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2.
Transplant Direct ; 8(6): e1342, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35651584

ABSTRACT

Long-term liver outcome in hepatitis C virus (HCV)-negative kidney recipients who acquired HCV infection from viremic donors is of intense interest in the transplant community. We evaluated the incidence of fibrosis in liver biopsy specimens of recipients who were transplanted with HCV-infected grafts. Methods: Patients were evaluated in the hepatology clinic, and 29 patients agreed to undergo liver biopsy. The liver histology was scored by the meta-analysis of histological data in viral hepatitis scoring system and was assessed by hepatopathologists. The fibrosis score was compared between patients who initiated direct-acting antiviral (DAA) within 6 wk (n = 6) and after 6 wk (n = 29). Results: Eighty-nine aviremic patients were transplanted with HCV-infected grafts between March 2018 and October 2019. All patients developed HCV infection and were treated with DAA treatment after kidney transplantation (median, 70 d; interquartile range, 55-85 d). All patients (n = 89) achieved sustained virologic response with DAA. The median follow-up time from kidney transplant to liver biopsy was 28 mo (interquartile range, 26-30 mo). Twenty-five patients (86%) had F0, and 4 patients (14%) had F1 fibrosis. No patient had advanced fibrosis (F3-F4). Grade 1 inflammation was present in 6 (21%) patients, whereas 26 (90%) patients had iron accumulation in the hepatocytes and reticuloendothelial cells. There was no difference in the fibrosis score between patients who received treatment within 6 wk versus after 6 wk (P = 0.55). Conclusions: Kidney transplantation of HCV-infected graft to HCV-negative recipients is safe and has no long-term liver-related complications with successful eradication of HCV. In our cohort, delayed treatment did not affect sustained virologic response or liver histology.

3.
Case Reports Hepatol ; 2021: 5512883, 2021.
Article in English | MEDLINE | ID: mdl-34188961

ABSTRACT

Infection with hepatitis A virus is usually a self-limited illness that rarely results in fulminant liver failure. Severe hemolysis is an uncommon complication but has been reported in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Here, we report a case with undiagnosed G6PD deficiency who presented with hyperbilirubinemia, severe hemolysis, and acute renal failure precipitated by acute hepatitis A infection.

4.
Hepatol Res ; 51(12): 1242-1246, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34114715

ABSTRACT

The opioid epidemic has led to increased availability of organs for liver transplantation. The success of direct-acting antiviral therapy for hepatitis C (HCV) has led to the acceptance of HCV viremic donor organs. Nucleic acid testing (NAT) has led to increased detection of HCV and hepatitis B (HBV) in potential donors. A total of 36 patients underwent liver transplantation from donation after brain death donors who were HCV NAT-positive, and three of them were diagnosed with HBV several months after. All three recipients received livers from HCV viremic donors who were negative for HBV by serology and NAT. Soon after liver transplantation, HCV was treated, and all achieved sustained virologic response. They became HBV DNA-positive shortly thereafter. To date, there have been no reported cases of unexpected HBV transmission since universal donor NAT was implemented in 2013. We postulate that the inhibitory effect of HCV viremia on HBV may have prolonged the "NAT window period" in these donors beyond the 20-22 days quoted for solitary HBV infection. These cases highlight the need for more intensive and prolonged screening for HBV in recipients of livers from HCV viremic donors.

5.
Clin Transplant ; 35(5): e14281, 2021 05.
Article in English | MEDLINE | ID: mdl-33690929

ABSTRACT

BACKGROUND: The virologic and histologic outcomes of a hepatitis C virus (HCV)-infected liver graft into an HCV-negative recipient are not well understood. We aimed to evaluate the sustained virologic response (SVR) rate and the liver histology at 1 year post-Orthotopic liver transplantation (OLT) with an HCV-infected graft. METHODS: A total of 33 patients received the HCV antibody (Ab)+/nucleic acid amplification test (NAT)+ graft. Of these patients, 23 were HCV-negative recipients and 10 were HCV-positive recipients. The 1-year biopsy data were available for 24 patients: 15 patients in HCV-negative group who received an HCV Ab+/NAT+graft and 9 patients in HCV-positive group who received an HCV Ab+/NAT+ graft. Patients with (+) HCV ribonucleic acid (RNA) were started on direct-acting antiviral (DAA) treatment approximately 107 days after OLT using either a Glecaprevir-Pibrentasvir or Sofosbuvir-Velpatasvir or Sofosbuvir-Ledipasvir. RESULTS: All patients (n = 33) were treated with DAA and achieved SVR. The 1-year post-OLT liver biopsies were available in 24 patients: 9 patients had F1 and F2 fibrosis and 17 patients had minimal to moderate inflammation. There was no statistical difference in fibrosis and inflammation between the HCV-negative vs. HCV-positive recipients. All patients who received the NAT+ graft developed viremia and subsequently achieved SVR with treatment. CONCLUSION: At 1 year protocol liver biopsy, patients had inflammation consistent with viral hepatitis despite the successful eradication of HCV.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Liver Transplantation , Antiviral Agents/therapeutic use , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , RNA, Viral , Treatment Outcome
6.
Clin Exp Hepatol ; 7(4): 390-395, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35402726

ABSTRACT

Aim of the study: Cirrhotic cardiomyopathy encompasses systolic dysfunction, left ventricular diastolic dysfunction (LVDD), and conduction abnormalities. This study aims to investigate the impact of LVDD on mortality in patients undergoing liver transplantation (LT). Material and methods: A retrospective review of 400 consecutive patients who underwent LT at our institution was performed. Patient demographics, clinical data, and transthoracic echocardiogram (TTE) were reviewed to identify LVDD. The total cohort consisted of 266 patients after excluding patients with insufficient TTE data (n = 56), patients with indeterminate LVDD (n = 71), and patients with ejection fraction (EF) < 55% (n = 7). Statistical analysis was performed using descriptive statistics. Cox regressions with hazard ratios (HRs) and 95% confidence intervals (CI) were applied to predict 5-year all-cause mortality. Kaplan-Meier survival analysis was conducted to understand the impact of LVDD on 5-year all-cause mortality. Results: Patients with LVDD have higher incidence of hyperlipidemia (36% vs. 17%, p = 0.003), hypertension (50% vs. 27%, p = 0.001) and diabetes (52% vs. 30%, p = 0.003). In addition, patients with non-alcoholic steatohepatitis (NASH) were more likely to have LVDD (48% vs. 24%, p = 0.001). A multivariate logistic regression analysis was performed with age, body mass index (BMI), NASH, alcoholic cirrhosis, hepatitis C, history of diabetes, history of hyperlipidemia, and history of hypertension. In this multivariate logistic regression analysis, NASH (odds ratio [OR] = 4.43 [1.10-17.8], p = 0.04), and history of hypertension (OR = 2.33 [1.16-4.66], p = 0.01) were independent predictors of LVDD. The Kaplan-Meier survival analysis and multivariate Cox regression demonstrated that the presence of LVDD had no impact on 5-year all-cause mortality (log-rank test nonsignificant). Conclusions: This study indicates that LVDD in end-stage liver disease (ESLD) patients does not affect immediate post-transplant outcomes or 5-year all-cause mortality.

7.
Cureus ; 12(11): e11673, 2020 Nov 24.
Article in English | MEDLINE | ID: mdl-33262920

ABSTRACT

Hilar cholangiocarcinoma, also known as Klatskin tumor, is the most common type of cholangiocarcinoma. It usually has a lymphatic spread and is rarely associated with an umbilical nodule, also known as Sister Mary Joseph nodule. We report a case of a 53-year-old Caucasian man with hilar cholangiocarcinoma. The patient had an inoperable tumor and was referred to our center for liver transplantation. Post liver transplantation, the patient presented with a recurrence of the carcinoma in the umbilical region. The patient was found to have Sister Mary Joseph nodule. It carries a poor prognosis, and our patient succumbed to the illness in four months. Cholangiocarcinoma carries a poor prognosis. Surgical resection and liver transplantation with neoadjuvant chemoradiation are the preferred treatment strategies. Association of cholangiocarcinoma with umbilical metastasis is rare, and our patient had an even rarer presentation in the form of recurrence with umbilical nodule post-liver transplantation. We want to increase the awareness of the rare presentation, association, and recurrence of hilar cholangiocarcinoma in the form of umbilical nodule post-liver transplantation.

8.
Clin Exp Hepatol ; 6(2): 158-162, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32728634

ABSTRACT

AIM OF THE STUDY: Cardiovascular death is an important cause of mortality in end stage liver disease (ESLD) patients undergoing orthotopic liver transplant (OLT). Left ventricular diastolic dysfunction (LVDD) is often the early manifestation and only measurable manifestation of cirrhotic cardiomyopathy. Therefore, it is important to understand the risk factors for LVDD in ESLD patients undergoing OLT and its immediate impact post-operatively. MATERIAL AND METHODS: Electronic medical records (EMR) of 100 consecutive patients who underwent OLT were reviewed at the University of Tennessee/Methodist University Hospital in Memphis, Tennessee, USA. Transthoracic echocardiogram (TTE) reports were accessed to evaluate for LVDD based on the latest 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines. The clinical and demographic variables were obtained and variable quality measures, incidence of cardiac arrhythmias, and 30-day all-cause mortality were compared. RESULTS: Patients with LVDD were older (62.7 ±6.3 years vs. 55.9 ±12.3 years, p = 0.017) and were more often female (57% vs. 31%, p = 0.026). In addition, patients with non-alcoholic steatohepatitis (NASH) were more likely to have LVDD (48% vs. 12%, p = 0.001). In contrast, patients with alcoholic liver disease were less likely to have LVDD (10% vs. 33%, p = 0.032). In a multivariate logistic regression analysis, NASH (OR = 4.4 [95% CI: 1.33-14.5], p = 0.015) and female gender (OR = 3.31 [95% CI: 1.09-9.99], p = 0.033) were independent predictors of LVDD. CONCLUSIONS: In our cohort of patients, the presence of NASH was associated with a higher risk of LVDD. However, presence of LVDD did not influence immediate post-transplant outcome or 30-day all-cause mortality.

9.
Clin Transplant ; 34(9): e14003, 2020 09.
Article in English | MEDLINE | ID: mdl-32506677

ABSTRACT

BACKGROUND: Alcohol-associated liver disease (AALD) is a rapidly growing indication for liver transplantation (LT). We aimed to examine various clinical, demographic, and behavioral factors to predict post-LT alcohol relapse and graft survival. METHODS: Retrospective analysis was performed on 241 LT recipients with AALD as either a primary or secondary indication for LT (2006-2015). RESULTS: Patients with <6 months of alcohol abstinence had significantly increased cumulative incidence for alcohol relapse compared to those with >6 months of abstinence (P = .0041, Log-Rank). We identified four variables to predict harmful alcohol relapse post-LT: age at LT, non-alcohol-related criminal history, pre-LT abstinence period (Ref >6 months of alcohol abstinence), and drinks per day (Ref <10 drinks/day). Area under the curve (AUC) for the final model was 0.79 (95% CI: 0.68-0.91). Our multivariable model was evaluated with internal cross-validation; random sampling of the study subjects 100 times yielded a median C statistic of 75 (±SD 0.097) and accuracy of 91 (±SD 0.026). The four-variable model served to form the harmful alcohol use post-LT (HALT) score. Graft survival remained significantly lower in patients with <6 months of pre-LT alcohol abstinence and those with blue-collar jobs. CONCLUSION: The HALT score identifies LT candidates with AALD at significant risk for alcohol relapse, potentially guiding transplant centers for pre- and post-LT interventions for improved patient outcomes.


Subject(s)
Liver Diseases, Alcoholic , Liver Transplantation , Alcohol Abstinence , Humans , Liver Diseases, Alcoholic/etiology , Liver Diseases, Alcoholic/surgery , Recurrence , Retrospective Studies , Risk Factors
10.
Case Reports Hepatol ; 2020: 8247960, 2020.
Article in English | MEDLINE | ID: mdl-32231818

ABSTRACT

Crizotinib is a first-line tyrosine kinase inhibitor used for the treatment of metastatic lung cancer. Crizotinib-induced hepatotoxicity is a rare event. We report a case of a 46-year-old female with a history of metastatic lung cancer who presented with acute liver failure after being on crizotinib for two months. The medication was discontinued, and she was treated with N-acetylcysteine for seven days. Her liver function tests returned to normal limits after 26 days after admission. The precise mechanism and risk factors of crizotinib-induced hepatotoxicity remain unknown. Physicians should be aware of the potentially lethal side effect caused by crizotinib.

11.
Transplant Direct ; 6(4): e544, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32309630

ABSTRACT

The impact of acute-on-chronic liver failure (ACLF) defined by European Association for the Study of the Liver-Chronic Liver Failure in liver transplant (LT) recipients has not been well characterized. The aim of the study was to assess early posttransplant morbidity and survival of ACLF patients. METHODS: Eight hundred twenty-five consecutive LT patients (04/2006-03/2013) were included in a retrospective analysis. Of the 690 evaluable patients, 589 had no ACLF, and the remaining 101 were grouped into ACLF Grades 1-3 (ACLF Grade 1: 50 [49.5%], ACLF Grade 2: 32 [31.7%], and ACLF Grade 3: 19 [18.8%]). RESULTS: LT recipients transplanted in the context of ACLF had significantly increased serum creatinine (2.27 ± 1.16 versus 0.98 ± 0.32; P < 0.0001), and inferior 1-year graft (90% versus 78%; P < 0.0001) and patient survival (92% versus 82%; P = 0.0004) by Kaplan-Meier survival analysis; graft and patient survival correlated negatively with increasing severity of ACLF. One-year graft and patient survival were lower in those with high ACLF (Grade 2 and 3) irrespective of Model for End-Stage Liver Disease compared with other groups. The ACLF group had longer intensive care unit stays (10.6 ± 19.5 versus 4.2 ± 9; P < 0.0001), hospital stays (20.9 ± 25.9 versus 11.7 ± 11.4; P < 0.0001), and increased surgical re-exploration (26.7 % versus 14.6%, P = 0.002). CONCLUSIONS: Patients with ACLF undergoing LT have significantly higher resource utilization, inferior graft survival and patient survival, and renal dysfunction at 1 year. The combination of ACLF and Model for End-Stage Liver Disease can be considered when determining the suitability for potential transplantation.

12.
Clin Transplant ; 34(6): e13845, 2020 06.
Article in English | MEDLINE | ID: mdl-32096883

ABSTRACT

BACKGROUND: Opioid medications are frequently used to address pain among patients with cirrhosis, including those on the liver transplant (LT) waitlist and after transplantation. However, opioid use has been associated with poor allograft outcomes and reduced transplant survival. We examined the impact of opioid use across the spectrum of advanced liver disease, from the initial hepatology consultation for cirrhosis through transplant referral, listing, and the post-LT process. METHODS: The study includes all patients referred for cirrhosis management in a single healthcare system in the United States. Data were extracted retrospectively through medical chart review. RESULTS: Of 414 patients included in the study, 104 (25%) were treated with opioid. Patients on opioids were more likely to be White, have body mass indices (BMI) >30, have HCV, suffer from hepatic encephalopathy, cigarette smokers, and use benzodiazepines concurrently. Higher doses of opioids were associated with multiple emergency department (ED). Eighty-nine underwent LT, including 20 opioid-treated patients. There was no difference found between the opioid and non-opioid groups with regard to allograft loss, ED visits, and hospital readmissions at 2 years post-LT follow-up. CONCLUSIONS: Opioid treatment was common among patients with cirrhosis. We did not find increased negative outcomes among opioid users across the spectrum of cirrhosis. However, the sample for LT patients was small.


Subject(s)
Analgesics, Opioid , Liver Transplantation , Analgesics, Opioid/therapeutic use , Humans , Liver Cirrhosis , Retrospective Studies , United States/epidemiology , Waiting Lists
13.
BMJ Case Rep ; 12(8)2019 Aug 28.
Article in English | MEDLINE | ID: mdl-31466981

ABSTRACT

Liver transplant recipients are immunocompromised by the virtue of being on immunosuppressive agents which put them at risk of having infections from unusual and even multiple concomitant pathogens. We present a case of a 39-year-old man who developed septicaemia with Enterococcus casseliflavus, Streptococcus equinus and Klebsiella oxytoca in the setting of perinephric haematoma which resulted following a kidney biopsy performed to evaluate his nephrotic range proteinuria. E. casseliflavus has been known to cause infections in patients with liver disease/cirrhosis; however, simultaneous infection with S. equinus and K. oxytoca along with E. casseliflavus has never been reported earlier in post-transplant state.


Subject(s)
Hematoma/etiology , Kidney Diseases/complications , Klebsiella oxytoca/isolation & purification , Liver Transplantation/adverse effects , Sepsis/microbiology , Adult , Allografts/pathology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Biopsy/adverse effects , Drainage/methods , Enterococcus/isolation & purification , Hematoma/surgery , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Infusions, Intravenous , Kidney/diagnostic imaging , Kidney/microbiology , Kidney/pathology , Kidney Diseases/diagnostic imaging , Kidney Diseases/microbiology , Kidney Diseases/pathology , Liver Cirrhosis/complications , Male , Proteinuria/diagnosis , Sepsis/complications , Sepsis/drug therapy , Streptococcus/isolation & purification , Streptococcus bovis , Treatment Outcome
14.
Transplant Direct ; 4(5): e347, 2018 May.
Article in English | MEDLINE | ID: mdl-29796418

ABSTRACT

BACKGROUND: Biliary strictures (BS) are common complication after liver transplantation. We aimed to determine the accuracy of magnetic resonance cholagiopancreatography (MRCP) in diagnosing BS in liver transplant recipients (LTRs) when compared to direct cholangiographic methods (endoscopic resonance cholagiopancreatography [ERCP] and/or percutaneous transhepatic cholangiography [PTC]). METHODS: Retrospective chart review of 910 LTRs (July 2008 to April 2015) was performed, and a total of 39 patients with duct-to-duct anastomosis (22 males; 56.4%; mean age, 52.8 ± 8.3 years) were included who had an MRCP followed by either ERCP and/or PTC within 4 weeks. A cholangiographic narrowing (on ERCP and/or PTC) that required balloon dilation and/or stent placement was considered a BS and was considered clinically significant if the intervention resulted in at least 30% improvement of bilirubin within 2 weeks. Sensitivity, specificity, accuracy, positive predictive values and negative predictive values of MRCP in diagnosing BS were calculated. RESULTS: Magnetic resonance cholagiopancreatography showed anastomotic BS in 17 of 39 patients, and subsequent ERCP and/or PTC revealed a total of 25 BS (positive predictive value of 0.94). Nine BS on cholangiography (ERCP, 8; PTC, 1) were not detected on earlier MRCP (sensitivity, 0.64; 95% CI, 0.45-0.82); 2 were clinically significant BS and 6 of the remaining 7 had no improvement in their liver function test with biliary intervention. Thirteen LTRs had no BS on either modality (specificity, 0.93; 95% CI, 0.66-0.99). The negative predictive value of MRCP was 0.59 for cholangiographic BS. The overall accuracy of MRCP is 0.74 (exact 95% CI, 0.58-0.87). Inclusion of age, race, and alanine aminotransferase level improved the predictive value of MRCP (area under the curve = 0.94, 95% CI: 0.86-1.00). CONCLUSIONS: Magnetic resonance cholagiopancreatography has high specificity but low sensitivity in diagnosing cholangiographic BS in LTRs, although the predictive value further improved with inclusion of age, race, and alanine aminotransferase. Clinical significance of BS in LTRs not identified on MRCP is questionable because ERCP with intervention did not improve their liver function tests in the vast majority.

15.
Clin Transplant ; 32(5): e13246, 2018 05.
Article in English | MEDLINE | ID: mdl-29577449

ABSTRACT

BACKGROUND: Sorafenib has shown survival benefits in patients with advanced HCC; however, limited data are available on its role in OLT recipients with advanced HCC in the explant. AIM: Evaluate the role of preemptive sorafenib therapy on HCC recurrence and survival after OLT with advanced HCC on explant pathology. METHODS: We retrospectively reviewed the outcome after OLT of all HCC recipients with advanced HCC in the explant pathology from 04/2006 to 12/2012 based on preemptive treatment with sorafenib. RESULTS: During the observation period, 217 HCC recipients underwent OLT; 50 explants revealed advanced HCC. After exclusion of 5 patients who were lost to follow-up, 45 LT recipients were finally included for analysis. Recipients were grouped as sorafenib Gr (N = 25) and nonsorafenib Gr (N = 20). Both recurrence-free survival (RFS) (P = .67) and overall survival were similar between groups (P = .53) on Kaplan-Meier analysis. Additionally, sorafenib use was neither associated with HCC recurrence-free survival (HR 0.74, 95% CI [0.32-1.70]; P = .48) nor overall survival (HR 0.92, 95% CI [0.39-2.15], P = .84) on multivariate Cox proportional hazard model with sorafenib use as time-varying covariates. CONCLUSION: Preemptive treatment with sorafenib in OLT recipients with high-risk features in explant does not improve HCC recurrence-free or overall survival.


Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/mortality , Graft Rejection/mortality , Liver Neoplasms/mortality , Liver Transplantation/mortality , Neoplasm Recurrence, Local/mortality , Sorafenib/adverse effects , Aged , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Survival , Humans , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Liver Transplantation/adverse effects , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/therapy , Preoperative Care , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
16.
Liver Transpl ; 24(8): 1040-1049, 2018 08.
Article in English | MEDLINE | ID: mdl-29573131

ABSTRACT

The effect of antiviral therapy (AVT) on kidney function in liver transplantation (LT) recipients has not been well described despite known association of hepatitis C virus (HCV) infection with chronic kidney disease (CKD). We compared the incidence of CKD and end-stage renal disease (ESRD) in 204 LT recipients with HCV based on treatment response to AVT. The mean estimated glomerular filtration rate (eGFR) at baseline (3 months after LT) was similar in the sustained virological response (SVR; n = 145) and non-SVR group (n = 59; 69 ± 21 versus 65 ± 33 mL/minute/1.73 m2 ; P = 0.27). In the unadjusted Cox proportional regression analysis, the presence of SVR was associated with an 88% lower risk of CKD (hazard ratio, 0.12; 95% confidence interval [CI], 0.05-0.31) and 86% lower risk of ESRD (odds ratio, 0.14; 95% CI, 0.05-0.35). Similar results were found after adjusting for propensity score and time-dependent Cox regression analyses. The estimated slopes of eGFR based on a 2-stage mixed model of eGFR were calculated. Patients with SVR had a less steep slope in eGFR (-0.60 mL/minute/1.73 m2 /year; 95% CI, -1.50 to 0.30; P = 0.190) than recipients without SVR (-2.53 mL/minute/1.73 m2 /year; 95% CI, -3.99 to -1.07; P = 0.001), and the differences in the slopes were statistically significant (P = 0.026). In conclusion, in LT recipients with chronic HCV infection, achieving SVR significantly lowers the risk of decline in renal function and progression to ESRD independent of the AVT therapy used.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Kidney Failure, Chronic/epidemiology , Liver Cirrhosis/surgery , Liver Transplantation/adverse effects , Postoperative Complications/epidemiology , Disease Progression , Drug Therapy, Combination/methods , Female , Glomerular Filtration Rate , Hepacivirus/isolation & purification , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Humans , Incidence , Kidney/physiopathology , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/physiopathology , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Male , Middle Aged , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Retrospective Studies , Severity of Illness Index , Sustained Virologic Response
17.
Transplant Direct ; 3(7): e178, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28706981

ABSTRACT

BACKGROUND: Liver transplant (LT) recipients with autoimmune liver disease (primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis) are at increased risk of developing acute cellular rejection (ACR), and in many cases graft failure due to recurrent disease. We describe our experience with dual immunosuppression without steroid maintenance and analyze its effect on disease recurrence; ACR; patient and graft survivals; and complications, such as sepsis and de novo malignancy. METHODS: We included 74 consecutive LT recipients (April 2006 to April 2013) with autoimmune liver disease (primary sclerosing cholangitis, 20; primary biliary cholangitis, 23; autoimmune hepatitis, 31) from a single transplant center. Immunosuppression protocol included rabbit antithymocyte globulin for induction and mycophenolate mofetil with tacrolimus or sirolimus/everolimus indefinitely for maintenance. RESULTS: Overall 1-, 3-, 5-, and 7-year patient survival was 95.9%, 90.4%, 82,2% and 74.9%, re-graft-free survival was 93.2%, 86.3%, 79.9%, and 72.8%, respectively (median follow-up, 5.5 years). In a multivariate Cox regression analysis, sepsis during post-LT period (P = 0.040; hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.04-6.11), steroid use for ACR (P = 0.037; HR, 2.60; 95% CI, 1.06-6.34), and younger age (<40 years) at LT (P = 0.038; HR, 2.53; 95% CI, 1.05-6.10) predicted graft survival, whereas steroid use for ACR was the only variable that was predictive of overall patient survival (P = 0.004; HR, 4.10; 95% CI, 1.59-10.52). Overall, 34 biopsy-proven ACR was noted in 22 LT recipients (30%), 13 (17.5%) had disease recurrence, and 34 episodes of sepsis occurred in 19 patients. CONCLUSIONS: Dual immunosuppression protocol in LT recipients with autoimmune liver disease without corticosteroid maintenance had acceptable rates of survival and ACR without predisposing patients to the adverse effects of long-term steroid therapy.

18.
Clin Transplant ; 31(7)2017 07.
Article in English | MEDLINE | ID: mdl-28489291

ABSTRACT

BACKGROUND: Endoscopic treatment of anastomotic biliary stricture (ABS) after liver transplantation (LT) has been proven to be effective and safe, but long-term outcomes of early compared to late onset ABS have not been studied. The aim of this study is to compare the long-term outcome of early ABS to late ABS. METHODS: Of the 806 adult LT recipients (04/2006-12/2012), 93 patients met the criteria for inclusion, and were grouped into non-ABS (no stenosis on ERCP, n=41), early ABS (stenosis <90 days after LT, 18 [19.3%]), and late ABS (stenosis ≥90 days after LT, 34 [36.5%]). A propensity matched control group for the ABS group (n=42) was obtained matched for outcome variables for age, gender, and calculated MELD score at listing. RESULTS: Mean number of ERCPs (2.33±1.3 vs 2.56±1.5, P=.69) were comparable between the groups; however, significantly better long-term resolution of the stricture was noted in the early ABS group (94.44% vs 67.65%, P=.04). Kaplan-Meier analysis revealed worst survival in the early ABS group compared to the non-ABS, late ABS, and control groups (P=.0001). CONCLUSION: LT recipients with early ABS have inferior graft survival despite better response to endoscopic intervention.


Subject(s)
Anastomosis, Surgical/mortality , Biliary Tract/pathology , Cholestasis, Extrahepatic/mortality , Constriction, Pathologic/mortality , Graft Rejection/mortality , Liver Transplantation/adverse effects , Postoperative Complications/mortality , Adult , Case-Control Studies , Cholestasis, Extrahepatic/etiology , Cholestasis, Extrahepatic/therapy , Constriction, Pathologic/etiology , Constriction, Pathologic/therapy , Female , Follow-Up Studies , Graft Rejection/etiology , Graft Rejection/therapy , Graft Survival , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Time Factors
19.
Transplantation ; 101(4): 793-803, 2017 04.
Article in English | MEDLINE | ID: mdl-28099403

ABSTRACT

BACKGROUND: Coronary artery disease (CAD) is a significant problem during evaluation for liver transplantation (LT). We aim to assess survival in LT recipients based on presence, severity, extent of CAD, and cardiac events within 90 days of LT. METHODS: Eighty-seven LT recipients with history of pre-LT angiogram (December 2005 to December 2012) were compared with 2 control groups without prior angiogram, 72 LT recipients matched for cardiovascular risk factors (control group I), and 119 consecutive LT recipients without any CV risk factors (control group II). CAD was assessed by (1) vessel score (≥50% reduction in luminal diameter), and (2) Extent score (Reardon scoring system). RESULTS: Of the 87 LT recipients (study group), 58 (66.7%) had none or less than 50% stenosis, 29 (33.3%) had obstructive CAD (≥50% stenosis), 7 (8%) with single-vessel disease, and 22 (25.3%) with multivessel disease. In the study group, irrespective of prerevascularization severity of CAD (P = 0.357), number of segments involved (0, 1-2, > 2 segments, P = 0.304) and extent of CAD based on Reardon score (0, 1-9, >10, P = 0.224), comparable posttransplant survival was noted. Overall, patient survival in the revascularized CAD group was comparable to angiogram group without obstructive CAD, and both control group I and control group II (P = 0.184, Log Rank). Postoperative cardiac events within 90 days of LT predicted poor survival in study group as well as control groups. CONCLUSIONS: Severity or extent of CAD does not impact post-LT survival, if appropriately revascularized. Early postoperative cardiac events are associated with inferior survival in LT recipients, irrespective of underlying CAD.


Subject(s)
Coronary Artery Disease/surgery , Coronary Stenosis/surgery , End Stage Liver Disease/surgery , Liver Transplantation , Myocardial Revascularization , Adult , Coronary Angiography , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/mortality , Coronary Stenosis/complications , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/mortality , End Stage Liver Disease/complications , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , Female , Humans , Kaplan-Meier Estimate , Liver Function Tests , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Medical Records , Middle Aged , Myocardial Revascularization/adverse effects , Myocardial Revascularization/mortality , Postoperative Complications/etiology , Proportional Hazards Models , Retrospective Studies , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome
20.
Br Poult Sci ; 57(6): 763-770, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27635666

ABSTRACT

Activin receptor type 2A (ACVR2A) acts as receptor for myostatin (MSTN) protein involved in inhibiting satellite cell proliferation and differentiation. The importance of the ACVR2A gene during embryonic and post-hatch periods in broiler and layer chicken was studied in an in vitro cell culture system. The expression pattern of the ACVR2A gene during embryonic stages was similar in broiler and layer lines. Post-hatch expression of the ACVR2A gene varied significantly between broiler and layer lines. Five shRNA molecules were designed to knockdown expression of the ACVR2A gene in chicken myoblast cells. The silencing of the ACVR2A gene in a cell culture system varied from 60% to 82%. It is concluded that between broiler and layer lines, there were no significant changes in expression of the ACVR2A gene during embryonic stages but it varied significantly during the post-hatch period. The shRNA showed silencing of the ACVR2A gene under an in vitro cell culture system.


Subject(s)
Activin Receptors, Type II/genetics , Chickens/genetics , Gene Expression , Gene Silencing , Activin Receptors, Type II/metabolism , Animals , Chick Embryo/metabolism , Chickens/metabolism , Myoblasts/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism
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