Rapid Development of De Novo Thoracic Aneurysm After Liver Transplant.

The development of aortic aneurysms in post-transplant patients is a rare but potentially lethal problem. De novo aortic aneurysm formation and rapid growth are postulated to result from an imbalance between pro- and anti-inflammatory vascular endothelial factors after transplant. Here, we present a case of de novo thoracic aneurysm formation within 2 months of orthotopic liver transplant. Prompt clinical recognition allowed for successful endovascular repair. Transplant clinicians should be aware of this potentially life-threatening complication and monitor at-risk recipients accordingly.

Immune Reconstitution Syndrome with Initiation of Treatment of HBV/HIV Co-infection: Activity Flare associated with E antigen Seroconversion.

Immune reconstitution syndrome is a recognized complication with initiation of highly active antiretroviral therapy for acquired immune deficiency syndrome patients co-infected with hepatitis B. Hepatitis B flares are seen in 20%-25% of patients after initiation of highly active antiretroviral therapy, an estimated 1%-5% of whom develop clinical hepatitis. We present a case of highly active antiretroviral therapy initiation for HIV that led to a flare of HBV activity despite antiviral therapy directed towards both. Liver biopsy and longitudinal serologic evaluation lend support to the hypothesis that the flare in activity was representative of IRIS. Importantly, we document eAg/eAb seroconversion with the IRIS phenomenon.

Real-Time Ultrasound-Guided Paracentesis by Radiologists: Near Zero Risk of Hemorrhage without Correction of Coagulopathy.

PURPOSE: To evaluate the rate and risk factors for hemorrhage in patients undergoing real-time, ultrasound-guided paracentesis by radiologists without correction of coagulopathy. MATERIALS AND METHODS: This was a retrospective study of all patients who underwent real-time, ultrasound-guided paracentesis at a single institution over a 2-year period. In total, 3116 paracentesis procedures were performed: 757 (24%) inpatients and 2,359 (76%) outpatients. Ninety-five percent of patients had a diagnosis of cirrhosis. Mean patient age was 56.6 years. Mean international normalized ratio (INR) was 1.6; INR was > 2 in 437 (14%) of cases. Mean platelet count was 122 x 103/µL; platelet count was < 50 x 103/µL in 368 (12%) of patients. Seven hundred seven (23%) patients were dialysis dependent. Patients were followed for 2 weeks after paracentesis to assess for hemorrhage requiring transfusion or rescue angiogram/embolization. Univariate analysis was performed to determine risk factors for hemorrhage. Blood product and cost saving analysis were performed. RESULTS: Significant post-paracentesis hemorrhage occurred in 6 (0.19%) patients, and only 1 patient required an angiogram with embolization. No predictors of post-procedure bleeding were found, including INR and platelet count. Transfusion of 1125 units of fresh frozen plasma and 366 units of platelets were avoided, for a transfusion-associated cost savings of $816,000. CONCLUSIONS: Without correction of coagulation abnormalities with prophylactic blood product transfusion, post-procedural hemorrhage is very rare when paracentesis is performed with real-time ultrasound guidance by radiologists.

Race and Gradient Difference Are Associated with Increased Risk of Hepatic Encephalopathy Hospital Admission After Transjugular Intrahepatic Portosystemic Shunt Placement.

BACKGROUND/AIMS: Hepatic encephalopathy (HE) is a well-recognized complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. The aim of this investigation was to evaluate incidence and predictors of post-TIPS HE necessitating hospital admission in a non-clinical trial setting. METHODS: We performed a retrospective cohort study identifying 273 consecutive patients undergoing TIPS from 2010 to 2015 for any indication; 210 met inclusion/exclusion criteria. The primary endpoint was incidence of post-TIPS HE defined as encephalopathy with no other identifiable cause requiring hospitalization within 90 days of TIPS. Clinical demographics and procedural variables were collected and analyzed to determine predictors of readmission for post-TIPS HE. Categorical variables were analyzed using Fisher's exact test; continuous variables were compared using Levene's t-test and student's t-test; P < 0.05, significant. RESULTS: Forty-two of 210 patients (20%) developed post-TIPS HE requiring hospitalization within 90 days. On analysis of cohorts (post-TIPS HE vs. no post-TIPS HE): non-white race (31.0% vs. 17.5%, P = 0.022) and increased hepatic venous pressure gradient (HVPG) difference during TIPS (10.5 vs. 8.9 mmHg, P = 0.030) were associated with an increased incidence of HE requiring readmission within 90 days. CONCLUSIONS: HE remains a common complication of TIPS. Non-Caucasian race is a significant clinical demographic associated with increased risk for readmission. Independent of initial or final HVPG, HVPG difference appears to be a significant modifiable technical risk factor. In the absence of clear preventative strategies for post-TIPS encephalopathy, non-Caucasians with HVPG reductions >9 mmHg may require targeted follow up evaluation to prevent hospital readmission.

Refractory Hepatic Encephalopathy After Elective Transjugular Intrahepatic Portosystemic Shunt: Risk Factors and Outcomes with Revision.

BACKGROUND AND AIMS: Hepatic encephalopathy (HE) is a common complication of elective transjugular intrahepatic portosystemic shunt (TIPS) placement and is often successfully medically managed. Risk factors for refractory hepatic encephalopathy (RHE) necessitating revision of TIPS are not well defined. We evaluated the incidence, predictors, and outcomes of post-TIPS RHE necessitating TIPS revision. METHODS: In a retrospective cohort study of 174 consecutive patients undergoing elective TIPS placement (2010-2015), we evaluated the incidence of post-TIPS RHE. Clinical demographics and procedural variables were collected. 1-year outcomes after revision were collected. RESULTS: Ten of 174 patients (5.7%) developed post-TIPS RHE requiring revision. Significant differences between RHE and non-refractory groups were shunt size > 8 versus ≤ 8 mm (18.5 vs. 3.4%, p = 0.001), history of HE (14 vs. 2%, p = 0.007), and serum albumin levels ≤ 2.5 versus > 2.5 g/dL (13.1 vs. 3.1%, p = 0.020). On multivariate analysis, shunt size > 8 mm (p = 0.001), history of HE prior to TIPS (p = 0.006), and low serum albumin (≤ 2.5 g/dL) (p = 0.022) remained independent predictors of RHE, controlling for age and Model for End-Stage Liver Disease score. RHE improved in 8 of 10 patients but survival at 1 year without liver transplantation (LT) was only 10%. CONCLUSION: While TIPS revision successfully improves RHE in most cases, 1-year mortality rates are high, limiting the value of revision in non-LT candidates. Patients with previous history of HE and low serum albumin levels prior to TIPS may benefit most from the use of shunt sizes < 8 mm to mitigate the risk of RHE. LEVEL OF EVIDENCE: Level 4, case series.

Profiling Neutrophil-to-Lymphocyte Ratio Changes in Response to Nucleoside Analog Therapy for Chronic Hepatitis B Infection.

BACKGROUND/AIM: The neutrophil-lymphocyte ratio (NLR) has gained attention as an index of inflammation in patients with chronic hepatitis B virus (HBV); however, changes with nucleoside analog therapy require investigation. PATIENTS AND METHODS: We carried out a retrospective study identifying monoinfected HBV patients initiated on therapy with NLR follow-up over 1 year. Biochemistries recorded at treatment initiation and 1 year included alanine aminotransferase (ALT), Model for End Stage Liver Disease (MELD) score, and NLR. RESULTS: A total of 67 patients were initiated on therapy and had baseline characteristics including e-antigen (eAg) (50, 74.6%) and cirrhosis (19, 28.4%). On subgroup analysis among those with HBV-associated cirrhosis, the NLR decreased over 1 year (3.08±0.39 vs. 1.77±0.18, p<0.001) as did MELD and ALT. Among the non-cirrhotic cohort, there was no difference in NLR (1.99±0.89 vs. 2.14±1.03, p=0.134) despite a decrease in ALT. CONCLUSION: Nucleoside analog therapy in HBV cirrhosis is associated with a decrease in NLR over 1 year that tracks with changes of established indices of inflammation/global hepatic function.

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.

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.

Hepatic arterioportal fistula presenting as gastric variceal hemorrhage.

Hepatic arterioportal fistulae (APF) are abnormal communications between the hepatic artery and the portal vein. In this report, we present the second case in the literature of a symptomatic APF presenting as a gastric variceal bleeding. A 55-year-old female presented to our facility with hematemesis. Upper endoscopy revealed a bleeding gastric varix. A computed tomography scan identified a large left hepatic lobe APF between the left hepatic artery and the left portal vein. Through angiography coil embolization was performed and with resultant loss of arterial flow, the APF was decompressed. On hospital day 3, the patient developed new melena. Portovenogram was performed and a TIPS stent was deployed. The patient subsequently did well. Hepatic arterioportal fistulae can result in portal hypertension secondary to arterial blood flowing directly into the portal vein bypassing the hepatic sinusoids. Iatrogenic causes (e.g. percutaneous liver biopsy) represent more than 50% of published cases of APFs. Most APFs resolve spontaneously as they are small and peripherally located. In rare instances, when APFs are centrally located, clinical symptoms develop. There have been 30 reported cases of symptomatic intrahepatic APFs following percutaneous liver biopsy. Of those, only one case presented as a gastric variceal bleed. Digital subtraction angiography is the gold standard in the diagnosis and treatment of APFs. In addition to initial embolization, we elected to treat the patient with TIPS due to the magnitude of her bleed. Although rare, intrahepatic APF should be kept on the differential of a patient presenting with isolated gastric varices.

Validation of the Prague C & M criteria for the endoscopic grading of Barrett's esophagus by gastroenterology trainees: a multicenter study.

BACKGROUND: The Prague C & M criteria, developed for the endoscopic grading of Barrett's esophagus (BE), (C = circumferential length, M = maximal length) were previously validated among a panel of 29 expert endoscopists with a special interest in BE. Its performance among gastroenterology trainees is unknown. OBJECTIVE: To test interobserver agreement among gastroenterology trainees for the Prague C & M criteria, identification of the gastroesophageal junction (GEJ) and the diaphragmatic hiatus. DESIGN: A prospective study. SETTING: Two tertiary referral centers. PATIENTS AND INTERVENTIONS: Standardized endoscopic videos were used. MAIN OUTCOME MEASUREMENTS: Interobserver agreement. RESULTS: Eighteen high-quality videos (normal esophagus, short and long lengths of BE, equally distributed) were independently evaluated by 18 gastroenterology trainees (year 1, n = 5; year 2, n = 6; year 3, n = 7) after administration of a formal teaching module by an expert endoscopist. Overall intraclass correlation coefficients for assessment of the C and M extent of the endoscopic BE segment above the GEJ were 0.94 (95% CI, 0.89-0.98) and 0.96 (95% CI, 0.94-0.98), respectively. The overall intraclass correlation coefficients for GEJ and diaphragmatic hiatus location recognition were 0.92 (0.86-0.96) and 0.90 (0.82-0.95), respectively. The year of training did not affect interobserver agreement. LIMITATIONS: The use of videos for endoscopic evaluation. CONCLUSION: After standardized teaching, the Prague C & M criteria have high overall validity among gastroenterology trainees irrespective of the level of training for endoscopic evaluation of visualized BE lengths as well as key endoscopic landmarks.

Temporal association between increased virus-specific Th17 response and spontaneous recovery from recurrent hepatitis C in a liver transplant recipient.

BACKGROUND: Spontaneous clearance of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) is a rare occurrence. Here, we present detailed immunological analysis of an interferon naive OLT recipient receiving uninterrupted immunosuppression who cleared HCV spontaneously 2 years after transplantation. METHODS: Enzyme-linked immunospot assay analysis of peripheral T-cell interferon gamma (IFN-γ), interleukin (IL)-10, and IL-17 response to HCV core and nonstructural antigen 4 and enzyme-linked immunosorbent assay (ELISA) to collagen (Col) subtypes I, II, IV, and V were performed in the index patient at the time of viral clearance and compared with an OLT cohort with persistent viremia matched for time from OLT, immunosuppression, and histology. Enzyme-linked immunospot assay and ELISA analysis were repeated on the patient 4 years after OLT. Transcription-mediated amplification assays were used to confirm viral clearance. RESULTS: Compared with a cohort of post-OLT and nontransplanted viremic HCV patients, the index patient with HCV clearance demonstrated higher IL-17, IL-10, and lower IFN-γ response to nonstructural antigen 4 and core antigen and a higher titer of antibodies (Abs) to Col subtypes I, II, and V during clearance. On follow-up 2 years later, HCV-specific IFN-γ was increased in the index patient, with a decline in IL-17 and IL-10 response and Col I, II, and V Ab titer. CONCLUSIONS: Virus-induced activation of Th-17 cells may contribute to HCV clearance post-OLT. Maintenance of viral suppression may be facilitated by restoration of Th1 (IFN-γ) responses. Modulation of Th17 immunity deserves further attention as a therapeutic strategy in the treatment of HCV recurrence post-OLT.

Donor graft steatosis influences immunity to hepatitis C virus and allograft outcome after liver transplantation.

BACKGROUND: Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is universal, often with accelerated allograft fibrosis. Donor liver steatosis is frequently encountered and often associated with poor early postoperative outcome. The aim of this study was to test the hypothesis that allograft steatosis alters immune responses to HCV and self-antigens promoting allograft fibrosis. METHODS: Forty-eight HCV OLT recipients (OLTr) were enrolled and classified based on amount of allograft macrovesicular steatosis at time of OLT. Group 1: no steatosis (0%-5% steatosis, n=21), group 2: mild (5%-35%, n=16), and group 3: moderate (>35%, n=11). Cells secreting interleukin (IL)-17, IL-10, and interferon gamma (IFN-γ) in response to HCV antigens were enumerated by Enzyme Linked Immunospot Assay. Serum cytokines were measured by Luminex, antibodies to Collagen I, II, III, IV, and V by ELISA. RESULTS: OLTr of moderate steatotic grafts had the highest incidence of advanced fibrosis in protocol 1 year post-OLT biopsy (10.8% vs. 15.8% vs. 36.6%, r=0.157, P<0.05). OLTr from groups 2 and 3 had increased HCV-specific IL-17 (P<0.05) and IL-10 (P<0.05) with reduced IFN-γ (P<0.05) secreting cells when compared with group 1. This was associated with increase in serum IL-17, IL-10, IL-1ß, IL-6, IL-5, and decreased IFN-γ. In addition, there was development of antibodies to Collagen I, II, III and V in OLTr with increased steatosis (P<0.05). CONCLUSION: The results demonstrate that allograft steatosis influences post-OLT HCV-specific immune responses leading to an IL-17 T-helper response and activation of humoral immune responses to liver-associated self-antigens that may contribute to allograft fibrosis and poor outcome.