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NYU Medical Grand Rounds Clinical Vignette

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. Chief Complaint. 47 year-old man with chronic hepatitis C infection who is referred for further evaluation and treatment of hepatitis C.

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NYU Medical Grand Rounds Clinical Vignette

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  1. NYU Medical Grand Rounds Clinical Vignette Joseph Shin MD, PGY-2 March 31, 2010 UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  2. Chief Complaint 47 year-old man with chronic hepatitis C infection who is referred for further evaluation and treatment of hepatitis C. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  3. History of Present Illness • 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. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  4. Additional History • 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 UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  5. Outpatient Medications • Glyburide 5mg po daily • Sitagliptin 100mg po daily • Nadolol 20mg po daily • Multivitamin daily • Allergies: Penicillin (rash) UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  6. Physical Examination General: Well-appearing, obese man in no acute distress Vitals: T 99.0, BP 110/68, HR 73, RR 18, BMI 30 O2 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. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  7. Laboratory Results • 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 UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  8. Laboratory Results • 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) UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  9. Working Diagnoses • Chronic Hepatitis C Infection • Thrombocytopenia UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  10. 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. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  11. Pathology • 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 UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  12. 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. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  13. 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. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  14. 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. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  15. 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. UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  16. Eltrombopag 30mg Eltrombopag 60mg Peg-IFN & Ribavirin UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  17. Final Diagnoses • Thrombocytopenia • Improved on Eltrombopag • Chronic Hepatitis C Infection • Currently on peg-interferon/ribavirin • Cirrhosis • Portal hypertension • Non-bleeding varices • Splenomegaly UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

  18. Clinical Correlations The NYU Internal Medicine Blog A Daily Dose of Medicine http://clinicalcorrelations.org UNITED STATES DEPARTMENT OF VETERANS AFFAIRS

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