bluuebunny/crossref_metadata_2025_split huggingface dataset:
2207 Blinatumomab-Induced Hepatic Sinusoidal Obstruction Syndrome
Authors: Tabbalat Aya , Walradt Trent , Mehta Amit , Wan David 
Published: October 2019

INTRODUCTION:
Hepatic sinusoidal obstructive syndrome (SOS) occurs when sinusoidal endothelial cells are damaged leading to occlusion of hepatic venules. Causes include hematopoietic stem cell transplantation, chemotherapy, toxins, and radiation. Here, we report the case of a man with blinatumomab induced SOS.

CASE DESCRIPTION/METHODS:
A 39-year-old male with a recent history of drug induced liver injury presented with relapsed t (9;22) negative ALL and was started on blinatumomab therapy. On clinical examination, the patient was jaundiced with a distended abdomen. Prior to starting blinatumomab the patient’s aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin were 162 U/l, 71 U/L, and 12.3 mg/dL respectively. These levels rose over the next several weeks (ALT, 100 U/L; AST, 364 U/L; total bilirubin, 28.4 mg/dL). Abdominal CT showed large volume ascites, gastric varices, and hepatomegaly with numerous hypodense lesions (Figure 1). Transjugular liver biopsy (Figure 2) revealed SOS as well as cholestatic liver disease, consistent with sepsis. The patient’s condition progressed despite treatment with defibrotide, and he died of multiple organ failure 1 month after starting blinatumomab.

DISCUSSION:
Hepatic SOS occurs when hepatic terminal venules and sinusoids become obstructed. SOS is commonly seen in the setting of hematopoietic stem cell transplantation, but also occurs after chemotherapeutic agents, radiation therapy, liver tumor embolization and transplantation. The incidence of SOS varies widely between studies. Pre-existing liver disease, patients age, and prior radiation therapy are known risk factors. Clinical features of SOS include RUQ pain, jaundice, and ascites as well as elevated ALT, AST, and bilirubin. In severe disease, PT and platelet counts may also be abnormal. SOS is a clinical diagnosis, and imaging studies, such as an abdominal US, are frequently done during initial evaluation. Liver biopsy is not commonly used for diagnosis, but will show dilated and congested liver sinusoids with RBCs. Although SOS has been previously reported in the setting of chemotherapy, blinatumomab induced SOS is rare. Moreover, even though hepatotoxicity in the setting of blinatumomab has been documented, the mechanism of liver injury remains unknown. Further studies can explore whether SOS could relate directly to the method of liver injury in the setting of blinatumomab.
2211 The Ghost of TB: Danger of an Indolent Infection in the Setting of Alcoholic Hepatitis
Authors: Elkhattib Ismail , Villavicencio Jaimy , Phachu Deep , Disiena Michael , Sotil Eva 
Published: October 2019

INTRODUCTION:
The benefits of corticosteroids in patients with severe alcoholic hepatitis has recently been questioned. Corticosteroids should be used with caution for a febrile patient in the setting of ETOH Hepatitis. We present a case in which steroids lead to a flare-up of an indolent infection and dissemination of tuberculosis.

CASE DESCRIPTION/METHODS:
A 23-year-old male who migrated from Mexico 8 years earlier with a past medical history of alcohol-related liver disease presented with fever, diarrhea and abdominal pain. On admission, labs were suspicious for alcoholic hepatitis (Table 1), paracentesis showed SAAG of 1.6 (Table 2) and complicated by portal HTN and SBP. He was started on Ceftriaxone and flagyl. He was started on steroids for 2 days that was replaced by pentoxifylline for the diagnosis of SBP then back to steroids after peritoneal fluid culture was negative. He continued to have a persistent fever which was attributed to severe alcoholic hepatitis for which he had a repeat paracentesis (2) that showed a lymphocytic predominance with SAAG 1.7. TB tests were ordered and showed indeterminate Quantiferon, negative AFB smear/TB PCR from paracentesis x2 and HIV was negative. Antibiotics (Zoysn) was restarted due to the persistent fever. A liver biopsy was consistent with alcoholic steatohepatitis with grade 3-4 fibrosis. Lille score was calculated at 0.010 so steroids were continued. The patient developed hemoptysis with EGD showing only grade I nonbleeding esophageal varices. Repeat CT of the lung revealed numerous new pulmonary nodules. Steroids were stopped by a rapid taper given the new pulmonary nodules. He had a diagnostic bronchoscopy and BAL grew mycobacterium TB. His ascitic fluid culture from three weeks prior eventually revealed Mycobacterium species. He was initiated on treatment for disseminated tuberculosis with RIPE therapy. The patient then developed extensive hemoptysis complicated by PEA. CPR achieved ROSC but he was made CMO and passed away.

DISCUSSION:
Tuberculous peritonitis is rare in the United States but continues to be reported to occur in certain high-risk populations. The diagnosis of this disease requires a high clinical index of suspicion especially in the presence of ascites with a lymphocyte predominance and serum-ascitic albumin gradient of <1.1 mg/dl. Microbiological or pathological confirmation remains the gold standard for diagnosis. Ascitic fluid cultures have a low yield, but peritoneoscopy with biopsy or cultures frequently confirms the diagnosis.
2229 Peripheral Eosinophilia; An Unusual Presentation of Autoimmune Hepatitis
Authors: Akanbi Olalekan , Kato Hirotaka , Tripathi Nishant , Singh Tushi , Karri Kishore , Thakur Kshitij 
Published: October 2019

INTRODUCTION:
Autoimmune hepatitis (AIH) is a chronic inflammatory condition of the liver characterized by elevated hepatocellular enzymes, autoantibodies, immunoglobulins, periportal inflammation and rapid improvement with steroids. Associated peripheral eosinophilia has been rarely reported. We report a case of AIH presenting with eosinophilia.

CASE DESCRIPTION/METHODS:
A 48-year-old Caucasian male with a past medical history of splenectomy a year ago following a motor vehicle accident presented to the emergency department with a 2-week history of diarrhea, malaise, anorexia, chills and dark urine. He also observed yellowish discoloration of his eyes 5 days prior to presentation. No history of over-the-counter medications, supplements, alcohol or drug use. Vital signs were normal while physical exam was only notable for scleral icterus. Labs on admission showed: WBC 21.9K/mL (35% eosinophils), AST 820U/L, ALT 350U/L, ALP 204U/L, total bilirubin 13mg/dl (conjugated bilirubin 8.7mg/dl), INR 1.8. Due to concerns for acute liver injury, evaluation by CT abdomen and MRCP revealed nodular contours of the liver suggestive of chronic hepatic parenchymal disease, no evidence of biliary ductal pathology. He was managed conservatively with fluids while further extensive work-up to determine etiology of liver injury and eosinophilia such as acute hepatitis panel, CMV PCR, EBV IgM, alpha-1 antitrypsin, ceruloplasmin, mycoplasma IgM, stool studies for infection and parasites, strongyloides, histoplasma antigen were negative. IgG (2084mg/dl) and IgA (732mg/dl) were elevated as ANA and smooth muscle antibody were positive. As liver enzymes, eosinophilia and INR continued to rise, a liver biopsy was performed which showed extensive bridging fibrosis, ballooning degeneration of hepatocytes, mild fatty change, mixed inflammatory infiltration with lymphocytes, plasma cells, eosinophils and occasional neutrophils in the portal areas, prominent interface changes all consistent with autoimmune hepatitis. No evidence of ductopenia, periductal fibrosis or granulomas was seen. He was started on steroids with immediate resolution of eosinophilia and improvement of symptoms and labs.

DISCUSSION:
With this report, we hope to draw awareness to this unusual presentation of AIH. As eosinophilia resolved rapidly with treatment of liver disease, AIH should be strongly considered in patients with elevated liver enzymes and peripheral eosinophilia especially in the absence of other predisposing conditions for eosinophilia.
2233 Emergent Living Donor Liver Transplantation for Fulminant Hepatic Failure Secondary to Wilson’s Disease
Authors: Kumar Shiva 
Published: October 2019

INTRODUCTION:
Liver transplantation (LT) is indicated for patients with Wilson’s disease (WD) who present with either fulminant hepatic failure (FHF) or end-stage liver disease. However, there is very limited information regarding emergent LDLT in adult patients with WD presenting with FHF. Here we report a case of FHF due to decompensated WD in an adult treated with emergent LDLT.

CASE DESCRIPTION/METHODS:
A 25-year-old female with no prior medical history presented with jaundice and fatigue. At presentation, lab tests showed: Br 14.8 mg/dL, ALT 42 U/L, AST 165 U/L, ALP 65 IU/L, INR 3.2. Serum ceruloplasmin level was low: 70 (Range 190-390) and 24 hour urine copper was markedly elevated at 7269 μg /24 Hr (Range 5–50). Subsequent clinical course was characterized by progressive encephalopathy and coagulopathy. Lab tests 4 days later revealed: Br 36.42, ALT 30, ALT 217, ALP 30, Cr 2.75 mg/dL, INR 5.8 (MELD > 40). She was diagnosed with FHF due to WD and underwent emergent LDLT utilizing a left lobe graft from her 33-year-old brother, who had a normal screening ceruloplasmin. Explant revealed a cirrhotic liver with necrosis, cholestasis and positive copper immunostain (Figures 1 and 2). Quantitative hepatic copper content was 2119 mcg/g (Range 10−35). Recipient genetic testing revealed c.2930C>T p. (Thr977Met) variant in homozygosity in the ATP7B gene. Donor was heterozygous. The patient gradually improved and continues to do well 8 months later with normal ceruloplasmin and 24 hour urinary copper excretion.

DISCUSSION:
WD is an autosomal recessive disorder of copper metabolism caused by a mutation in the ATP7B gene on chromosome 13. It affects one in 30 000 individuals with a reported carrier frequency of one in 90. LT is the only effective option in WD presenting with FHF and corrects the underlying hepatic metabolic defect. The overwhelming majority of reported cases of emergent LT for FHF secondary to WD in adults utilized deceased donor LT, with a few reported cases of LDLT in children. Given the narrow window of opportunity for LT in FHF and concerns related to heterozygosity in donors, emergent LDLT is rarely performed in this setting. In recipients with cirrhosis secondary to WD, LT using heterozygous donors for the WD gene has been shown to have outcomes comparable to that from a deceased, unrelated donor. Given the scarcity of deceased donor organs, LDLT may be a viable option for patients with decompensated WD presenting with FHF, even if the donor could potentially be heterozygous for the WD mutation.
2246 Rifampin-Induced Decompensation of Cirrhosis: A Tuberculosis Dilemma
Authors: Kolli Sindhura , Aamar Ali , Etienne Denzil 
Published: October 2019

INTRODUCTION:
Tuberculosis (TB) is highly prevalent in cirrhotic patients. Due to the underlying depressed immune system and damaged hepatocytes, the metabolism of anti-tuberculous drugs can be variable, given 3 out of the 4 drugs are potentially hepatotoxic. Currently, there are no established guidelines for treatment and monitoring of TB patients with cirrhosis. We present a case of hepatic decompensation in a patient with underlying cirrhosis who was started on anti-tuberculous drugs.

CASE DESCRIPTION/METHODS:
A 62-year-old African American female with a history of hepatitis C cirrhosis presented with altered mental status. She was on rifampin, isoniazid (INH), pyrazinamide and ethambutol for active TB. Labs showed elevated bilirubin, liver enzymes and INR and hypoalbuminemia. US abdomen showed ascites and cirrhosis. Patient was diagnosed with hepatic encephalopathy in the setting of decompensated cirrhosis secondary to rifampin use. Autoimmune workup was negative except for a weakly positive ANA. Rifampin and INH were discontinued resulting in improved clinical status and lab abnormalities. Treatment for her tuberculosis was restarted with one drug at a time with ethambutol, INH, and moxifloxacin with weekly monitoring of LFTs for a total of 18 months.

DISCUSSION:
Routine treatment for TB is a 4-drug regimen consisting of INH, rifampin, pyrazinamide and ethambutol. INH and rifampin are the most potent anti-TB drugs, but they both have transient hepatotoxic effect. A true hepatotoxic effect from either drug is idiosyncratic in nature and more common in those with underlying hepatic dysfunction. Monitoring with weekly LFTs for the initial 2 months is recommended. Rifampin can cause centrilobular necrosis within hepatocytes and competes with bilirubin for clearance leading to cholestasis. It increases the hepatotoxicity of other anti-TB drugs. In those cases, all 4 drugs should be stopped immediately to see if there is a reversal of transaminase levels. Once AST/ALT/bilirubin have returned to baseline, drugs should be reintroduced one at a time consecutively at lower doses for hepatic adaptation while withholding the offending agent. If the rechallenge is not tolerated in the setting of worsening cirrhosis, an urgent liver transplant must be considered. Intermittent short course drug regimens are being studied to diminish the effects of worsening hepatotoxicity in patients with underlying cirrhosis.
2291 Drug-Induced Autoimmune Hepatitis Secondary to Infliximab
Authors: Reinhart Evan , Diocares Juan , Powell Priscilla R. , Jeffries Mark A. 
Published: October 2019

INTRODUCTION:
The increased utilization of Infliximab therapy has produced a small number of reported cases associating Infliximab with varying patterns of drug-induced liver injury. We present a rare case report of drug-induced autoimmune hepatitis that embodies a realistic presentation of a potentially underreported liver injury pattern that can occur following the induction of Infliximab therapy.

CASE DESCRIPTION/METHODS:
A 36 yo female with a PMHx significant for Crohn’s Disease, HTN and chronic alcohol abuse was admitted for generalized body aches, right upper quadrant abdominal pain, and shortness of breath. The patient described a recent increase to her alcohol consumption from 48 to 120 oz of beer daily for the last two weeks. The patient otherwise denied: smoking tobacco, illicit drugs, and naturopathic or over the counter medications. Physical examination revealed jaundice and tenderness to the RUQ of the patient’s abdomen. No evidence of ascites, palmar erythema, spider angiomata or protein malnutrition were present. Lab Findings revealed: AST/ALT: 1135/175, T. Bili: 10.9, AP: 230, Albumin: 2.7, Platelets: 233, INR: 1.1. The patient’s lab findings and subjective history validated continued concern for alcoholic hepatitis. Viral hepatitis serologies and autoimmune markers were collected and produced negative results except for a positive Anti-Nuclear Ab; ANA Titer: 1:2560. A RUQ Ultrasound with Doppler revealed hepatomegaly without signs of cirrhosis. Histopathologic results from biopsy revealed florid lymphoplasmacytic portal inflammation, stage 2-3 with periportal/bridging fibrosis and was without steatosis or steatohepatitis; findings consistent with the diagnosis of autoimmune hepatitis and drug induced liver injury.

DISCUSSION:
A detailed review of the patient’s medications revealed Infliximab infusions were initiated 5 months prior ,with the most recent being 3 weeks before presentation. The patient had no new medication exposures. Despite an initial concern for alcoholic hepatitis, the patient’s biopsy results showed no evidence of an alcoholic liver injury pattern. The positive ANA, histopathology, favorable response to infliximab withdrawal followed by steroid induced immunosuppression was consistent with the diagnosis of drug-induced autoimmune hepatitis (DIAIH). This case suggests patients receiving Infliximab therapy with elevations in liver function tests require thorough evaluation and strong consideration of biopsy for appropriate diagnosis.
2297 Tyrosine Kinase Inhibitor-Induced Hepatotoxicity: A Case Series
Authors: Khurana Shruti , Herman Andrew , Dedania Bhavtosh , Younes Mamoun , Machicao Victor 
Published: October 2019

INTRODUCTION:
Tyrosine kinase inhibitor (TKI) is indicated for the treatment of multiple cancers. Known side effects include vomiting, myalgia, skin rash, bone marrow suppression and mild hepatotoxicity. We report two cases of TKI-mediated hepatotoxicity with variable outcomes in patients with no prior history of chronic liver disease (CLD).

CASE DESCRIPTION/METHODS:
CASE 1: A 66-year-old Caucasian woman developed maculopapular rash, fatigue, low-grade fevers, neutropenia and significant transaminemia (hepatocellular injury) a month after initiation of Imatinib for GIST (Table 1). Workup for alternative explanation of abnormal liver function test (LFT) including autoimmune markers were unremarkable and TKI was discontinued due to presumed hepatotoxicity. A liver biopsy was performed showing features of drug-induced liver injury (DILI) with patchy perivenular, focal bridging, necrosis, mild cholestasis, portal and mild periportal fibrosis. Her LFTs worsened despite a trial of prednisone. Six months later, a repeat liver biopsy and imaging showed cirrhotic changes (Figure 1). CASE 2: A 85-year-old Hispanic woman with metastatic renal cell carcinoma was started on TKI complained of fatigue and new onset jaundice (Table 2). After a negative work-up for her abnormal LFTs, a liver biopsy was performed which showed changes consistent with drug-related hepatitis (Figure 2). Hence, systemic steroids were started with a gradual normalization of LFTs without any cirrhotic changes on imaging.

DISCUSSION:
Hepatotoxicity is a known side effect of Imatinib generally manifesting as hepatocellular injury in as many as 2.7% of patients. Cases have ranged from mild elevation in transaminases to progressive irreversible cirrhosis, which has resulted in death. Histologic features of TKI-induced hepatotoxicity include inflammation, fatty degeneration, and liver necrosis. Most hepatotoxicity improves after discontinuation of the drug with limited date on use of systemic steroids. However, cirrhosis due to TKI in-spite of drug discontinuation and treatment with prednisone is not common. Since there are no guidelines on treatment, oral steroids should be considered, apart from periodic monitoring of LFTs for patients on TKI. Infrequently, orthotopic liver transplantation in patients with decompensated cirrhosis is required. We present two cases of TKI mediated hepatocellular injury with different overall outcomes in spite of similar treatment protocol suggests different mechanisms for DILI.
2298 Novel Use of N-Acetylcysteine in the Management of Immunotherapy-Induced Acute Liver Injury
Authors: Patel Tarang , Hudhud Dania , Tarun Tushar , Krvavac Armin 
Published: October 2019

INTRODUCTION:
There is limited research regarding the use of N-Acetylcysteine (NAC) to manage non-acetaminophen induced acute liver failure (NAI-ALF). NAC has an anti-inflammatory, antioxidant effect, and improves oxygenation by vasodilating microcirculation. A mortality benefit and association with lower hospitalization length has been seen when using NAC in NAI-ALF. Use of immunotherapy to treat cancer has recently increased, and acute liver injury has been reported with many agents. This case examines using NAC to manage immunotherapy induced acute liver injury (ITI-ALI).

CASE DESCRIPTION/METHODS:
Patient is a 67-year-old Caucasian female with a medical history of hyperlipidemia and well-differentiated angiosarcoma of the right breast, diagnosed in 2011. She had mastectomy and adjuvant chemo-radiotherapy resulting in remission. Surveillance abdominal CT, in 2017 showed new enhancing hepatic lesions. Abdominal MRI confirmed these concerning lesions. A cervical mass was noted, which was biopsied, and diagnostic of metastatic angiosarcoma. She was started on Pazopanib. Two weeks into therapy, she experienced darkened urine, myalgia, and abdominal pain. Labs just prior to admission showed transamninits, ALT of 522 units/L and AST of 456 units/L. Admission labs showed worsening transaminitis, ALT 1377 units/L and AST 1212 units/L. Exam showed jaundice and diffuse abdominal pain. Acetaminophen levels were undetectable. Abdominal ultrasound showed patent hepatic vasculature, normal liver size, appearance, echogenicity, and no intrahepatic ductal dilation or masses. Additionally, serologies for herpes simplex virus, Ebstein Barr virus, cytomegalovirus, viral hepatitis, anti-nuclear antibody, and anti-smooth muscle antibody were negative. Ultimately, her acute liver injury was suspected to be ITI-ALI. NAC was started and Pazopanib was held. Hepatic function was serially monitored, and her acute liver injury rapidly improved. She was discharged and repeat labs on follow-up continued showing improvement in transaminases (Figure 1).

DISCUSSION:
The use of NAC in NAI-ALF was described in a prospective study by Mumtaz, Azam, et al, and in a randomized, case-control trial by Nabi, et al. Neither studies had patients who had developed ITI-ALI. Both studies were able to conclude that using NAC in NAI-ALF reduced mortality and hospitalization length. Further prospective studies should be conducted to identify if there is a statistically significant effect on mortality and length of hospitalization by using of NAC in ITI-ALI.
2326 Primary Squamous Cell Carcinoma of the Liver: A Rarity
Authors: Mago Sheena , Rawi Sarah , Ramlal Bharat 
Published: October 2019

INTRODUCTION:
Primary liver squamous cell carcinoma (PLSCC) is a very rare entity with less than 40 reported cases since 1970. PLSCC has been known for late diagnosis, high malignancy rate, and poor prognosis of less than 1 year. The exact pathogenesis of PLSCC is unclear, though various theories exist.

CASE DESCRIPTION/METHODS:
A 72-year-old male with a history of NASH cirrhosis and hepatocellular carcinoma (HCC) status post right hepatic lobectomy 11 years prior and microwave ablation of a presumed recurrent HCC mass just 5 months prior, presented with a 2-month history of progressive fatigue, shortness of breath, lower extremity edema, and abdominal pain. He was hypotensive with an initial blood pressure of 90/54mmHg and had a distended abdomen without evidence of jaundice, encephalopathy, or acholic stools. Labs were notable for WBC 16.9 × 10^3/uL, lactic acid of 4.5mmol/L, and alpha-fetoprotein marker of 1.9ng/mL. CT Abdominal/Pelvis revealed a large burden of diffuse intrahepatic lesions spanning all lobes—findings compatible with HCC—and multiple bilateral kidney simple cysts. Patient underwent an ultrasound guided biopsy of the largest hepatic lesion measuring 2.3 × 2.0 × 2.8 cm. Unfortunately, his condition rapidly worsened with significant elevation in liver enzymes and lactic acid and he passed away. Pathology results resulted shortly after his passing and showed a partially necrotic high grade carcinoma favoring squamous cell carcinoma. It was strongly positive for immunomarkers: CK5, CK7, p40, HSP70 (non-specific), but negative for GATA3, CK20, glypican 3, Hep Par1, S100 protein.

DISCUSSION:
In this case, the patient was thought to have HCC, but its aggressive clinical course was highly unexpected. Data on the diagnosis of PLSCC is limited and the mechanism is uncertain, though it has a strong association with hepatic cysts, stones, and cirrhosis. Hepatic cysts were not clearly visualized on imaging, though studies do show a positive correlation between the incidence of kidney and hepatic cysts. As this patient had multiple benign bilateral kidney cysts, we suspect that hepatic cysts could have also been present which makes PLSCC very likely given the lack of evidence of a different primary source. A liver carcinoma with such an aggressive clinical course should increase clinical suspicion for PLSCC, however further understanding of the pathogenesis of this disease needs to be investigated.