bluuebunny/crossref_metadata_2025_split huggingface dataset:
2398 Are Herbal and Dietary Supplements Really Safe?
Authors: Goel Siddharth , Garg Chandi , Debnath Dipanjan , Shrimanker Isha , Nookala Vinod , McLaughlin John 
Published: October 2019

INTRODUCTION:
The use of herbal and dietary supplements (HDS) has been on a rise in the United States in the last couple of decades with roughly one half of the population consuming it. Artemisinin is found in the leaves of Artemisia annua and has been in use for a long time for its medicinal purposes. It is also a key ingredient in HDS and is generally considered safe and effective with no major side effects but very rarely, may lead to liver injury. Due to the HDS being unregulated, its increased use has led to an increase in adverse effects with hepatic injury being the most notable one. Here we present a case of HDS causing severe hepatic injury.

CASE DESCRIPTION/METHODS:
A 63-year-old female with a past medical history of generalized anxiety disorder and recurrent major depression, and with a recent history of over the counter supplement Microb-Clear consumption, presented with pruritus and generalized rash, of one week duration, associated with malaise, anorexia, intermittent nausea, yellow discoloration of the skin, dark urine and light stools. Her physical examination was significant for jaundice and diffuse maculopapular rash. Laboratory investigations revealed direct hyperbilirubinemia (7.3 mg/dl) with a cholestatic pattern of liver injury, with an upward trend in direct bilirubin and alkaline phosphatase noticed during the treatment course. The patient improved following discontinuation of the over the counter supplement, leading to a diagnosis of exclusion of HDS induced liver injury.

DISCUSSION:
The current regulations regarding supplements are inadequate and irrational. The general perception about safety and easy availability without the requirement of a medical prescription is one of the major causes of their misuse. They have unpredictable pharmacokinetics and pharmacodynamics as well as unknown drug interactions, increasing the probability of toxicity. As with our patient, discontinuing the supplements caused rapid symptomatic relief with improvement in liver function, which points towards a causal relationship between consumption of artemisinin-containing supplements and hepatic injury. The mechanism of the liver injury caused by artemisinin is still unknown. Further studies are required to study the relationship between HDS consumption and hepatic injury. A high index of suspicion is required to identify and minimize such adverse reactions in the future.
2403 Adefovir-Induced Fanconi Syndrome: Missed Diagnosis and Misdiagnosis
Authors: Weeber Kaitlyn , Kluesner Joseph , Whang Charles , Viswanathan Lavanya 
Published: October 2019

INTRODUCTION:
Nucleotide reverse transcriptase inhibitors (NRTIs), e.g., adefovir (ADV), are commonly used to treat chronic hepatitis B, which affects approximately 240 million worldwide and 2.2 million in the US. We report a case of ADV-induced Fanconi Syndrome (AIFS) in a patient who was undiagnosed for 5 y.

CASE DESCRIPTION/METHODS:
A 75 yo Spanish female with history of osteoporosis and CHB on ADV 10 mg/d for 15 y presents to the ED for bilateral hip pain. Over the past 2 y, her hip pain was refractory to steroid injections and complicated by traumatic bilateral hip and atraumatic clavicular fractures. One year ago she was diagnosed with osteoporosis and started on teriparatide (synthetic parathyroid hormone). Exam reveals bilateral hip tenderness and she is unable to bear weight. Labs reveal renal phosphorous wasting and glucosuria, proteinuria, hyperaminoaciduria and low fibroblast growth factor 23 confirm diagnosis of FS (Table 1). Bone scan is consistent with osteomalacia (Figure 1). Teriparatide is stopped to prevent worsening of osteomalacia. Lab review shows otherwise normal phosphorous prior to starting ADV (Table 2), and patient is diagnosed with AIFS. Phosphorous supplementation is started and ADV is changed to entacavir (ETV) due to decreased renal toxicity. Patient reports complete resolution of hip pain within 1 week, over which time labs also improve (Table 2).

DISCUSSION:
heavy metal or drug toxicity. Classic features include hyperphosphaturia, hyperuricosuria, hypercalciuria, modest proteinuria and glycosuria. In addition to hyperchloremic acidosis, rickets or osteomalacia are the predominant effects of FS. Osteomalacia can exist despite normal calcium and vitamin D levels. FS and osteomalacia affect 30% and 10% of patients on long-term NRTI therapy, respectively. Nephrotoxicity is reported at dosages of 10-120 mg. Risk factors for developing AIFS include old age, low BMI and >8 y treatment with ADV, all of which apply to this patient. While this patient's CMP was checked yearly, her metabolic derangements were overlooked for 5 y. Treatment of her osteoporosis likely worsened her underlying FS. This highlights the need for awareness of this clinically significant syndrome as a more timely diagnosis may have prevented fractures. While AIFS is well reported in Endocrine literature, it is not as widely reported in GI literature, which may contribute to this knowledge gap in Gastroenterologists. GI clinicians should consider FS in patients on longstanding ADV with low phosphorous.
2411 Acute Liver Injury in a Patient Treated With Rosuvastatin: A Rare Adverse Effect
Authors: Shah Jamil M. , Lingiah Vivek A. , Pyrsopoulos Nikolaos T. , Galan Mark A. 
Published: October 2019

INTRODUCTION:
As recently as 2014, Rosuvastatin was the most prescribed brand name drug in the US, with 22.3 million prescriptions filled and $5.8 billion in sales. Its use is associated with mild, asymptomatic, and usually transient, serum aminotransferase elevations, occurring in 1-3% of patients. However, levels above 3 times the ULN occur no more frequently among rosuvastatin-treated [0.2%] as placebo-treated [0.3%] recipients. Rarely, patients can present with clinically apparent acute liver injury, occurring in 1/10,000 patients.

CASE DESCRIPTION/METHODS:
A 47 y/o Peruvian man was told by his PCP that he had high cholesterol, and he was started on rosuvastatin 5 mg daily. At the time, his LFTs showed AST 17 and ALT 19. However, labs performed a month later showed AST 1282, ALT 2245, ALP 295, total bilirubin (TB) 7.1 (direct 5.5). He was advised to visit his local ER. He was admitted, the rosuvastatin was stopped, he received mainly supportive care, his LFTs continued to rise, and he underwent a liver biopsy. He was then transferred to a tertiary care hospital. His labs upon arrival showed AST 1400, ALT 2253, ALP 277, TB 9.9, and INR 1.1. He was admitted for acute liver failure due to drug-induced liver injury from rosuvastatin. Despite IV NAC therapy for five days and initiation of Ursodiol, his LFTs showed no recovery. His liver biopsy showed acute severe hepatitis with a mixed inflammatory infiltrate with many plasma cells. There was interface activity and bile duct damage. The histopathology was consistent with an immune-mediated drug reaction. He was approved to be listed for liver transplantation due to a high MELD score of 21. Before discharge, his labs improved to AST 942, ALT 1312, and ALP 167, but the TB rose to 17.2. He remained hemodynamically stable with no mental status changes during the hospital course. Afterward, repeated labs showed improvement in the LFTs, except for increasing hyperbilirubinemia. He was re-admitted and given a trial course of IV methylprednisolone after which the TB proceeded to decrease. Ultimately, his liver enzymes improved, he remained asymptomatic, and he was removed from the liver transplantation waitlist.

DISCUSSION:
The acute liver failure attributed to rosuvastatin is often accompanied by autoimmune features and may be caused by immune mechanisms. Corticosteroids have been used when recovery does not occur promptly. If used, the dose and duration of treatment should be kept to a minimum, and careful follow up after discontinuation is essential.
2423 A Case of Budd-Chiari in the Setting of Paroxysmal Nocturnal Hemoglobinuria
Authors: Parker Kasey 
Published: October 2019

INTRODUCTION:
Paroxysmal nocturnal hemoglobinuria has an incidence of 1.3 case per 1 million, but the incidence is significantly increased in patients with aplastic anemia. We present a patient with a history of aplastic anemia who presents with findings concerning for Budd-Chiari.

CASE DESCRIPTION/METHODS:
A 44 year old man with a history of aplastic anemia presented with dyspnea and abdominal distention that started over the course of several days. At time of presentation, he appeared uncomfortable, but was hemodynamically stable. Due to initial concern for PE, CT chest was obtained and negative for pulmonary process. CT did note liver changes concerning for cirrhosis, however patient denied history of liver disease or risk factors associated with cirrhosis. Work up for causes of cirrhosis was initiated, and lab studies were unrevealing. SAAG score of 2.1 indicating portal hypertension as a cause of ascites. Due patient's fairly rapid onset of symptoms and otherwise unremarkable work up, CT liver protocol was performed with concern for Budd-Chiari. Imaging was suggestive of cirrhosis, and could not rule out Budd-Chiari, however no evidence of thrombosis was identified. Portal venous duplex suggested patent portal system without thrombosis. Given high level of suspicion for Budd-Chiari, hepatic venography was obtained, and significant for partial or complete thrombosis of all hepatic veins. In the setting of a patient with aplastic anemia and Budd-Chiari, work up for PNH was initiated and consistent with PNH. With diagnosis of cirrhosis due to Budd-Chiari, patient was referred to transplant clinic. With new diagnosis of PNH, he was started on Eculizumab with Hematology follow up.

DISCUSSION:
If there is concern for Budd-Chiari, diagnosis is generally with doppler ultrasonography. If US unremarkable, CT or MRI can be performed. If noninvasive diagnostic tools are nondiagnostic, hepatic venography can be performed given there is strong clinical suspicion. In PNH, thrombosis is the leading cause of death, though rare as a presenting symptom. Thromboses typically occur in unusual locations, and approximately two-thirds of thrombosis occur in intra-abdominal locations. The incidence of PNH is significantly increased in patients with aplastic anemia. In a patient with high concern for Budd-Chiari and unremarkable noninvasive testing, hepatic venography is a helpful diagnostic tool. In a patient with significant thrombosis such as this with a history of aplastic anemia, it is important to consider PNH.
2458 Autoimmune Hepatitis-Induced Hepatic Lobar Atrophy
Authors: Anucha Jeff C. , Pinto Jonathan , Culpepper-Morgan Joan 
Published: October 2019

INTRODUCTION:
Lobar atrophy of the liver can be a morphologic manifestation of benign and malignant liver or biliary duct disease. Rarely has it been associated with autoimmune hepatitis (AIH).

CASE DESCRIPTION/METHODS:
A 26 year old woman presented with a 2 month history of severe RUQ abdominal pain associated with anorexia, 10 lb weight loss, pruritus, and scleral icterus. Physical exam was notable for cachexia, jaundice, abdominal distension and tender hepatomegaly. Initial labs revealed: hemoglobin 10.1 g/dl, MCV 80, platelets 107, AST 968 U/L, ALT 487 U/L, ALP 369 U/L, total bilirubin 12.0 mg/dl, DB 9.0 mg/dl, total protein 6.4 g/dL, albumin 2.1 g/dl and INR 1.65. Serological data were as follows: AMA <1:20; ANA 1:160; and anti-smooth muscle antibody 1:20. Viral markers for hepatitis A, B and C were negative. CT abdomen revealed a large area of infiltrative hypoattenuation of the right hepatic lobe. Abdominal MRI noted a diffuse edema within both hepatic lobes. N-acetylcysteine was started for impending acute liver failure and prednisone for AIH. She improved clinically. A liver biopsy done showed diffuse liver cell necrosis with lobular collapse, acute and chronic inflammation in the portal tracts, and in the interface. She was deemed stable for discharge to return to clinic but she was lost to follow up. A year later, she returned with worsening RUQ pain, further weight loss of 30 pounds. Her LFTs were within normal limits but a CT abdomen showed portal hypertension, hypoattenuation of the right lobe, and cirrhosis with left hepatic lobe atrophy. Azathioprine was started in addition to Prednisone.

DISCUSSION:
This patient's left lobar atrophy was not deemed to be congenital due to the presence of the left hepatic lobe on prior imaging studies. Hepatic neoplasms which can as well cause lobar atrophy was also ruled out with imaging. This is one of the few reported cases of hepatic lobar atrophy attributed to AIH which is a chronic disease characterized by increased autoantibodies in circulation and inflammation around the portal vein. This inflammation can result in lobar atrophy via occlusion of the portal vein resulting in impairment of liver blood flow as well as a reduction in the supply of hepatotrophic substances, particularly insulin. This may cause ischemia in certain areas of the liver and subsequently, atrophy secondary to necrosis and apoptosis. This patient also had significant cholestasis on initial presentation which could also contribute to cellular apoptosis through the Fas ligand pathway.
2466 Surprisingly Uncommon Trigger of Massive Ascites
Authors: Benrajab Karim , Ali Saad Emhmed , Frandah Wesam , Almuwaqqat Zakaria , Ismail Bahaaeldeen 
Published: October 2019

INTRODUCTION:
Systemic Mastocytosis (SM) is a group of disorders characterized by excessive mast cells accumulation into single or multiple organs. It affects mainly skin, but it may involve extracutaneous sites, such as the bone, liver, spleen, GI tract, and lymph node. If it involves the liver, it can lead to noncirrhotic portal hypertension. We present a case of systemic mastocytosis with an associated hematologic neoplasm (SM-AHN) that mimics a decompensated cirrhosis with massive ascites.

CASE DESCRIPTION/METHODS:
A 73-year-old male presented with progressive abdominal distention, lower extremity swelling for 3 months. Also, he had a poor appetite, 20 pounds of weight loss, shortness of breath, diarrhea, and recurrent skin bruises. He was a non-smoker, denied any alcohol or illicit drugs. Past medical history was remarkable for chronic myelomonocytic leukemia. Vitals were normal. Physical exam was remarkable for the presence of significant ascites & legs edema. Labs revealed ALP 456 U/L, ALT 33 U/L, AST 36 U/L, bilirubin 2.8 mg/dl, albumin 3.3 g/dl, Hgb 10.5 g/dl, WBC 3.9 k/uL, and Platelet 37 k/uL. Hepatitis A, B, and C serology was negative. The abdominal US showed normal liver morphology, splenomegaly, and ascites. The echocardiogram showed LVEF of 60% and no abnormalities. Paracentesis was performed with removal of 8.5 liters. The ascitic fluid analysis was negative for infection with a low total protein, and SAAG was >1.1. Trans-jugular liver biopsy was significant for HVPG 15 mmHg, and pathology showed dense portal and sinusoidal infiltration by clusters of atypical cells with relatively abundant cytoplasm and irregular nuclei. These atypical cells stained positive for CD117, CD 25, and mast cell tryptase by immunohistochemistry, consistent with systemic mastocytosis. Serum tryptase was 230. The patient was going to follow up with hematologist for cytoreductive therapy and evaluation for hematopoietic stem cell transplantation.

DISCUSSION:
Liver involvement in a patient with systemic mastocytosis is a poor prognostic factor associated with increased mortality due to disease progression. Our patient presented with massive ascites and hepatic involvement due to systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). The diagnosis is with high clinical suspicion and aided with liver biopsy. The survival rate is months to a year in case of (SM-AHN). Early diagnosis could limit unnecessary management and lessen any potential harm.
2480 Nivolumab-Induced Hepatitis and Vesiculopustular Skin Rash in a Patient With Metastatic Melanoma
Authors: Khan Abdul Moiz , Naseer Usman , Shahzad Sheikh Raza , Wazir Ali , Rahman Haider , Mehdi Syed 
Published: October 2019

INTRODUCTION:
The advent of immunotherapy has been hailed as a breakthrough in cancer treatment. However, it comes with a multitude of immune mediated adverse effects. Gastrointestinal adverse effects include hepatitis and colitis. Immunotherapy related hepatitis can range from asymptomatic elevation of liver enzymes (grade 1) to decompensated liver failure (grade 4).

CASE DESCRIPTION/METHODS:
82 years old male with stage IIC Malignant Melanoma of right posterior diagnosed in 2014, treated with wide excision. In December 2016, PET scan revealed right chest wall lesion, treated with re-excision. c-kit and BRAF were negative. In June 2017, PET scan showed metastatic disease involving lung, pancreas, gluteus maximus and left flank. The patient was started on Nivolumab. After 7 cycles, the PET scan became negative for any metastatic lesions. After 8 cycles, he had a severe morbilliform, vesiculopustular rash secondary to Nivolumab. Skin Biopsy showed a lymphocytic infiltrate with scattered eosinophils and numerous neutrophils. High dose prednisone was started with tapering for 3 months. Nivolumab was temporarily held and resumed after a good response to steroids. After 14 cycles, the patient developed malaise, fatigue, nausea and mild abdominal pain. ALT was 393, AST 302, ALK 164. Bilirubin was 1.1. Hepatitis A, B, and C testing were negative, anti-liver kidney microsomal antibody and anti-mitochondrial antibody was negative, acetaminophen level was normal, CT and Ultrasound of the liver were negative for metastatic lesions or other hepatic pathology. No recent change in medication or alcohol use was reported. As per ASCO guidelines, hepatitis was classified as Grade III (ALT and AST >5-20 times the upper limit of normal). The patient was started on 100 mg prednisone daily with tapering for 2 months. Liver enzymes normalized and symptoms resolved. Nivolumab was discontinued. PET scan 6 months from the last cycle showed disease in remission.

DISCUSSION:
Treatment of immunotherapy induced hepatitis depends on severity. Immunotherapy can be continued in grade 1, temporarily held in grade 2, and permanently discontinued in grade 3 and 4 as per guidelines. High dose steroids (prednisone 1-2 mg/kg) with tapering serve as the mainstay of treatment. Mycophenolate or azathioprine can be considered in refractory cases. However, it needs further research whether immunotherapy can be re-trialed in patients with grade 3 toxicity, who have responded well to the steroids, and would potentially benefit from a repeat trial.
2482 Scrotal Gallstones: A Not-So-Silent Gallbladder Perforation With Streptococcus sanguinis Peritonitis
Authors: Shenoy Abhishek , Stratton Leland , Buerlein Ross C. , Henry Zachary 
Published: October 2019

INTRODUCTION:
Gallbladder perforation (GBP) is rare and potentially life-threatening. Diagnosis is difficult, and high index of suspicion should be maintained for a patient presenting with cholecystitis. Prompt operative consideration for GBP is recommended. Gallstone disease is more common in patients with cirrhosis, though risk of morbidity and mortality with surgery is often high. We present a case of GBP complicated by peritonitis to illustrate the complexity of managing this condition in a patient with comorbid cirrhosis.

CASE DESCRIPTION/METHODS:
A 58 year-old man with alcohol-related cirrhosis (Child Pugh C) presented with fatigue, abdominal pain 2 weeks after a large volume paracentesis (LVP), LLQ approach with US. He was afebrile with a distended abdomen, jaundice, and lower quadrant tenderness. Ascitic fluid analysis showed 27 k/μL WBC with 90% neutrophils, initially concerning for peritonitis secondary to bowel perforation from the recent LVP. CT imaging was consistent with gallstones in the pelvic ascites fluid, and a large left hydrocele with stones in the scrotal sac (Figures 1–3). Diagnosis was presumed peritonitis secondary to GBP, though ultrasound and HIDA scan were negative for a gallbladder wall defect or active bile leak. Peritoneal fluid cultures grew Streptococcus sanguinis, and the patient improved with IV antibiotics. Repeat LVP and fluid analysis showed reduced WBC count. Cholecystectomy and peritoneal washout were deferred due to surgical risksin the setting of decompensated cirrhosis. Unfortunately, he developed mixed septic/hemorrhagic shock from a duodenal ulcer bleed and expired shortly thereafter.

DISCUSSION:
This case exemplifies the complexity in diagnosing and managing GBP in a patient with decompensated cirrhosis. Were it not for his high peritoneal fluid WBC and recent LVP prior to admission, it would be reasonable to suspect spontaneous bacterial peritonitis, CT imaging would be deferred and his GBP unrecognized. Therefore, maintaining high suspicion for GBP in a cirrhotic patient with severe peritonitis or concern for cholecystitis is recommended to avoid complications of GBP. This case also highlights the difficulty in treating GBP, or any symptomatic gallstone disease, in a decompensated cirrhotic where surgery is high risk. This patient's initial stability and decompensated cirrhosis led to deferral of operative consideration, leaving his peritoneal stones as a nidus for infection. His GI bleed was felt to be unrelated, but his septic shock expedited his decompensation.
2483 Amoxicillin-Induced Eosinophilia in Portal Tracts—A Rare Case of Idiosyncratic Acute Cholestatic Hepatitis
Authors: Bhardwaj Gaurav , Haider Tehseen , Timsar Ali Kazerouni , Tow Clara 
Published: October 2019

INTRODUCTION:
Drug induced liver injury (DILI) accounts for approximately 10 percent of all cases of acute hepatitis. Amoxicillin/clavulanic acid induced liver injury is a well-recognized complication but amoxicillin alone has rarely been linked with clinically significant idiosyncratic liver injury. It is exceedingly uncommon to see eosinophilic penetration of portal tracts with amoxicillin induced liver injury.

CASE DESCRIPTION/METHODS:
A 21 year old obese woman presented with jaundice preceded by fever and right upper quadrant abdominal pain for 1 week. She had completed a 10 day course of amoxicillin for an ear infection 3 weeks back. She denied any alcohol, acetaminophen, herbal medications, recent travels or exposure to sick contacts. She had scleral icterus and tender hepatomegaly with no rash on exam. Serum AST, ALT and ALP were moderately elevated with peaks of 216 U/L, 296 U/L and 466 U/L respectively. Serum bilirubin peaked at 13.1 mg/dL with direct component of 9.7 mg/dL. Blood differential count was significant for elevated eosinophils 0.8 k/uL (range 0.1-0.3 k/uL). Work up was negative for viral and autoimmune hepatitis. The levels of ceruloplasmin, alpha-1-antitrypsin and immunoglobulins were normal. Ultrasound and MRCP showed an enlarged fatty liver with no evidence of biliary ductal dilatation. Liver biopsy showed expanded portal tracts with marked inflammatory infiltrate composed predominantly of neutrophils with many eosinophils, and scattered lymphocytes and plasma cells. There was hepatocellular and canalicular cholestasis with no bile ductular reaction.

DISCUSSION:
The incidence of DILI with amoxicillin alone is 0.3 per 10,000 prescriptions compared to 1.7 per 10,000 prescriptions with amoxicillin/clavulanic acid. Risk factors are older age, female sex, pregnancy, high BMI and excessive alcohol intake. Signs and symptoms begin within 6 weeks of initiating amoxicillin, including nausea, abdominal pain, jaundice, fever, pale stools, dark urine, and pruritus. The mechanism of amoxicillin hepatotoxicity is unknown with possibility of idiosyncratic immune allergic reaction. Histologically liver injury appears most often as a cholestatic hepatitis and may have associated bile duct injury manifesting as extensive infiltration of the biliary epithelium with inflammatory cells accompanied by nuclear irregularity, cytoplasmic vacuolization and eosinophilia of the biliary epithelium. The primary treatment is the withdrawal of the drug.