Chronic Hepatitis
Emmet B. Keeffe, M.D.
Stanford University School of Medicine
Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References
Definition/Key
Clinical Features
- Most common etiologies
- Chronic hepatitis C
- Chronic hepatitis B
- Autoimmune hepatitis
- Highly variable course
- Asymptomatic to rapidly progressive with fulminant
hepatic failure
- Most common symptoms
- Fatigue
- Malaise
- Mild abdominal pain
- Symptoms of advanced disease
- Anorexia
- Jaundice
- Spider angiomas
- Palmar erythema
- Ascites
- Edema
- Hepatomegaly
- Encephalopathy
- Extrahepatic manifestations
- Arthralgias
- Arthritis
- Cryoglobulinemia
- Glomerulonephritis
- Skin rashes
- Amenorrhea
- Acne
- Hirsutism
- Thyroiditis
Differential Diagnosis
- Primary biliary cirrhosis
- Primary sclerosing cholangitis
- Drug-induced chronic hepatitis
- Wilson disease
- α1-Antitrypsin deficiency
Best Tests
Serologic Testing
Autoimmune Hepatitis
- Type 1
- Hypergammaglobulinemia
- Presence of ANA, anti–smooth muscle antibody (ASMA),
or both
- Type 2
- Absence of ANA and ASMA
- Presence of antibody to liver/kidney microsome
(anti-LKM) type 1
- Type 3
- Presence of antibody to soluble liver antigen, liver/pancreas
antigen, or both
- Some patients also positive for ASMA, antimitochondrial
antibody, or both
Chronic Hepatitis B
- Positive HBsAg
- Negative IgM
- Negative anti-HBc
- HBeAg-positive (wild type HBV) or HBeAg-negative (precore
or core promoter mutant HBV)
- Detectable HBV DNA with active viral replication
Chronic Hepatitis D
- Positive HBsAg
- Positive anti-HDV
Chronic Hepatitis C
- Positive anti-HCV (second-generation ELISA or recombinant
immunoblot assay)
- Detectable HCV RNA
- Determination of genotype
- 75% genotype 1
- 20% genotypes 2 to 3
- < 5% genotypes 4 to 6
Routine Laboratory Tests
- Serum ALT and AST usually elevated, often only minimally
in chronic hepatitis B and C
- Increased γ-globulin level in autoimmune hepatitis
- Low serum albumin level and prolonged PT suggest advanced
disease
- Abdominal CT, MRI, or ultrasound to determine
- Liver and spleen size and contour
- Evidence of portal hypertension
- Presence of ascites
- Presence or absence of hepatocellular carcinoma
Liver Biopsy
- Helps confirm diagnosis
- Establish grade of inflammation
- Establish stage of fibrosis
- Exclude coexistent liver disease
Best Therapy
Drug Therapy for Autoimmune Hepatitis
Corticosteroids
- 65% remission in 1 yr
- 80% remission in 3 yr
- 50% relapse with discontinuance of therapy
- Long-term therapy needed in some
- Prednisone
- Dose
- Initial: 40 mg/day, tapered over 6 wk
- Maintenance: 15–20 mg/day
- Cost/mo: $7.99
- Prednisone + azathioprine
- Combination preferred for avoiding toxicity
of corticosteroids, e.g., in diabetics, elderly
- Dose:
- Prednisone, initial: 30 mg/day, tapered over
6 wk
- Prednisone, maintenance: 10 mg/day
- Azathioprine (initial and maintenance): 50
mg/day
- Cost/mo: $7.99 + $27.99
Drug Therapy for Chronic Hepatitis B
Interferon alfa-2b
- Tolerance poor
- Should avoid in ESLD
- Peginterferon under study
- Loss of HBV DNA and HBeAg in one third
- Loss of HBsAg in 10%–20% at 5 yr
- Dose: 30–35 million U/wk, S.C. or I.M. x 4
mo given as 5 million U/day or 10 million U t.i.w.
- Cost/mo: $2,066.54
Lamivudine
- Well tolerated
- Safe in ESLD
- Dose adjustments needed for patients with significant
renal failure
- Resistance common
- 15% at 1 yr, increasing to
65% at 5 yr. HbeAg seroconversion in 16%–18% at 1 yr
- Long-term therapy often needed, especially in HbeAg-negative patients
- Dose: 100 mg/day
- Cost/mo: $146.00
Adefovir
- Well tolerated
- Safe in ESLD; dose adjustments needed for patients
with significant renal failure
- Resistance rare
- HBeAg seroconversion in 12% at 1 yr
- Long-term therapy often needed, esp. in HBeAg-negative patients
- Dose: 10 mg/day
- Cost/mo: $450.00
Liver Transplantation for Chronic Hepatitis B
- HBV infects allograft in 80%–100% of cases if antiviral
prophylaxis not given
- Use of HBIG and lamivudine/adefovir
reduces reinfection to 5%–20%
- Long-term survival good in absence of reinfection
Drug Therapy for Chronic Hepatitis D
Interferon alfa
- Dose: 9 million U t.i.w. x 48 wk
- Cost/mo: $1549.91
Drug Therapy for Chronic Hepatitis C
Interferon and Ribavirin Combination Therapy
- Interferon
- Overall SVR in 55%–60%
- 1 yr Rx for genotype 1
- 6 mo Rx for genotypes 2 to 3
- Side effects
- Flu-like
- Psychiatric
- Hematologic
- Dose:
- Peg alfa-2a: 180 μg/wk
- Peg alfa-2b: 1.5 μg/kg/wk
- Cost/mo: $1,294.99
- Ribavarin
- Teratogenic; avoid in pregnancy
- Reduce dose or discontinue if severe anemia develops
- Dose: 800-1,200 mg/day in two divided doses
- 800 mg/day adequate for genotypes 2 or 3
- 1,000–1,200 mg/day for genotype 1
- Cost/mo: $1,632.98
Liver Transplantation for Chronic Hepatitis C
- HCV reinfects allograft in nearly 100% of cases, but
subsequent illness is usually mild and progresses to liver failure in the
minority—15%–20% of cases
Best References
Czaja, et al: Hepatology 36:479, 2002
Lok, et al: Hepatology 34:1225,
2001
NIH Consensus Statement: Hepatology 36:S3,
2002
July 2004
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