Hepatitis%20c Diagnosis

Important Points in the Clinical History of Patients with Suspected Viral Hepatitis

• Contacts with jaundiced patients
• IV drug use
• History of blood transfusion
• Surgery or hospitalizations
• Family history of chronic liver disease
• Occupation
• Food and water sources
• Past or current medication use 
• Alcohol use

Serological Tests

• Anti-hepatitis C virus (anti-HCV) antibodies are the first-line diagnostic test and are determined via enzyme immunoassay in plasma or serum 
  • HCV RNA (or HCV core antigen) should be determined to identify viremia or current HCV infection in patients with detected anti-HCV antibodies 
• Acute hepatitis C can be reliably diagnosed if recent seroconversion to anti-HCV antibodies (ie a prior negative HCV antibody test becomes positive) can be documented; however, antibody tests often do not become positive until 3 months after infection
  
  • If the clinical suspicion is high, the patient should be tested for HCV RNA (or HCV core antigen) to establish the diagnosis
• Chronic hepatitis C is continued HCV infection of ≥6 months after acquiring the disease and is diagnosed based on the presence of both anti-HCV antibodies and HCV RNA (or HCV core antigen)
•  HCV RNA quantitative testing to determine baseline viral load is recommended before starting antiviral therapy
  • End of therapy is indicated by undetectable HCV RNA in a sensitive assay (≤15 IU/mL) 12 and 24 weeks after therapy
  • Recommended test for assessment of HCV recurrence 
• Undetectable HCV core antigen can be an alternative endpoint of therapy in patients with detectable HCV core antigen before therapy 

• HCV genotype, including subtyping of genotype 1a/1b, should be determined, if possible (if a non-pangenotypic regimen will be prescribed), in all HCV-infected persons prior to treatment to determine type and duration of therapy and chances of response; predominant genotypes in Asia are:
  
  • Genotypes 1b and 2: East Asia (China, Taiwan, South Korea, Japan)
  • Genotype 3: South Asia (India and Pakistan)
    
    • Genotype 3 is considered difficult to treat and is associated with a poor prognosis
  • Genotypes 1 and 6: Southeast Asia (Vietnam, Cambodia, Laos, Indonesia, Myanmar, Malaysia, Philippines, Thailand)

• Liver biopsy may be done if it is thought that the results will influence clinical decision, but biopsy is not mandatory to start therapy in patients with genotypes 2 and 3
  
  • Liver biopsy may be obtained to provide prognostic information

• Depending on local health services, the following groups should be tested for chronic HCV infection:
  
  • Persons who have in the recent or remote past used illicit IV/intranasal drugs, men who have sex with men (MSM)
  • Persons with conditions associated with high prevalence of HCV infection:
    
    • Positive human immunodeficiency virus (HIV), sexually active individuals taking pre-exposure prophylaxis for HIV, hemophiliacs who received clotting factor prior to 1987, history of hemodialysis, persons who received blood/blood products or organ transplants prior to July 1992, children born to HCV-infected mothers, healthcare workers after needle stick injury or mucosal exposure to HCV-positive blood, current sexual partners of HCV-infected persons, incarcerated individuals

Tests to Rule Out Other Viral Hepatitis

• Hepatitis A: Anti-hepatitis A virus (anti-HAV) IgM; nucleic acid amplification test (NAAT) for HAV RNA may be considered
• Hepatitis B: Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B e antigen (HBeAg)
• Hepatitis D: Anti-hepatitis D virus (anti-HDV) antibody, HDV RNA test
• Hepatitis E: IgM anti-HEV, IgG anti-HEV in combination with HEV RNA; NAAT for HEV RNA may be considered
• Please see Hepatitis A & E and Hepatitis B disease management charts for further information

Other Recommended Lab Tests in Patients Suspected of Viral Hepatitis

• Liver function tests (LFTs)
  
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
  • Serum bilirubin, alkaline phosphatase (ALP)
• Prothrombin time (PT), international normalized ratio (INR), renal function tests, complete blood count (CBC) with platelets
• Noninvasive tests such as the aminotransferase/platelet ratio index (APRI) or fibrosis-4 (FIB-4) must be used to assess the degree of hepatic fibrosis when resources are limited prior to initiating HCV therapy
  
  • Transient elastography may be an option for patients with contraindications to liver biopsy
• Ultrasound of the liver helps identify hepatocellular carcinoma (HCC) and subclinical ascites

Consequences of HCV Infection

• 55-85% of patients who acquire acute hepatitis C will remain HCV infected
  
  • 5-20% of these patients may develop cirrhosis over the next 20-25 years
  • HCV-related cirrhosis is associated with risk of developing end-stage liver disease (30% risk over 10 years) as well as HCC
• In patients with persistent infection, the evolution to cirrhosis is the primary concern
  • Usually occurs ≥20 years after initial infection and occurs more often in patients at older ages (especially men), those who drink >50 g of alcohol/day, those who are obese or have substantial hepatic steatosis and in those with HIV infection

Antiviral therapy is currently widely accepted for the following hepatitis C patient groups:

• ≥18 years of age
• Normal and abnormal ALT levels
• Liver biopsy showing chronic hepatitis with significant fibrosis or cirrhosis (stage F1 or above)
• HCV genotype 2 or 3 regardless of stage
• Compensated liver disease
• Acceptable hematological and biochemical indices
• If there is a history of depression, the condition is well controlled
• Willing to be treated and conform to patient requirements
• Treated previously for HCV infection

Therapy should be individualized in patients with any of the following:

• Failed prior treatment of either Interferon given alone or in combination with Ribavirin or Peginterferon given alone
• Current PWID or alcoholic but willing to participate in substance abuse program or alcohol support program
• No or mild fibrosis on liver biopsy
• Acute hepatitis C
• Coinfected with HIV
• <18 years of age
• Chronic renal disease
• Decompensated cirrhosis
• Liver transplant recipient

Therapy is contraindicated in patients with any of the following¹:

• Major, uncontrolled depressive illness
• Renal, heart or lung transplant recipient
• Autoimmune hepatitis or other condition known to be exacerbated by Interferon and Ribavirin
• Untreated hyperthyroidism
• <3 years of age
• Pregnant or unwilling/unable to comply with adequate contraception
• Severe concurrent disease (eg hypertension, HF, uncontrolled DM, etc)
• Known hypersensitivity to drugs used to treat HCV
• Hepatic decompensation

¹Patients have detectable HCV RNA