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NYU Medical Grand Rounds
Clinical Vignette
Joseph Shin MD, PGY-2
March 31, 2010
UNITED STATES
DEPARTMENT OF VETERANS AFFAIRS
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
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
Additional History
Past Medical History
• Diabetes
• Depression
Past Surgical History
• None
Family History
• Diabetes
• Coronary artery disease
UNITED STATES
DEPARTMENT OF VETERANS AFFAIRS
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
• Glyburide 5mg po daily
• Sitagliptin 100mg po daily
• Nadolol 20mg po daily
• Multivitamin daily
• Allergies: Penicillin (rash)
UNITED STATES
DEPARTMENT OF VETERANS AFFAIRS
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
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
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
Working Diagnoses
• 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.
UNITED STATES
DEPARTMENT OF VETERANS AFFAIRS
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
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.
UNITED STATES
DEPARTMENT OF VETERANS AFFAIRS
Platelet Response on Eltrombopag and peg-IFN/ribavirin
Platelet counts (thousands/mL)
200
Eltrombopag 30mg
180
Eltrombopag 60mg
Peg-IFN & Ribavirin
160
140
120
100
80
60
40
20
1/
12
/2
01
0
1/
19
/2
01
0
1/
26
/2
01
0
2/
2/
20
10
2/
9/
20
10
2/
16
/2
01
0
2/
23
/2
01
0
3/
2/
20
10
3/
9/
20
10
3/
17
/2
01
0
3/
23
/2
01
0
0
Date
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
Clinical Correlations
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UNITED STATES
DEPARTMENT OF VETERANS AFFAIRS