E-Case 8-C

Heather Kelly-Hedrick

April 8-12, 2002

43 yo woman presents to establish care and reveals h/o IVDU in her late 20s.  No hx of HIV, told had "hepatitis" in past but doesn't remember what kind and never received treatment.  Doesn't recall episode of jaundice, denies abdominal pain and fatigue.  Abd exam was normal, no HSM or ascites.  Skin was clear.  Hep C Ab was positive, Hep A, Hep B and HIV serologies negative.

"How did I get this?"

1. Factors most strongly associated with infection:

   1. IVDU

   2. Blood transfusion before 1990

2. Linked, but reasons why unclear:

   1. Poverty

   2. High risk sexual behavior

   3. < 12 years of education

   4. Divorced or separated

3. Maternal-fetal transmission infrequent, often assoc with coinfection with HIV

4. Sexual transmission inefficient

5. Virus can be detected in saliva of infected persons, but casual household contact and contact with saliva of infected thought to be inefficient mode of transmission

6. Nosocomial infections documented (colonoscope, HD, surgery).   Needle stick injuries 0-10% risk of transmission

7. In some cases, no risk factors can be identified

What are the clinical features and natural course of the disease?

1. Acute infection occurs within 7 - 8 weeks, usually mild or no symptoms (jaundice, malaise, and nausea).  Fulminant hepatitis rare.

2. Chronic in most cases, 74 - 86% persistent viremia.  Fatigue with hepatitis and some fibrosis.

3. Cirrhosis develops in 15 - 20% (can exceed 30 yrs).  Can lead to severe complications and death.  Risk of hepatocellular cancer is 1 - 4% per year.

4. Alcohol intake, coinfection with HIV-1 or HBV, male sex, and an older age at infection all accelerate clinical progression.

5. Cryoglobulins found in up to half of persons, 10 to 15% of whom are symptomatic (weakness, arthralgias, and purpura).  Membranoproliferative GN, nerve and brain involvement can occur. 

HCV RNA, PCR qnt was 277,000 IU/ml, Hep C genotype was 3a, ALT was 132, protime was normal.  Liver biopsy showed chronic hepatitis with bridging fibrosis with possible cirrhosis, stage 3-4 of 4, moderate lobular and portal inflammation grade 3 of 4.

What is the significance of these tests?

1. Serologic assays for antibodies detected 4 to 10 weeks after infection.  In low risk patients test misses only 0.5 to 1% of cases.  False negatives occur in persons with immune compromise (HIV-1, renal failure).

2. HCV RNA tests based on PCR technique have lower limit of detection of <100 copies of HCV RNA/ml, hence used for confirmation of viremia and treatment response.

3. Viral genotyping helps predict outcome of therapy and influences choice of therapeutic regimen.

4. ALT best test for monitoring infection and efficacy of therapy.

5. Histologic eval (liver biopsy) gold standard for determining activity of HCV-related liver disease, only reliable predictor of prognosis and likelihood of disease progression.

Patient was treated with Rebetron therapy starting 4/01 for 6 months.  Fatigue, malaise and depressive symptoms developed.  Mild anemia occured with Hct to 33.  By July, HCV RNA, PCR Qnt <600, ALT was 38.  She did complete 6 month treatment course.  One month later, HCV RNA by PCR,Qual was neg and ALT was normal.  GI recommended following these q 6 months and if negative for 2 years, hep C could be considered eradicated.

Is her response typical?

1. Less than half (40%) have favorable response (normalization of ALT and negative result on Qual PCR assay).  Patients with a sustained treatment response six months after cessation of treatment have a high probability of having durable response.

2. Clear indication for therapy is detectable levels of HCV RNA, elevated ALT levels, and liver biopsy showing fibrosis or moderate necrosis and inflammation.

3. Virologic response is assessed at 24 weeks.  If HCV RNA is positive, considered no response and therapy discontinued.  Those with HCV genotype 2 or 3 with neg HCV RNA can also stop, but an additional 24 wks of therapy is recommended for other genotypes.

4. Pegylated  Interferon (attachment of polyethylene glycol to interferon alfa) extends half life and duration of therapeutic activity, hence can be given less often (weekly).  Now FDA approved.  Trials underway to determine role of this drug in HCV treatment.

5. Liver transplantation only option for decompensated HCV-related cirrhosis and some stages of early HCC.

Reference

Lauer G, Walker B.  Hepatitis C Virus Infection.  N Engl J Med 2001;345:41-52.