Faculty Bibliography

Transplanting hepatitis C viremic donor organs into hepatitis C virus (HCV)-negative recipients is becoming increasingly common; however, practices for posttransplant direct-acting antiviral (DAA) treatment vary widely. Protracted insurance authorization processes for DAA therapy often lead to treatment delays.

INTRODUCTION/BACKGROUND:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 virus, is a predominantly respiratory tract infection with the capacity to affect multiple organ systems. Abnormal liver tests, mainly transaminase elevations, have been reported in hospitalized patients. We describe a syndrome of cholangiopathy in patients recovering from severe COVID-19 characterized by marked elevation in serum alkaline phosphatase (ALP) accompanied by evidence of bile duct injury on imaging. METHODS:We conducted a retrospective study of COVID-19 patients admitted to our institution from March 1, 2020, to August 15, 2020, on whom the hepatology service was consulted for abnormal liver tests. Bile duct injury was identified by abnormal liver tests with serum ALP > 3x upper limit of normal and abnormal findings on magnetic resonance cholangiopacreatography. Clinical, laboratory, radiological, and histological findings were recorded in a Research Electronic Data Capture database. RESULTS:Twelve patients were identified, 11 men and 1 woman, with a mean age of 58 years. Mean time from COVID-19 diagnosis to diagnosis of cholangiopathy was 118 days. Peak median serum alanine aminotransferase was 661 U/L and peak median serum ALP was 1855 U/L. Marked elevations of erythrocyte sedimentation rate, C-reactive protein, and D-dimers were common. Magnetic resonance cholangiopacreatography findings included beading of intrahepatic ducts (11/12, 92%), bile duct wall thickening with enhancement (7/12, 58%), and peribiliary diffusion high signal (10/12, 83%). Liver biopsy in 4 patients showed acute and/or chronic large duct obstruction without clear bile duct loss. Progressive biliary tract damage has been demonstrated radiographically. Five patients were referred for consideration of liver transplantation after experiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitis. One patient underwent successful living donor liver transplantation. DISCUSSION/CONCLUSIONS:Cholangiopathy is a late complication of severe COVID-19 with the potential for progressive biliary injury and liver failure. Further studies are required to understand pathogenesis, natural history, and therapeutic interventions.

Chronic hepatitis B is a persistent and progressive inflammatory liver disease caused by infection with the hepatitis B virus (HBV). More than 240 million individuals are infected with HBV worldwide and hepatitis B accounts for an estimated 650 000 deaths annually. Approximately up to 30% of chronically infected patients will develop complications of HBV infection including, but not limited to, liver cirrhosis, end-stage liver disease, and hepatocellular carcinoma. Currently approved therapies have improved clinical outcomes, but have a considerable side-effect profile, elevated cost, and a finite course of treatment. This has led to a growing interest in research for new therapies. As the mechanisms for HBV replication are becoming better understood, new potential targets have been discovered, leading to the development of new therapies. In this article, we describe the promising therapies that are under evaluation, showing their mechanisms of action, effects, and stage of development.

Introduction: Nodular regenerative hyperplasia (NRH) is a known etiology of noncirrhotic portal hypertension. Cases of biopsy-proven NRH in human immunodeficiency virus (HIV)-positive patients have been described. While these patients often have normal synthetic liver function, several reports described disease progression to liver failure. Case: We here present a 26-year-old woman with history of congenital HIV on antiretroviral therapy complicated by Pneumocystis carinii pneumonia at age 14. CD4 counts have been >300 with undetectable viral load. She was referred to our Hepatology service for evaluation of splenomegaly, elevated liver tests, and thrombocytopenia. On initial presentation, she reported easy bruising and gingival bleeding, and abdominal imaging showed evidence of portal hypertension without associated cirrhosis. Upper endoscopy was significant for large esophageal varices without bleeding stigmata. Liver biopsy showed minimal fibrosis around the portal areas without significant inflammation. The lobules showed focal zones of thin hepatocyte plates on reticulin stain with adjacent areas showing mild regenerative changes. The diagnosis of NRH was made and patient was placed on propranolol for variceal bleeding prophylaxis. Two years later, the patient presented with bleeding gastric varices warranting transjugular intrahepatic portosystemic shunt. Postprocedure course was complicated by mild encephalopathy. Subsequent magnetic resonance imaging showed a 1.7 × 1.3 cm lesion suggestive of hepatocellular carcinoma (HCC). The patient was deemed to be a candidate for liver transplantation, and she is now delisted due to ongoing pregnancy. Conclusion: This report describes the first case of HCC in an HIV patient with NRH. The possible association of NRH with HCC warrants further investigation.

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common cause of liver disease in the United States. The prevalence varies dramatically when comparing individuals of different races and ethnicities. Rates are highest in Hispanic patient populations compared with non-Hispanic whites and African Americans, despite similar rates of the metabolic syndrome and risk factors. This observation remains poorly characterized; variations in genes that effect lipid metabolism may play a role. This article describes the prevalence of NAFLD in patients of different races or ethnicities, and discusses pathophysiologic mechanisms that may explain why these differences exist.

We explored potential genetic risk factors implicated in nonalcoholic fatty liver disease (NAFLD) within a Caribbean-Hispanic population in New York City. A total of 316 individuals including 40 subjects with biopsy-proven NAFLD, 24 ethnically matched non-NAFLD controls, and a 252 ethnically mixed random sampling of Bronx County, New York were analyzed. Genotype analysis was performed to determine allelic frequencies of 74 known single-nucleotide polymorphisms (SNPs) associated with NAFLD risk based on previous genome-wide association study (GWAS) and candidate gene studies. Additionally, the entire coding region of PNPLA3, a gene showing the strongest association to NAFLD was subjected to Sanger sequencing. Results suggest that both rare and common DNA variations in PNPLA3 and SAMM50 may be correlated with NAFLD in this small population study, while common DNA variations in CHUK and ERLIN1, may have a protective interaction. Common SNPs in ENPP1 and ABCC2 have suggestive association with fatty liver, but with less compelling significance. In conclusion, Hispanic patients of Caribbean ancestry may have different interactions with NAFLD genetic modifiers; therefore, further investigation with a larger sample size, into this Caribbean-Hispanic population is warranted.

Hepatitis B virus (HBV) infection remains an important cause of liver disease in the renal transplant (RT) population, potentially diminishing survival. Consequences of HBV infection after RT include progression to decompensated cirrhosis and an increased risk of hepatocellular carcinoma. Although precautions initially recommended by the Centers for Diseases Control and Prevention 30 years ago have substantially reduced HBV transmission within hemodialysis units, acute HBV outbreaks continue to be reported in patients with chronic kidney disease on maintenance hemodialysis. In addition, immigration from areas of high HBV prevalence implies that HBV-infected organs with chronic kidney disease will continue to enter the RT pool. Fortunately, the advent of oral therapy for HBV infection now reduces the risk of HBV progression post-RT.

There continues to be a high prevalence of hepatitis C virus infection in patients with chronic kidney disease (CKD) on maintenance hemodialysis, despite screening of blood products and precautions to prevent the transmission of viral hepatitis within dialysis units. In addition, an increased rate of mortality from liver disease has been observed in infected patients on long-term dialysis, despite the frequent absence of biochemical dysfunction. Hepatitis C-infected renal transplant recipients have diminished patient and graft survivals compared to uninfected controls. Treatment with interferon in renal transplant candidates has resulted in sustained viral responses that have been long lasting even after subsequent renal transplant. A major concern limiting the use of interferon following renal transplant is graft dysfunction due to rejection. Ribavirin's induction of hemolytic anemia is the major reason why it is avoided in patients with CKD. Cautious use of reduced-dose ribavirin in small studies has been promising in these patients with close monitoring of hematocrit and additional measures to enhance compensatory erythropoiesis.

Myocardial Blush Grade (MBG) is an angiographic method of assessing myocardial microcirculation and provides independent risk stratification among patients with normal TIMI 3 flow. Although the beneficial effect of abciximab on microvascular perfusion is well established, the efficacy of eptifibatide in the prevention of platelet aggregation and distal microembolization is less proven. After a pharmacologic shift by our institution towards the use of eptifibatide in patients with unstable angina presenting for PCI, we sought to evaluate our experience by retrospectively comparing the effect on myocardial perfusion between abciximab and eptifibatide following PCI in stable angina or acute coronary syndrome. Microcirculatory perfusion was reviewed in 101 consecutive patients (23 stable angina, 61 unstable angina, 17 non-q MI) undergoing PTCA/stenting. This comparison was between the last group of 51 patients who routinely received standard bolus and infusion of abciximab and the first group of 50 patients who began receiving standard bolus and infusion of eptifibatide. Baseline characteristics between the two groups were balanced, except for more patients with previous CABG in the eptifibatide group. Angiograms were evaluated by 2 blinded independent reviewers for MBG as follows: 0, no blush; 1, minimal blush; 2, moderate blush; and 3, normal blush. TIMI 3 flow was seen in 98 patients. MBG scores were not significantly different in the abciximab group (67% MBG 3; 31% MBG 2; 2.0% MBG 0 1) than in the eptifibatide group (58% MBG 3; 36% MBG 2; 6.0% MBG 0 1); p = 0.34. Patients with prior PTCA/stenting had lower MBG scores (0 2) compared to patients without prior PTCA (58% vs 31%; p = 0.03). There were significantly lower MBG scores in all patients with prior PTCA or CABG compared to patients without (55% vs 30%; p = 0.03). MBG scores significantly and inversely correlated with peak troponin I levels (r = -0.18, one-tailed p = 0.04). The similarity in myocardial perfusion between abciximab and eptifibatide suggests that both compounds are equally effective in reducing platelet aggregation and microembolization during mechanical reperfusion. Lower MBG scores in patients with prior PTCA or revascularization may be explained by irreversible microvascular dysfunction resulting from distal microembolization during the previous procedure. Lower MBG scores in patients with higher troponin I levels may reflect more frequent microemboli and microinfarcts during an ischemic event. Larger prospective studies need to be performed to validate these findings