectiveness estimates were obtained from published literature. A lifetime analysis and a US payer perspective were used. Probabilistic sensitivity analyses were performed for different hypothetical scenarios.ResultsAnalysis of cohort A showed moderate cost-effectiveness of HEPLISAV-B ($88,114 per quality-adjusted life year). Analysis of cohort B showed increased cost-effectiveness ($35,563 per quality-adjusted life year). Changing Engerix-B to HEPLISAV-B in a hypothetical group of 100,000 patients prevented 6 and 30 cases of acute hepatitis; and 4 and 5 cases of chronic hepatitis annually for cohorts A and B, respectively. It also prevented 1 and 2 cases of cirrhosis, and 1 and 2 deaths over 20 years for each cohort. Cost-effectiveness was determined by vaccination costs, patient age, and progression rate from chronic hepatitis to cirrhosis.ConclusionsHEPLISAV-B is cost-effective over Engerix-B in patients receiving immunosuppressive therapy for IBD. Benefits increase with population aging and lower costs of vaccines. We advocate measuring levels of HBV antibodies in patients with IBD and favor adjuvanted vaccines when vaccination is needed.

Previous large registry studies have demonstrated inferior outcomes for simultaneous liver‐kidney transplantation (SLKT) recipients of grafts from donation after circulatory death (DCD) donors compared with those from donation after brain death (DBD) donors in the era from 2000 to 2010. Given the improving national results in liver transplantation alone using grafts from DCD donors, the present study aimed to investigate if results with DCD‐SLKT have improved in the modern era. Patients undergoing SLKT between 2000 and 2018 were obtained from the United Network for Organ Sharing Standard Analysis and Research file and divided into 2 eras based on the date of SLKT: era 1 (2000‐2010) and era 2 (2011‐2018). Improvement in DCD‐SLKT patient, liver graft, and kidney graft survival rates was seen between era 1 and era 2 (P < 0.001). Concurrently, there was a decrease in the proportion of critically ill (P = 0.02) and retransplant (P = 0.006) candidates undergoing DCD‐SLKT. When DCD‐SLKT in era 2 was compared with a propensity‐matched cohort of DBD‐SLKT in era 2, no differences in patient (P = 0.99), liver graft (P = 0.19), or kidney graft (P = 0.90) survival were observed. In addition, both bilirubin (0.5 versus 0.5 mg/dL; P = 0.86) and creatinine (1.2 versus 1.2 mg/dL; P = 0.68) at last follow‐up were not different between the DCD‐SLKT and DBD‐SLKT patients in era 2. In conclusion, in the most recent era, patients undergoing DCD‐SLKT were able to achieve similar outcomes compared with matched patients undergoing DBD‐SLKT. DCD‐SLKT represents a viable option for appropriately selected recipients.

Objectives Recent studies have suggested that small intestinal bacterial overgrowth (SIBO) could be a predisposing factor for nonalcoholic fatty liver disease (NAFLD) although the results were inconsistent. This systematic review and meta-analysis was conducted with the aim to summarize all available data. Methods A comprehensive literature review was conducted utilizing MEDLINE and EMBASE databases through September 2018 to identify all studies that compared the risk of NAFLD among patients with SIBO versus those without SIBO. Effect estimates from each study were extracted and combined together using the random effect, generic inverse variance method of DerSimonian and Laird. Results A total of 10 studies with 1093 participants fulfilled the eligibility criteria and were included in the meta-analysis. A significant association between NAFLD and SIBO was observed with the pooled odds ratio of 3.82 (95% confidence interval, 1.93–7.59; I 2 65%). Funnel plot is relatively symmetric and is not suggestive of the presence of publication bias. Conclusion A significant association between NAFLD and SIBO was observed in this meta-analysis.

Background. The present multicenter study investigated whether equivalent outcomes to primary liver transplant (LT) could be achieved with liver retransplant (reLT) and whether improvements in outcomes have taken place over time, particularly in the direct-acting antiviral era. Methods. All reLT performed at Mayo Clinic Florida, Mayo Clinic Rochester, and Mayo Clinic Arizona were divided into era 1 (2002–2007), era 2 (2008–2012), and era 3 (2013–2017) based on the date of reLT. Results. Improvement in graft survival (GS) after reLT was seen over the 3 eras (P < 0.001). In era 1, GS after reLT was inferior to primary LT (P < 0.001), whereas no difference was seen between reLT and primary LT in era 2 (P = 0.68) or era 3 (P = 0.36). A significantly higher proportion of patients achieved sustained viral response (SVR) within the first year after reLT in each subsequent era (era 1: 10.3%, era 2: 22.5%, and era 3: 100%) (P < 0.001). Graft survival was superior in patients undergoing reLT for recurrent hepatitis C virus who achieved SVR after reLT compared with those who did not (P = 0.03). Conclusions. Results similar to primary LT were achieved in era 3. These improvements coincide with the availability of direct-acting antivirals, which resulted in a 100% SVR rate in era 3 and a decrease in the number of patients undergoing reLT for recurrent hepatitis C virus. The historic dogma that reLT results in inferior outcomes should be revisited.

Background/ObjectivesA negative association between cigarette smoking and celiac disease has been observed but results were inconsistent across the published studies. A meta‐analysis was conducted with the aim to identify all studies that investigated this association and to summarize the results of those studies.MethodsA comprehensive literature review was conducted utilizing MEDLINE and Embase databases through March 2018 to identify all cohort studies and case‐control studies that compared the risk of celiac disease among current and/or former smokers versus never‐smokers. Effect estimates from each study were extracted and combined together using the random‐effect, generic inverse variance method of DerSimonian and Laird.ResultsA total of seven studies with 307,924 participants fulfilled the eligibility criteria and were included in the meta‐analysis. The pooled analysis found a significantly decreased risk of celiac disease among current smokers compared with never‐smokers with the pooled odds ratio (OR) of 0.52 (95% confidence interval (CI), 0.32–0.84; I2 86%). However, the risk of celiac disease among former smokers was not significantly different from never‐smokers with the pooled OR of 1.10 (95% CI, 0.76–1.60; I2 of 73%).ConclusionsA significantly decreased risk of celiac disease among current smokers compared with never‐smokers was demonstrated in this meta‐analysis.