Recurrent hepatitis with Halogenated Anesthetics

History 36 y/o female resident in St Kitts HPI: PMH PSH nausea, vomiting, epigastric discomfort, jaundice Usual state of health until 1 week prior One week prior to presentation 3rd Liposuction Abnormal liver profile Admitted at local hospital in St. Kitts Transferred to JMH after worsening liver parameters PMH No known medical problems PSH Breast reduction in April 2007 First liposuction/breast scar removal June 2007 Second liposuction in April 2008

History Medications: SOCH: FAMH: Allergies: Diclofenac No OTC or herbal supplementation No wt reduction medications SOCH: Divorced with 3 children Bank employee Occasional alcohol/smokes/but no substance abuse FAMH: HTN DM-2 No significant h/o liver diseases Allergies: Sulfa

Physical Examination General: sleepy but was able to answer questions HEENT: jaundiced Heart and lung clear Abdomen: soft, tenderness in the RUQ, +hepatomegaly, no ascites No edema, no skin rashes Neuro: (grade 1-2 encephalopathy)

Lab data ANA/AMA: Negative AST: 734 u/L ASMA: 44.8 (nl <20) Immunoglobulins were not processed Hepatitis A, B and C negative. HCV PCR <25 IU/ml Alpha 1 AT: 108 (nl 90-200) Ceruloplasmin: 16.7mg/dl (nl 20-60) Pregnancy test: negative Tox screen: not performed Acetaminophen: negative AST: 734 u/L ALT: 348 u/L Alk phos : 194 u/L Total bilirubin: 19.6mg/dl Direct bilirubin:14.6mg/dl Total protein 7.1 g/dl Albumin 3.2 g/dl PT: 32.2. INR 3.47. WBC: 8.1, Hb: 10.3, Hct: 31.3, Plt: 324

Imaging U/S with Doppler study CT-head: no acute pathology CT-abdomen: Peri-hepatic fluid No intra/extra hepatic dilatation, gall stone All vessels patent CT-head: no acute pathology CT-abdomen: Minimal amount of fluid in abdomen Edema in the sub-cutaneous tissue in the both inguinal areas consistent with recent surgery

Over the Next 72 hours Worsening of laboratory & clinical parameters TBil: 21.8 INR: 7.95 Grade-4 encephalopathy Patient underwent an emergent orthotropic liver transplantation

Explant Sub-massive confluent centri-lobular necrosis of liver with chronic inflammatory infiltration Above findings are consistent with fulminant hepatic failure 8

Post Op Liver Chemistries Pattern Transplant POD 6

Post Operative Liver function pattern Transplant POD 6

Differential Diagnosis Hepatic artery thrombosis Early Acute Cellular Rejection Primary Non-function of Graft Ischemic Hepatitis Viral hepatitis Drug induced hepatitis Cold ischemic injury or Preservation Injury

Re-evaluation Donor status: 61 Y M serology negative for viral infection Donor tissue stains were negative for CMV/HSV and other viral etiology No hypotensive episodes Blood cx’s negative No hepatic artery thrombosis Meds tacrolimus levetiracetam thymoglobulin piperacillin/tazobactam midazolom dapsone etomidate labetolol amphotericin B During perioperative time isoflurane propofol. 12

Post Transplant – Day # 6 Liver biopsy - centri-lobular necrosis/mild acute rejection/bile duct injury 13

Post Transplant – Day # 14 Liver Biopsy – centri-lobular necrosis No evidence of acute cellular rejection 14