Faculty Bibliography

This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.

Introduction: Pregnant patients with antiphospholipid syndrome (APLS) are at risk for thromboembolic complications. They are more likely to present with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. Hepatic infarction is a rare complication which can lead to hepatic rupture, fulminant liver failure and death. We present a case of a pregnant patient with known history of APS who presented with HELLP and a large liver infarction despite treatment with anticoagulation. Case Description/Methods: A 36-year-old pregnant female with history of pulmonary embolism, prothrombin gene mutation and APLS, presented to an outside hospital with right upper quadrant pain. Labs showed AST 255, ALT 274 and platelets 116. Labs also showed evidence of hemolytic anemia. Her medications included enoxaparin and aspirin. Due to concern for HELLP syndrome she underwent an emergent cesarean section. Post-delivery her labs worsened with AST 2712, ALT 2783, and platelets 43. Abdominal CT showed a large ill-defined hypodensity within segment 3 of the liver concerning for hepatic infarcts. She was treated with plasmapheresis and methylprednisolone. Given concern for impending acute liver failure she was transferred to a liver transplant center. After transfer, MRI abdomen confirmed a large infarction of the liver which involved the entirety of segments 6 and 7, as well as adjacent portions of segments 5 and 8 (Figure 1). The hepatic and portal veins appeared normal. She was observed in the ICU and over several days her abdominal pain and labs improved, with repeat showing AST 577, ALT 975 and platelets 51. Additional workup including viral hepatitis panels were normal. She was continued on enoxaparin and transitioned to warfarin for long term anticoagulation. Her hepatic panel 1 month later showed AST 39, ALT 29.
Discussion(s): Hepatic infarction is a rare complication of APS due to the dual blood supply of the liver. 93% of reported cases of hepatic infarction in pregnant women with APS were associated with HELLP syndrome. Even when patients are on anticoagulation it is important to consider hepatic infarction as a complication in patients with APS and HELLP who presents with abdominal pain, worsening lab values and hepatic failure. Multidisciplinary care with maternal-fetal medicine, hematology, and hepatology, and transfer to a transplant center should be considered given the high morbidity associated with this condition. (Figure Presented)

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

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.

INTRODUCTION: Variceal hemorrhage represents a major life threatening event in patients with decompensated cirrhosis. In comparison to esophageal varices, gastric variceal hemorrhage has a worse prognosis with higher rates of morbidity, mortality, and rebleeding. Gastric varices (GV) are currently classified based on anatomical location, but this approach fails to distinguish between different vascular compensatory mechanisms that develop in portal hypertension. Unlike esophageal variceal bleeds where endoscopic management is largely successful, endovascular approaches including transjugular intrahepatic portosystemic shunt (TIPS) and balloon-occluded retrograde transvenous obliteration (BRTO) play a more crucial role. We performed a retrospective review of patients with GV hemorrhage with and without splenorenal shunt (SRS) who underwent TIPS or BRTO to document outcomes that would help further our understanding of this disease process.
METHOD(S): A retrospective chart review of patients at NYU Langone Health with ICD-9/10 codes for GV was performed. We extracted data for the presence of GV on endoscopy (i.e. Sarin Classification) and radiographic findings from contrast-enhanced imaging to determine the presence or absence of vascular shunt. Analysis was performed on patients with GV hemorrhage who underwent either TIPS or BRTO.
RESULT(S): Thirteen patients with GV bleeds were included in our analysis; 5 with SRS and 8 without SRS shunt. We found that hepatic encephalopathy, as well as 30-day and 1-year readmissions were higher in the TIPS group, compared with patients who underwent BRTO (Table 1). Average MELD-Na score and platelets after a GV bleed trended toward improvement in patients with SRS who underwent either BRTO or TIPS (Table 2, P . 0.05) after an average of 47 days. This trend was not seen in patients without SRS.
CONCLUSION(S): Our data suggest that patients who presented with GV hemorrhage with underlying SRS trended toward improved hepatic function (based on MELD-Na and platelets) 2 weeks after intervention compared to patients without SRS. We propose that mapping of gastrointestinal vas-culature early in the course of GV hemorrhage has a role in determining prognosis and treatment. In the presence of a splenorenal shunt, BRTO should be highly considered if technically feasible irrespective of Sarin classification. Further understanding of the vascular anatomy and pathogenesis of shunt formation may assist in future management of GV hemorrhage

Hepatitis E virus (HEV), of the family Herpeviridae, is a virus which infects nearly 20 million people per year throughout the world. HEV is most commonly transmitted via the fecal-oral route and has long been described as a virus which afflicts only those in resource-poor countries. However, HEV has been detected in numerous animal carriers, various food sources, and even in human blood products in resource-rich regions of the world. HEV is of importance in the transplant patient population, for its ability to cause chronic viral infection in these patients can lead to graft loss and cirrhosis. In this review, we discuss the current knowledge of HEV as it pertains to the liver transplant patient population and discuss diagnosis and treatment of this infection.

Although hepatitis B virus (HBV) reactivation has been reported in hepatitis C patients who received interferon therapy, rare cases of HBV reactivation occur in the context of direct-acting antiviral (DAA) agent therapy for treatment of hepatitis C virus (HCV) infection. Recent studies observed that the reactivations were predominantly in hepatitis B surface antigen (HBsAg) positive patients, but reactivation can rarely occur in patients who are HBsAg negative and hepatitis B core antibody (HBcAb) positive. The severity of an HBV flare varies. In some cases, severe liver injury or fulminant hepatic failure may occur. HBV reactivation may occur regardless of HCV genotype and type of DAA regimens. The onset of HBV reactivation can range from 4 to 48 weeks after initiating DAA therapy. These patients may have undetectable levels of HBV deoxyribonucleic acid (DNA) prior to DAA treatment. Pre-emptive antiviral therapy for HBV should be considered in HBsAg-positive patients with high levels of viremia who are not receiving HBV treatment. If HBV DNA viral load is less than the guideline criteria for HBV treatment, one should consider pre-emptive HBV antiviral versus HBV DNA monitoring during DAA therapy. For patients who are HBsAg negative but HBcAb positive, close monitoring of serum alanine aminotransferase (ALT) levels during/post-treatment is highly recommended. The current review summarizes the recommendations of different society guidelines and discusses the appropriate management strategies in various patient profiles.

Learning Objective #1: Recognize protein malnutrition and cirrhosis as potential complications of biliopancreatic diversion with duodenal switch (BPD-DS). CASE: A 37-year-old man with a history of severe obesity status post laparoscopic BPD-DS presented with diffuse swelling. The patient was admitted six months previously for severe protein-calorie malnutrition requiring initiation of total parental nutrition (TPN). During that admission, he was found to have elevated liver enzymes and ascites. Workup for autoimmune, infectious, and hereditary etiologies of cirrhosis was unremarkable; a liver biopsy showed steatosis without evidence of alcoholic hepatitis or cirrhosis. He now complained of abdominal distension and lower extremity edema that had progressed over several weeks, requiring multiple large-volume paracenteses. He endorsed past heavy alcohol use, but denied recent exposure. On physical examination, he was grossly anasarcic with a distended abdomen and appreciable fluid wave, 3+ pitting edema to the hips, and scrotal edema. His admission Model for End-Stage Liver Disease (MELD) score was 14. Repeat biopsy demonstrated prominent portal fibrosis and focal nodularity indicative of advanced-stage cirrhosis, with an interval decrease in steatosis from his previous biopsy. The rapidity of fibrosis and reversal of fatty change suggested the etiology was his bariatric surgery. He was treated with intravenous diuretics with improvement in his anasarca. At one-month follow-up, he had a stable MELD and diuretic-responsive ascites. He has been approved for liver transplant evaluation, with plans to reverse his bypass prior to transplant. IMPACT/DISCUSSION: BPD-DS is classically associated with improvement in hepatic function due to reversal of nonalcoholic steatohepatitis (NASH). However, case reports of hepatic failure following BPD-DS do exist. Clinicians should be alert to this complication and monitor post-surgical patients closely for signs of hepatic decompensation.
Conclusion(s): BPD-DS is the most effective bariatric surgery technique for sustained weight loss in the super-obese (BMI > 50 kg/m, ²). Nevertheless its widespread adoption has been limited by technical complexity and concerns over vitamin deficiencies and malnutrition. Loss of hepatotrophic factors due to protein malnutrition has been advanced as a mechanism to explain its contribution to the development of cirrhosis. With the increasing prevalence of obesity and the documented effectiveness of BPD-DS for sustained weight loss this surgery will likely become more commonplace. Awareness of this potential complication and vigilance to ensure adequate protein intake, with aggressive intervention-including the initiation of TPN-to preserve nutritional status is paramount to effective management of BPD-DS patients post-operatively

Spontaneous bacterial peritonitis (SBP) is a potentially life-threatening complication of ascites diagnosed by paracentesis. We determined predictors of SBP to facilitate patient selection. The 301 paracenteses performed in 119 patients (51 women, 68 men) from July to November 2015 were retrospectively reviewed. Presentation, lab data, depth of the deepest ascites pocket on ultrasound, total volume of ascites removed, absolute neutrophil count, and complications were studied. Of 301 paracenteses, 16 (5%) diagnosed SBP. On univariate analysis, SBP was associated negatively with history of cirrhosis and positively with history of cancer, abdominal pain, greater depth of the fluid pocket, prior SBP, and leukocytosis. Multivariate analysis using these variables to predict SBP was significant (P < 0.0001); only depth of the largest fluid pocket (P = 0.008) and complaint of abdominal pain (P = 0.006) were independent predictors. Receiver-operator curve analysis showed that a 5-cm cutoff of pocket depth yielded 100% sensitivity and 32% specificity. Two (0.1%) hemorrhagic complications occurred, one causing death and one necessitating laparotomy. In conclusion, deeper ascites pockets and abdominal pain are independent predictors of SBP. When the largest ascites pocket is <5 cm, the probability of SBP is nearly negligible. Given the potential for hemorrhagic complications, findings may help triage patients for paracentesis.