Clindamycin-induced acute cholestatic hepatitis

We report a case of acute hepatotoxicity in a 42-yearold woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase （ALT）, 1795 IU/L （normal range 0-40）; aspartate aminotransferase （AST）, 1337 IU/L （normal range 5-34）; alkaline phosphatase （ALP）, 339 IU/L （normal range 40-150）; 7-glutamyl transpeptidase （GGT）, 148 IU/L （normal range 9-64 IU/L）; total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time （PT）, 13.5 s, with international normalized ratio （INR）, 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type （both hepatocellular and cholestatic） hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixedtype liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.     

Fulminant chemical hepatitis possibly associated with donepezil and sertraline therapy

OBJECTIVE: To describe a case of fulminant hepatitis possibly related to concomitant donepezil and seratriline therapy. PATIENT AND SETTING: An 83-year-old woman treated in a dementia care facility and later in a tertiary medical center. INTERVENTION AND MANAGEMENT: Discontinuation of donepezil and sertraline therapy with subsequent improvement evidenced by liver biopsy and liver function tests. RESULTS: An older woman with Alzheimer's disease was admitted to a dementia care facility because of aggressive behavior. Treatment with sertraline was initiated in February 1998. Sertraline doses were increased gradually to 200 mg daily by May 1998, and some improvement in behavior was seen. Concomitant therapy with donepezil 5 mg qhs was initiated June 26, 1998. Ten days later, confusion and jaundice were noted. Total bilirubin was 5.6 mg/dL, GGTP was 1,208 IU/L, and alkaline phosphatase was 369 IU/L. Computed tomography revealed cholelithiasis without ductal dilation. Liver, spleen, and pancreas seemed normal. Donepezil and sertraline were discontinued. The patient was admitted to our institution and treated for dehydration. A liver biopsy revealed scattered portal eosinophils and prominent cholestasis consistent with acute chemical hepatitis. The GGTP and total bilirubin of this patient peaked at 2,235 IU/L and 22.6 mg/dL, respectively. The patient improved, and her liver function tests normalized over the next 2 months.     

Mastabol induced acute cholestasis: A case report

A 26-year-old male presented with three weeks of jaundice after the self-initiation of the injectable anabolic steroid, Mastabol [Dromastanolone Di-Propionate (17 beta-Hydroxy-2alpha-methyl-5alpha-androstan-3-one propionate)]. He reported dark urine, light stools, and pruritus. He denied abdominal pain, intravenous drug use, intranasal cocaine, blood transfusions, newly placed tattoos, or sexually transmitted diseases. He used alcohol sparingly. Physical exam revealed jaundice with deep scleral icterus. The liver was palpable 2 cm below the right costal margin with no ascites. The peak bilirubin was 23.6 mg/dL, alkaline phosphatase was 441 units/L, and aspartate aminotransferase/alanine aminotransferase were 70 units/L and 117 units/L respectively. A working diagnosis of acute intrahepatic cholestasis was made. Liver biopsy revealed a centrilobular insult with neutrophilic infiltrates and Ito cell hyperplasia consistent with acute drug induced cholestasis. The patient’s clinical symptoms resolved and his liver enzymes, bilirubin, and alkaline phosphatase normalized. Anabolic steroids with 17 alpha carbon substitutions have been associated with a bland variety of cholestatic injury with little hepatocellular injury. Cholestasis, under these circumstances, may be secondary to the binding of drugs to canalicular membrane transporters, accumulation of toxic bile acids from canalicular pump failure, or genetic defects in canalicular transport proteins. Mastabol is an injectable, 17 beta hydroxyl compound with no alpha alkyl groups at the 17 carbon position. As such, it has been reported to have little potential toxic effects on the liver. This is the first known reported case of Mastabol-induced cholestatic liver injury. It highlights the need for physicians to consider such widely available substances when faced with hepatic injury of unclear etiology.     

Rotavirus Causes Hepatic Transaminase Elevation

Rotavirus is one of the leading causes of acute gastroenteritis among children. While clinical complaints are generally intestinal including vomiting and diarrhea, there is evidence to suggest that disease outside the gastrointestinal tract occurs. This study examines the frequency of hepatic transaminase elevation in children with rotavirus gastroenteritis. Patients identified with rotavirus gastroenteritis by stool antigen testing between November 2005 and March 2006 had available serum analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total bilirubin, direct bilirubin, and creatinine phoshosphokinase (CPK). Chart review was conducted to identify patients with possible liver injury unrelated to rotavirus. Among the 92 patients identified with rotavirus during the study period, 75 had serum specimens available for testing. Fifteen patients (20%) had elevated ALT and AST, including one patient with an increase in AST, ALT, alkaline phosphatase, and total and direct bilirubin. The mean ALT elevation was 56 IU/L (range, 44 to 114 IU/L), and the mean AST elevation was 80 IU/L (range, 57 to 126 IU/L). Fifty-three patients (71%) had an increase in AST alone, and three patients (4%) had an increase in AST and alkaline phosphatase. The mean AST values in these groups were 61 IU/L (range, 42 to 110 IU/L) and 79 IU/L (range, 59 to 96 IU/L), respectively. In conclusion, rotavirus commonly causes elevation of liver transaminases.     

Relapsing hairy cell leukemia presenting as fulminant hepatitis.

PURPOSE: We report the first known case of fulminant hepatitis due to hairy cell infiltration. CASE REPORT: A 43-year-old woman with hairy cell leukemia returned 1 year after diagnosis with spider angiomata of the face and neck, palmar erythema, and diffuse telangiectasias. The liver span was normal. Laboratory studies included: aspartate aminotransferase, 56 U/L; alkaline phosphatase, 283 U/L; gamma-glutamyltransferase, 157 U/L; and normal bilirubin. A liver biopsy demonstrated modest infiltration of hairy cells with hemosiderosis and intact hepatocytes. RESULTS: The patient responded to interferon-alpha with resolution of the angiomata, decreased palmar erythema, and improved liver function tests. Five months later, she presented with right upper quadrant pain, anorexia, fatigue, and diffuse myalgias. The physical examination was unchanged. Laboratory studies included: aspartate aminotransferase, 299 U/L; alkaline phosphatase, 1,388 U/L; total bilirubin, 43 mumol/L; and direct bilirubin, 29 mumol/L. Two weeks later, she was admitted to the hospital. Her liver span was 15 cm. Laboratory studies showed the following values: aspartate aminotransferase, 618 U/L; alkaline phosphatase, 2,319 U/L; total bilirubin, 311 mumol/L; direct bilirubin, 233 mumol/L; and alanine aminotransferase, 462 U/L. Intensive investigation of contributing causes was not revealing. A subsequent liver biopsy demonstrated extensive portal and intralobular hairy cell infiltration with loss of normal architecture. Liver function deteriorated as shown by the following values: aspartate aminotransferase, 1,100 U/L; alkaline phosphatase, 3,645 U/L; bilirubin, 477 mumol/L; and ammonia, 47 mumol N/dL. The patient died 9 days after admission. CONCLUSIONS: Although liver infiltration is often present and mild elevations of liver function tests have been noted, evidence of such extensive hepatic injury caused by hairy cell leukemia has not been reported previously. Hairy cell infiltration of the liver can cause typical cutaneous changes of liver disease and even fulminant hepatitis.     

Case of AIDS‐related cholangitis treated by endoscopic sphincterotomy

A 21‐year‐old man with an 8‐year history of acquired immunode?ciency syndrome (AIDS) presented with abdominal pain, jaundice and dark urine. Laboratory data on admission revealed cholestasis. The total bilirubin concentration was 10.0 mg/dL. Alanine transaminase and aspartate transaminase were 198 IU/L and 195 IU/L, respectively. The serum alkaline phosphatase level was 2724 IU/L. γ‐Glutamyl transferase was 1770 IU/L. Abdominal ultrasonography and computed tomography revealed dilation of the common bile duct and intrahepatic ducts without gallstones. Endoscopic retrograde cholangiopancreatography showed dilation of the common bile duct up to the level of the ampulla of Vater with partial stenosis. Endoscopic sphincterotomy was performed. The abdominal pain and jaundice resolved immediately and the liver function tests were signi?cantly improved. The patient developed a subarachnoid hemorrhage and died of respiratory arrest 2 months after the endoscopic sphincterotomy.     

Evaluation of colchicine therapy in primary biliary cirrhosis

We have conducted a double-blind controlled trial of colchicine in patients with primary biliary cirrhosis. Fifty-seven patients with biopsy-proven primary biliary cirrhosis were randomized to receive either 0.6 mg of colchicine twice daily or an identically appearing placebo. Patients underwent clinical and laboratory evaluation every 3 mo and liver biopsy annually. Differences in mean alkaline phosphatase and alanine aminotransferase values between the colchicine and placebo recipients were statistically significant at 4 yr. Differences in mean bilirubin and immunoglobulin M values, although lower in the colchicine group, did not reach statistical significance. In colchicine-treated patients, mean alkaline phosphatase values fell significantly compared with controls, from 281 to 112 IU/L (p less than 0.01). Similarly, mean alanine aminotransferase values fell significantly compared with controls, from 129 to 86 IU/L (p less than 0.05). Bilirubin values remained stable in drug-treated patients, even in those patients with initially elevated bilirubin values, whereas they nearly doubled in subjects receiving placebo. Although biochemical parameters of disease activity improved or stabilized in colchicine-treated subjects, no difference in histologic progression was detected between the two treatment groups. We conclude that colchicine is of clinical benefit to patients with primary biliary cirrhosis as judged by improvement in alkaline phosphatase and alanine aminotransferase activities as well as a tendency for stabilization of bilirubin values.     

Thyrotoxicosis hepatitis: a case report]

Abnormal liver function in thyroid disorders may be secondary to thyrotoxicosis or to autoimmune injury to the liver. We report the case of a 36-year-old female who developed jaundice and pruritus with mild cholestasis and moderately elevated transaminase levels. The diagnosis of Graves' disease was made shortly thereafter. Laboratory findings were: alanine and aspartate aminotransferase 219 (IU/I (N: 9-50) and 102 IU/I (N: 10-15) respectively, alkaline phosphatase 336 IU/I (N: 40-135), bilirubin 24 micromol/I (N: 2-23), and gamma-glutamyl transpeptidase 232 IU/I (N: 9-43). Abdominal ultrasonography showed normal bile ducts; echocardiography ruled out heart failure; viral and autoimmune markers for hepatitis and cirrhosis were negative. Percutaneous liver biopsy showed moderate intrahepatic steatosis, anisokaryosis, lymphocyte infiltration in the portal areas, and Kupffer cell hyperplasia. Outcome was favorable after seven months of iodine therapy, confirming the diagnosis of thyrotoxicosis hepatitis.     

Androgenic/Anabolic steroid-induced toxic hepatitis

Athletes and bodybuilders often misuse androgenic/anabolic steroids. When used in therapeutic doses, these drugs produce clinical jaundice in just a small number of recipients. We present a 26-year-old male bodybuilder who self-administered high doses of androgenic/anabolic steroids that induced liver damage. One month before admission to the hospital, he used testosterone enanthate (500 mg intramuscularly, twice weekly), stanozolol (40 mg/d), and methylandrostenediol (30 mg/d by mouth, for 5 weeks). On admission, his bilirubin level was 470 micromol/L (direct, 360 micromol/L), his aspartate aminotransferase (AST) level was 5,870 IU/L, his alanine aminotransferase (ALT) level was 10,580 IU/L, his alkaline phosphatase (ALP) level was 152 IU/L, his gamma-glutamyl-transpeptidase level was 140 IU/L, his albumin level was 27.6 g/L, and his prothrombin time was 29%. During the patient's prolonged hospitalization, multiple tests and liver biopsy were performed, showing only toxic hepatic lesions. The patient was provided with supportive medical treatment. Clinical signs and laboratory findings improved substantially 12 weeks after the patient discontinued androgenic/anabolic steroids. The reasons for presenting this case were the much higher values of AST and ALT levels than reported in other studies, although the values of bilirubin and ALP were similar to those found in the literature. To our knowledge, it is the first case of toxic hepatitis induced by androgenic/anabolic steroids with predominantly hepatocellular necrosis instead of intrahepatic cholestasis.     

Treatment of primary biliary cirrhosis with low-dose weekly methotrexate

Nine women with symptomatic precirrhotic primary biliary cirrhosis have been treated with oral pulse methotrexate, 15 mg/wk, for 12-34 months. Three women had pruritus, two fatigue, and four pruritus and fatigue. Itching disappeared and fatigue lessened or disappeared in all within 4-11 months after starting methotrexate. All who itched were able to discontinue cholestyramine (five) or antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when methotrexate was discontinued or the dose lowered. Mean serum alkaline phosphatase decreased from 471 to 171 U/L (P less than 0.01), serum bilirubin from 0.99 to 0.59 mg/dL (P less than 0.05), and serum alanine aminotransferase from 132 to 61 U/L (P = 0.02), and serum cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum cholesterol was significant, P = 0.05, if data were used just from the six women whose baseline serum cholesterol levels were elevated. Serum albumin remained normal in all. The serum bilirubin levels became normal in three of four patients with elevated levels. The serum alkaline phosphatase levels became normal in four patients and the alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that methotrexate may be effective treatment for precirrhotic primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity.     

Two cases of food additive-induced severe liver damage associated with positive results on lymphocyte stimulation test and for antinuclear antibodies

Two cases of severe liver injury and positive result for antinuclear antibodies induced by food additives are reported. The first patient reported long-term intake of Mabo Ramen^? noodle soup, nutritional supplements, and over-the-counter drugs. Total bilirubin, aspartate aminotransferase, and alanine aminotransferase were 9.6?mg/dL, 1,048, and 1,574?IU/L, respectively. Antinuclear antibody was 80×. The drug-induced lymphocyte stimulation test (DLST) was positive for Mabo Ramen^? and its additives such as Xanthan gum, guar gum, and Doubanjiang. Histologic examination of a liver biopsy specimen showed lymphocyte infiltration and necrosis. The autoimmune hepatitis score was 3. The second patient reported intake of dietary supplements, including Bimore C^? and Chokora BB^?. Laboratory tests revealed that total bilirubin was 9.8?mg/dL, aspartate aminotransferase was 1,130?IU/L, and alanine aminotransferase was 1,094?IU/L. Antinuclear antibody was 320×. Co-existing pancreatic damage was confirmed by the findings on abdominal CT and elevation of serum lipase, span-1, and DUPAN-2. DLSTs were positive for both supplements. These two supplements contained additives such as titanium oxide, magnesium stearate, and hydroxypropylcellulose. DLSTs for all three additives were positive. Histologic examination revealed periportal necrosis and lymphocyte infiltration of lobular and portal areas. These two cases demonstrate that repeating DLSTs is useful for identifying causative constituents in foods and supplements.     

Screening of ethyl acetate extract of Bridelia micrantha for hepatoprotective and anti-oxidant activities on Wistar rats

ObjectiveTo explore the hepatoprotective and anti-oxidant activities of the methanolic leaf extract of Bridelia micrantha (B. micrantha) on paracetamol induced liver damage in Wistar rats.MethodsParameters were measured including alanine aminotransaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and total protein. The anti-oxidant effects were studied using the 1, 1-Diphenynl-2-Picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assay methods.ResultsB. micrantha extract decreased the level of AST in the rats given PCM from (129.47±0.92I) IU/L to (57.78±1.71) IU/L (P<0.05). This was lower than the value for Silymarin which was (59.92±1.41) IU/L. ALT concentration was reduced from (150.18±2.23) IU/L to (79.10±2.01) IU/L (P<0.05). ALP was reduced from (49.86±0.85) IU/L to (29.64±1.53) IU/L (P<0.05). Total bilirubin was reduced from (2.14±0.10 mg/dL) to (0.18±0.07) mg/dL (P<0.05) while total protein was increased from (4.26±0.30) mg/dL to (6.20±0.19) mg/dL (P<0.05). Concentrations ranging from 10 – 400 μg/mL of B. micrantha were assayed for antioxidant activities. The DPPH assay showed 98% antioxidant activity at concentration of 400 μg/mL. The FRAP values were 0.016, 0.39, 0.455, 0.601 and 1.382 μM at 10, 50, 100, 200 and 400 μg/mL respectively.ConclusionsResults suggest that B. micrantha has hepatoprotective and anti oxidant potentials. However, further work involving fractionation needs to done to isolate the active compound responsible for the hepatoprotective activity.     

临床诊断的肝细胞型急性药物性肝损伤患者血清ALT/ALP比值变化特点与组织病理学特征分析

目的 探讨药物性肝损伤(DILI)患者临床分型的变化及其组织病理学特征。方法 2018年8月～2019年8月入院临床诊断为肝细胞型DILI患者43例,在入院治疗2周后行肝穿活检,在病理学检查当日再次根据临床指标确定临床分型,观察组织病理学特征。结果 43例临床诊断的肝细胞型DILI患者在肝穿时血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)和总胆汁酸(TBA)水平已显著降低,其R值较入院时也显著下降(19.6±13.6对3.29±3.26),差异具有统计学意义(P<0.05);组织病理学检查诊断急性炎症型21例,炎症淤胆型22例;在入院时,急性炎症型与炎症淤胆型患者血清ALT、AST、TBIL、ALP和GGT水平无显著性差异(P>0.05),仅急性炎症型患者R值显著小于炎症淤胆型(13.8±6.2对25.5±16.5,P=0.004),血清TBA水平显著低于炎症淤胆型(61.0±60.8 μmol/L对115.3±80.9μmol/L,P=0.017);入院时诊断为肝细胞型DILI的43例患者在肝穿时仅9例符合肝细胞型临床分型;经ROC曲线分析,以R值等于14.9为截断点,其曲线下面积(AUC)为0.708,具有一定的诊断意义。结论 药物性肝损伤的临床分型会随着病情的变化而呈动态变化,入院时以较高的R值诊断胆汁淤积具有一定的指导意义,值得进一步观察。     

Clinical and histologic features of Azathioprine-induced hepatotoxicity

Background: Hepatoxicity is a relative uncommon complication related with Azathioprine, however most studies were performed in inflammatory bowel diseases patients. The aim of this study is to report the clinical profile of patients with Azathioprine-induced hepatotoxicity.

Methods: All medical records of patients received Azathioprine from 2010 to 2015 were retrospectively reviewed. Hepatotoxicity was defined as serum alanine aminotransferase (ALT) or aspatate aminotransferase (AST) or total bilirubin >2 times upper limit normal. Other causes of liver diseases were excluded. All subjects were followed until the resolution of liver injury.

Results: Two-hundred and ninety-three patients receiving Azathioprine were retrospectively reviewed. Eight patients (2.7%) were diagnosed with Azathioprine-induced hepatotoxicity. The median age was 45 year with female preponderance. The latency to onset of liver injury ranged from 7 to 236 d, and 4 patients were symptomatic. Median peak levels were ALT 295?U/L, alkaline phosphatase 169?U/L, and total bilirubin 1?mg/dl. According to R-ratio, mixed pattern (50%) was more frequent than cholestatic (37.5%) and hepatocellular pattern (12.5%). Liver biopsies were performed in 2 patients, and showed hepatocellular and canalicular cholestasis with mild portal and peri-portal inflammation. All patients recovered fully with a median time of 41.3 days. Two patients developed prolonged cholestasis >2 months, hence none had liver failure or required liver transplantation.

Conclusion: Hepatotoxicity is relative uncommon in patients receiving Azathioprine, and predominantly is mixed hepatocellular and cholestatic in nature. Even though all patients recover fully after drug withdrawal, severe cholestasis can occur.     

Situs inversus totalis and secondary biliary cirrhosis: a case report

Situs inversus totalis is is a congenital anomaly associated with various visceral abnormalities, but there is no data about the relationship between secondary biliary cirrhosis and that condition. We here present a case of a 58 year-old female with situs inversus totalis who was admitted to our clinic with extrahepatic cholestasis. After excluding all potential causes of biliary cirrhosis, secondary biliary cirrhosis was diagnosed based on the patient's history, imaging techniques, clinical and laboratory findings, besides histolopathological findings. After treatment with tauroursodeoxycholic acid, all biochemical parameters, including total/direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gama glutamyl transferase, returned to normal ranges at the second month of the treatment. We think that this is the first case in literature that may indicate the development of secondary biliary cirrhosis in a patient with situs inversus totalis. In conclusion, situs inversus should be considered as a rare cause of biliary cirrhosis in patients with situs inversus totalis which is presented with extrahepatic cholestasis.     

Ursodeoxycholic acid treatment of refractory chronic graft-versus-host disease of the liver.

OBJECTIVE: To determine the safety and efficacy of ursodeoxycholic acid treatment in patients with chronic graft-versus-host disease (GVHD) of the liver. DESIGN: Open-label study in which each patient served as his or her own control. SETTING: Private practice and a university bone marrow transplant center. PATIENTS: Twelve patients with refractory chronic GVHD of the liver were studied after allogeneic bone marrow transplantation. INTERVENTIONS: After baseline data collection, patients were given ursodeoxycholic acid (UDCA, 10 to 15 mg/kg body weight per day) for 6 weeks. After discontinuation of the drug, patients were followed for an additional 6 weeks. Doses of immunosuppressive drugs were unchanged for these 12 weeks. MEASUREMENTS: Signs, symptoms, Karnofsky performance scores, hematocrit, total leukocyte count, absolute neutrophil count, platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyltransferase (GGT), total serum bilirubin, prothrombin time, serum creatinine, and blood urea nitrogen were assessed. RESULTS: Serum tests of cholestatic liver injury measured at 2, 4, and 6 weeks showed improvement compared with baseline. At 6 weeks, the percent decrease from baseline in total serum bilirubin was 33% (P less than 0.005); in alkaline phosphatase the decrease was 32% (P less than 0.038); and in AST the decrease was 37% (P less than 0.007). After discontinuation of UDCA therapy, 11 patients were followed for 6 additional weeks. All showed significant worsening in liver function test results. Symptom scores were unchanged throughout the study. One patient with pruritus improved while receiving therapy with UDCA. No adverse effects were observed. CONCLUSION: Therapy with UDCA was safe, well-tolerated, and efficacious in the short-term treatment of refractory chronic GVHD of the liver. Further investigation is needed to evaluate the long-term effects of UDCA therapy.     

Evolution from primary biliary cirrhosis to primary biliary cirrhosis/autoimmune hepatitis overlap syndrome

An asymptomatic 70-year-old Hispanic woman with type 2 diabetes was found in 2004 to have an AST of 132 U/L, ALT 146 U/L, alkaline phosphatase 1107 U/L, total serum bilirubin 3.5 mg/dL, and albumin 2.9 g/dL. Viral hepatitis testing was negative. Serum IgG, IgA, and IgM were all elevated, antimitochondrial antibody was weakly positive, and antinuclear antibody was negative. Liver biopsy was reported to show "evolving cirrhosis with marked lymphoid hyperplasia." Although the indication was nowhere stated, she was prescribed ursodeoxycholic acid 500 mg b.i.d, on which her biochemical tests initially improved. One year later she developed itching and jaundice. Imaging studies revealed multiple gallstones. An MRCP was suggestive of cirrhosis with a questionable common bile duct stricture, and she underwent ERCP with removal of gallbladder and common bile duct stones and placement of a biliary stent. A periampullary mass, which proved to be a somatostatinoma, was excised in 2006 via an open laparotomy, at which the stent was removed and a second liver biopsy performed. It was reported as showing chronic active hepatitis, activity stage 2, and fibrosis grade 3 with bridging. Her subsequent course was complicated by recurrent bleeding from small bowel arteriovenous malformations. Seen for the first time at Columbia University Medical Center in January 2007, she complained of continuing pruritus. AST was 69 U/L, ALT 43 U/L, alkaline phosphatase 491 U/L, and total bilirubin 3.3 mg/dL. Serum albumin was 2.6 g/dL. Antinuclear antibodies, negative in 2004, were now positive at 1:320, and antimitochondrial M2 antibodies were strongly positive. Serum IgG and IgA, but NOT IgM, were elevated. Review of her outside liver biopsies revealed features of primary biliary cirrhosis (PBC) in the first, and of both PBC and autoimmune hepatitis (AIH) in the second. The patient exhibits an overlap syndrome, in which both histologic and serologic features of AIH evolved in a setting initially most suggestive of PBC alone. The phenomenon of autoimmune overlap syndromes is discussed.     

Epstein-Barr virus induced hepatitis: An important cause of cholestasis.

INTRODUCTION:: Epstein-Barr virus (EBV) infection frequently involves the liver, presenting as elevations in transaminases. EBV infection associated hepatitis, presenting with hyperbilirubinemia is rare. We describe a case of infectious mononucleosis that presented with cholestatasis, and summarize 23 cases from the literature to categorize this increasingly recognized clinical spectrum of EBV infection induced cholestatic hepatitis. METHODS:: We conducted an extensive literature review of all cases of EBV in pediatric and adult literature with cholestatasis using MEDLINE and EMBASE. We also included information on one case from our institution. RESULTS:: We identified 24 cases. Median age was 20 years (range 1-72 years), with 14 (58%) females. On presentation, fever (72%), jaundice (67%) and splenomegaly (62%) were the most common signs. Laboratory data revealed the median asparate aminotransferase (AST), or alanine aminotransferase (ALT) level was 179IU/L (range 56-2518IU/L), median serum bilirubin level 12.6mg/dL (range 2.2-47.5mg/dL) and median alkaline phosphatase level 749IU/L (range 31-3105IU/L). Diagnosis was confirmed using EBV viral capsid antigen IgM in 20 (83%) patients. HIV testing was done in 7 (29%) of the cases, and was negative. One patient died from the illness, while full recovery was reported in all other cases, with median follow-up of 30 days (range 5-180 days). CONCLUSIONS:: Cholestatasis is associated with EBV infection, and should be part of the differential diagnosis in all age groups, presenting with hyperbilirubinemia.