Stigmata Of Chronic Liver Disease Research Articles

PTU-117 Cutaneous Stigmata Of Chronic Liver Disease; What Do They Mean?

IntroductionAs clinicians we are taught to assess all patients for cutaneous signs of chronic liver disease (CLD). However, there is limited evidence available in the literature regarding their significance or...

Late‐Onset Ornithine Transcarbamylase Deficiency Presenting With Asymptomatic Liver Dysfunction

Late‐Onset Ornithine Transcarbamylase Deficiency Presenting With Asymptomatic Liver Dysfunction

Nitrofurantoin-induced Autoimmune Hepatitis: A Case Report

Introduction: Several commonly used medications are well-established in triggering drug-induced autoimmune hepatitis (DIAIH), with nitrofurantoin being a widely used antibiotic in the treatment of recurrent urinary tract infections (UTIs), which has been reported to elicit a wide spectrum of hepatic insults ranging from acute self-limited hepatitis to chronic hepatitis. Case Presentation: A 54-year-old woman with CAD and recurrent urinary tract infections on prophylactic nitrofurantoin for over 2 years was evaluated for sudden onset lower extremity edema, jaundice, and dark urine. She is not known to have liver disease, alcohol, or intravenous drug abuse. Examination was significant for jaundice and lower extremity edema in the absence of other stigmata of chronic liver disease. Labarotary evaluation showed abnormal liver function tests (ALT 535, AST 650, ALK-P 362, total bilirubin /direct bilirubin 4.7/3.6), along with normal blood count, coagulation screen, cardiac, and renal function. Serologic evaluation was negative for viral hepatitis. RUQ US with mild-to-moderate ascites with cirrhotic liver appearance. Abdominal CT showed a shrunken nodular liver with patent portal and hepatic veins. Immunologic evaluation was positive ANA and ASMA, but negative for AMA, anti ds-DNA, and anti LKM. Liver biopsy confirmed liver cirrhosis with no evidence of steatohepatitis or other superimposed liver disease. Expectant management with nitrofurantoin withdrawal alone only achieved partial recovery that was eventually hastened and maintained with additional limited course of high-dose corticosteroids. Discussion: Drug-induced autoimmune hepatitis represents a significant percentage of all AIH cases (9-17%). A definite association exists between commonly used medications (nitrofurantoin, minocycline) and DIAIH that we should be aware of as practicing clinicians. The time course between introduction of nitrofurantoin and DIAIH can be variable with tendency to present with acute symptomatology at various stages of treatment, with certain predilection for elderly females on prolonged prophylactic treatment for recurrent urinary tract infections. Nitrofurantoin, unlike minocycline, could present with significant fibrosis and cirrhosis, which is clearly reflected in our patient. Partial recovery upon drug withdrawal is to be expected in nitrofuratoin-induced AIH, with tendency for complete resolution on steroid challenge.

Secondary Hepatocellular Carcinoma Following Hepatic Infiltration of Chronic Lymphocytic Leukemia

Purpose: A 75-year-old Hispanic female from Puerto Rico, who presented to our hospital in 2008 for oncology evaluation. She had been diagnosed of chronic lymphocytic leukemia (CLL) 4 months earlier. This was confirmed by a sternal bone marrow aspiration. At that time, she was completely asymptomatic and had no palpable lymphadenopathy. Other pertinent past medical histories were diabetes mellitus, hypertension, hyperlipidemia, and migraine headaches. Laboratory exams were notable for mild lymphocytosis. Flow cytometry showed typical CLL with CD 19+/CD5+ (co-expression), CD20+ (dim), CD23+, CD38- and kappa light chain+ (dim), 0% of ZAP 70 positive. Bone marrow cytogenetics showed normal karyotype. Since her presentation, she had an abnormal elevation in alkaline phosphatase that ranged from 288 U/L to 440 U/L. Hepatitis C antibody and hepatitis B surface antigen were negative. All work-up for chronic liver disease was negative. She underwent a liver biopsy, which showed liver parenchyma with a patchy infiltrate of small lymphocytes expressing CD20, PAX-5, CD5, CD23, CD43, and BCL-2 characteristic of B-small lymphocytic lymphoma/chronic lymphocytic leukemia. Serial CT scans showed progressive intra-abdominal lymph node affectation; however, she did not meet criteria for treatment for her CLL, as her WBC count, as well as other markers of disease activity remained stable. In 2012, as part of the routine evaluation of her progressive intra-abdominal lymphadenopathy, an abdominal CT scan showed an 8-cm liver mass. Though initially asymptomatic, she developed a right upper quadrant pain that was severe, associated with malaise, constipation, and loss of appetite. Physical examination showed submandibular lymphadenopathy and right upper quadrant tenderness. She had no peripheral stigmata of chronic liver disease. The presence of a large liver mass with an underlying history of liver biopsy being positive for CLL/B-lymphocytic lymphoma made a suspicion of a rapidly growing lymphoma likely. Alpha fetoprotein was also normal. She underwent a second liver biopsy that now revealed grade II hepatocellular carcinoma (HCC). Being Child-Pugh stage B, with a huge liver mass and maintaining a good functional status, she only met the Barcelona Clinic Liver Cancer (BCLC) criteria for treatment with sorafenib, which she was started on, but tolerated for only few weeks. Unfortunately, she continued to decline while the tumor increased exponentially. She was eventually placed in a hospice, and died 3 weeks later. There may be a real association between HCC and CLL. Future studies are required to establish evidence and the goals of treatment.

Mitragyna Speciosa (Kratom)-Induced Cholestatic Hepatitis

Purpose:Mitragyna speciosa Korth (vernacular name: kratom) is a tall, leafy tree in the family Rubiaceae. Kratom leaves have long been used as a narcotic and central nervous system stimulant. Herein, we report the first case of cholestatic hepatitis due to kratom use. Methods: A 34-year-old female with no significant past medical history was referred for evaluation of her extreme fatigue, pruritus, and jaundice. She was well until two weeks prior, when she started having back aches, for which she took a half-spoon of kratom for two consecutive days. Within a week, she started feeling fatigued, which subsequently worsened, and extreme pruritus ensued. The patient also noticed dark-colored urine and clay-colored stools. She denied any abdominal pain, fever, nausea, vomiting, chills, melena, rashes, confusion, excessive alcohol drinking, recent travel, intravenous drug abuse, or recent antibiotic use. She endorsed taking less than 2 grams of acetaminophen daily for the last three days. On examination, she was oriented to person, place, and time, with scleral icterus and multiple excoriation marks. No stigmata of chronic liver disease were noticed. Abdominal and neurological examinations were unremarkable. Upon presentation, liver biochemistries revealed alanine aminotransferase (ALT) 93 U/L [range: 12-78 U/L], aspartate aminotransferase (AST) 61 U/L [range: 15-37 U/L], alkaline phosphatase (ALP) 298 U/L [range: 50-136 U/L), and total bilirubin: 10.6 mg/dl [range: 0.2- 1.0 mg/dl]. No evidence of coagulopathy was noted. Serological tests for Hepatitis A, B, C, Epstein-Barr virus, cytomegalovirus, and auto immune hepatitis were negative. Her urine toxicology was negative, and alcohol level was normal. Wilson's disease, alpha 1 antitrypsin deficiency, primary biliary cirrhosis, and hemochromatosis were ruled out by appropriate testing. The patient was initially started on N-Acetylcysteine (NAC) protocol for potential acetaminophen toxicity. Abdominal ultrasound and hepatobiliary scan revealed no evidence of common bile duct obstruction. She was started on ursodiol 10 mg/kg/day and hydroxyzine for pruritus. Liver biopsy was preformed, which revealed cholestasis, lobular inflammation, and increased eosinophils within sinusoids, consistent with drug-induced liver injury. Given the absence of coagulopathy or encephalopathy, she was discharged home with follow-up. An appointment 40 days later revealed complete normalization of liver function tests and resolution of clinical symptoms. Conclusion: To our knowledge, this is the first reported case of kratom-induced cholestatic hepatitis. This case highlights the need for physicians to consider widely available substances, especially herbal supplements, when evaluating cholestatic liver injury.

An Unusual Cystic Mass of the Liver

Clinical Presentation: A 43-year-old female with a history of migraines and hypertension presented with 3 months of dull, constant, right upper quadrant abdominal pain with no associated symptoms. She denied weight loss. Exam was significant for a non-tender abdomen without hepatosplenomegaly, and no stigmata of chronic liver disease. Significant labs were: Cr 0.7, Alb 4, AST 17, ALT 14, AP 64, TB 0.24. A RUQ ultrasound showed a hypoechoic mass appearing in the right lobe of the liver. An abdominal CT revealed a heterogeneous-appearing cyst in the liver with no evidence of ascites. An EGD was performed for evaluation of her abdominal pain, which showed esophagitis. A PPI was started, but she continued to have abdominal pain after several weeks of treatment. An MRI was obtained to further characterize the hepatic cyst, and revealed a 3.9 x 4.3 x 5.1-cm circumscribed cyst within segment 4b, which contained a large enhancing complex mural nodule of 3.2 cm in diameter. The mural nodule was composed of multiple thin and thick septations surrounding tiny cystic spaces. Echinococcus antibodies were weakly positive. She was referred for hepatobiliary surgical consultation. She was given preoperative albendazole for the possibility of an echinococcal cyst. A left hepatectomy and cholecystectomy were successfully performed after several days of albendazole. Surgical findings were significant for a large, mildly steatotic liver with the cyst located predominantly in segment 4b, but also extending into segment 3. Surgical pathology revealed a 5-cm multilocated mucinous biliary cystadenoma, lined by simple cuboidal to columnar mucinous epithelium with ovarian-type stroma, which was negative for malignancy. Immunohistochemical studies showed stromal spindle cells positive for ER and PR. Discussion: Biliary cystadenomas are rare, slow-growing hepatic neoplasms that typically occur in middle-aged women and account for less than 5% of cystic lesions of the liver. The clinical symptoms can be non-specific, but often include abdominal pain. Cystadenomas have the potential for malignant transformation with progression to biliary cystadenocarcinomas, which can be focal and undetectable on imaging. Patients with a suspected cystadenoma should be promptly referred for surgical resection due to the potential for progressing to malignancy, and a high risk of recurrence with non-surgical management strategies.

Time to Consider Empiric Acyclovir

Purpose: A 63-year-old female presented to the emergency department with a two-day history of fever of 101.9°F and worsening fatigue. She denied a history of liver disease and was otherwise in good health, aside from a history of arthritis. She denied any recent changes in medications, use of antibiotics or travel history. Urine toxicology screen, acetaminophen level and hepatitis A-C serology were negative. Her laboratory assessment was notable for AST 4755 IU/L, ALT 3569 IU/L and an INR of 1.4. She was admitted into her local hospital and started on intravenous N-acetylcysteine. Overnight, she developed subtle changes in behavior without any change in level of consciousness. She was subsequently transferred to a liver transplant center. Upon arrival, the patient was oriented, but very somnolent, and remained febrile at 103.1°F. Physical exam was negative for stigmata of chronic liver disease, rash or asterixis. Laboratory assessment revealed total bilirubin 0.6 mg/dl, AST 7392 IU/L, ALT 5942 IU/L, INR of 2.2, WBC 2900 cells/ mm3, hemoglobin 16 g/dL and platelets of 29,000/mm3. Abdominal ultrasound showed a normalappearing liver with normal hepatic and portal flow. Further history from family revealed the patient was taking oral prednisone the past few weeks for chronic joint pain. Given this history, combined with fever, leukopenia and anicteric hepatitis, she was started on empiric IV acyclovir for possible herpes simplex virus (HSV)-induced liver failure. She underwent expedited liver transplant evaluation. A trans-jugular liver biopsy revealed minimal inflammation with scattered hepatocyptes with glassy nuclear inclusions, azonal areas of necrosis and positive HSV stain. Her serum HSV DNA testing by PCR was 1.2 x 10ˆ6 copies/ml, although her initial HSV IgM was within reference range. Her laboratory values normalized completely within 15 days, and she was discharged to a local rehab center. HSV-induced liver failure accounts for only 1% of all ALF, but confers a mortality rate of 75%. Although immunocompetent patients can be affected, 75% of affected patients are immunosuppressed or pregnant in the third trimester. Patients who present with fever, vesicular skin lesions, leukopenia and anicteric hepatitis need to be considered for empiric acyclovir therapy and transferred to a liver transplant center. Serological testing with antibodies against HSV in the serum is nonspecific and has low utility in early treatment decisions. Confirmation of diagnosis is best performed with liver biopsy and serum HSV PCR. Empiric therapy with acyclovir for patients at risk may obviate the need for liver transplantation.

AugmentinTM-induced DILI: A Case of Severe Cholestatic Jaundice with Spontaneous Resolution

Introduction: Drug-induced liver injury (DILI) is a major cause of iatrogenic illness, and may present with an array of histologic signatures. Establishing a diagnosis of DILI requires a careful exclusion of other etiologies and an awareness of the hepatotoxicity profile of suspected agents. Case: A 70-year-old man with a history of HTN, CAD, AF, and BPH was referred for a six-day history of intense pruritus, associated with jaundice, dark urine, and acholic stool. He denied any abdominal pain, weight loss, recent travel, fevers/chills, or sick contacts. Physical exam revealed a jaundiced patient with no cutaneous stigmata of chronic liver disease, and no hepatosplenomegaly, ascites, or asterixis. On presentation, his LFT's were as follows: T bili 7.5, D bili 4.6, AST 34, ALT 45, ALP 232, GGTP 63, alb 3.8, and normal INR. Serologies revealed a negative HAV IgM, HBSAg, HB core IgM, HCV PCR, ANA, SMA, AMA, anti-LKM, P-ANCA, ACE, and normal immunoglobulins. Doppler U/S revealed a normal liver morphology with a small hepatic cyst, patent hepatic vessels, normal gallbladder, no biliary ductal dilation and no hepatosplenomegaly or ascites. MRCP revealed a normal biliary tree with no pruning. Within 10 days of presentation, his T bili peaked at 20.9 with an ALP of 274. On further inquiry, the patient recalled a two-week course of amoxicillin/clavulanate (AugmentinTM) for a URI, with his symptoms beginning one week after discontinuation of the antibiotics. A liver biopsy revealed mild cholestasis, spotty necrosis/apoptosis, lymphocyte, neutrophil, and eosinophil infiltration consistent with a drug-induced hepatitis. There was no bile duct damage, ductopenia, granulomas, or fibrosis. The patient was prescribed cholestyramine four g BID for pruritus, and urso 250 mg BID. Within eight weeks, his LFT's had completely normalized. Discussion: Amoxicillin/clavulanate- induced DILI is estimated to occur with an incidence of 17/100,000 prescriptions, and the clavulanic acid component is the likely injurious agent. This idiosyncratic reaction is thought to be immunoallergic in origin, and autoantibody formation is uncommon. Men over 50 years of age and prolonged/repeated courses of AugmentinTM are associated with an increased risk of DILI. Although cases of acute liver failure and chronic ductopenia have been described with AugmentinTM, a delayed cholestatic or a mixed cholestatic-hepatocellular liver injury pattern is the norm, and usually resolves within two months. Despite our patient being an elderly male who developed marked jaundice, his course was ultimately benign, with full resolution of symptoms.

An Unusual Cause of Jaundice: Cholestasis-lymphedema Syndrome “Aagenaes Syndrome”: ACG/AstraZeneca Clinical Vignette Award: Presidential Poster

Purpose: A 61-year-old Caucasian male of Norwegian descent presented to the emergency department with complaints of progressive jaundice, pruritus, dark urine, clay-colored stools, and lower extremity edema for one month. This patient had history of intermittent jaundice all of his life, with chronic lower extremity edema. As an infant, he had an exploratory laparotomy for biliary atresia, but no definitive intervention was done. There was no family history of liver disease, no history of alcohol use, and his only medication was furosemide. On examination, he had no stigmata of chronic liver disease, reduced air entry in both lower lung fields, a healed laparotomy scar, and 2 + bilateral pedal edema. Initial labs showed a normal complete blood count and renal function, but a total bilirubin of 6.7 (Direct 4.2), alkaline phosphatase of 422 with AST 41, and ALT 32. A chest X-ray done in the ED revealed bilateral pleural effusions. Subsequent work-up for chronic liver disease was negative, and liver ultrasound with Dopplers and MRI of the liver were negative. A liver biopsy showed chronic lymphocytosis. Thoracentesis demonstrated chylothorax with triglycerides of 815 mg/dl. In summary, this is a 61 year-old Caucasian male of Norwegian heritage with recurrent, intermittent, cholestatic jaundice with chronic lymphedema, pruritus, and chylothorax. Given this constellation of findings, we diagnosed our patient with Aagenaes syndrome. This syndrome was first described in six large Norwegian families, and is characterized by chronic lymphedema and cholestasis. Its inheritance is autosomal recessive, with a prevalence of < 1 in 100,000. Pathogenesis involves a defect in lymphangiogenesis with generalized hypoplasia of lymphatics and the abnormal development of lymphatics around small biliary tracts. Patients present with severe neonatal cholestasis, which decreases during early childhood and becomes episodic later. Lymphedema is present at birth, but is usually noticed later, and affects the small bowel and thoracic soft tissue leading to chylothorax. Liver histology may show non-specific inflammation (as in our patient), giant cell transformation, fibrosis, or cirrhosis. Prognosis for liver disease is good. Management involves eating a fat-reduced diet during cholestasis, with supplementation of fat-soluble vitamins. We used subcutaneous octreotide for the chylothorax, with resolution of his pleural effusions. The patient is doing well currently, and is being followed in the hepatology clinic.

Vanishing Bile Duct Syndrome: A Rare Cause of Cholestasis in Hodgkinʼs Lymphoma

Case: A 46 year-old Hispanic male presented with a 3-day history of jaundice, poor appetite, and abdominal pain. Past medical history was unremarkable, and the patient was not taking medications, illicit drugs, or alcohol. He denied B symptoms. Physical exam was unremarkable except for jaundice; no stigmata of chronic liver disease. Investigations showed total bilirubin of 14.2 mg/dL (direct 9mg/dL), GGT 362, AP 581, AST 120, ALT 248, albumin 4.1g/dL. Serology was negative for HIV, hepatitis A, B and C. CT showed normal liver without intra or extra-hepatic duct dilatation, and multiple large para-aortic and peri-hepatic lymph nodes (LN). Biopsy of a LN showed mixed cellularity Hodgkin lymphoma (HL), stage I/II. Bilirubin continued to rise to 27.2 mg/dL, and despite two cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), bilirubin increased to 41 g/dL, which lead to ABVD cessation and initiation of radiotherapy (RT) to the abdomen. An ERCP was normal. A liver biopsy showed marked canalicular and focal hepatocytic cholestasis, minimal inflammation, and ductopenia; no malignant cells, steatosis or iron deposition were seen, and a diagnosis of vanishing bile duct dyndrome (VBDS) as the cause of cholestasis was established. Ursodeoxycholic acid was started, RT was completed, and ABVD was restarted when bilirrubin decreased. Treatment was completed and a followup CT showed a decrease of LN size, and a PET scan was negative. Currently,18 months after diagnosis, the patient remains well and in remission. His bilirubin has normalized, and LFT have improved to near normal. Discussion: Cholestasis as the presenting symptom of HL is very uncommon (<4%). It can be caused by lymphomatous infiltration of the liver, extrahepatic biliary obstruction by lymphadenopathy, concurrent viral infections, or drug toxicities. Rarely, it can be due to a paraneoplastic phenomenon, which can be divided into VBDS and pure intrahepatic cholestasis without ductopenia. The pathophysiology of VBDS is unknown, but is thought to be caused by release of toxic cytokines from lymphoma cells, leading to destruction of bile ducts without significant inflammation. Diagnosed by exclusion and supported by histology in the absence of liver involvement by HL. VBDS is rare, and usually fatal. Only 18 cases of VBDS have been reported since its description in 1993. The overall mortality is 65%, liver failure being the leading cause, followed by sepsis and recurrence of HL. However, 30% of cases have normal LFT without recurrence at 24 months. There is no difference in outcome across sex, age, type of HL, B-symptoms, or chemotherapy or steroids, but those who are stage I/II at presentation and receive radiotherapy appear to have a better outcome.

Lower GI Bleeding in a Patient with Cirrhosis and History of Colorectal Cancer

Question: A 65 year old man with history of colorectal cancer treated with left hemicolectomy and transverse colon colostomy 6 years ago was admitted to the hospital with bloody colostomy output. His other medical history was notable for type II diabetes, obesity and heavy alcohol use. He has had intermittent bloody colostomy output for the past three years. It was bright red blood that would fill his ostomy bag. This has been treated at other hospitals with periodic admission for blood transfusion and also with local cautery. A stomal revision was planned but was not performed because of unknown reasons. On admission he was hemodynamically stable, and his blood pressure was 190/100. Physical examination was unremarkable except for pallor, mild splenomegaly and colostomy. There were no stigmata of chronic liver disease. His labs included white blood cell count 2.7/mm3, hemoglobin 9.7 g/dl, platelets 56,000/mm3, normal electrolytes, urea nitrogen 12 mg/dl, creatinine 1.0 mg/dl, AST 30 IU/ml, ALT 18 IU/ml, alkaline phosphatase 55 IU/ml, total bilirubin 1.4 mg/dl, and International Normalized Ratio of prothrombin time 1.2. On the third day of admission, he had another episode of bright red blood that filled the colostomy bag associated with light-headedness and hypotension. His hemoglobin dropped to 7.6 g/dl. He responded well to resuscitation with 0.9% normal saline and 4 units of packed red blood cells. An EGD showed a normal esophagus and mild portal hypertensive gastropathy. The colonoscopy through his colostomy showed normal colon and terminal ileum. A CT-angiography was performed (Figure A) and the patient was referred to Interventional Radiology for further management. Figure A What is the diagnosis?

Hematemesis in a Patient With Diabetic Ketoacidosis and Chronic HCV Infection

292 Question: A 55-year-old man with past medical history of poorly controlled diabetes mellitus, recurrent infective endocarditis (last episode 2 months ago), and chronic hepatitis C presented to the emergency department with 2 episodes of coffee ground emesis. He also complained of fatigue, polyuria and lightheadedness for 2 days before admission. He denied any abdominal pain, prior retching,melena, or hematochezia. He denied using any nonsteroidal anti-inflammatory drugs, smoking, and recent alcohol or illicit drug use. On admission he was afebrile, tachycardic at 116 bpm, with a blood pressure of 121/92 mmHg, was breathing 24 times a minute and saturating well on room air. On physical examination, his skin and oral mucosa were dry. He was alert and oriented, with lungs clear to auscultation, heart sounds normal, and abdomen soft, nondistended, and nontender. He had no stigmata of chronic liver disease. Laboratory examination revealed blood sugar of 331 g/dL, sodium of 127 mEq/L, potassium of 6.4 mEq/L, bicarbonate of 7 mEq/L, anion gap of 29, and pH of 7.023. His blood urea was 69 mg/dL and creatinine 2.6 mg/dL. His hemoglobin was 16.7 g/dL; white blood cell count and platelets were normal. He was treated for diabetic ketoacidosis with an insulin drip and his electrolytes were corrected as needed. Nasogastric lavage was done and was clear. He was started on pantoprazole drip and an upper gastrointestinal endoscopy was performed which revealed diffuse blackish discoloration of the mid and distal esophagus (Figure A), which abruptly ended at the gastroesophageal junction. There was also evidence of erosive gastritis and erosive duodenitis (Figure B) in the bulb and second portion of duodenum. What is the diagnosis? What is the appropriate management? Look on page 491 for the answer and see the GASTROENTEROLOGY web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI.

Valproic acid‐induced hyperammonaemic coma and unrecognised portosystemic shunt

Hyperammonaemic encephalopathy is a rare and potentially fatal complication of valproic acid treatment. The clinical presentation of hyperammonaemic encephalopathy is wide and includes seizures and coma. We present a case of hyperammonaemic coma precipitated by sodium valproate use for symptomatic epilepsy in a patient with unrecognised portosystemic shunt, secondary to earlier alcoholism. The absence of any stigmata of chronic liver disease and laboratory markers of liver dysfunction delayed the recognition of this alcohol-related complication. The portal vein bypass led to a refractory, valproic acid-induced hyperammonaemic coma. The patient fully recovered after dialysis treatment.

Acute Kidney Injury in Patients With Cirrhosis: Perils and Promise

A 62-year-old man with cirrhosis secondary to hepatitis C and chronic alcohol abuse was admitted to the intensive care unit with hematemesis and mental status changes. Physical examination showed ascites and stigmata of chronic liver disease. Blood pressure was noted as 87/42 mm Hg and laboratory studies showed a serum creatinine level of 0.8 mg/dL, an estimated glomerular filtration rate of 84 mL/min/1.73 m(2) calculated using the Modification of Diet in Renal Disease Study equation, a serum sodium level of 123 mEq/L, a total serum bilirubin level of 4.3 mg/dL, and an international normalization ratio of 1.6. The patient was resuscitated with packed red blood cells and fresh-frozen plasma and bleeding was controlled. However, on the third day of admission, creatinine level increased to 1.5 mg/dL. Examination of urine sediment showed 1 to 5 bilirubin-stained granular casts per high-powered field and a few renal tubular epithelial cells. The urine sodium level was 21 mEq/L and the fractional excretion of sodium was 0.43%.

Double Vision

Question: A 43-year-old woman presented with progressively worsening right upper quadrant abdominal pain. The episodic pain occurred after high-fat meals and lasted from minutes to hours with accompanying nausea. Her previous medical history was notable for endometriosis. She denied other constitutional symptoms. Physical examination revealed no hepatosplenomegaly, jaundice, right upper quadrant mass, or stigmata of chronic liver disease.

Primary hypothyroidism masquerading as hepatocellular necrosis

Hepatic failure and encephalopathy has many causes, ranging from viral infections to medications to metabolic disorders. Severe primary hypothyroidism as a cause of severe liver failure and encephalopathy is very uncommon and, therefore, may be diagnosed late. The following is a case of severe myxoedematous hepatic failure which improved significantly following thyroxine therapy. A 47-year-old woman was presented with a 2-month history of progressive lethargy and malaise. She presented acutely in a semiconscious state and barely rousable following a rapid 2-day deterioration when jaundice was noticed. There was no other significant medical history and she denied taking any medications, prescribed or otherwise. She also denied any alcohol intake, intravenous drug use or recent overseas travel. There was no family history, particularly, of thyroid disease. She had been diagnosed with hypothyroidism 5 years ago, the exact cause was uncertain. She ceased the thyroxine herself after her practitioner had left the area and had been without medical care for some time. Clinical examination showed a semicomatose patient, unkempt and delirious but with stable vital signs. Her pulse rate was 96 beats per minute and blood pressure was 180/110 with no postural change. She was jaundiced with fetor hepaticus. There were no peripheral stigmata of chronic liver disease. Her liver span was normal. There was no splenomegaly, no ascites and no peripheral oedema. Her liver function tests showed a mixed pattern with aspartotransferase (AST) 599 U/l [Normal (N), <35], alaninetransferase (ALT) 569 U/l (N, <26), γ-glutamyltransferase (GGT) 121 U/l (N, <35), alkaline phosphatase (ALP) 272 U/l (N, 30–115) and bilirubin 130 μmol/l (N, <15). Albumin was slightly low at 33 g/l (N, 36–48), serum creatinine was 153 μmol/l and coagulation assay levels were increased with INR (international normalized ratio) 1.8 (N, 0.8–1.0) and APTT (activated pro-thrombin time) 38 s (N, 20–30). The initial …

Peritoneal Tuberculosis in an Immunocompetent, Unknown Risk Patient

A 36-year-old man with no significant past medical history presented with two-month abdominal distention, night sweats, and weight loss of 15 Ib. He had no known exposure to tuberculosis. PPD test was negative prior to the hospital admission. Physical examination was notable for new onset ascites, but no superficial lymphadenopathy or stigmata of chronic liver disease was found. CT scan demonstrated enlarged mesenteric lymph nodes, and prominent retroperitoneal lymph nodes along with moderate ascites and omental infiltration. Diagnostic paracentesis yielded WBC of 295/mm3, lymphocytic predominance (70%), and serum ascitic albumin gradient of 0.1, consistent with exudate. Both the ascitic culture and AFB smear were negative, and ascitic cytology revealed nonmalignant cells. Exploratory laparoscopy for excisional biopsy of mesenteric lymph nodes was performed. Pathologic findings revealed caseous granulomas with scattered multinucleated giant cells. Mesenteric lymph node tissue culture subsequently grew Mycobacterium tuberculosis complex and the diagnosis of peritoneal tuberculosis was confirmed. The patient was started on quadruple therapy. A couple of days after the antibiotics were started, the small bowel obstruction started to resolve with resumption of bowel movements and tolerance of oral intake. A week later, ascites stopped accumulating and fever was no longer noted. He has been well and continues to be under observation.

Tense Ascites in a Postpartum Woman

Question: A 36-year-old woman originally from Haiti presented to the emergency department with 2 weeks of abdominal distention, diarrhea, and blood-tinged emesis. She had given birth to her first child by uncomplicated caesarean section 9.5 weeks earlier. There was no history of recent travel, diet change, or sick contacts. She denied alcohol, tobacco, or illicit drug use and was not taking any medications or supplements. She was allergic to chloroquine (itchiness) and had no history of atopy. She was not aware of any family history of liver disease or allergy, although her paternal history was unknown. Upon being admitted to the general medicine service, the patient was afebrile and hemodynamically stable. She did not have any stigmata of chronic liver disease. Her abdomen was distended and diffusely tender with rebound tenderness and guarding (Figure A). Serum studies were notable for white blood cell count of 14.5 k/μL with 46% eosinophils (absolute count 6660/mm3). Other values, including serum human chorionic gonadotropin, were normal. Computed tomography of the abdomen and pelvis (Figure B) showed a large amount of abdominal and pelvic ascites (arrow) with mild small bowel wall thickening. There was no evidence of organomegaly or vessel thrombosis. Subsequent diagnostic paracentesis demonstrated an exudative effusion with total nucleated cells 4545/mL, with 82% eosinophils. Large-volume paracentesis of 4000 mL of straw-colored fluid relieved the patient's abdominal pain. Fluid bacterial and tuberculosis cultures were negative, and cytology showed no evidence of malignancy. Peripheral blood smear was unremarkable. Stool culture, stool ova and parasites, urine culture, and blood culture were all negative. Because of these findings, the gastroenterology service was consulted. Esophagoduodenoscopy and colonoscopy showed mild rectal mucosal erythema (arrow) without masses, bleeding, ulcers, or polyps (Figure C). What is the diagnosis? What is the appropriate management? Look on page 467 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Colonic (Figure D) and esophageal (Figures E and F) mucosal biopsies were obtained, which showed dense eosinophilic infiltrate of the esophageal and rectal submucosa and the rectal deep mucosa. These findings were consistent with eosinophilic gastroenteritis (EGE), mural type. She was empirically treated with 2 doses of ivermectin given the concern for possible underlying parasitic infection given her country of origin, and she was started on oral prednisone 40 mg/d. Eosinophilia and symptoms improved rapidly with this regimen. One month after discharge, her parasitic serology was notable for antifilarial immunoglobulin (Ig)G and IgG4 being positive. At 2-month follow-up, she felt well and denied any abdominal pain or distention with resolution of her peripheral eosinophilia. The diagnosis of EGE is usually made by endoscopic biopsy showing proliferation of eosinophils in areas of the gastrointestinal tract where eosinophils are uncommon (eg, esophagus, small bowel).1Chen M.J. Chu C.H. Lin S.C. et al.Eosinophilic gastroenteritis: clinical experience with 15 patients.World J Gastroenterol. 2003; 9: 2813-2816Crossref PubMed Scopus (161) Google Scholar It is associated with allergy or atopy, and eosinophil-predominant ascites is a rare presentation of EGE.2Hepburn I.S. Sridhar S. Schade R.R. Eosinophilic ascites, an unusual presentation of eosinophilic gastroenteritis: a case report and review.World J Gastrointest Pathophysiol. 2010; 1: 166-170Crossref PubMed Google Scholar Eosinophilic ascites in the context of postpartum EGE has been described at least twice in case reports.3Ogasa M. Nakamura Y. Sanai H. et al.A case of pregnancy associated hypereosinophilia with hyperpermeability symptoms.Gynecol Obstet Invest. 2006; 62: 14-16Crossref PubMed Scopus (6) Google Scholar It should be noted that eosinophilic infiltration of the gastrointestinal tract may be present in certain conditions including IgE-mediated food allergies and inflammatory bowel disease. Although certain dietary restrictions can rarely lead to resolution of EGE, systemic steroids are most often used and lead to improved symptomatic response. Our patient's positive filarial serology, although not associated with EGE in the literature, is the first known documented association between likely filariasis and EGE. She is presently being further evaluated for active filarial parasitemia and consideration of diethylcarbamazine therapy. The authors thank Dr Jay Luther for his guidance and manuscript review and Dr Daniel Pratt for obtaining images.

A Rare Case of Drug-Induced Liver Injury Arising from Pain Balls: Case Report and Review of Literature

Purpose: “Pain balls” are elastomeric pumps that provide continuous infusion of a local anesthetic directly into a surgical site for effective, non-narcotic postoperative pain relief [Dowling R, et al 2003]. Although it has excellent safety profile, it may cause rare complications. We present an unusual case of drug-induced liver injury (DILI) secondary to the use of bupivacaine pain ball with accompanying review of literature. Results: A 50 y.o. Caucasian male with recent bilateral inguinal hernia repair presented with a 3-day history of severe fatigue, nausea without vomiting, anorexia, jaundice, low grade fever, right upper quadrant (RUQ) abdominal pain and dark urine. He denies any high risk behavior or illicit drug use. He was using bupivacaine pain ball and ibuprofen only. On admission, he had scleral icterus, mild RUQ tenderness with no hepatosplenomegaly. There were no stigmata of chronic liver disease. Laboratory work-up showed Hct 45%, creatinine 0.9 mg/dl, total bilirubin 2.7 mg/dL (direct 1.9 mg/dL), AST 218 U/L, ALT 1018 U/L, Alk Phos 285 U/L, INR 1, and Lipase- 154 U/L. Further work-up for his hepatic dysfunction showed negative viral hepatitis panel except (+) Hepatitis B surface Ab and negative ANA, anti-mitochondrial and anti-smooth muscle, CMV and EBV antibodies. His acetaminophen level was <2 mcg/ml. Imaging included normal US abdomen with a non-dilated CBD of 3.3 mm. The patient underwent upper endoscopy that showed mild gastritis with normal biopsy results. Since workup had been non-revealing, a diagnosis of DILI from bupivacaine use was made. His pain ball was stopped. Shortly afterwards, his symptoms and liver enzymes improved and eventually normalized. Discussion: Pain ball usually uses local anesthetics such as ropivacaine, bupivacaine, or lidocaine to provide analgesia without causing significant systemic absorption. Bupivacaine undergoes hepatic metabolism once absorbed. We searched PubMed (inception to 2012) and found only four cases of DILI arising from locally given anesthetics [Yokoyama M, et al 2001]. Pathophysiologic mechanism remains unclear but these cases pointed to the development of allergic reaction or metabolic alteration as the cause. A recent trial of 48 mastectomy patients suggested the use of lower doses of locally given anesthetics to decrease overall systemic toxicity [Bhuvaneswari, et al. 2012]. Conclusion: Our case highlights a rare complication of locally given anesthetics. The pathophysiology remains unclear. Treatment involves withdrawal of the local anesthetic and all hepatotoxic drugs that leads to rapid clinical improvement.

Cholangiocarcinoma Presenting as Jaundice in a 34-Year-Old Woman

Purpose: Introduction: Cholangiocarcinoma (CCA) results from the abnormal proliferation of the biliary epithelium. CCA is the second most common primary liver malignancy and is now the leading cause of death from primary liver cancer. The incidence of CCA peaks in the seventh decade of life, and affects males more than females. The only effective treatment currently is surgical resection. The 5-year mortality of CCA in all patients, including those with resection is <5%. The overall incidence of intrahepatic CCA is increasing worldwide according to data from the World Health Organization. The reason for this increase is not currently understood. The increased incidence cannot simply be attributed to lead time bias, as there is not an increase in smaller tumors or decreased burden of disease at the time of diagnosis. Case: A 34-year-old female with no past medical or surgical history presented to emergency department when her family noticed that she appeared yellow for 1 week. She denied any nausea, vomiting, abdominal pain, weight loss, fever or chills. She denied any drug, alcohol, or tobacco use. Her family history is negative for any malignancy or autoimmune disorders. Physical exam was notable for jaundice and a protuberant abdomen with hepatomegaly. There was no ascites, asterixis, edema, or stigmata of chronic liver disease. Laboratory data revealed a transaminitis, elevated alkaline phosphatase, and total bilirubin of 10.0. INR was 0.9 and platelet count was 269,000. Ultrasound revealed a left hepatic lobe mass and mild intrahepatic biliary ductal dilatation. Triphasic computed tomography showed an 8.5 cm x 6.8 cm mass in left hepatic lobe and an occluded left main portal vein. Endoscopic retrograde cholangiography showed a 3-cm stricture of the common hepatic duct with dilatation right hepatic system proximally. The left hepatic system was unable to be visualized. Brush biopsies of the biliary stricture were obtained, but biliary stenting was unsuccessful so an external biliary drainage catheter was placed by radiology with successful drainage of the right biliary tree. The cytology brushings revealed cholangiocarcinoma. Discussion: This case is very unique in that the patient presented at such a young age with no risk factors. While risk factors are not commonly recognized at the time of diagnosis, especially in the western hemisphere, our patient presented in her fourth decade of life, which is about 30 years earlier than is expected. This case reiterates the importance of keeping a high burden of suspicion for cholangiocarcinoma in patients, regardless of their age or known risk factors, in the setting of a primary liver malignancy.