NYU Medical Grand Rounds Clinical Vignette

Joseph Shin MD, PGY-2

March 31, 2010

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

47 year-old man with chronic hepatitis C infection who is referred for further

evaluation and treatment of hepatitis C.

Chief Complaint

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

History of Present Illness

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

• 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

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

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

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

• Glyburide 5mg po daily

• Sitagliptin 100mg po daily

• Nadolol 20mg po daily

• Multivitamin daily

• Allergies: Penicillin (rash)

Physical Examination

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

General: Well-appearing, obese man in no acute distress

Vitals: T 99.0, BP 110/68, HR 73, RR 18, BMI 30O2 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

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

• 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

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

• 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

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

• Chronic Hepatitis C Infection• Thrombocytopenia

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

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

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

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

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

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

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

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.

Platelet Response on Eltrombopag and peg-IFN/ribavirin

0

20

40

60

80

100

120

140

160

180

200

1/12

/2010

1/19

/2010

1/26

/2010

2/2/

2010

2/9/

2010

2/16

/2010

2/23

/2010

3/2/

2010

3/9/

2010

3/17

/2010

3/23

/2010

Date

Pla

tele

t co

un

ts (

tho

usa

nd

s/m

L)

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

Eltrombopag 30mg Eltrombopag 60mg

Peg-IFN & Ribavirin

UNITED STATES

DEPARTMENT OF VETERANS

AFFAIRS

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

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