Mark R. Pedersen

Infections after orthotopic liver transplantation.

Opportunistic infections are a leading cause of morbidity and mortality after orthotopic liver transplantation. Systemic immunosuppression renders the liver recipient susceptible to de novo infection with bacteria, viruses and fungi post-transplantation as well to reactivation of pre-existing, latent disease. Pathogens are also transmissible via the donor organ. The time from transplantation and degree of immunosuppression may guide the differential diagnosis of potential infectious agents. However, typical systemic signs and symptoms of infection are often absent or blunted after transplant and a high index of suspicion is needed. Invasive procedures are often required to procure tissue for culture and guide antimicrobial therapy. Antimicrobial prophylaxis reduces the incidence of opportunistic infections and is routinely employed in the care of patients after liver transplant. In this review, we survey common bacterial, fungal, and viral infections after orthotopic liver transplantation and highlight recent developments in their diagnosis and management.

Pretransplant Factors and Associations with Postoperative Respiratory Failure, ICU Length of Stay, and Short-Term Survival after Liver Transplantation in a High MELD Population

Changes in distribution policies have increased median MELD at transplant with recipients requiring increasing intensive care perioperatively. We aimed to evaluate association of preoperative variables with postoperative respiratory failure (PRF)/increased intensive care unit length of stay (ICU LOS)/short-term survival in a high MELD cohort undergoing liver transplant (LT). Retrospective analysis identified cases of PRF and increased ICU LOS with recipient, donor, and surgical variables examined. Variables were entered into regression with end points of PRF and ICU LOS > 3 days. 164 recipients were examined: 41 (25.0%) experienced PRF and 74 (45.1%) prolonged ICU LOS. Significant predictors of PRF with univariate analysis: BMI > 30, pretransplant MELD, preoperative respiratory failure, LVEF < 50%, FVC < 80%, intraoperative transfusion > 6 units, warm ischemic time > 4 minutes, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted PRF (OR 1.14, p = 0.01). Significant predictors of prolonged ICU LOS with univariate analysis are as follows: pretransplant MELD, FVC < 80%, FEV1 < 80%, deceased donor, and cold ischemic time > 240 minutes. On multivariate analysis, only pretransplant MELD predicted prolonged ICU LOS (OR 1.28, p < 0.001). One-year survival among cohorts with PRF and increased ICU LOS was similar to subjects without. Pretransplant MELD is a robust predictor of PRF and ICU LOS. Higher MELDs at LT are expected to increase need for ICU utilization and modify expectations for recovery in the immediate postoperative period.

25-Vitamin D levels in chronic hepatitis C infection: association with cirrhosis and sustained virologic response

Background Low serum 25-Vitamin D levels are associated with advanced fibrosis in hepatitis C infection. Vitamin D supplementation has been hypothesized to augment response rates to interferon-based therapy. To date, no investigation has evaluated vitamin D levels during direct-acting antiviral therapy. We aimed to evaluate the prevalence of vitamin D deficiency in cirrhotic and non-cirrhotic cohorts, the predictive value of pretreatment levels for a sustained virologic response, and the changes in 25-OH vitamin D levels during direct-acting antiviral therapy. Methods Two hundred eighteen patients with chronic hepatitis C who completed direct-acting antiviral therapy were consecutively enrolled. Vitamin D levels were measured using chemiluminescence immunoassay, prior to initiation and at completion of therapy. Advanced liver fibrosis (cirrhosis) was determined by biopsy, FibroSURE blood test, or imaging. Results A sustained virologic response was achieved in 79% (n=172) of patients, with 19% (n=44) relapsing. A total of 123 (56.4%) patients were cirrhotic. The prevalence of Vitamin D deficiency (10-20 ng/mL) and severe deficiency (<10 ng/mL) was significantly higher in cirrhotic patients (P=0.04). Pre-treatment vitamin D levels in cirrhotic patients were negatively correlated with Model for End-Stage Liver Disease score, total bilirubin and INR (P<0.05). Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response. Conclusions The prevalence of vitamin D deficiency is higher in hepatitis-C–related cirrhotic cohorts compared to non-cirrhotic patients and correlates with components of hepatic function. Neither pretreatment vitamin D level nor the change during therapy was associated with an increased rate of sustained virologic response.

Direct intrahepatic portocaval shunt for treatment of portal thrombosis and Budd-Chiari syndrome

Budd-Chiari syndrome (BCS) refers to hepatic venous outflow obstruction that in severe cases can lead to acute liver failure prompting consideration of revascularization or transplantation. Here, a 22 year old female with angiographically proven BCS secondary to JAK2/V617F positive Polycythemia vera on therapeutic warfarin presented with acute liver failure (ALF). Imaging revealed a new, near complete thrombotic occlusion of the main portal vein with extension into the superior mesenteric vein. An emergent direct intrahepatic portocaval shunt (DIPS) was created and liver function promptly normalized. She has been maintained on rivaroxaban since that time. Serial assessment over 1 year demonstrated continued shunt patency and improved flow in the mesenteric vasculature on ultrasound as well as normal liver function. DIPS is a viable alternative in the treatment of ALF from BCS when standard recanalization is not feasible. Improved blood flow may also improve portal/mesenteric clot burden. While further investigation is needed, new targeted anticoagulants may be viable as a long term anticoagulation strategy.Budd-Chiari syndrome (BCS) refers to hepatic venous outflow obstruction that in severe cases can lead to acute liver failure prompting consideration of revascularization or transplantation. Here, a 22 year old female with angiographically proven BCS secondary to JAK2/V617F positive Polycythemia vera on therapeutic warfarin presented with acute liver failure (ALF). Imaging revealed a new, near complete thrombotic occlusion of the main portal vein with extension into the superior mesenteric vein. An emergent direct intrahepatic portocaval shunt (DIPS) was created and liver function promptly normalized. She has been maintained on rivaroxaban since that time. Serial assessment over 1 year demonstrated continued shunt patency and improved flow in the mesenteric vasculature on ultrasound as well as normal liver function. DIPS is a viable alternative in the treatment of ALF from BCS when standard recanalization is not feasible. Improved blood flow may also improve portal/mesenteric clot burden. While further investigation is needed, new targeted anticoagulants may be viable as a long term anticoagulation strategy.

Genotype specific peripheral lipid profile changes with hepatitis C therapy.

AIM To evaluate magnitude/direction of changes in peripheral lipid profiles in patients undergoing direct acting therapy for hepatitis C by genotype. METHODS Mono-infected patients with hepatitis C were treated with guideline-based DAAs at a university-based liver clinic. Patient characteristics and laboratory values were collected before and after the treatment period. Baseline demographics included age, ethnicity, hypertension, diabetes, hyperlipidemia, treatment regimen, and fibrosis stage. Total cholesterol (TCHOL), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), and liver function tests were measured prior to treatment and ETR. Changes in lipid and liver function were evaluated by subgroups with respect to genotype. Mean differences were calculated for each lipid profile and liver function component (direction/magnitude). The mean differences in lipid profiles were then compared between genotypes for differences in direction/magnitude. Lipid profile and liver function changes were evaluated with Levene’s test and student’s t test. Mean differences in lipid profiles were compared between genotypes using ANOVA, post hoc analysis via the Bonferroni correction or Dunnett T3. RESULTS Three hundred and seventy five patients enrolled with 321 (85.6%) achieving sustained-viral response at 12 wk. 72.3% were genotype 1 (GT1), 18.1% genotype 2 (GT2), 9.7% genotype 3 (GT3). Baseline demographics were similar. Significant change in lipid profiles were seen with GT1 and GT3 (ΔGT1, p and ΔGT3, p), with TCHOL increasing (+5.3, P = 0.005 and +16.1, P < 0.001), HDL increasing (+12.5, P < 0.001 and +7.9, P = 0.038), LDL increasing (+7.4, P = 0.058 and +12.5, P < 0.001), and TG decreasing (-5.9, P = 0.044 and -9.80 P = 0.067). Among genotypes (ΔGT1 v. ΔGT2 v. ΔGT3, ANOVA), significant mean differences were seen with TCHOL (+5.3 v. +0.1 v. +16.1, P = 0.017) and HDL (+12.3 v. +2 v. +7.9, P = 0.040). Post-hoc, GT3 was associated with a greater increase in TCHOL than GT1 and GT2 (P = 0.028 and P = 0.019). CONCLUSION Successful DAA therapy results in increases in TCHOL, LDL, and HDL and decrease in TG, particularly in GT1/GT3. Changes are most pronounced in GT3.

Su1016 Risk Factors for Post-Operative Respiratory Failure in Liver Transplant Recipients

Rationale: Post-operative respiratory failure (PRF) is a common complication after liver transplant (LT). PRF leads to increased length of intensive care unit (ICU) and hospital stay and predisposes to increased morbidity in the post-operative period. Further investigation is needed to identify risk factors for PRF in LT recipients. Aim: To evaluate pre-operative cardiopulmonary testing, recipient, donor, and surgical variables and their utility in prediction of PRF after LT. Methods: Retrospective case-control study performed on LT recipients from 2010-2012. Post-operative course was reviewed to evaluate for cases of PRF, defined as failure to extubate before or unplanned re-intubation within 48 hours from completion of LT surgery. Pre transplant recipient demographic characteristics were recorded. Donor and surgical characteristics including: simultaneous kidney transplant, cytomegalovirus (CMV) status, gender, donor source (deceased or living), age, warm and cold ischemic times were assessed. Pre-transplant cardiopulmonary testing examined included: the presence or absence of heart failure, diastolic dysfunction, left ventricular ejection fraction, right ventricular systolic pressure, forced expiratory volume in one second to forced vital capacity ratio (FEV1/ FVC), forced vital capacity (FVC), total lung capacity (TLC), forced expiratory volume in one second ( FEV1), and diffusion limit of carbon monoxide (DLCO). Variables of interest were analyzed using univariate logistic regression with an end point of PRF. Factors deemed most significant (p < 0.25) in predicting PRF were included in a multivariate regression analysis to estimate adjusted odds ratios (OR) for each variable. Variables with p < 0.05 were considered significant predictors of PRF in the final model. Results: A total of 170 patients were identified. Of those, 23.7% experienced PRF. Significant predictors including pre-transplant MELD, pre-operative respiratory failure, FVC <80%, FEV1 <80%, TLC <80%, and deceased donor source from univariate logistic regression [Table 1] were entered into multivariate logistic regression. In the final model, pre-operative respiratory failure (OR= 161.48, p = 0.002) was found to be predictive of PRF, in a model that explained 26.3 to 41.7% of variance [Table 2].Conclusions: Pre-operative respiratory failure from any etiology was identified as a significant predictor of PRF after LT. Pre-LT echocardiogram and pulmonary function testing had no predictive value for PRF. These findings support the development of protocols to aggressively wean ventilatory support immediately prior to LT. Univariate Analysis: Post-Operative Respiratory Failure