Bupivacaine-Induced Hepatotoxicity in a Healthy Patient Without Chronic Liver Disease After Shoulder Arthroscopy

Introduction: Bupivacaine is a local anesthetic which has been increasingly used in the post-operative state for pain control. Hepatotoxicity is a rare complication, and few cases are reported in patients with chronic liver disease. We present a case of acute liver injury from bupivacaine use in a healthy patient without prior history of liver disease. Case Description/Methods: A 68-year-old female with a past medical history of primary hypertension and recent nontraumatic complete tear of the right rotator cuff, presents to the hospital with fatigue, loss of appetite, and nausea. She recently underwent an arthroscopy of the right shoulder with repair of the rotator cuff two weeks prior. Her surgery was uncomplicated, and patient was started on bupivacaine ONQ pump infusion at 5 ml/hr for three days for post-operative pain. Further history reveals patient is non-alcoholic without prior liver disease, including cirrhosis. Review of systems is concerning for associated generalized abdominal discomfort. Physical exam demonstrated jaundice with scleral icterus with mild periumbilical tenderness to palpation without hepatosplenomegaly or ascites. Labs demonstrated elevated total bilirubin of 10.2 mg/dL with Alkaline phosphatase, ALT, and AST being 924 U/L, 429 U/L, and 279 U/L, respectively. Imaging studies including CT abdomen and pelvis with contrast, abdominal ultrasound, MRCP, and portal vein doppler were negative. Additional work up for underlying liver disease including acetaminophen and ethanol levels, SARS-CoV2, Hepatitis panel, EBV antigen, and urine toxicology were negative. It was determined patient had bupivacaine induced hepatotoxicity. Patient's health improved with conservative management and she was discharged with instructions for close monitoring of her LFTs. Discussion(s): Bupivacaine is an amino-amide anesthetic which binds to the intracellular portion of voltage-gated sodium channels and prevents depolarization of pain signals. It is metabolized by the liver and thus reports of hepatotoxicity, although rare, occur in patients with underlying liver pathology. Our patient became symptomatic with acute rise in LFTs. An extensive workup for other etiologies of acute liver toxicity was negative. Rapid vascular uptake of the drug is the most common reason for bupivacaine toxicity;and this remains a possibility for the mechanism of toxicity in our patient. A prior case report of bupivacaine hepatotoxicity demonstrated a cholestatic pattern, which is consistent with our findings.

A Diagnostically Challenging Case of Primary Pancreatic Lymphoma

Introduction: Primary Pancreatic Lymphoma (PPL) is the exceedingly rare instance of extranodal Non-Hodgkin's Lymphoma developing mainly in the pancreas.We report a diagnostically challenging case of a patient presenting with a rapidly growing pancreatic mass, found to have PPL. Case Description/Methods: A 48-year-old female with past history of tobacco use presented with several months of cramping abdominal pain following COVID-19 infection. She denied weight loss, fevers, or night sweats. Her physical exam, CBC, CMP, lipase, LDH, and CA 19-9 were unremarkable. An abdominal ultrasound revealed a 2.8 x 1.9 x 3 cm cystic mass of the pancreatic head, most congruent with a pseudocyst. Worsening abdominal pain prompted repeat ultrasound one month later, which showed a doubling in size. Endoscopic ultrasound (EUS) with fine needle aspiration of the cystic mass and surrounding lymph nodes yielded cystic contents and reactive lymphadenopathy. Two months later, her abdominal pain worsened and repeat imaging showed further doubling in size with encasement of the celiac plexus. A second FNA performed via EUS redemonstrated cystic contents. An ultrasound-guided core needle biopsy of the mass revealed necrotic CD301 diffuse large B cell lymphoma (DLBCL). PET scan was suggestive of stage IV PPL (Figure). Imaging also identified an inguinal lymph node that returned as CD101 BCL61 high grade follicular lymphoma, which was thought to be a distinct lesion. She was started on R-CHOP. Her clinical course was complicated by the formation and subsequent rupture of a splenic artery pseudoaneurysm, gastrointestinal bleeding, anuric kidney injury, and intestinal ischemia. She ultimately transitioned to comfort care. Discussion(s): Primary pancreatic lymphoma comprises 0.6% of extranodal lymphomas and 0.2% of primary pancreatic tumors. The clinical presentation is often vague and includes abdominal pain, B symptoms, jaundice, or bowel obstruction. The diagnostic criteria according to the WHO requires that the (1) majority of tumor burden be localized to the pancreas and (2) existing nearby and distant lymph node involvement should be secondary to pancreatic presentation. A biopsy is required to diagnose PPL, which is histologically most often DLBCL. Our case highlights the challenges associated with diagnosing PPL despite two EUS with FNA. Although rare, one should proceed with a high index of suspicion for PPL in any patient presenting with a rapidly enlarging pancreatic mass.

Syphilis: "The Great Imitator" Presenting as Acute Hepatitis

Introduction: Syphilis is a multi-systemic disease caused by spirochete Treponema pallidum. Very rarely, it can affect the liver and cause hepatitis. Since most cases of hepatitis are caused by viral illnesses, syphilitic hepatitis can be missed. Here, we present a case of syphilitic hepatitis in a 35-year-old male. Case Description/Methods: Patient was a 35-year-old male who presented to the hospital for jaundice and mild intermittent right upper quadrant abdominal pain. His medical history was only significant for alcohol abuse. His last drink was 4 weeks ago. He was sexually active with men. On exam, hepatomegaly, mild tenderness in the right upper quadrant, jaundice, and fine macular rash on both hands and feet were noted. Lab tests revealed an ALT of 965 U/L, AST of 404 U/L, ALP of 1056 U/L, total bilirubin of 9.5 mg/dL, direct bilirubin of 6.5 mg/dL, INR of 0.96, and albumin of 2.0 g/dL. Right upper quadrant ultrasound showed an enlarged liver but was negative for gallstones and hepatic vein thrombosis. MRI of the abdomen showed periportal edema consistent with hepatitis without any gallstones, masses, or common bile duct dilation. HIV viral load and Hepatitis C viral RNA were undetectable. Hepatitis A & B serologies were indicative of prior immunization. Hepatitis E serology and SARS-CoV-2 PCR were negative. Ferritin level was 177 ng/mL. Alpha-1-antitrypsin levels and ceruloplasmin levels were normal. Anti-Smooth muscle antibody titers were slightly elevated at 1:80 (Normal < 1:20). Anti-Mitochondrial antibody levels were also slightly elevated at 47.9 units (Normal < 25 units). RPR titer was 1:32 and fluorescent treponemal antibody test was reactive which confirmed the diagnosis of syphilis. Liver biopsy was then performed which showed presence of mixed inflammatory cells without any granulomas which is consistent with other cases of syphilitic hepatitis. Immunohistochemical stain was negative for treponemes. Patient was treated with penicillin and did have Jarisch-Herxheimer reaction. ALT, AST, ALP, and total bilirubin down trended after treatment. Repeat tests drawn exactly 1 month post treatment showed normal levels of ALT, AST, ALP, and total bilirubin (Figure). Discussion(s): Liver damage can occur in syphilis and can easily be missed because of the non-specific nature of presenting symptoms. In our patient, the fine macular rash on both hands and feet along with history of sexual activity with men prompted us to test for syphilis which ultimately led to diagnosis and treatment in a timely manner. (Figure Presented).

A Case Report of Ivermectin-Induced Liver Failure

Introduction: Ivermectin is an antiparasitic medication that is primarily metabolized by the liver. During the COVID-19 pandemic, researchers demonstrated that Ivermectin successfully inhibited the replication of SARS-COV-2 in vivo, but current research has failed to demonstrate clinical benefit for treatment of COVID-19. Despite this, misinformation campaigns have misled patients to ingest Ivermectin at concentrations meant for domestic animals. Here, we present a case of acute liver failure secondary to the use of Ivermectin. Case Description/Methods: A 61-year-old man with medical history of ischemic cardiomyopathy with last echocardiogram showing ejection fraction at 21%, atrial fibrillation on warfarin for oral anticoagulation, and previously treated Hepatitis C presented with generalized weakness and yellowish discoloration of the skin worsening over the last two weeks. The patient denied significant alcohol use, acetaminophen use, or illicit drugs. He admitted to injecting himself with two doses of weight-based horse ivermectin, for COVID prophylaxis, two weeks prior to his presentation. Physical exam was pertinent for scleral icterus and hepatomegaly with no abdominal tenderness. Initial labs revealed elevated liver chemistries in a mixed pattern (Figure 1). Acute hepatitis panel, HSV, and CMV were negative. Hepatitis C antibodies were positive, but the patient was in sustained virologic response. Full workup for chronic liver disease was unremarkable. Ultrasound revealed hepatosplenomegaly with patent portal and hepatic vasculature. Subsequently, the patient developed hepatic encephalopathy along with his coagulopathy, raising concern for acute hepatic failure. The patient was transferred to the ICU and started on NAcetylcysteine, rifaximin, and supportive care. The patient recovered well and fortunately did not require liver transplant. Discussion(s): While the FDA recommends against the use of Ivermectin for COVID-19, many continue to inappropriately consume it. Ivermectin-induced liver failure is a rare but deadly side effect. Given our patient's rapid onset of symptoms post-self injection of Ivermectin, his liver injury was presumed to be related to Ivermectin. The drug interaction between Ivermectin and warfarin had worsened the patients coagulopathy. Physicians should be aware of the ways Ivermectin overdose may clinically present to avoid delayed treatment. This case demonstrates the detriments of perpetuation of medical misinformation to care.

Covid-19 Associated Hepatitis in Children (Cah-C) during the Rise of Delta Variant in India: A New Covid-19 Complication or a Superinfection

Intro: While the pediatric population has largely remained free of severe COVID- 19, in some situations SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). Recently, cases of hepatitis in children have caused tremendous worry across the globe, we describe a unique presentation from 2021, subsequent to asymptomatic infection of SARS-CoV-2, a unique form of severe hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The clinical presentations, temporal association, and viral parameters of CAH-C cases, and contrast to that of MIS-C cases are presented here. Method(s): As a retrospective and follow-up case-control study we reviewed all children within 14 years presenting with "sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice. After performing all routine tests among them, those lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis (A-E) or previous underlying liver disease, and (b) multi-system involvement", being unique such cases were classified as CAH-C, and are described here. Finding(s): Among 475 children who tested positive, 37/47 cases had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers, 100% positivity for SARS-CoV-2 antibodies, and uneventful recovery. The remaining 10/47 having MIS-C had protracted illness, multiple system involvement, required admission to critical care, and a mortality rate of 30%. Among controls, only 26/50 (52%) had SARS-CoV-2 antibodies. Discussion(s): During the pandemic, various COVID-19 complications have been observed posing safety concerns, where our study identified a unique form of acute hepatitis in children designated as CAH-C. Conclusion(s): With the emergence of newer variants, including the Delta variant which predominated the second wave of infections in India and spread worldwide with changing presentations and complications, CAH-C is such new entity in children. It needs early identification and differentiation from other emerging syndromes during the ongoing pandemic for preventing adversities through timely intervention.Copyright © 2023

Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient's improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion(s): DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient's supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent livertransplantation. Our patient's unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. (Table Presented).

A Rare Case of Congenital Choledochal Cyst (CCC) Resulting in Recurrent Acute Pancreatitis in an Otherwise Healthy Young Woman

Introduction: Congenital choledochal cyst (CCC) is a rare cystic dilatation of intrahepatic or extrahepatic biliary ducts. We present a case of a type IVb choledochal cyst presenting as recurrent acute pancreatitis in a young healthy female with initial negative screenings. Case Description/Methods: An 18-year-old-female with a history of COVID-19 presented to the emergency department with one month of persistent abdominal pain, nausea, and vomiting. She was hospitalized once prior for similar symptoms and was diagnosed with acute pancreatitis. This admission, blood work showed elevated lipase, elevated liver enzymes, mild bilirubinemia with a normal lipid panel and urine was significant for infection. She received fluids, antiemetics and was started on prophylactic antibiotics for ascending cholangitis. A right upper quadrant ultrasound ruled out cholelithiasis or acute cholecystitis, but showed dilation of the common bile duct. MRCP confirmed dilation with bulbous termination in the periampullary region diagnosed as type IVb choledochal cyst. Discussion(s): CCCs are rare in Western countries with an incidence between 1 in 100,000 to 150,000. 80% of these cysts are diagnosed in patients under the age of 10. They are difficult to diagnose due to variable clinical presentations. A study of 214 CCC patients demonstrated the most common symptom was abdominal pain, followed by jaundice and fever. When cysts are found in adults, symptoms resemble atypical acute biliary tract disease. Surgical cyst removal may be needed for patients with significant risk factors such as older age and age of symptom onset, due to increased risk of malignant transformation. Longer periods of observation have been documented to be associated with an increased chance of developing late complications, such as anastomotic stricture, biliary calculi and recurrent cholangitis. Type IVb CCCs, as seen in this case, consist of multiple extrahepatic cysts and hepaticojejunostomy is the treatment. This patient's young age and recurrent acute pancreatitis combined with her lab and imaging findings strongly suggest the diagnosis of CCC. The anatomical location of the CCC impeded flow of pancreatic enzymes through the ampulla of vater, leading to recurrent pancreatitis in an otherwise healthy young female. CCC, although very rare, should be considered in the differential of acute pancreatitis when other causes such as gallstones and heavy alcohol consumption cannot be identified, as prompt diagnosis and surgical removal is imperative.