bluuebunny/crossref_metadata_2025_split huggingface dataset:
2455 Nivolumab-Induced Immune Cholestatic Hepatitis in a Liver Transplant Recipient
Authors: Anugwom Chimaobi , Wongjarupong Nicha , Leventhal Thomas M. 
Published: October 2019

INTRODUCTION:
Cancer treatment has taken giant strides in recent years with the advent of immunotherapy including check-point inhibitors. We present a case of cholestatic hepatitis following treatment of recurrent HCC with Nivolumab.

CASE DESCRIPTION/METHODS:
A 62-year-old male with a history of alcoholic cirrhosis and hepatocellular carcinoma (HCC), was seen 5 years after liver transplantation. Approximately one year after transplant, he developed metastatic HCC in his lung and anterior abdominal wall with progression of tumor burden after several chemotherapy regimens. Two months prior to admission, he began palliative Nivolumab. He developed elevated serum alkaline phosphatase (ALP), aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin; so, he was hospitalized. Admission labs showed ALP of 813, ALT of 1265, AST of 696 and bilirubin of 8.3. Investigations were negative for viral or autoimmune hepatitis. Acute cellular rejection was unlikely given time from transplant and stable tacrolimus trough levels. Given the concern for Nivolumab-induced liver injury, high dose intravenous steroids at 2 mg/kg daily was started with temporary improvement in his liver tests. A trans-jugular liver biopsy confirmed the diagnosis of immune-induced liver injury due to Nivolumab. By hospital day 7, his liver tests continued to rise precipitously (Figure 1). Ultimately, he developed massive hematemesis and hemodynamic instability, necessitating intubation and intensive care unit (ICU) admission. An emergent upper endoscopy showed severe esophagitis with denudation of the esophageal mucosa (Figure 2) and gastric blood and clot precluding completion of the endoscopy. Steroids were increased to 4 mg/kg, for worsening hepatitis. However, his family decided to pursue comfort cares considering his rapid decline and metastatic cancer. He expired within minutes of implementing comfort care measures.

DISCUSSION:
We believe that Nivolumab caused a cholestatic liver injury in our patient. Nivolumab-induced liver injury has been previously reported but with paucity of data in transplants recipients or cholestatic pattern of injury. The difference in clinical, biochemical and histopathologic features may suggest subtle differences in strategies for management of Nivolumab-induced liver injury. Further prospective studies are needed to understand the pathophysiology and management of this type of liver injury as well as the benefits of PD-1 inhibitors in liver transplant recipients.
2456 Fibrosing Cholestatic Hepatitis Following Transplantation of a Hepatits C Virus Positive Donor Liver
Authors: Abdulhamid Ahmed , Jafri Syed-Mohammed 
Published: October 2019

INTRODUCTION:
Fibrosing cholestatic hepatitis (FSC) is a rare disorder, typically seen in immunosuppressed patients with a history of chronic hepatitis B and C infections. We present a case of a 67-year-old recipient of a hepatitis C virus positive donor liver with subsequent development of FSC.

CASE DESCRIPTION/METHODS:
We present a case of a 67 year-old gentleman, with a past medical history of HCV cirrhosis and multifocal hepatocellular carcinoma (HCC), who underwent orthotopic liver transplantation (OLT). Prior to transplantation, the patient was treated for HCV with Vosevi/ribavirin with sustained viral response. His course was complicated by multifocal HCC, for which he received treatments with DEB-TACE and Y90. He subsequently underwent OLT with a HCV positive (RNA quantitative positive) donor liver. The patient's post-operative course was complicated by marked elevation in AST and ALT (1610 and 647 respectively) and HCV RNA quantitative (1.5 million), concerning for fibrosing cholestatic hepatitis. A liver biopsy was performed and showed both mild acute cellular rejection (ACR) and cholestasis. The patient was treated with Epclusa for HCV and immunosuppression (prednisone, tacrolimus) for ACR with improvement in his liver enzymes.

DISCUSSION:
Fibrosing cholestatic hepatitis (FSC) is a rare disorder, typically seen in immunosuppressed patients with a history of chronic hepatitis B and C infections. It is particularly seen in patients following transplantation, namely recipients of donor liver and kidneys. Patients with FSC present with a number of symptoms including malaise, fatigue, jaundice, abdominal pain and progressive liver failure, which may occur over a period of weeks to months. The pathophysiology is related to direct cytotoxic effect of viral antigens on hepatocytes in the setting of immunosuppression. High viral titers and elevated liver enzymes in an immunosuppressed patient should raise concern for FSC. The diagnosis is established with a liver biopsy, which typically reveals hepatocyte ballooning, bridging fibrosis, pericellular and sinusoidal fibrosis as well as intracellular and canalicular cholestasis. This ultimately leads to acute liver failure and may result in rapid graft loss. Given the high rates of mortality associated with FSC, prompt diagnosis and treatment with direct-acting antiviral regimens may be effective in treatment, even in severe cases.
2464 A Case of Acute Icteric Hepatitis Caused by Epstein Barr Virus in an Immunocompetent Adult
Authors: Sieloff Martin , Tariq Tooba , Nguyen Minh 
Published: October 2019

INTRODUCTION:
Epstein Barr Virus (EBV) is a viral infection that can often remain asymptomatic but is also a major cause of infectious mononucleosis. Patients often present with sore throat, fever, lymphadenopathy and can develop splenomegaly. EBV-associated hepatitis is uncommon and cases with clinical jaundice are rare.

CASE DESCRIPTION/METHODS:
A 23-year old male without significant past medical history presented with one week of flu-like symptoms and acute onset of a generalized pruritic rash, right upper quadrant (RUQ) abdominal pain and dizziness. He denied any recent alcohol consumption, IV drug use or new medication initiation. On arrival to the emergency department the patient was afebrile with a blood pressure 130/84. Physical exam revealed scleral icterus and cutaneous jaundice, a diffuse macular rash was across his face, chest and arms and he had tender hepatomegaly. He was alert and oriented without confusion. Laboratory examination revealed a leukocytosis of 11.8, a total bilirubin of 15.8, direct bilirubin of 13.3, an INR of 1.2, ammonia of 26, an alkaline phosphatase of 499, and an ALT of 615 with AST of 405 signifying acute hepatitis. A urine drug screen was negative. A RUQ ultrasound with doppler showed no evidence of Budd-Chiari or portal vein thrombus; fatty infiltration of the liver was seen with no evidence of cholelithiasis or common bile duct obstruction. Hepatitis A, B and C viral screen was negative, acetaminophen level was within normal limits, HIV antibody test was negative, herpes virus IgM negative, CMV IgM negative, anti-smooth muscle antibody negative for autoimmune hepatitis. Ceruloplasmin and alpha-1 antitrypsin levels were not suggestive of Wilson's disease or alpha-1 antitrypsin deficiency. A peripheral smear showed reactive lymphocytosis. There was significant elevation in EBV IgM and heterophile antibody suggesting systemic Epstein Barr viral infection as the cause of acute hepatitis. Over the next 3 days, his liver enzymes began trending down slowly with symptomatic management and he was determined stable for discharge with plans for 2 and 4 week follow ups to monitor for resolving acute EBV hepatitis.

DISCUSSION:
It is important to remember that, although rare, EBV can cause hepatitis with diffuse jaundice and significant hyperbilirubinemia along with AST and ALT levels over 10 times the upper limit of normal. Such presentation could easily be misconstrued as an alternative diagnosis and patient safety compromised with unnecessary treatment.
2467 Recognizing Macrobid as a Potential Cause for Major Liver Injury
Authors: Khan Faizan , Davis Michael , Khan Nasir 
Published: October 2019

INTRODUCTION:
Nitrofurantoin is one of the most commonly prescribed antibiotics for urinary tract infections. It is also one of the most common medications known to cause drug-induced liver injury (DILI). Nitrofurantoin can cause acute or chronic liver injury. Acute liver injury occurs within a few weeks of nitrofurantoin use and resolves quickly after discontinuation. Chronic liver injury typically presents months or years after use of nitrofurantoin and can also present as an autoimmune type reaction. This case demonstrates the need to have high suspicion for DILI when patients present with elevated liver enzymes with recent use of nitrofurantoin.

CASE DESCRIPTION/METHODS:
The patient is a 56 year old female with a past medical history of recurrent urinary tract infections including ESBL who presented with abdominal pain, diarrhea, and nausea for one month. Prior to symptoms onset, she had developed burning and odor in her urine and was treated with nitrofurantoin for 14 days. Urinary symptoms resolved after antibiotic completion. Two weeks later, the patient began to develop worsening abdominal pain that was accompanied by diarrhea and subjective fevers and chills. On presentation, the patient's vitals were found to be: 98.5F, HR 107, 156/74, and saturating well on room air. On labs, she was found to have elevated alkaline phosphatase of 200 U/L, ALT 1014 U/L, AST 2011 U/L, Total Bilirubin 1.0 mg/dL, Lipase 59 U/L, negative alcohol level, negative acetaminophen level, and negative viral hepatitis panel. CT Abdomen and Pelvis showed hepatic steatosis but no acute processes. Secondary workup for liver injury was largely negative except an ANA titer of 1:320. The patient was treated supportively and had a gradual decrease in her liver enzymes over the course of three days.

DISCUSSION:
DILI can be a difficult diagnosis to make because it is a diagnosis of exclusion. In our case, the patient experienced marked elevations in her liver enzymes that resolved with only supportive care. Her workup was negative and the only identifiable etiology of her acute liver injury was her nitrofurantoin use. Additionally, our patient was seen to have features of drug-induced autoimmune hepatitis with her ANA elevation suggesting a component of chronic liver injury. She had been treated with Nitrofurantoin in past infections as well. Since Nitrofurantoin can cause sometimes severe liver damage, the indication for its use should be evidence-based, and signs/symptoms of liver injury should lead to prompt cessation of therapy.
2469 Extracapsular Hepatocellular Adenoma: A Diagnostic Dilemma
Authors: Comba Isin Y. , Henriquez Richard , Kumar Sundeep , Srinivasamurthy Ruthvik , Wallis-Crespo Maria , Karasik Olga , Bhatia Lakhinder 
Published: October 2019

INTRODUCTION:
Hepatocellular adenoma (HCA) is a benign tumor of the liver and almost always located intracapsular. Bleeding (25%), and malignant transformation (5%) can complicate the disease course if left untreated. Herein, we present a case of extracapsular HCA of ectopic liver in the omentum complicated with intraperitoneal hemorrhage.

CASE DESCRIPTION/METHODS:
A 43-year-old lady with no past medical history presented to emergency department with two-day history of left shoulder pain and epigastric discomfort. Her only medication was an oral contraceptive pill (OCP). On physical exam, the patient had persistent sinus tachycardia, and epigastric tenderness. Initial labs were unremarkable except for mildly elevated AST at 58 IU/L (10-37). CT of the abdomen with IV contrast showed a heterogeneously enhancing mass likely arising from the anterior wall of the stomach. T2-weighted MRI abdomen demonstrated a hypoenhancing mass measuring 4 × 7 × 8 cm with adjacent hemorrhage (Figure 1). Exploratory laparotomy revealed an infarcted, hemorrhagic mass between the fundus of the stomach, spleen, and diaphragm with a large amount of clots and free blood occupying the greater curvature. The mass was separated from surrounding viscera however, slightly attached to the diaphragm. The mass was removed with the completely resolved tachycardia and epigastric pain postoperatively. Initially, the lesion was thought to be an accessory spleen based on location and gross examination. Microscopically, an infarcted, hemorrhagic mass composed of cords of degenerated epithelioid cells with vacuolated cytoplasm was surrounded by reactive fibro- and myofibroblastic tissue. Epithelioid cells were diffusely stained for HerPar-1 (hepatocyte origin), and CK AE1/AE3 (Figure 2). These findings were consistent with HCA.

DISCUSSION:
HCA is an overlooked diagnosis and can result in serious complications if unrecognized. Among the well-known risk factors of HCA are OCPs or anabolic steroids, pregnancy, and steatohepatitis. The prevalence of these lesions has been rising parallel to increasing use of OCP and abdominal imaging. In females, lesions <5 cm with no associated symptoms or complications can be managed conservatively by terminating OCP use, and surveillance. Our patient presented with acute left shoulder pain which was likely due to phrenic nerve irritation by bleeding (Kehr's sign). To best of our knowledge, there are only three cases of extracapsular HCA reported in the English literature.
2473 The Mystery of the “Vanishing” Bile Ducts
Authors: Shah Apurva , Leung Galen , Sun Edward , Mockler Daniel 
Published: October 2019

INTRODUCTION:
The etiologies of cholestatic liver disease is extensive, including immunological, ischemic, infectious, metabolic, and toxic causes. We present a rare case of a patient who was diagnosed with idiopathic vanishing bile duct syndrome (VBDS) after a thorough work-up.

CASE DESCRIPTION/METHODS:
A 61-year-old female with a history of hypertension, type II diabetes mellitus, congestive heart failure, and end stage renal disease presented with generalized pruritus and jaundice. Laboratory tests revealed a total bilirubin 10.5 mg/dL, AST 27 IU/L, ALT 27 IU/L, alkaline phosphatase 596 IU/L. Further workup was negative for viral hepatitis, autoimmune hepatitis, hemochromatosis, alpha-1 antitrypsin deficiency, and Wilson's Disease. An MRCP showed hepatosplenomegaly without ductal dilatation, and upper endoscopy with ultrasound revealed a normal biliary duct without evidence of obstruction. Pathology from fine needle biopsy was significant for chronic cholestatic changes with ductopenia (43% duct loss), obliterative portal venopathy, and congestive hepatopathy. Without an identifiable cause, these findings are most consistent with idiopathic VBDS. The patient was referred for liver transplant evaluation due to concern for progression to cirrhosis.

DISCUSSION:
VBDS is a rare hepatic condition characterized by progressive loss of the interlobular and septal bile ducts resulting in cholestasis and potentially biliary cirrhosis and liver failure. The cause of bile duct destruction is poorly understood but likely results from biliary apoptosis due to immunologic, ischemic, infectious, metabolic, and toxic assaults.
1
Approximately 1% of cases classify as idiopathic VBDS, which likely comprises of several disease processes with atypical features, such as late-onset non-syndromic paucity of intrahepatic bile ducts, small-duct primary sclerosing cholangitis without large duct involvement, non-suppurative viral cholangitis, and autoimmune cholangitis without typical autoantibodies.
2
The disease course is unpredictable, ranging from benign to fatal or necessitating transplantation.2 Treatment of VBDS includes drug withdrawal, choleretic agents, and immunosuppression. The uncertain etiology of idiopathic VBDS precludes a causative treatment. Liver transplantation has been the only successful treatment.
2
2476 Fibrinogen-Positive Ground Glass Hepatocytes in a Patient With Ulcerative Colitis
Authors: Koprowski Steven T. , Ando Yumi , Jou Janice 
Published: October 2019

INTRODUCTION:
Ground-glass hepatocyte cytoplasmic inclusions (eosinophilic, glassy cytoplasmic changes) carry a unique differential diagnosis with significant diagnostic implications. This cytoplasmic change is thought to occur from accumulation of metabolic products including glycogen, fibrinogen, or viral proteins. Few cases of patients with ground-glass, fibrinogen-positive inclusions have been observed and are thought to occur from acute states of metabolic stress.

CASE DESCRIPTION/METHODS:
A 64-year-old male with history of poorly controlled ulcerative colitis presented with diffuse abdominal pain, weight loss, and two months of frequent bloody bowel movements. On arrival, he was afebrile without abnormal vital signs. His appearance was non-toxic but malnourished. Abdominal exam produced diffuse tenderness but no evidence of peritonitis. Labs were notable for AST 233 U/L, ALT 486 U/L, and Alk phos 140 U/L (normal 56-119 U/L). He failed trial of medical therapy and required total abdominal colectomy. His aminotransferase levels during this time continued to worsen without explanation (peak AST 710 U/L and ALT 1145 U/L). Serum infectious disease workup including Hepatitis C antibody, HIV Antibody/Antigen screen, Hepatitis B core antibody and surface antigen, Hepatitis E IgM antibody, HSV-1 and 2 PCR, and Varicella-zoster PCR were all negative. Serum IgG, IgA, TTG-IgA, anti-smooth muscle antibody and anti-nuclear antibody testing were unremarkable. Abdominal ultrasound with doppler showed patency of the portal, splenic, and hepatic veins without thrombus. Liver biopsy showed moderately active steatohepatitis, and hepatocytes displayed ground-glass cytoplasmic appearance. PAS staining showed weak to no staining of ground-glass regions. Due to the lack of positive PAS staining, fibrinogen staining of the liver specimen was obtained, which showed diffuse positivity within hepatocytes.

DISCUSSION:
A rarely reported finding, fibrinogen accumulation in hepatocytes can occur from inherited disease and from acquired errors in endoplasmic reticulum processing in a setting of metabolic stress. Ground glass hepatocyte inclusions staining positive with fibrinogen have only been associated with the acquired causes in humans. Only 3 cases, to our knowledge, have shown similar findings. After 1 year follow-up from total colectomy, his aminotransferases had returned to normal range.
2490 A Rare Initial Presentation of HCC
Authors: Rivera Arturo Suplee , Katkoria Gopal , Castano Juan J. , Rapoport Grigoriy , Zamir Asif 
Published: October 2019

INTRODUCTION:
Metastasis accounts for approximately 1-4% of all oral malignancies. Other cancers that spread to the mandible include lung, breast, kidney and colon. Hepatocellular carcinoma (HCC) has the fifth highest prevalence worldwide but only 68 cases of mandibular metastasis have been documented between 1957 to 2011. The following is a rare case of HCC presenting as mandibular metastasis.

CASE DESCRIPTION/METHODS:
The patient is a 73-year old Hispanic male with history of diabetes mellitus type 2, hypothyroidism, mild dementia, and alcoholic liver cirrhosis who presented with a one-month history of progressively enlarging painless mass in the left mandible, anemia and a 9-month history of weight loss. Additionally, one month ago the patient suffered a traumatic fall. Physical exam was significant for the presence of a malodorous, bleeding oral mass and a left humeral fracture. Initial CT imaging revealed a well-defined, expansile lytic mass in the left mandible, with an additional mass in the right mandible and the right paraspinal area of C1. Additional imaging revealed multiple hepatic lesions, a left humeral mass associated with the fracture and multiple lytic spinal lesions. Alfa-fetoprotein was significantly elevated. Biopsy of the mandibular mass revealed HCC with positive staining of hep par 1 glypican-3 and focal villin. After discussion, the patient and family decided to pursue conservative management with hospice care.

DISCUSSION:
Mandibular metastasis has been reported during the late stages of HCC, however mandibular involvement as an initial presenting sign is extremely uncommon. Therefore primary liver malignancy should always be considered in patients who present with mandibular tumors with HCC risk factors.
2491 The Alternative Outcome of Drug Induced Liver Injury
Authors: Bader Nimrah , Tardibono George 
Published: October 2019

INTRODUCTION:
Drug Induced Liver Injury (DILI) is a common cause for hepatoxicity seen in the emergency room. In this setting inquiring about herbal and over the counter medications becomes important. Kratom is a plant derived psychoactive extract from the Mitragyna speciosa plant indigenous to Southeast Asia. It is used by chronic pain patients to avoid the withdrawal effects from narcotics. Although banned by the FDA, it is widely available for purchase on the internet. Several case reports have described its association with DILI. In cases where liver biopsies were obtained, kratom-toxicity was histologically characterized by acute cholestatic liver injury and canalicular cholestasis. Here we present a patient with features typical for DILI secondary to kratom-toxicity but was found to have an additional diagnosis.

CASE DESCRIPTION/METHODS:
A previously healthy 45-year-old woman consulted her primary care physician for jaundice. She was then referred to our hospital with elevated liver enzymes, nausea, pruritis and jaundice in the past 5 days. She reported she had been taking Kratom -an herbal medication- for back pain for the past 1 month. She had no prior history of liver disease. She was jaundiced, no stigmata of liver disease, and she had a benign abdominal exam. Based on this, a clinical diagnosis of acute liver injury secondary to drug injury was made. Pertinent labs results at the time of admission are summarized in Figure 1. Acetaminophen level and serologies for autoimmune hepatitis, viral hepatitis were non contributive. She was started on N-Acetyl Cysteine with subsequent improvement in her bilirubin, ALT and AST levels; ALP levels showed mild improvement. The patient's symptoms improved but minimal improvement in ALP was noted. A liver ultrasound was done which revealed mild dilation of the intrahepatic duct; the common bile duct was dilated at 1.1 cm, with hepatic steatosis. Further workup with MRCP revealed an ill-defined hypo enhancing soft tissue mass in the region of the pancreatic head. The patient's final diagnosis was pancreatic adenocarcinoma confirmed on pancreatic biopsy.

DISCUSSION:
This case demonstrates the value of imaging in cases of DILI. In this patient her timeline fit well with DILI; she was completely healthy before this acute illness and did not have symptoms suggestive of an underlying malignancy. It is likely that this patient may have delayed seeking care if not for the acute manifestations of her symptoms. She is currently undergoing chemotherapy.