The impact of induction therapy on the risk of posttransplant lymphoproliferative disorder in adult kidney transplant recipients with donor-recipient serological Epstein-Barr virus mismatch.

Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.

Phase I Trial of a Therapeutic DNA Vaccine for Preventing Hepatocellular Carcinoma from Chronic Hepatitis C Virus (HCV) Infection.

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.

Smoking & risk of advanced liver fibrosis among patients with primary biliary cholangitis: A systematic review & meta-analysis.

Background & objectives: Studies have suggested that smoking may accelerate the progression of fibrosis among patients with primary biliary cholangitis (PBC), although the data are limited. The current review was undertaken with the aim to comprehensively analyze this possible association by identifying all relevant studies and summarizing their results. Methods: A comprehensive literature review on MEDLINE and EMBASE databases was performed from inception through February 2019 to identify all relevant studies. Eligible studies included cross-sectional studies that recruited patients with PBC and collected data on the smoking status and presence or absence of advanced liver fibrosis for each participant. Odds ratios (OR) with 95 per cent confidence intervals (CI) was desirable for inclusion or sufficient raw data to calculate the same for this association. Adjusted point estimates from each study were extracted and combined together using the generic inverse variance method of DerSimonian and Laird. I2 statistic, which quantifies the proportion of total variation across studies was used to determine the between-study heterogeneity. Results: Three cross-sectional studies with 544 participants were included. The pooled analysis found a significantly increased risk of advanced liver fibrosis among patients with PBC who were ever-smokers compared to those who were nonsmokers with the pooled OR of 3.00 (95% CI, 1.18-7.65). Statistical heterogeneity was high with I2 of 89 per cent. Interpretation & conclusions: This meta-analysis found that smoking is associated with a significantly higher risk of advanced liver fibrosis among patients with PBC. Further prospective studies are still required to determine whether this association is causal.

Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C.

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.

Cost-Effectiveness of an Adjuvanted Hepatitis B Vaccine (HEPLISAV-B) in Patients With Inflammatory Bowel Disease.

Background: Compare the cost-effectiveness of 2 recombinant hepatitis B virus (HBV) vaccines in patients with inflammatory bowel disease (IBD). Methods: Markov 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. Results: Analysis 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. Conclusions: HEPLISAV-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.

Outcomes following liver transplantation from HCV-seropositive donors to HCV-seronegative recipients.

BACKGROUND & AIMS: Grafts from HCV-seropositive donors can now be considered for liver transplantation (LT) owing to the advent of direct-acting antivirals (DAAs). We report on our multicenter experience of transplanting liver grafts from HCV-seropositive donors into HCV-seronegative recipients. METHODS: This is a prospective multicenter observational study evaluating outcomes in adult HCV-seronegative LT recipients who received grafts from HCV-seropositive donors in 3 US centers. RESULTS: From 01/18 to 09/19, 34 HCV-seronegative LT recipients received grafts from HCV-seropositive donors (20 HCV-viremic and 14 non-viremic). Seven grafts were from cardiac-dead donors. The median MELD-Na score at allocation was 20. Six recipients underwent simultaneous liver-kidney transplant and 4 repeat LT. No recipient of an HCV-non-viremic graft developed HCV viremia. All 20 patients who received HCV-viremic grafts had HCV viremia confirmed within 3 days after LT. DAA treatment was started at a median of 27.5 days after LT. Median pre-treatment viral load was 723,000 IU/ml. All (20/20) patients completed treatment and achieved SVR12. Treatment was well tolerated with minimal adverse events. One patient developed HCV-related acute membranous nephropathy that resulted in end-stage kidney disease, despite achieving viral clearance. This patient died due to presumed infectious complications. A recipient of an HCV-non-viremic graft died with acute myocardial infarction 610 days post LT. CONCLUSIONS: Transplantation of liver grafts from HCV-seropositive donors into HCV-seronegative recipients resulted in excellent short-term outcomes. Antiviral therapy was effective and well tolerated. Careful ongoing assessment and prompt initiation of antiviral therapy are recommended. Longer term follow-up in carefully conducted clinical trials is still required to confirm these results. LAY SUMMARY: This study shows that livers from donors exposed to HCV expand the donor pool and can be used safely in patients who are seronegative for hepatitis C infection. Treatment, initiated early post transplantation, is effective and resulted in cure in all patients.

Simultaneous liver transplant and sleeve gastrectomy not associated with worse index admission outcomes compared to liver transplant alone - a retrospective cohort study.

Sleeve gastrectomy (SG) at the time of liver transplant (LT) has been argued to decrease resource utilization. However, larger studies examining outcomes are lacking. We aim to determine the outcomes of simultaneous SG and LT compared to LT alone. This is a retrospective cohort study using the 2011-2017 National Inpatient Sample (NIS). The primary outcome was the odds of inpatient mortality in patients undergoing simultaneous SG and LT compared with LT alone. Secondary outcomes included inpatient morbidity, resource utilization, hospital length of stay (LOS), and inflation-adjusted total hospital costs and charges. A total of 45 361 patients underwent LT in the study period, 49 underwent simultaneous SG. Patients undergoing simultaneous LT and SG had lower crude mortality (0.0%) compared to LT alone (2.97%; P = 0.52). There were no statistically significant differences in morbidity, resource utilization, and hospital costs and charges. Patients undergoing simultaneous LT and SG did not have significantly different mortality rates, morbidity, resource utilization, or LOS during the index admission when compared to LT alone. SG may be feasible at the time of LT in very carefully selected patients. Studies should focus in determining which patients are the optimal candidates to undergo simultaneous LT and SG.

The Association between Periodontitis and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Recent studies have suggested an association between periodontitis and nonalcoholic fatty liver disease (NAFLD) although the results were inconsistent. The current systematic review and meta- analysis was conducted with the aim to comprehensively investigate this possible association by identifying all relevant studies and combining their results together. METHODS: A comprehensive literature review was conducted utilizing the MEDLINE and EMBASE databases through December 2019 to identify all studies that compared the risk of NAFLD among patients with periodontitis to individuals without periodontitis. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: A total of five studies with 27,703 participants fulfilled the eligibility criteria and were included in the meta-analysis. All five studies reported the magnitude of association between NAFLD and periodontitis that was diagnosed based on the periodontal pocket depth of > 3.5-4 mm. The pooled OR of unadjusted analysis was 1.48 (95%CI: 1.15-1.89; I 2 92%). However, when adjusted results from the primary studies were used, pooled OR decreased to 1.13 and lost its statistical significance (95%CI: 0.95-1.35; I 2 67%). Three studies reported the magnitude of association between NAFLD and periodontitis that was diagnosed based on a clinical attachment level of ≥ 3 mm. The pooled OR of unadjusted analysis was 1.13 (95%CI: 1.07-1.20; I 2 0%). However, when adjusted results from the primary studied were used, pooled OR decreased to 1.08 and lost its statistical significance (95%CI: 0.94-1.24; I 2 58%). CONCLUSIONS: The study found a significant association between periodontitis and NAFLD. However, the association lost its significance when various metabolic parameters were adjusted, suggesting that those metabolic conditions, not periodontitis itself, were predisposing factors for NAFLD.

Association between sarcopenia and hepatic encephalopathy: A systematic review and meta-analysis.

Studies have suggested that the presence of sarcopenia in patients with cirrhosis could be a predisposing risk factor for hepatic encephalopathy. This systematic review and meta-analysis were conducted to summarize all available evidence on this relationship. A systematic review was carried out in Medline and EMBASE database through December 2018 to identify studies that recruited patients with cirrhosis from any causes and collected data on the presence of minimal or overt hepatic encephalopathy as well as sarcopenia. All study designs (case-control, cohort and cross-sectional studies) were eligible for the meta-analysis. Odds ratio (OR) and 95% confidence interval (CI) were extracted from the included studies and were pooled together using random-effect, generic inverse variance method of DerSimonian and Laird. Five cross-sectional studies with a total of 1,713 patients met our eligibility criteria and were included into the meta-analysis. We found a significantly higher risk of both mild and overt hepatic encephalopathy among cirrhotic patients with sarcopenia when compared with cirrhotic patients without sarcopenia with the pooled OR of 3.34 (95% CI: 1.68-6.67; I2=37%) and 2.05 (95% CI: 1.28-3.29; I2=61%), respectively. This systematic review and meta-analysis demonstrated a significant association between sarcopenia and hepatic encephalopathy among patients with cirrhosis.

Improved National Results With Simultaneous Liver-Kidney Transplantation Using Donation After Circulatory Death Donors.

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.

Small intestinal bacterial overgrowth and nonalcoholic fatty liver disease: a systematic review and meta-analysis.

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 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.

Association between Smoking and Risk of Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Studies have suggested that smokers may have a higher risk of primary biliary cholangitis (PBC) although the results have been inconsistent. This systematic review and meta-analysis aim to better characterize the risk of PBC among smokers by identifying all relevant studies and summarizing their results together. METHODS: A comprehensive literature review was conducted using Embase and Pubmed/MEDLINE databases from inception to September 2018 to identify all studies which compared the risk of PBC among current, ever and former smokers to non-smokers. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Nine case-control studies with 21,577 participants met the eligibility criteria and were included in the meta-analysis. The risk of PBC among ever smokers was significantly higher than non-smokers with the pooled odds ratio (OR) of 1.31 (95% CI, 1.03-1.67; I 2 89%). Subgroup analysis found that the risk was higher in both former smokers (pooled OR 1.36; 95% CI, 1.01-1.84; I 2 75%) and current smokers (pooled OR 1.18; 95% CI, 0.94-1.50; I 2 79%), although the latter did not reach statistical significance. Immunomodulatory and cytotoxic effect of cigarettes were the possible mechanisms behind this increased risk. CONCLUSIONS: A significantly increased risk of PBC among individuals who ever smoked was observed in this study, adding to the already long list of harmful health consequences of smoking.

Equivalent Outcomes With Retransplantation and Primary Liver Transplantation in the Direct-acting Antiviral Era.

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.

Nonalcoholic Fatty Liver Disease and Urolithiasis. A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Recent studies have suggested that nonalcoholic fatty liver disease (NAFLD) could be a predisposing factor for urolithiasis but the results have been inconsistent. This systematic review and meta-analysis was conducted with the aim to summarize all available data. METHODS: A comprehensive literature review was conducted using MEDLINE and EMBASE databases through March 2018 to identify all studies that compared the risk of urolithiasis among patients with NAFLD versus those without NAFLD. 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 eight studies with 238,400 participants fulfilled the eligibility criteria and were included in the meta-analysis. The risk of urolithiasis among patients with NAFLD was significantly higher than in those without NAFLD with a pooled odds ratio of 1.81 (95% confidence interval, 1.29-2.56; I2 92%). CONCLUSIONS: A significantly increased risk of urolithiasis among patients with NAFLD was observed in this meta-analysis.

Cigarette smoking and risk of celiac disease: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: A 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. METHODS: A 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. RESULTS: A 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%). CONCLUSIONS: A significantly decreased risk of celiac disease among current smokers compared with never-smokers was demonstrated in this meta-analysis.

Association between diastolic cardiac dysfunction and nonalcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Recent studies have suggested an association between nonalcoholic fatty liver disease (NAFLD) and diastolic cardiac dysfunction, although the results were inconsistent. This study was conducted to investigate this possible association. METHODS: A comprehensive literature review was conducted utilizing the MEDLINE and Embase databases from inception through May 2018 to identify all cross-sectional studies that compared the prevalence of diastolic cardiac dysfunction among patients with NAFLD to individuals without NAFLD. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: A total of 12 studies with 280,645 participants fulfilled the eligibility criteria and were included in the meta-analysis. There was a significant association between NAFLD and diastolic cardiac dysfunction with a pooled odds ratio (OR) of 2.02 (95% confidence interval (CI), 1.47-2.79; I2 89%). Subgroup analysis based on the country of origin continued to demonstrate a significant association in subgroups of both Western and Eastern countries with pooled ORs of 1.76 (95% CI, 1.14-2.72; I2 85%) and 2.59 (95% CI, 1.42-4.69; I2 87%), respectively. Limitations included high between-study heterogeneity, lack of unified definition of diastolic dysfunction and presence of publication bias. CONCLUSIONS: A significant association between diastolic cardiac dysfunction and NAFLD was observed in this meta-analysis. This observation could suggest the need for careful cardiovascular surveillance among patients with NAFLD.

Multicenter Experience using Ledipasvir/Sofosbuvir ± RBV to Treat HCV GT 1 Relapsers after Simeprevir and Sofosbuvir Treatment.

INTRODUCTION AND AIM: Approximately 10%-15% of patients with hepatitis C genotype 1 (HCV GT1) experience virological relapse after all-oral antiviral regimen using simeprevir (SMV) and sofosbuvir (SOF). The efficacy and safety of treating such relapsers using ledipasvir/sofosbuvir (LDV/SOF) with/without ribavirin (RBV) has been limited. OBJECTIVE: Report the virological response and safety of LDV/SOF with/without RBV for 12-24 weeks in treating HCV GT1 relapsers after SMV + SOF. MATERIAL AND METHODS: Patients treated with standardized clinical protocol utilizing LDV/SOF with/without RBV at three transplant centers were retrospectively reviewed. RESULTS: Forty-five patients (29% post-LT, 82% male, 13% non-white, 73% subtype 1a, 86% IL28B CT/TT, 78% F3-4) started LDV/SOF with/without RBV at a median of 22 weeks (range 7-55 weeks) after the last dose of SMV+SOF treatment. Thirty-seven patients received LDV/SOF for 24 weeks (24/37 patients with RBV) and eight patients received LDV/SOF for 12 weeks (5/8 patients with RBV). RBV dose was adjusted for renal function. Sixteen patients who were RBV-ineligible received LDV/SOF without RBV for 12 or 24 weeks. SVR 12 was achieved in 96% (43/45) of patients. Baseline viral load, RBV use, or GT1 subtype did not impact SVR 12. Minimal adverse events were reported in those without RBV; 45% of patients who received RBV developed significant anemia requiring RBV dose reduction and/or discontinuation. In LT recipients, minimal immunosuppression dose adjustments were required and no biopsy-proven acute rejection occurred. CONCLUSIONS: Treatment with LDV/SOF with/without RBV for 12-24 weeks was very well tolerated and resulted in high SVR 12 rates (96%) in HCV GT1 relapsers to SMV + SOF treatment.

Association Between Juxtapapillary Duodenal Diverticula and Risk of Choledocholithiasis: a Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVES: Studies have suggested that the presence of juxtapapillary duodenal diverticula (JDD) could be a predisposing factor for choledocholithiasis. This systematic review and meta-analysis was conducted with the aims to summarize all available evidence to better characterize the risk. METHODS: A literature search was performed using MEDLINE and EMBASE database from inception to January 2018. Cross-sectional studies that reported odd ratios (OR) comparing the risk of choledocholithiasis among individuals with JDD versus individuals without JDD were included. Pooled OR and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Of 527 retrieved articles, 11 studies met our eligibility criteria and were included in analysis. We found a significant association between the presence of JDD and choledocholithiasis with the pooled OR of 2.30 (95% CI, 1.84-2.86). The statistical heterogeneity was moderate with an I2 of 60%. CONCLUSIONS: A significantly increased risk of choledocholithiasis among individuals with JDD was observed in this study.

Heavy Coffee Consumption and Risk of Pancreatitis: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Heavy consumption of coffee may have a protective effect against pancreatitis although results from previous studies were inconsistent. This meta-analysis was conducted with the aim to summarize all available data. METHODS: This meta-analysis included observational studies that compared the risk of pancreatitis between heavy coffee-drinkers and individuals who were not heavy coffee-drinkers. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Out of 219 retrieved articles, four studies with 351,137 participants met the eligibility criteria and were included in the analysis. The risk of pancreatitis among heavy coffee-drinkers was significantly lower than individuals who were not heavy coffee-drinkers with the pooled RR of 0.78 (95% CI 0.67-0.91). The statistical heterogeneity between the studies was insignificant (I2 = 0%). CONCLUSIONS: This meta-analysis demonstrated a significantly decreased risk of pancreatitis among heavy coffee-drinkers. However, further investigations are still required to determine causality and potential clinical application.