New-onset heart failure is a frequent complication after orthotopic liver transplantation (OLT). Left atrial enlargement (LAE) may be a sign of occult left heart disease. Our primary objective was to determine invasive hemodynamic and clinical predictors of LAE and then investigate its effect on post-transplant outcomes. Of 609 subjects who received OLT between January 1, 2010, and October 1, 2018, 145 who underwent preoperative right-sided cardiac catheterization and transthoracic echocardiography were included. Seventy-eight subjects (54%) had pretransplant LAE. Those with LAE had significantly lower systemic vascular resistance with higher cardiac and stroke volume index (61.0 vs 51.7 ml/m(2); p < 0.001), but there was no difference in pulmonary artery wedge pressure. There was a linear relation between left atrial volume index and stroke volume index (R-2 = 0.490, p < 0.001), but not pulmonary artery wedge pressure. The presence of severe LAE was associated with a reduced likelihood (hazard ratio = 0.26, p = 0.033) of reaching the composite end point of new-onset systolic heart failure, heart failure hospitalization, or heart failure death within 12 months post-transplant. There was also a significant reduction in LAE after transplantation (p = 0.013). In conclusion, LAE was common in OLT recipients and was more closely associated with stroke volume than left heart filling pressures. The presence of LAE was associated with a reduced likelihood of reaching composite outcomes and tended to regress after transplant. (C) 2022 Elsevier Inc. All rights reserved.

Doxycycline (DOX) is a tetracycline antibiotic that is prescribed for treating a variety of infections involving the skin, respiratory tract, and urogenital system. Adversely, esophageal mucosal injury due to DOX is well described; however, gastric mucosal injury is less commonly reported and may result in severe gastrointestinal hemorrhage and occasionally, perforation. In most reported cases of DOX-induced gastric lesions, patients are symptomatic upon presentation leading to endoscopic evaluation and diagnosis with biopsy. However, severe gastric insults may go unrecognized in rare cases of asymptomatic patients, increasing the risk of mortality.

Right heart catheterizations (RHC) are often performed prior to liver transplantation (LT) to rule out significant portopulmonary hypertension. Many times, elevated left heart filling pressures are found consistent with Heart Failure with Preserved Ejection Fraction (HFpEF). Pre-transplant HFpEF has

INTRODUCTION: Hepatic artery pseudoaneurysm is rarely seen as a result of aortic dissection. Life-threatening gastrointestinal bleeding requiring urgent therapeutic intervention can occur as a complication of pseudoaneurysm formation. CASE DESCRIPTION/METHODS: A 66 year-old male with a history of a type A aortic dissection which was repaired four years prior to presentation was evaluated in the the emergency department for multiple episodes of melena. He was previously treated at another institution for a biliary stricture with a metal stent. On physical exam, he was hemodynamically stable and had scleral icterus. Initial labs revealed hemoglobin 8.7 gm/dl, platelets 240 K/CUMM, aspartate aminotransferase 192 U/L, alanine aminotransferase 161 U/L, alkaline phosphatase 380 U/L, total bilirubin 21 mg/dl, and INR 1.6. ERCP revealed a patent stent in the common bile duct and no evidence of hemobilia. Subsequent esophagogastroduodenoscopy revealed three columns of large, non-bleeding esophageal varices with stigmata of recent bleeding. Endoscopic band ligation was performed. After completion of the procedure, abdominal aortic angiography revealed interval enlargement of a fusiform aneurysm of a false lumen of the common hepatic artery as well as resultant central compression of the adjacent portal venous system and intrahepatic bile ducts. The patient then had an episode of hypotension and tachycardia and required transfusion of four units of red blood cells. Interventional radiology emergently performed catheter-directed embolization of the common and right hepatic artery pseudoaneurysms, and the patient did not experience any further episodes of gastrointestinal bleeding. DISCUSSION: Our evaluation of this clinical case revealed two interesting points. In retrospect, the biliary stricture was the result of direct compression of the bile duct by the pseudoaneurysm, which may not have been appreciated by the endoscopist performing the initial procedure. Second, the etiology of this patient's portal hypertension was also a direct result of compression of the portal vein by the aneurysm. On his initial presentation, we did not make these associations, but further cross-sectional imaging led us to the correct answer. The patient benefited from early involvement of vascular interventional radiology, who were able to provide a therapeutic intervention via catheter-directed coil embolization. In cases where interventional radiology is unable to intervene, surgical management with vascular surgery may be necessary.Figure 1.: Aneurysmal dilation of the false lumen of the common hepatic artery (1.9 cm in diameter) causing extrinsic compression of the adjacent biliary tract and portal venous system.

Idiopathic adulthood ductopenia (IAD) is a chronic small duct cholestatic biliary disease that is characterized by the loss of interlobular bile ducts. It is diagnosed when there is biochemical evidence of cholestatic liver disease, ductopenia on liver biopsy, and no other identifiable cause of cholestasis. We present a patient with 10 days of progressive abdominal pain, jaundice, and worsening liver function tests who advanced to fulminant liver failure with no apparent underlying cause. He was found to have cirrhosis, with biopsy demonstrative of ductopenia, consistent with idiopathic adulthood ductopenia, which is a rare etiology of cirrhosis but should be considered when the typical workup yields no answer.

BACKGROUND & AIMS: Treatment options are limited for patients with hepatitis C (HCV) infection with treatment failure after sofosbuvir plus an NS5A inhibitor. There are some data for the efficacy of glecaprevir/pibrentasvir (G/P) in these patients. We performed a randomized trial of the safety and efficacy of 12 and 16 weeks of G/P, with or without ribavirin, in patients with HCV genotype 1 infection with treatment failure after sofosbuvir and an NS5A inhibitor. METHODS: We performed a phase 3b, open-label study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor. Patients without cirrhosis were randomly assigned to groups that received G/P for 12 weeks (n = 78, group A) or 16 weeks (n = 49, group B). Patients with compensated cirrhosis were randomly assigned to groups that received G/P and ribavirin for 12 weeks (n = 21, group C) or G/P for 16 weeks (n = 29, group D). The primary end point was a sustained virologic response 12 weeks after treatment. Samples collected at baseline and at time of treatment failure were sequenced for resistance-associated substitutions in NS3 and NS5A. RESULTS: Of the 177 patients in the 4 groups, 81% were men, 79% had HCV genotype 1a infection, and 44% were black. Proportions of patients with sustained virologic response 12 weeks after treatment in groups A, B, C, and D were 90%, 94%, 86%, and 97%, respectively. The treatment failed in 13 (7.3%) patients with HCV genotype 1a infection, 6 (7.9%) in group A, 3 (6.1%) in group B, 3 (6.1%) in group C (6.1%), and 1 (3.4%) in group D. Most patients had baseline resistance-associated substitutions in NS5A. Treatment-emergent resistance-associated substitutions in NS3 and NS5A were observed in 9 and 10 patients with treatment failure, respectively. G/P was well tolerated. Ribavirin increased adverse events but did not increase efficacy. CONCLUSIONS: In a randomized study of patients with chronic HCV genotype 1 infection who received previous treatment with sofosbuvir plus an NS5A inhibitor, 16 weeks treatment with G/P produced sustained virologic response 12 weeks after treatment in >90% of patients, including those with compensated cirrhosis.

Esophagitis dissecans superficialis is a rare clinical endoscopic finding with poorly understood pathogenesis and ill-defined management. A 71-year-old man is admitted with progressively worsening dysphagia and odynophagia with endoscopic features most consistent with severe esophagitis dissecans superficialis. Extensive workup did not reveal an etiology, and he was subsequently treated with steroids, resulting in rapid, almost complete clinical and endoscopic recovery.

INTRODUCTION: While liver transplantation itself is an invasive and specialized procedure, often with an arduous medical course preceding the surgery; post-transplant life is rarely without complication. Permanent immune suppression introduces its own cohort of increased risks including unique infections, malignancies, and side effects of immunosuppressive or prophylactic therapies. Special consideration should be given to these patients when potential complications arise. CASE DESCRIPTION/METHODS: A 51-year-old male with a an orthotopic liver transplant 6 years prior due to NASH cirrhosis presents with rapid significant weight loss and worsening abdominal pain. MRI revealed development of T2 hyper-intense peripherally enhancing lesions throughout the liver, as well as massive splenomegaly with possible areas of splenic infarct. Transjugular liver biopsy was expedited and ultimately revealed epitheliod hemangioendothelioma (EHE). Initial infectious work up was unrevealing outside of EBV viral load returning weakly positive; however, given possible association with EHE with EBV, treatment was initiated with valgancyclovir. Immunosuppression was also adjusted from tacrolimus to everolimus given anti-neoplastic properties of mTOR inhibitors over calcineurin inhibitors. He was started on pazopanib as an outpatient given anecdotal evidence of VEGF inhibitors in treating EHE, however, treatment was complicated shortly thereafter by syncope and refractory TTP, and palliative care was ultimately pursued. DISCUSSION: Epithelioid hemangioendothelioma is a rare vascular tumor originating from mesenchymal cells. While risk of malignancy is increased post transplant due to immunomodulators, post transplant Hepatic EHE remains an exceedingly rare diagnosis. EHE is considered to have intermediate behavior between hemangioma’s and hemangiosarcoma’s however HEHE is metastatic at diagnosis in 50% of diagnoses. Common presenting symptoms include vague abdominal pain, weight loss, and weakness/fatigue. Histopathological examination via biopsy is the gold standard of diagnosis and positivity of factor VIII-dependent antigen, CD-34, and CD-31 are important. Course is variable however prognosis is poor and there is no standardized management plan. VEGF inhibitors including Bevacizumab and Pazopanib have been a target of therapy given histologic positivity for target receptors, however results have been mixed to date.

Therapy for veno-occlusive disease of the liver (VOD) occurring after bone marrow transplantation should be directed at those with moderate or severe disease who will not recover on their own. Thrombolytic therapy may have a role in severe VOD as long as there is no renal or lung impairment. However, the risk of bleeding complications, including the risk of cerebral hemorrhage, must be considered in these patients. Defibrotide has shown promise for treatment of severe VOD but is not yet widely available in the United States. Therapy directed at reducing portal hypertension such as transjugular intrahepatic portosystemic shunts helps reduce ascites but has no effect on mortality. Liver transplantation has been reported but should be considered only in patients with severe liver failure who would have a good outcome in the absence of liver disease or have undergone bone marrow transplantation for benign disease. The most important advances in VOD has been in the prevention of this syndrome by recognizing the risk factors for it and changes in conditioning regimens before bone marrow transplantation.

1Division of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA. 2Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA. 3Division of Radiology, Medical University of South Carolina, Charleston, South Carolina, USA.

Objective Judicious selection of potential liver transplant candidates and close monitoring of progress are essential to successful outcomes. Pretransplant psychosocial evaluations are the norm, but the relationship between psychosocial (and neurocognitive status) and longer term medical outcomes is understudied. This exploratory study sought to examine the relationship between objective measures of pretransplant psychosocial and neurocognitive status and service utilization, transplant status, and all-cause mortality. Methods This retrospective chart review examined outcomes among 108 psychiatric, high-risk liver transplant candidates up to four years following initial evaluation. Predictor variables of outcomes included demographic, medical, neurocognitive, psychological, and mental health treatment variables. Results Transplant status and neurocognitive functioning were independently associated with all-cause mortality. None of the other variables were associated with outcomes. Conclusions Better neurocognitive functioning in high-risk liver transplant candidates may allow for greater involvement in medical care and/or compliance with treatment recommendations. More aggressive assessment and management of neurocognitive dysfunction may improve outcomes. Objective measures identified significant psychopathology typical of liver transplant candidates but were not associated with outcomes; engagement in specialized mental health care may have attenuated this relationship. Further study is needed to better understand the relationship between psychosocial functioning and outcomes.

BACKGROUND:Blood phosphatidylethanol (PEth) is a promising biomarker of alcohol consumption. This study was conducted to evaluate its performance in patients with liver disease.METHODS:This study included 222 patients with liver disease. Patient-reported alcohol use was obtained as a reference standard, and PEth was measured by tandem mass spectrometry. Receiver operating characteristic (ROC) and contingency table analyses were used to assess the performance of PEth in detecting any drinking and averaging 4 or more drinks daily in the past 30 days.RESULTS:At the limit of quantitation (20 ng/ml), PEth was 73% sensitive (95% confidence interval [CI] 65 to 80) and 96% specific (95% CI 92 to 100) for any drinking in the past month. Subjects who drank but had a negative PEth result were mainly light drinkers. Subjects who reported 30-day abstinence but with quantifiable PEth either reported heavy drinking within the past 6 weeks or had data that suggested underreported drinking. At the optimal cutoff concentration of 80 ng/ml, PEth was 91% sensitive (95% CI 82 to 100) and 77% specific (95% CI 70 to 83) for averaging at least 4 drinks daily.CONCLUSIONS:PEth is a useful test for detecting alcohol use in patients with liver disease, but cutoff concentrations for heavy drinking will result in misclassification of some moderate to heavy drinkers.

AIMS:Hair ethyl glucuronide (EtG) is a promising biomarker of moderate-to-heavy alcohol consumption and may have utility in detecting and monitoring alcohol use in clinical populations where alcohol use is of particular importance. This study evaluated the relationship between hair EtG and drinking in patients with liver disease.METHODS:The subjects (n = 200) were patients with liver disease who presented for care at a university medical center. Alcohol use during the 3 months preceding participation in the study was assessed, and a sample of hair was obtained for EtG testing. Classification of drinking status (any drinking or averaging at least 28 g per day) by hair EtG was evaluated, as well as the effects of liver disease severity and demographic and hair care factors.RESULTS:The area under the receiver operating characteristic curve for detecting an average of 28 g or more per day during the prior 90 days was 0.93. The corresponding sensitivity and specificity of hair EtG ≥8 pg/mg for averaging at least 28 g of ethanol per day were 92 and 87%, respectively. Cirrhosis and gender may have a modest influence on the relationship between drinking and hair EtG.CONCLUSION:Hair EtG was highly accurate in differentiating subjects with liver disease averaging at least 28 g of ethanol per day from abstainers and lighter drinkers.

Context Little systematic research has been conducted to understand pain among persons with end-stage liver disease, especially among liver transplant candidates. Appropriate pain assessment and management are important areas of consideration as treatment options are limited. Objective To describe the nature of chronic pain in patients with end-stage liver disease, the extent to which pain affects daily level of functioning, and the variety and effectiveness of current treatments. Design Retrospective chart review. Setting Academic medical center in the Southeastern United States. Patients Data were collected from 108 consecutive adult liver transplant candidates. Results Most (77%) reported having experienced moderate levels of bodily pain within the past 24 hours. Patients with only alcoholic cirrhosis reported less pain than patients with cirrhosis due to other causes (alcoholism and hepatitis C, nonalcoholic steatohepatitis, only hepatitis C). Pain interfered significantly across all 10 functional domains assessed. Although 90% reported being prescribed a variety of analgesic agents (most commonly short-acting opioids), patients reported experiencing only 33% pain relief. Conclusions Pain is a significant problem among liver transplant candidates, and current pain treatments are perceived to be relatively ineffective. Increased understanding is needed to safely and effectively evaluate and treat such medically complicated patients.