Hepatitis C

Hepatitis C - Chronic
Rahul Soman, M. Pharm

 

Definition  

Acute: An acute illness with a discrete onset of flu-like symptoms (eg, nausea, anorexia, fever, malaise, or abdominal pain) accompanied by jaundice or elevated serum aminotransferase levels with laboratory confirmation of hepatitis C infection

Chronic: Persistent infection by the hepatitis C virus (HCV) characterized by detection of HCV RNA in the blood for 6 months or more, causing ongoing liver inflammation with progressive fibrosis that may result in cirrhosis, endstage liver disease, and hepatocellular carcinoma

 

Suspected or known viral hepatitis C  

* Hepatitis C nucleic acid assay, Quantitative: The presence of viremia is definitively diagnostic for hepatitis C virus (HCV) infection .

 

Suspected or known viral hepatitis C  

* Hepatitis C nucleic acid assay, Qualitative: A positive serum qualitative HCV RNA test confirms active HCV infection regardless of antibody status and serum ALT levels .

 

Viral hepatitis C  

* Hepatitis C virus genotype determination: Genotype 1 is associated with a lower rate of sustained virologic response following antiviral therapy and a lower response to subsequent re-treatment .

 

Suspected or known viral hepatitis C  

* Alanine aminotransferase measurement: Serum ALT levels range from 0 to 20 times the upper limit of normal (ULN) in chronic hepatitis C infection; most patients have ALT levels <5 times the ULN .

 

Suspected liver disease  

* Aspartate aminotransferase measurement: Elevated serum aminotransferase levels suggest hepatocellular injury and death .

 

Hepatitis C  

* Complete blood count with white cell differential, automated

 

Monitoring During Therapy  

 

Suspected or known viral hepatitis C  

* Hepatitis C nucleic acid assay, Quantitative: The presence of viremia is definitively diagnostic for hepatitis C virus (HCV) infection .

 

Suspected or known viral hepatitis C  

* Hepatitis C nucleic acid assay, Qualitative: A positive serum qualitative HCV RNA test confirms active HCV infection regardless of antibody status and serum ALT levels .

 

Suspected or known viral hepatitis C  

* Alanine aminotransferase measurement: Serum ALT levels range from 0 to 20 times the upper limit of normal (ULN) in chronic hepatitis C infection; most patients have ALT levels <5 times the ULN .

 

Suspected liver disease  

* Aspartate aminotransferase measurement: Elevated serum aminotransferase levels suggest hepatocellular injury and death .

 

Hepatitis C  

* Complete blood count with white cell differential, automated

 

Monitoring after Therapy  

 

Suspected or known viral hepatitis C  

* Alanine aminotransferase measurement: Serum ALT levels range from 0 to 20 times the upper limit of normal (ULN) in chronic hepatitis C infection; most patients have ALT levels <5 times the ULN .

 

Suspected liver disease  

* Aspartate aminotransferase measurement: Elevated serum aminotransferase levels suggest hepatocellular injury and death .

 

Monitoring Patients who are Not Receiving Therapy  

 

Suspected or known viral hepatitis C  

* Alanine aminotransferase measurement: Serum ALT levels range from 0 to 20 times the upper limit of normal (ULN) in chronic hepatitis C infection; most patients have ALT levels <5 times the ULN .

 

Suspected liver disease  

* Aspartate aminotransferase measurement: Elevated serum aminotransferase levels suggest hepatocellular injury and death .

 

Hepatocellular Carcinoma Surveillance in Patients with Cirrhosis  

 

Screening for hepatocellular carcinoma in at-risk patients  

* Alpha-1-fetoprotein measurement, serum: Screening for hepatocellular carcinoma using alpha-fetoprotein (AFP) with ultrasonography (US) is indicated in patients with cirrhosis ; AFP screening in at-risk chronic hepatitis B patients is indicated when US is not available .

 

Hepatocellular carcinoma surveillance in patients with cirrhosis  

* Abdominal ultrasound

 

Medical History  

* Substance Abuse

* Sexual exposure

* HIV infection

* Surgical procedure

* Alcohol Abuse

* Hemodialysis

 

Findings  

* Jaundice

* Malaise

* Nausea

* Fatigue

* Loss of appetite

* Liver pain

* Hepatosplenomegaly

* Acholic stool

* Myalgia

* Arthralgia

* Erythema

* Spider nevus

* Pruritus

* Lichen planus

* Porphyria cutanea tarda

* Depression - Chronic

 

Tests  

 

Suspected hepatitis C in patients with evidence of clinical liver disease  

* Hepatitis C antibody test: A positive screening test with high signal-to-cutoff (s/co) ratio indicates past or present infection; positive screening tests with lower s/co ratios require confirmatory testing.

 

Suspected acute viral hepatitis A  

* Hepatitis A antibody level: The presence of IgM antibody to hepatitis A virus (anti-HAV) confirms acute infection; the presence of IgM and IgG antibody (total anti-HAV) confirms immunity to HAV but does not differentiate current from previous infection .

 

Suspected or known hepatitis B infection and screening  

* Hepatitis B surface antigen measurement: The presence of hepatitis B surface antigen (HBsAg) indicates acute or chronic active infection .

 

Suspected hepatitis B virus infection  

* Hepatitis B core antibody measurement: A positive antibody to hepatitis B core antigen (anti-HBc) test indicates hepatitis B virus infection. IgM class anti-HBc is consistent with an acute or recent infection, while IgG class anti-HBc is consistent with a chronic or past infection .

 

Suspected or known viral hepatitis C  

* Hepatitis C nucleic acid assay, Qualitative: A positive serum qualitative HCV RNA test confirms active HCV infection regardless of antibody status and serum ALT levels .

 

Suspected or known viral hepatitis C  

* Hepatitis C nucleic acid assay, Quantitative: The presence of viremia is definitively diagnostic for hepatitis C virus (HCV) infection .

 

Viral hepatitis C  

* Hepatitis C virus genotype determination: Genotype 1 is associated with a lower rate of sustained virologic response following antiviral therapy and a lower response to subsequent re-treatment .

 

Suspected or known viral hepatitis C  

* Alanine aminotransferase measurement: Serum ALT levels range from 0 to 20 times the upper limit of normal (ULN) in chronic hepatitis C infection; most patients have ALT levels <5 times the ULN .

 

Suspected liver disease  

* Aspartate aminotransferase measurement: Elevated serum aminotransferase levels suggest hepatocellular injury and death .

 

Suspected or known liver disease  

* Bilirubin, total measurement: Conjugated hyperbilirubinemia may suggest acute viral hepatitis, autoimmune hepatitis, or toxic or ischemic liver injury when it occurs in the presence of substantially elevated aminotransferase levels .

 

Viral hepatitis C  

* Complete blood count with white cell differential, automated: During treatment, an absolute neutrophil count that falls to <500 cells/mm3 or a platelet count that falls below 30,000 cells/mm3 requires a peginterferon dose adjustment .

 

Differential Diagnosis  

* Hepatitis B - Chronic

* Hepatitis A - Acute

* Hepatitis E, acute

* Drug-induced liver disease

* Alcoholic liver disease - Acute

* Cholecystitis - Acute

* Autoimmune hepatitis

* Non-alcoholic fatty liver

* Infectious mononucleosis - Acute

* Cytomegalovirus infection - Acute

* Passive congestion of liver, chronic

* Ischemic hepatitis

* Alpha-1-antitrypsin deficiency - Chronic

* Wilson's disease

 

Treatment  

 

Drug Therapy  

 

Adults with previously untreated chronic hepatitis C, genotypes 1 and 4  

 

PEGINTERFERON ALFA-2A - RIBAVIRIN

Adults (<75 kg): Peginterferon alfa-2a 180 mcg subcutaneously once weekly AND ribavirin 1000 mg orally in 2 divided doses for 48 weeks

Adults (?75 kg): Peginterferon alfa-2a 180 mcg subcutaneously once weekly AND ribavirin 1200 mg orally in 2 divided doses for 48 weeks

 

PEGINTERFERON ALFA-2B - RIBAVIRIN (Related toxicological information in RIBAVIRIN)  

Adults (<75 kg): Peginterferon alfa-2b 1.5 mcg/kg subcutaneously once weekly AND ribavirin 1000 mg orally in 2 divided doses for 48 weeks

Adults (?75 kg): Peginterferon alfa-2b 1.5 mcg/kg subcutaneously once weekly AND ribavirin 1200 mg orally in 2 divided doses for 48 weeks

 

 

Pediatric patients with chronic hepatitis C, genotype 1, with compensated liver disease  

 

PEGINTERFERON ALFA-2B - RIBAVIRIN

Pediatrics (age 3 to 17 years and weight <47 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 15 mg/kg/day oral solution for 48 weeks

Pediatrics (age 3 to 17 years and weight 47 to 59 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 800 mg/day in 2 divided doses for 48 weeks

Pediatrics (age 3 to 17 years and weight 60 to 73 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 1000 mg/day in 2 divided doses for 48 weeks

Pediatrics (age 3 to 17 years and weight >73 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 1200 mg/day in 2 divided doses for 48 weeks

 

 

Patients with previously untreated chronic hepatitis C, genotypes 2 and 3  

 

PEGINTERFERON ALFA-2A - RIBAVIRIN

Adults: (<75 kg): Peginterferon alfa-2a 180 mcg subcutaneously once weekly AND ribavirin 800 mg orally in 2 divided doses for 24 weeks

 

PEGINTERFERON ALFA-2B - RIBAVIRIN

Adults: (<75 kg): Peginterferon alfa-2b 1.5 mcg/kg subcutaneously once weekly AND ribavirin 800 mg orally in 2 divided doses for 24 weeks

Pediatrics (age 3 to 17 years and weight <47 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 15 mg/kg/day oral solution for 24 weeks

Pediatrics (age 3 to 17 years and weight 47 to 59 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 800 mg/day in 2 divided doses for 24 weeks

Pediatrics (age 3 to 17 years and weight 60 to 73 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 1000 mg/day in 2 divided doses for 24 weeks

Pediatrics (age 3 to 17 years and weight >73 kg): Peginterferon alfa-2b 60 mcg/m2 subcutaneously once weekly AND ribavirin 1200 mg/day in 2 divided doses for 24 weeks

 

 

Chronic hepatitis C patients for whom combination peginterferon/ribavirin therapy is contraindicated  

 

PEGINTERFERON ALFA-2A  

Adults: 180 mcg subcutaneously once weekly regardless of weight

 

PEGINTERFERON ALFA-2B  

Adults: 1 mcg/kg subcutaneously once weekly

 

PEGINTERFERON ALFA-2B - RIBAVIRIN

Adults (?75 kg): Peginterferon alfa-2b 3 million units subcutaneously 3 times weekly AND ribavirin 1000 mg orally daily in 2 divided doses

Adults (>75 kg): Peginterferon alfa-2b 3 million units subcutaneously 3 times weekly AND ribavirin 1200 mg orally daily in 2 divided doses

 

INTERFERON ALFA-2A  

Adults: 3 million units subcutaneously 3 times weekly

 

INTERFERON ALFA-2B  

Adults: 3 million units subcutaneously 3 times weekly

 

INTERFERON ALFACON-1  

Adults: 9 mcg subcutaneously 3 times weekly

Adults (nonresponders): 15 mcg subcutaneously 3 times weekly

 

 

Chronic hepatitis C patients at risk of acquiring hepatitis B with no evidence of preexisting antibody to hepatitis B  

 

HEPATITIS B VACCINE RECOMBINANT  

 

Chronic hepatitis C patients with no evidence of preexisting antibody to hepatitis A  

 

HEPATITIS A VACCINE, INACTIVATED  

 

 

Procedural Therapy  

 

Reportable infectious diseases  

* Infectious disease notification: In the United States, specific infectious diseases must be reported to the state or local public health department .

 

Acute and chronic liver failure  

* Transplantation of liver: Orthotopic liver transplantation is the accepted treatment for patients with acute and chronic liver failure who are otherwise unlikely to survive .

 

Non-Procedural Therapy  

 

Hepatitis C, chronic  

* Counseling To Avoid Hepatitis C Transmission