NYU Medical Grand Rounds Clinical Vignette Joseph Shin MD, PGY-2 March 31, 2010 U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

47 year-old man with chronic hepatitis C infection who is referred for further evaluation and treatment of hepatitis C. Chief Complaint U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS

History of Present Illness U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS The patient was in his usual state of health until approximately 6 months ago when he presented to his physician in Nashville with fatigue, insomnia, memory impairment and 25 lb weight loss. Routine laboratory screening eventually led to the diagnosis of hepatitis C.

Additional History U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Past Medical History Diabetes Depression Past Surgical History None Family History Diabetes Coronary artery disease Social History Egyptian-born Immigrated in 2006 Current smoker 5-10 cigarettes daily 10 pack-years Occasional alcohol use Denies IV drug abuse No tattoos

Outpatient Medications U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Glyburide 5mg po daily Sitagliptin 100mg po daily Nadolol 20mg po daily Multivitamin daily Allergies: Penicillin (rash)

Physical Examination U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS General: Well-appearing, obese man in no acute distress Vitals: T 99.0, BP 110/68, HR 73, RR 18, BMI 30 O 2 saturation: 99% on room air Abdomen: Soft, non-tender, mildly distended The remainder of the physical exam was normal. No stigmata of chronic liver disease was noted.

Laboratory Results U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS CBC: WBC 3.2 Hemoglobin 13.9 g/dL, Hematocrit 44.2% Platelets 53,000 Basic Metabolic Panel: Within normal limits Hepatic Panel: AST 55 U/L, ALT 46 U/L Alkaline Phosphatase 102 U/L Total Bilirubin 1.5 mg/dL Total protein 6.9 g/dL, Albumin 3.0 g/dL INR: 1.2

Laboratory Results U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Hepatitis A IgM: Negative Hepatitis A IgG: Reactive Hepatitis B serologies: Negative Hepatitis C Hepatitis C Ab: Reactive Hepatitis C RNA PCR: 57,100 IU/mL Genotype: Type 4 Alpha-fetoprotein: 13.6 ng/mL (normal range 0-20ng/mL)

Working Diagnoses U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Chronic Hepatitis C Infection Thrombocytopenia

U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Further work-up Imaging studies of the abdomen were obtained, including MRI with contrast, which demonstrated: Liver cirrhosis Portal hypertension Splenomegaly, splenic varices, splenorenal shunt Gastroesophageal varices Iron deposition Esophago-gastro-duodenoscopy was performed as a part of staging, and demonstrated large esophageal and gastric varices with portal gastropathy.

Pathology U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Liver Biopsy: Cirrhosis with mild chronic hepatitis 2+ iron deposition in hepatocytes Mild steatosis Batts-Ludwig Grading Classification System: Portal/Periportal activity: 2 of 4 (mild piecemeal necrosis) Lobular activity: 2 of 4 (mild lobular inflammation) Stage: 4 of 4 (cirrhosis) Hereditary Hemachromatosis DNA: negative for allele

U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Treatment Course Nadolol was continued for primary esophageal variceal hemorrhage prophylaxis. Citalopram was initiated for the treatment of depression. Immunizations for hepatitis B, seasonal influenza and pneumococcus were administered.

U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Treatment Course Treatment with recombinant human IL-11 (rHuIL-11) was initiated to improve thrombocytopenia prior to treatment with pegylated interferon and ribavirin. rHuIL-11 is a thrombopoietic growth factor that stimulates platelet production independent of the thrombopoietin receptor.

U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Treatment Course After week 4 of rHuIL-11 therapy, the patient developed dyspnea and lower extremity edema. A chest x-ray was performed and was normal. Spironolactone was started with resolution of the patient’s symptoms. After week 8, the patient remained thrombocytopenic, with platelet counts < 60,000. rHuIL-11 discontinued and patient was referred to NYU for further evaluation.

U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Treatment Course The patient was referred for screening and was enrolled in the ENABLE trial of Eltrombopag. Eltrombopag is a non-peptide thrombopoietin (TPO) mimetic that binds and activates the TPO receptor to stimulate increased platelet production. During the study, the patient’s platelet values increased from 51,000 to 136,000/mL. Treatment with peg-interferon and ribavirin was initiated for treatment of chronic hepatitis C.

U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Eltrombopag 30mgEltrombopag 60mg Peg-IFN & Ribavirin

U NITED S TATES D EPARTMENT OF V ETERANS A FFAIRS Final Diagnoses Thrombocytopenia Improved on Eltrombopag Chronic Hepatitis C Infection Currently on peg-interferon/ribavirin Cirrhosis Portal hypertension Non-bleeding varices Splenomegaly

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