Anti-smooth Muscle Antibodies Research Articles

3169 Drugs! A New Mimicker of Primary Sclerosing Cholangitis

INTRODUCTION: In the United States, drug-induced liver injury (DILI) is the most common cause of acute liver failure necessitating liver transplantation. DILI can be characterized biochemically based on specific patterns of injury - hepatocellular, cholestatic, or mixed. Detection of bile-duct strictures on magnetic resonance cholangiopancreatography (MRCP) is uncommon in DILI, and nearly pathognomonic for primary sclerosing cholangitis (PSC). Here we present two cases of “PSC-like DILI.” CASE DESCRIPTION/METHODS: Patient 1: A 68-year-old man with type 2 diabetes mellitus (T2DM) and hyperlipidemia was admitted for sepsis secondary to methicillin-sensitive staphylococcus aureus right wrist abscess, and subsequently started on cefazolin. He developed acute hepatitis with aspartate transaminase (AST) 665, alanine aminotransferase (ALT) 367, and alkaline phosphatase (ALP) 2317. Extensive work-up, including ferritin, anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), and viral serology, was unremarkable. MRCP showed multi-focal areas of intra-hepatic biliary ductal dilation and mild strictures without evidence of stones or malignancy, consistent with PSC. Liver biopsy was non-specific, demonstrating portal and lobular hepatitis with mild bile duct injury, and mild steatosis without steatohepatitis. Colonoscopy did not show inflammatory bowel disease. DILI with drug-induced PSC-phenomenon was suspected. The patient's liver function tests (LFTs) normalized within 24 hours of stopping cefazolin. Patient 2: A 63-year-old woman with T2DM was found to have AST 229, ALT 186, and ALP 652, 5 months after starting atorvastatin for stroke. MRCP revealed abnormal appearance of the central intrahepatic bile ducts (Figure 1). Ferritin, alpha-1 anti-trypsin, ceruloplasmin, and viral serology were unremarkable. ANA, SMA, and immunoglobulin G were elevated, suggestive of an immunologic process. Anti-liver-kidney-microsomal antibody and AMA, however, were negative. The patient was presumed to have a drug-induced autoimmune and cholestatic reaction with PSC-cholangiographic findings. LFTs normalized within 2-months after cessation of the statin. DISCUSSION: DILI with concurrent findings of bile-duct strictures on MRCP has yet to be described in the literature. The first case suggests cefazolin as the culprit, while the second points to atorvastatin as the suspected trigger for DILI and an “autoimmune-PSC overlap syndrome.” Clinicians should be aware that DILI can mimic PSC.

2443 Dealing With DILI: When the Diagnosis Is Not Always Clear Cut

INTRODUCTION: Drug induced liver injury (DILI) is a rare, mostly reversible cause of liver failure (ALF); however, in rare cases DILI can unmask or trigger underlying chronic liver disease. We present a case of DILI with two novel findings: one, the patient consumed tea extract not yet cited on the LiverTox registry, and two, the patient's DILI likely triggered autoimmune hepatitis (AIH), an occurrence noted only a few times in the literature. CASE DESCRIPTION/METHODS: Patient is a 43-year-old female with no medical history who presented with acute onset jaundice and dark urine. She endorsed a “tea cleanse” which included dandelion roots, milk thistle and barks one month prior to admission. Her jaundice persisted despite cessation of the herbal tea intake. Liver function tests (LFTs) showed AST 2553, ALT 3022, alkaline phosphatase 135, total bilirubin 23.8, direct bilirubin 15.5, INR 1.8 and MELD 25. MRCP was consistent with acute hepatitis. ALF workup was negative except for elevated IgG1 and IgG4. Liver biopsy revealed panlobular mixed inflammatory cell infiltrate and necrosis but absent fibrosis, concerning for DILI, viral infection or AIH. Patient was managed supportively for DILI with downtrending LFTs. However, her LFTs worsened with total bilirubin 20 and INR 2.1. She developed ascites and lower extremity edema. The patient received corticosteroids for AIH despite negative ANA, anti-smooth muscle and anti-LKM antibodies with marked improvement in synthetic liver function. DISCUSSION: Although acetaminophen is the most common offending drug associated with DILI (40-50% of ALF cases annually), herbal or dietary supplements are not an uncommon cause, seen in 11-12% of cases per year. Accurate diagnosis of DILI can be made with clinical history, exclusion of other etiologies of ALF on laboratory evaluation, and with liver biopsy. The database LiverTox documents etiologies of DILI. “Be Well Teas,” consumed by our patient, yields no results but should be included to prevent future DILI cases. Further, despite biopsy consistent with DILI, rebound of total bilirubin and INR in our patient demanded further investigation. Likely the patient had pre-existent AIH triggered by DILI given her improvement with immunosuppression, cited previously in only in a few case reports. Concurrent, underlying AIH should be considered with relapse of liver dysfunction despite cessation of the inciting drug.

2352 Herbal Teas: More Harmful Than Helpful?

INTRODUCTION: The objective of this case is to become aware of the increasing number of agents with the potential to cause acute liver injury, in the modern age of combined allopathic and naturopathic medicine. CASE DESCRIPTION/METHODS: A 45 year old woman, recently emigrated from Honduras, presented with three weeks of epigastric pain and progressive jaundice. She denied high risk behaviors and endorsed NSAID use for headaches. Her exam was notable for marked scleral icterus and jaundice, but no stigmata of chronic liver disease. Labs were notable for AST 1893 IU/L, ALT 1454 IU/L, total bilirubin 16 mg/dL (direct bilirubin 12.4), ALP 209 IU/L, protein 6.4 g/dL, albumin 3.1 g/dL, INR 1.2. Urine drug screen, ethanol and acetaminophen levels were undetectable. A complete acute hepatitis viral panel and ceruloplasmin was negative except for a borderline anti smooth muscle antibody (1:40). Further workup was done including an abdominal ultrasound with dopplers showing normal gallbladder, no gallstones, and patent hepatic and portal vasculature, and an MRCP with small hepatic cysts and normal liver. No etiology was identified and her transaminases continued to rise as to AST 2230 IU/L and ALT 1895 IU/L. Liver biopsy showed periportal and cholestatic hepatitis with bridging necrosis consistent with drug induced liver injury. Further detailed history eventually yielded that she started an herbal remedy, arnica, around the same time she was developing jaundice. She was treated with N-acetylcysteine, and with continued abstinence of arnica, her liver enzymes normalized. DISCUSSION: There are innumerable supplements available to patients with purported health benefits, making it challenging to identify safety of use. arnica herbs are used as a topical agent to help with joint and muscle aches given its anti-inflammatory properties. Our patient had been using the herbs to create a concentrated tea. It is likely that the ingestion and systemic absorption led to her liver injury. This emphasizes the importance of thorough history taking with direct questioning, especially when diagnostic testing is unrevealing. Treatment is avoidance of the agent with expected improvement in liver enzymes.

2499 Idiopathic Eosinophilic Syndrome With Hepatic Involvement

INTRODUCTION: Hepatic involvement in hypereosinophilic syndrome is rare. CASE DESCRIPTION/METHODS: A 66-year-old gentleman was referred for evaluation of persistent eosinophilia, cough, wheezing, and abnormal liver chemistries. No abdominal pain, fever, weight loss, and bowel habit changes. No traveling outside the U.S. On exam his vital signs were within normal range. Eyes, scleral icterus; Lungs; wheezing the bases; Abdomen, soft, nontender, nondistended, negative for, shifting dullness, no organomegaly, no distended veins on the abdominal wall; Extremities, no edema; Skin, no icterus no bruising. His initial laboratory findings were as follows, WBC 15.3 × 109/L, Hgb of 15.3 g/dL, platelets of 438 × 109/L, absolute neutrophil count of 6.7 × 109/L, absolute lymphocyte of 2.7 × 109/L, absolute eosinophil count of 4.5 × 109/L, alkaline phosphatase of 234 U/L, AST of 51 U/L, ALT of 94 U/L, total bilirubin of 0.4 mg/dL, albumin of 4.8 g/dL. With respect to the liver related laboratory findings: negative viral hepatitis panel, ANA of 1:160, total IgG of 1010 mg/dL, IgG1 of 659 mg/dL, IgG2 of 258 mg/dL, IgG3 of 12.9 mg/dL and IgG4 of 28 mg/dL; F-actin IgG antibody 23.3 units; negative anti-smooth muscle antibodies; soluble liver antibody <20 units; negative AMA, alpha-1 antitrypsin level of 167 mg/dL; and ceruloplasmin of 27 mg/dL. Comprehensive studies for stool ova and parasites was unremarkable. Peripheral blood smear showed eosinophilia. Bone marrow biopsy, with flow cytometric analysis revealing hypereosinophilia showing aberrant expression of CD 56. Abdominal MRI revealed a 5.8 cm hemangioma in the left lobe; no hepatic steatosis. Myeloproliferative neoplasms (MPN) and platelet-derived growth factor receptor α (PDGFRA A/B) workup was negative. Liver biopsy showed many eosinophils within portal areas with foci of sinusoidal involvement compatible with idiopathic eosinophilic syndrome; chronic hepatitis (grade 2/4), with portal and periportal fibrosis (stage II/IV); no steatosis. After starting prednisone 60 mg oral daily, tapered over 4 weeks, his cough, wheezing, hepatic enzymes' elevation and eosinophilia have resolved. DISCUSSION: Hypereosinophilic syndrome with hepatic involvement is rare, and should be in the differential diagnosis especially when hepatic enzymes' elevation is associated with eosinophilia.

2440 Acute Hepatitis C in an Elderly Woman With No Risk Factors: A Rare Presentation

INTRODUCTION: An estimated 4.1 million people of US have been exposed to hepatitis C (HCV), 70% of which were born between 1945 and 1964, known as the “baby boomer” cohort. While a majority of patients with acute HCV go undetected, 15% present as acute hepatitis. CASE DESCRIPTION/METHODS: A 77 year old woman presented with right upper quadrant pain, jaundice, loss of appetite and malaise for 2 weeks. She denied recent travel, alcohol or drug use, prior blood transfusions, acetaminophen ingestion and use of herbal supplements. Her exam was remarkable for scleral icterus and RUQ tenderness. Initial laboratory data showed normal chemistry and blood counts. Her liver tests disclosed ALP 128 U/L, AST 1,348 U/L, ALT 1003 U/L, total bilirubin 8.2 mg/dL, direct bilirubin 6.4 mg/dL and INR 1.4 consistent with acute hepatitis. Infectious workup was positive for HCV genotype 1b with a viral load of 27.2 M IU/mL. Ultrasound of the abdomen showed normal liver and biliary tree. Immunological workup was positive for anti-smooth muscle antibody 1:40 titer and elevated IgG at 2,070 mg/dL raising a concern for a concomitant autoimmune hepatitis (AIH). Patient's liver tests continued to climb and she had prolonged abdominal pain, so liver biopsy was performed. It showed moderate lobular lymphoplasmacytic and neutrophilic inflammation with marked hepatocellular injury and areas of hepatocyte loss consistent with active HCV hepatitis (Figures 1 and 2). She was then discharged and immediately started on sofosbuvir-ledipasvir and eventually achieved sustained virologic response. DISCUSSION: Acute HCV infection is usually transmitted via needle-stick injury or injection drug use. It is uncommon in elderly patients, however in nursing home residents, it is attributed to parenteral medications, hemodialysis and poor adherence to infection control measures. Our patient was from the community and it is not clear how she was exposed to HCV. Acute HCV hepatitis in elderly patients can be severe, occurring 2 to 26 weeks after exposure. Aminotransferases are often greater than 10 to 20 times normal; bilirubin may be elevated as well. Although HCV is known to induce AIH, the features of acute hepatitis can be mistaken for AIH. A biopsy aids in discerning these two entities with very different treatment strategies. Generally, a waiting period of 12 weeks is instituted to allow for spontaneous viral clearance, but immediate treatment can be initiated in cases of elderly patients with severe presentations.

2413 Another Downside for Depression: A Case of SNRI-Induced Liver Injury

INTRODUCTION: Antidepressants are one of the most prescribed medications in the United States with duloxetine being reported as one of the top fifty drug prescriptions. Self-limited liver test abnormalities have been reported with duloxetine use but only a few case reports describe clinically apparent hepatitis following duloxetine use. CASE DESCRIPTION/METHODS: A 35-year-old African American woman with a past medical history of depression presented with few days of worsening upper abdominal pain, nausea and multiple episodes of non-bloody emesis. Initial laboratory tests revealed liver test abnormalities with ALT of 1176 U/L, AST of 596 U/L, bilirubin of 1.6 mg/dL (but with normal ALP) and INR of 1.65. Full workup including viral hepatitis, EBV, CMV, drug toxicology screen (including acetaminophen), lipase, and ceruloplasmin among others turned out to be negative. Autoimmune hepatitis markers were negative other than mild elevation of anti-smooth muscle antibody at 33 units (normal < 19). Abdominal ultrasound with Doppler showed no abnormalities without any evidence of biliary obstruction. The patient denied any alcohol or illicit drug use. Patient endorsed having a recent contact with a sick squirrel so leptospira IgM was ordered which was non-reactive. The patient denied taking any medications other than duloxetine which she was started on within the last two months but she stopped taking it when she started to vomit a few days before presentation. In the second day of hospitalization, patient's LFTs peaked with ALT above 7000 U/L and AST of 5409 U/L but it then started to decrease in the following days with normalization of her bilirubin and INR as well as improvement of her symptoms with supportive care. No corticosteroids or antibiotics were given. Patient's clinical presentation with the timeline of her duloxetine use and laboratory finding indicate that duloxetine was the likely cause of her acute hepatitis. DISCUSSION: Few cases described clinically evident hepatotoxicity following duloxetine treatment. Most duloxetine-induced hepatotoxicity was seen in females with symptoms starting in the first few months following initiation of duloxetine. Typically there was an elevation of ALT > AST and with some cases having bilirubin elevation as well as elevation of one of the autoimmune hepatitis markers in some cases. Clinicians should be vigilant toward possible hepatotoxicity following initiation of antidepressant even in patients with no pre-existing chronic liver disease or alcohol abuse history.

2479 Autoimmune Hepatitis Triggered by Hepatitis A: An Interesting Case and Review of Pathophysiology

INTRODUCTION: Autoimmune hepatitis (AIH) is an immune-mediated disorder of the liver, whose pathophysiology involves triggering of T-cell mediated events by environmental agents in the liver in a host genetically predisposed to this disease. One trigger described in literature has been the hepatitis A virus (HAV). Hence, occasionally cases which clinically appear to be that of relapsing HAV are in fact concealing underlying autoimmune hepatitis that has been provoked from the initial episode of HAV. We describe one such case. CASE DESCRIPTION/METHODS: A 45 year old Caucasian male with past medical history of chronic hepatitis C and acute hepatitis two months prior to admission was admitted for multifocal pneumonia. During his initial evaluation, the patient was found to have generalized jaundice, and laboratory evaluation revealed elevated transaminases with a hepatocellular pattern. He was initially thought to have reactivation of the hepatitis A, however non-improvement with conservative measures led to further serological testing, which revealed positive anti-smooth muscle antibody. Autoimmune hepatitis was confirmed by biopsy, and patient was started or oral steroids. The patient's clinical status and liver function improved significantly, and he was discharged with outpatient follow-up. DISCUSSION: It is hypothesized that environmental agents trigger T-cell–mediated events directed at liver antigens in a host genetically predisposed to AIH, leading to a progressive necro-inflammatory and fibrotic process in the liver. Studies have shown hepatotropic viruses including HAV to be associated with AIH. Defects in suppressor-inducer T lymphocytes specifically controlling immune responses to the asialoglycoprotein receptor may be the cause of susceptibility. It has also been shown that humoral immune responses to liver cell surface antigens are frequently provoked by hepatitis A and B viruses. Newer research is also exploring molecular mimicry between the infectious particle and the liver constituent as the mechanism, although specific data has not been discovered on HAV. In the setting of the recent outbreaks of HAV, such pathology may become more commonplace. It is important for a clinician to distinguish between relapses of HAV (documented to be between 3-20% of patients in the first 6 months) and onset of AIH, as treatment modalities and prognosis are vastly different. A high level of awareness of this pathology allows for its prompt recognition and the potential for successful treatment.

2361 A Rare Presentation of Acute Hepatitis in the Setting of Wilson’s Disease

INTRODUCTION: Wilson’s disease is a genetic disorder that leads to impairment in the transportation of cellular copper. The worldwide incidence of Wilson’s disease is estimated at one per 30,000 live births. Autoimmune hepatitis (AIH) has a varying degree of prevalence, anywhere from 0.9-25 cases per 100,000 globally. We describe a rare case of a patient presenting with acute hepatitis in the setting of known Wilson’s disease with nonadherence to therapy who was diagnosed with concomitant autoimmune hepatitis. CASE DESCRIPTION/METHODS: A 19-year-old woman with a history of biopsy-proven Wilson’s disease diagnosed at age 17, non-adherent to trientine chelation therapy, presented to her primary care physician with nausea and abdominal pain. Physical exam was benign and workup revealed an elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of 1500. She was referred for hospital admission. Acute viral hepatitis was ruled out and trientine was resumed as it was felt the presentation may be due to untreated Wilson’s Disease. Evaluation for drug-induced liver injury, human immunodeficiency virus, and thrombosis was negative. Despite therapy with trientine, transaminases continued to rise. Autoimmune serologies revealed a positive anti-smooth muscle antibody. A liver biopsy showed copper granules in hepatocytes consistent with Wilson’s disease, in addition to moderately active hepatitis with frequent plasma cells supporting the diagnosis of AIH. Prednisone was initiated for treatment of AIH and her hepatitis rapidly improved. One week follow up showed further improvement in her liver chemistries. She was transitioned to azathioprine for AIH. Trientine was continued for treatment of Wilson’s disease. DISCUSSION: Given the multiple causes of acute hepatitis and targeted therapies available, determining the etiology remains the cornerstone of management. This is an unusual case of biopsy-proven Wilson’s disease who presented with acute hepatitis. She was found to have serology and biopsy consistent with both Wilson’s disease and AIH. She responded rapidly to steroid therapy for AIH followed by treatment with an immunomodulator. This combination of a rare inherited disease coupled with an uncommon autoimmune phenomenon highlights the need for diagnostic precision in the patient with acute hepatitis, even when pre-existing liver disease is known. Ultimately liver biopsy findings directed specific therapy.

2441 Hepatotoxicity by Methoxsalen: The Innocuous Culprit

INTRODUCTION: Drug-induced liver injury (DILI) is the second most common cause of acute liver failure; 15-20% cases of DILI can be attributed to damage caused by herbal or dietary supplements. Methoxsalen, commonly known as psoralen, is the active ingredient in Bakuchi seeds and is used for treatment of vitiligo and psoriasis. DILI caused by Psoralen is rare, with only three cases reported in literature. This case demonstrates the importance of eliciting a history of herbal supplement use in patients with acute liver failure and the need for regulation of herbal supplements. CASE DESCRIPTION/METHODS: A 60-year-old female presented with two-week history of jaundice and right upper quadrant pain (RUQ). She started taking Bakuchi seeds four weeks prior to presentation and would apply it topically and consume it daily. Patient denied history of alcohol use, blood transfusions, or illicit drug use. Physical exam was notable for scleral icterus and jaundice. Labs revealed abnormal liver function tests (LFTs) (Figure 1) with a peak total bilirubin of 19 mg/dL and a MELD-Na on admission of 19. Work up revealed positive anti-smooth muscle antibodies and AFP elevation to 15.9 ng/mL. Pertinent negatives included viral hepatitis serologies, HSV, EBV, factor V activity, and hemochromatosis. A RUQ ultrasound showed no abnormalities. An MRI abdomen was done which revealed mild periportal edema and mildly dilated common bile duct without choledocholithiasis or obvious mass. Given concerns for DILI, patient was started on acetylcysteine. Hospital course was complicated by episodes of confusion; an ammonia level was elevated at 75 umol/l. Patient was started on lactulose. Because patient's LFTs improved with a stabe PT/INR of 12/1.2, she did not meet criteria for a liver transplant. A liver biopsy was performed which revealed submassive necrosis and collapse; hepatitis with plasma cells and eosinophils with significant cholestasis. Given biopsy results consistent with DILI, patient was discharged on oral prednisone and lactulose to follow up with hepatology in one week. DISCUSSION: LFT abnormalities were seen in 2% to 12% of subjects taking psoralen; the elevations were mild-moderate in severity, asymptomatic and self-limited in course with recovery of LFT seen in 6 to 8 weeks. However, severe jaundice and death from hepatic failure has been described in patients with preexisting cirrhosis. This case emphasizes the need for increased surveillance to formulate guidelines regarding regulation and use of herbal supplements.

2464 A Case of Acute Icteric Hepatitis Caused by Epstein Barr Virus in an Immunocompetent Adult

INTRODUCTION: Epstein Barr Virus (EBV) is a viral infection that can often remain asymptomatic but is also a major cause of infectious mononucleosis. Patients often present with sore throat, fever, lymphadenopathy and can develop splenomegaly. EBV-associated hepatitis is uncommon and cases with clinical jaundice are rare. CASE DESCRIPTION/METHODS: A 23-year old male without significant past medical history presented with one week of flu-like symptoms and acute onset of a generalized pruritic rash, right upper quadrant (RUQ) abdominal pain and dizziness. He denied any recent alcohol consumption, IV drug use or new medication initiation. On arrival to the emergency department the patient was afebrile with a blood pressure 130/84. Physical exam revealed scleral icterus and cutaneous jaundice, a diffuse macular rash was across his face, chest and arms and he had tender hepatomegaly. He was alert and oriented without confusion. Laboratory examination revealed a leukocytosis of 11.8, a total bilirubin of 15.8, direct bilirubin of 13.3, an INR of 1.2, ammonia of 26, an alkaline phosphatase of 499, and an ALT of 615 with AST of 405 signifying acute hepatitis. A urine drug screen was negative. A RUQ ultrasound with doppler showed no evidence of Budd-Chiari or portal vein thrombus; fatty infiltration of the liver was seen with no evidence of cholelithiasis or common bile duct obstruction. Hepatitis A, B and C viral screen was negative, acetaminophen level was within normal limits, HIV antibody test was negative, herpes virus IgM negative, CMV IgM negative, anti-smooth muscle antibody negative for autoimmune hepatitis. Ceruloplasmin and alpha-1 antitrypsin levels were not suggestive of Wilson's disease or alpha-1 antitrypsin deficiency. A peripheral smear showed reactive lymphocytosis. There was significant elevation in EBV IgM and heterophile antibody suggesting systemic Epstein Barr viral infection as the cause of acute hepatitis. Over the next 3 days, his liver enzymes began trending down slowly with symptomatic management and he was determined stable for discharge with plans for 2 and 4 week follow ups to monitor for resolving acute EBV hepatitis. DISCUSSION: It is important to remember that, although rare, EBV can cause hepatitis with diffuse jaundice and significant hyperbilirubinemia along with AST and ALT levels over 10 times the upper limit of normal. Such presentation could easily be misconstrued as an alternative diagnosis and patient safety compromised with unnecessary treatment.

2389 Nivolumab-Induced Hepatitis: A Rare Side Effect of Programmed Cell Death-1 (PD-1) Inhibitor

INTRODUCTION: Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that blocks the function of programmed cell death (PD-1) activity by binding to the PD-1 receptor. This prevents suppression of T-cell activity, which can lead to T-cells targeting cancer cells. Unfortunately, these medications induce various types of immune related adverse events including colitis, pneumonitis, endocrinopathies and hepatitis. We report rare case of of nivolumab-induced hepatitis. CASE DESCRIPTION/METHODS: An 86-year-old female with history of metastatic melanoma and was started on nivolumab 3 mg/kg every 3 weeks. Patient noted to have abnormal liver chemistries, nausea and yellowing of skin after 6 months of nivolumab. On presentation she was found to have a total bilirubin of 7.79 mg/dL, INR 1.3, AST 885 IU/L and ALT 999 IU/L. Physical examination was significant for mild scleral icterus only. An ultrasound of liver was notable prominent left lobe of liver but no focal hepatic masses and s/p cholecystectomy with no bile duct dilation. Infectious etiologies were unrevealing for viral hepatitis and acute EBV. Her autoimmune serologies were negative for anti-smooth muscle antibody and anti-mitochondrial antibody. Work up was negative for herbal supplements, illicit substance or other medications. The most likely culprit for her hepatitis was due to nivolumab. Patient was started on prednisone at 1 mg/kg daily for a total of 100 mg prednisone daily and her nivolumab dose was held. On discharge her total bilirubin was 2.45, INR 1.2, AST 62, ALT 249 and Alk Phos 252. Patient continued prednisone taper over 30-day period and by end of the month her liver chemistries had normalized and patient was asymptomatic. DISCUSSION: Nivolumab-induced hepatoxicity is rare and accounts for 3-6% of all immune-related adverse effects. The median time of onset was 3.3 months (range: 6 days to 9 months). In addition to systemic corticosteroid, alternative immunosuppressive therapies may be employed if symptoms continue after 3-5 days. Etiologies of liver dysfunction such as viral infection, obstruction and other forms of autoimmune hepatitis must be excluded. In such an event, oral mycophenolate mofetil 500 mg every 12 hours can be used for treatment. Our patient showed rapid improvement in liver chemistries and had minimal physical side effects. Healthcare provides managing patients with liver injury should be able to recognize and treat prior to development of fulminant hepatitis.

Autoimmune hepatitis in human immunodeficiency virus-infected patients: A case series and review of the literature.

BACKGROUNDAbnormal liver chemistry is a common problem in human immunodeficiency virus (HIV)-infected patients. Common causes of abnormal liver enzymes in this population include viral hepatitis B/C or opportunistic infection, drug toxicity, and neoplasm. Autoimmune hepatitis is a rare cause of hepatitis in HIV-infected individuals; however, this condition has been increasingly reported over the past few years.CASE SUMMARYWe present 13 HIV-infected patients (5 males and 8 females) who developed autoimmune hepatitis (AIH) after their immune status was restored, i.e. all patients had stable viral suppression with undetectable HIV viral loads, and median CD4+ counts of 557 cells/× 106 L. Eleven patients presented with chronic persistent elevation of aminotransferase enzyme levels. One patient presented with acute hepatitis and the other patient presented with jaundice. The median levels of aspartate aminotransferase and alanine aminotransferase enzymes were 178 and 177 U/mL, respectively. Elevation of immunoglobulin G levels was present in 11 (85%) patients. Antinuclear antibody and anti-smooth muscle antibody were positive in 11 (85%) and 5 (38%) patients. Liver biopsy was performed in all patients. They had histopathological findings compatible with AIH. The patients were started on prednisolone for remission induction, with good response. After improvement of the liver chemistry, the dose of prednisolone was tapered, and azathioprine was added as life-long maintenance therapy. At the last follow-up visit, all were doing well, without HIV viral rebound or infectious complications.CONCLUSIONThis report underscores the emergence of autoimmune hepatitis in the context of HIV infection.

Pregnancy outcomes of the patients with anti-smooth muscle antibody positivity.

To evaluate the management and the pregnancy outcomes of patients positive for anti-smooth muscle antibody (ASMA). We retrospectively evaluated the pregnancy outcomes of the patients with ASMA positivity compared to patients without any known autoantibody positivity and/or autoimmune diseases. We have also evaluated the obstetric outcomes of the patients with ASMA positivity in terms of existence of MTHFR polymorphisms, other hereditery thrombophilias and other autoantibody positivities. In this study, 40 ASMA positive patient were evaluated and compared with 80 control cases. Gestational week at delivery, birthweight and APGAR scores for the 1st, 5th, 10th were significantly lower at patients with ASMA positivity (p< 0.01; p< 0.01; p< 0.01; p< 0.01; p: 0.030 respectively). Further analysis regarding to existence of additional risk factors revealed no significant difference between each pair of groups in terms of any obstetric outcome. ASMA positivity may be associated with adverse pregnancy outcomes.

17. Tick-borne relapsing fever: a fever syndrome mimic

17. Tick-borne relapsing fever: a fever syndrome mimic

Obez çocuklarda alkolik olmayan yağlı karaciğer hastalığı ve eşlik eden diğer karaciğer hastalıkları

Objective: The prevalence of non-alcoholic fatty liver disease (NAFLD) in children increased parallel to the increment of childhood obesity. Also, NAFLD may be the presenting feature of different liver diseases in non-obese children. We aimed to determine whether there were co-existing liver diseases in overweight and obese children with NAFLD. Material and Methods: Pediatric gastroenterology outpatient clinic records of obese and overweight patients, aged between 5-18 years, were retrospectively reviewed. Seventy patients who had liver steatosis on ultrasonography, and alanine aminotransferase (ALT) levels were higher than 1.5 times the upper limit of normal were recruited to the study. The demographic findings, laboratory tests for infectious, metabolic, and autoimmune causes, abdominal ultrasonography and liver biopsy findings of patients were recorded. Results: At presentation, 94.2% of the patients (n: 66) had mild transaminase elevation. All patients were negative for viral hepatitis, anti-tissue transglutaminase immunoglobulin (Ig) A, anti-liver-kidney-microsome type 1 and anti-smooth muscle antibody. They had normal erythrocyte sedimentation rate (ESR) , C-reactive protein (CRP), ceruloplasmin, and total IgG levels . O nly one patient with low alpha-1 antitrypsin levels had heterozygotes of the PiMZ phenotype. Three (4.3%) patients had antinuclear antibody ( ANA) positivity. 44.7% of patients were given ursodeoxycholic acid treatment. On follow-up, normalization of ALT was achieved in 31 (44.2%) patients at mean 6.1 ±4.6 (2-19) months, but no relation was found between normalization and ursodeoxycholic acid treatment. A patient with ANA positivity had increased ALT, ESR , CRP , IgG levels and ANA titers o n follow-up, and she was diagnosed with autoimmune hepatitis with the support of liver biopsy. Under prednisolone and azathioprine treatment, ESR and IgG levels were normalized, ALT and ANA titers decreased. Conclusion: Other causes of chronic hepatitis should be screened in obesity-related non-alcoholic fatty liver disease and the development of autoimmune hepatitis should be kept in mind in the presence of ANA.

Hepatobiliary case report and literature review of hepatic reactive lymphoid hyperplasia with positive anti-smooth muscle antibody and anti-nuclear antibody tests

Hepatic reactive lymphoid hyperplasia (RLH) is a rare benign tumor of the liver that exhibits similar imaging characteristics to those of other hepatic malignant tumors; therefore, it requires novel biomarkers to be differentiated from the other tumors. A 69-year-old female was found to have a mass in the liver and was admitted to Peking Union Medical College Hospital for further evaluation. Most laboratory tests, including liver function tests, tumor biomarkers, and autoimmune markers were within normal range, except for positive antinuclear antibody and anti-smooth muscle antibody (SMA) tests. Diagnostic imaging, including ultrasonography, computerized tomography and magnetic resonance imaging displayed a small hepatic mass suggestive of hepatocellular carcinoma (HCC). Partial hepatectomy was performed, and histological diagnosis suggested RLH. Postoperative treatments included anti-infection, nutritional enhancement and liver protection. The suspicion of autoimmune hepatitis could not be confirmed. No recurrence or autoimmune disease was observed over 6-month follow-up. Positive anti-nuclear antibody (ANA) and anti-SMA may be potential biomarkers for hepatic RLH.

Acute onset autoimmune hepatitis: Clinical presentation and treatment outcomes

Introduction and aimAutoimmune hepatitis (AIH) may present acutely, which can rapidly progress to fulminant type. This pattern has been described worldwide but is generally under-reported. We aim to describe the clinical presentation and treatment outcomes of patients with acute onset AIH. Materials and methodsA multicenter retrospective cohort study of patients with acute onset AIH. Clinical, biochemical, and histological data were analyzed and the outcomes were reported. ResultsSeventy patients were included. The mean age was 33.8±1.5 years and 58.6% were female. Upon initial presentation, 94% had jaundice, 44% had fatigue, 31% had pruritus, and 29% had abdominal pain. Biochemical analysis revealed elevated alanine transaminase (733±463.6), aspartate transaminase (699±423), and total bilirubin (210±181.8). Antinuclear antibody (ANA) was positive in 61% of patients, anti-smooth muscle antibody (ASMA) in 69%, and both in 31%; immunoglobulin G (IgG) was elevated in 86% of patients. Advanced fibrosis was found in 39%. Complete remission was achieved in 74.3%, two patients required liver transplants and six died. No specific biomarkers were identified as predictive of remission; however, advanced age was associated with poor prognosis. ConclusionAcute onset AIH is a disease that requires early diagnosis and management. We confirmed that elevated transaminases are the hallmark of biochemical presentation of acute AIH. High IgG, ANA and ASMA are typically present in such patients upon presentation, however, their absence does not totally exclude the diagnosis. Initial response to treatment was excellent; however, the long-term mortality was higher than the general patient population.

SUN-578 Severe Hyperbilirubinemia Due to Graves' Thyrotoxicosis

Introduction: Graves’ disease is the most common cause of hyperthyroidism in the United States. Though hepatic dysfunction has been described in patients with thyrotoxicosis due to Graves’ disease, it is an extremely rare cause of severe hyperbilirubinemia. There is limited evidence to guide physicians in the management of hyperthyroidism associated with liver dysfunction, making it a diagnostic and therapeutic challenge. Case Report: 30-year-old woman with no significant history presented with complaints of diarrhea and yellowish discoloration of skin for more than a month. She had generalized itching, hand tremors and a 30 lb. weight loss during this period. On physical examination, she was noted to have tachycardia, scleral icterus, a diffuse non-nodular non-tender goiter, bilateral fine tremors and hyperreflexia. Abdomen was soft and non-tender with no hepatosplenomegaly. Laboratory evaluation showed normal compete blood count, total bilirubin 26 mg/dL, direct bilirubin 17.7 mg/dL, indirect bilirubin 9.1 mg/dL, ALT 49 IU/L, AST 26 IU/L, ALP 265 IU/L. She had biochemical hyperthyroidism with TSH less than 0.01 UIU/ml (0.45-4.5), free T4 of 4 ng/dL (0.6-1.3), total T3 371 ng/dL (79-149). TSI was elevated 2.13 (0-0.55). Further work up of hyperbilirubinemia including hepatitis viral panel, anti-nuclear antibody, anti-mitochondrial and anti-smooth muscle antibodies were negative. Ultrasound of the liver showed no abnormalities. Liver biopsy revealed benign liver with bland canalicular stenosis in central zones. There were no features of autoimmune hepatitis or chronic hepatitis. She underwent I131 ablation with normalization of ALP and bilirubin levels at 3 months follow-up. Discussion: Hepatic dysfunction has been described in patients with hyperthyroidism since it was reported in 1874. It may occur because of hyperthyroidism per se, drug treatment of hyperthyroidism and conditions associated with autoimmune thyroid disease like autoimmune hepatitis and primary biliary cirrhosis. The causes could also be unrelated to hyperthyroidism like viral hepatitis, alcohol abuse, sepsis, cholangitis, medications. Several theories have been hypothesized, but the mechanism of the hepatic dysfunction due to hyperthyroidism per se is not clear. A thorough work up is essential to rule out other potential etiologies. If clinically feasible, liver biopsy may be deferred initially. However, it should be considered if liver function fails to improve despite normalization of thyroid hormone levels. I131 ablation is a safe and effective method of treatment in these patients.

SAT-086 A Rare Case of Cholestatic Liver Disease Causing Markedly Elevated LDL Successfully Managed with Plasmapheresis and Ursodeoxycholic Acid

Background Hypercholesterolemia (HC) in cholestatic liver disease commonly involves a high lipoprotein-X (LpX) and low LDL receptors. No evidence has been found to suggest the association of LpX with an increased risk of cardiovascular disease (CVD). Hence, lipid lowering therapy is unnecessary as HC improves with treatment of cholestasis, but plasmapheresis should be considered in markedly elevated LDL values given the uncertainty of short term complications. Clinical Case A 47-year-old man with HTN, DMT2, nephrotic syndrome secondary to DM glomerulosclerosis and CKD stage 3 was admitted for an NSTEMI and acute heart failure due to non-ischemic cardiomyopathy. On exam he had jaundice and hepatomegaly without xanthelasma or tendon xanthomas. Laboratory evaluation revealed elevated HDL 200 [35-75 mg/dl], LDL 2,182 [0-130 mg/dl] and triglyceride 326 [30-150 mg/dl] although his lipid panel four months ago was normal. He had no family history of HC or premature CAD. Interestingly, two months prior the patient was seen in GI clinic due to jaundice, pruritus, acholia and coluria. Work-up showed cholestasis with total bilirubin 5.2 [0.1-1.2 mg/dl], AST 148 [0-40 U/L], ALT 112 [5-25 U/L], alkaline phosphatase 1,874 [20-120 U/L] and GGT 2,307 [3-60 U/L]. Further evaluation was unrevealing with negative viral hepatitis serologies, antinuclear antibodies, anti-smooth muscle antibody, anti-mitochondrial antibody, ceruloplasmin, α-1antitrypsin. He underwent liver biopsy which demonstrated cholestatic hepatitis with advanced biliary fibrosis, lymphocytic cholangitis and perivenular infiltrate thought secondary to an atypical autoimmune cholangiopathy. Due to concern for hyperviscosity and potential CVD complications, two sessions of plasma exchange were performed with a rapid lowering of LDL to 661 mg/dL. He was given a dose of evolocumab and discharged on ursodeoxycholic acid with improvement in liver function and normalization of lipid panel within three weeks. His HC was presumed mainly from atypical autoimmune cholangiopathy. LpX was unlikely since his Apolipoprotein B was elevated at 239 [RR 52-109 mg/dl]. Once his liver function normalized, he was started on high intensity statin and ezetimibe due to an elevated CVD risk with a low ApoA 30 mg/dL [RR 94-176]. Conclusion This is a rare case of cholestatic liver disease causing markedly elevated LDL, successfully managed with plasma exchange and ursodeoxycholic acid with subsequent resolution of LDL abnormality.

SAT-582 Autoimmune Hepatitis Presenting with Graves Disease

Graves disease, the most common cause of hyperthyroidism in the world has an incidence peak between 30 and 50 years of age. It is more frequent in women that in men with a ratio of 5:1. The typical presentation is thyrotoxicosis, goiter and opthalmopathy. The most specific laboratory finding is the activating autoantibodies directed against the thyrotropin receptor, present in up to 98% of untreated patients. Considering the autoimmune nature of the disease, it is not uncommon that patients with the disease present with other autoimmune identities. We present a 22 year old woman diagnosed with Graves disease two years previous, taking methimazole irregularly for 1.5 years. Iodine treatment was given with previous suspension of methimazole a week before. Three days before Iodine she presents jaundice and malaise and comes into the emergency room. Laboratory studies showed transaminases that reached a maximum level of AST 1601U/L (NV: 12-38U/L) ALT 1407U/L (NV: 7-41), total bilirubin of 34.4mg/dl (NV: 0.3-1.3mg/dl) with a conjugated bilirubin of 29.9mg/dl (NV: 0.1-0.4mg/dl) and alkaline phosphatase of 762U/L (NV: 33-96U/L), TSH 0.015 mUI/L T4L 90 pmol/L, abdominal ultrasound showed cholecystitis without cholelithiasis or enlargement of the bile duct and markers of viral hepatitis were negative. A liver biopsy was performed due to hepatocellular injury that reported chronic severe inflammatory infiltrate and acute portal with focal interfase lesion with plasmocytes. Mild fibrous expansion of portal spaces compatible with chronic active hepatitis of probable autoimmune etiology. The autoimmune labs reports showed IgG 2146mg/dl, Antinuclear antibodies negative, Anti smooth muscle antibodies negativa and anti mitochondrial antibodies that were positive. In this case the diagnosis of autoimmune hepatitis and primary biliary cirrhosis was made considering an overlap disease in the context of hyperthyroidism. Patients with Graves disease can have other autoimmune diseases such as autoimmune hepatitis which should be actively searched as a differential diagnosis. Other hepatic diseases such as viral hepatitis, drug induced hepatitis or deposit disease should be ruled out. Smith, T; Hegedüs, L. Review Article: Graves` Disease. N Engl J Med 2016;375:1552-65. Menconi, F; Marcocci, C; Marinò, M. Review: Diagnosis and Classification of Graves` disease. Autoimmun Rev (2014), http://dx.doi.org/10.1016/j.autrev.2014.01.013. Teufel, A; Weinmann, A; Kahaly, G; et all. Concurrent Autoimmune diseases in patients with Autoimmune hepatitis. J Clin Gastroenterol 2010;44:208-213. Wang, R; Tan, J; Zhang, G; et all. Risk factors of hepatic dysfunction in patients with Graves´ hyperthyroidism and the efficacy of 131iodine treatment. Medicine (2017) 96:5. Jhee, J; Kim, H; Kang, W; et all. A case of autoimmune hepatitis combined with graves disease. Korean J Gastroenterol; 2015; 65, 48-51.