Hepatitis C

Aka: Hepatitis C, Metavir Scoring System

1. See Also
   1. Viral Hepatitis
   2. Bloodborne Pathogen Exposure
2. Epidemiology
   1. Prevalence
      1. U.S. Population: 1.8% (4 to 6.5 million)
         1. Chronic hepatitis Prevalence is estimated at 2.7 million
         2. Prevalence is underestimated due to as yet undiagnosed patients infected in the 1960s and 1970s
         3. Mortality from Hepatitis C in the United States is more than any other infectious disease
      2. World Prevalence estimated at >185 million
         1. Associated with 350,000 deaths per year
      3. Intravenous Drug Abuse: 97% (some communities)
   2. Incubation 7-8 weeks
      1. HCV RNA found in blood within 3 weeks post-exposure
   3. Transmission by Blood Products and blood exposure
      1. Intravenous Drug Abuse (43-60% of acute cases in U.S.)
      2. Intravenous Immunoglobulin
      3. Transfusion
         1. Accounts for 85% transfusion associated hepatitis
         2. Risk from transfusion low after July 1992
            1. Now <1 case per 1,000,000 units transfused (2015)
      4. Tattoo needles
      5. Organ transplant (before July 1992)
      6. Vertical transmission from mother to child
         1. Delivery method does not alter transmission rate
         2. Average rate: 6%
         3. HIV coinfection: 17%
      7. Needle stick injury (4-10% rate of infectivity)
         1. Seroconversion in 2200 healthcare workers per year
      8. No apparent parenteral risk factor in 40% of cases
   4. Transmission by other body fluid is less common
      1. Transmission to simple household contacts is rare
      2. No association with Lactation
      3. Sexual transmission is much less common
         1. Prevalence 1.5% in longterm partners
         2. Higher risk behaviors that raise transmission (blood to blood transmission)
            1. Multiple partners
            2. Early sex
            3. Non-Condom use
            4. Sex with associated Trauma or open lesions
            5. Comorbid Sexually Transmitted Disease
            6. Anal sex
            7. Sex during Menses
            8. Shared sexual paraphernalia
3. Pathophysiology
   1. Similar to Flavivirus with RNA genome
   2. Similar viruses
      1. Yellow Fever virus
      2. DengueVirus
4. Signs and Symptoms
   1. Acute infection
      1. See Viral Hepatitis
      2. Jaundice is uncommon in acute infection
      3. Constitutional symptoms in up to 35%
         1. Malaise
         2. Weakness
         3. Anorexia
         4. Minor Fatigue
         5. Right upper quadrant abdominal ache
         6. Nausea
         7. Arthralgias
   2. Chronic disease
      1. Most patients are asymptomatic
      2. Observe for signs of Cirrhosis
5. Differential Diagnosis
   1. Acute Hepatitis Causes
6. History: Screening Indications
   1. Screen once all patients born between 1945 and 1965 for Hepatitic C
   2. Screen periodically (up to annually) for continued high risk behavior
      1. Intravenous Drug Abuse
      2. HIV positive Men who have Sex with Men (unprotected)
   3. Other screening indications
      1. Received blood Clotting Factor concentrate before 1987
      2. Received Blood Transfusion or transplant before 1993
      3. Received blood from donor later found with HCV
      4. Received Hemodialysis
      5. Symptoms or signs of liver disease, or persistently elevated serum transaminases
      6. Mother with HCV at the time of delivery
7. Labs: Diagnosis
   1. See Hepatitis C Serology
   2. Screening: EIA for Anti-HCVAntibody
      1. Negative
         1. Consider false negative if immunocompromised
         2. Repeat in 12 weeks if HCV exposure in prior 6 months
            1. Alternatively, HCV RNA may be obtained every 4-8 weeks for 6 months
      2. Positive
         1. Confirm with HCV RNA (see below)
   3. Confirmation of positive xHCV: RT-PCR for HCV RNA
      1. Start with qualitative PCR (more sensitive)
      2. Positive EIA xHCV with negative PCR HCV RNA suggests resolved
      3. Repeat in 1-2 months if negative
      4. Also indicated before initiating HCV therapy
   4. Viral Genotype
      1. Indicated before initiating HCV therapy
      2. Of 6 HCV Genotypes, types Ia, Ib, 2 and 3 account for 97% of U.S. HCV infections
      3. HCV Genotypes 2 and 3 have better prognosis than 1
8. Labs: Assessment of liver disease
   1. Liver Function Tests
      1. Serum Albumin
      2. ProTime (PT) with INR
      3. Partial Thromboplastin Time (PTT)
   2. Liver Transaminase (Indicate hepatocellular necrosis)
      1. Serum AST
      2. Serum ALT
         1. Increases by 2-21 weeks from onset (mean 7 weeks)
         2. Normal in up to one third of patients
   3. Comorbid Infections
      1. Human Immunodeficiency Virus Test (HIV Test)
      2. Anti-HAV (Hepatitis A VirusAntibody)
      3. Hepatitis B Surface Antigen (HBsAg)
   4. Other tests
      1. Serum Iron (for Hemochromatosis)
      2. Renal Function Tests
         1. Serum Creatinine
         2. Blood Urea Nitrogen (BUN)
9. Labs: Post-exposure to Hepatitis C Virus
   1. Indications
      1. Blood-borne Exposure to Hepatitis C positive source (xHCV positive with detectable HCV RNA)
   2. Protocol
      1. Baseline (at time of exposure)
         1. Hepatitis C Antibody
         2. Hepatitis C RNA
         3. Alanine Transaminase (ALT)
      2. Week 4-6 post-exposure
         1. Hepatitis C RNA
      3. Month 4-6 post-exposure
         1. Hepatitis C Antibody
         2. Hepatitis C RNA
         3. Alanine Transaminase (ALT)
10. Grading: Metavir Scoring System (liver fibrosis, Cirrhosis)
    1. Score 0: No fibrosis
    2. Score 1: Minimal scarring
    3. Score 2: Positive scarring AND extension beyond area containing blood vessels
    4. Score 3: Bridging fibrosis connecting other areas of fibrosis
    5. Score 4: Cirrhosis or advanced liver scarring
11. Management: General
    1. See Prevention of Liver Disease Progression
    2. Avoid Alcohol
       1. Alcohol and Hepatitis C work synergistically
       2. Alcohol decreases response to interferon therapy
    3. Avoid Hepatotoxins
    4. Avoid iron supplements
    5. Maintain a Low Fat Diet
    6. Vaccination (decreases Hepatitis C progression risk)
       1. Hepatitis A Vaccine
       2. Hepatitis B Vaccine
    7. Prevent transmission
       1. Do not share razors or ToothBrushes
       2. Cover skin lesions
       3. Do not donate Blood Products
       4. Use protection for intercourse
12. Management: HCV-Related Cirrhosis
    1. Refer for consideration of liver transplantation (see below)
    2. Hepatocellular Carcinoma monitoring
       1. Obtain RUQ Ultrasound and a-fetoprotein every 6-12 months
    3. Esophageal Varices monitoring
       1. Obtain upper endoscopy every 1-2 years
13. Management: Antiviral Agents
    1. See Hepatitis C Antiviral Regimen
    2. Consider early treatment for Acute Hepatitis C (started within 4 weeks of onset)
       1. Improves prognosis and decreases risk of chronic infection
       2. Wiegand (2006) Hepatology 43(2): 250-6 [PubMed]
14. Management: Liver Transplantation
    1. Hepatitis C is most common cause of liver transplant
    2. Post-transplant survival similar to other liver failure
       1. One year survival post-transplant: 84%
       2. Five year survival post-transplant: 68%
       3. Ten year survival post-transplant: 60%
    3. Predictors of poorer outcome
       1. Female liver donor
       2. Recipient over age 52 years
       3. Preoperative Serum Creatinine >1 mg/dl
       4. More urgent UNOS status
       5. Increased Serum AST and Serum ALT levels
    4. References
       1. Ghobrial (2001) Ann Surg 234:384-94 [PubMed]
15. Complications
    1. Cirrhosis (20% in 20 years)
       1. Individualized risk can be calculated (see below)
    2. Decompensated Cirrhosis
       1. One Year: 3.9%
       2. Five Years: 18%
       3. Ten Years: 29%
    3. Hepatocellular Carcinoma
       1. Annual risk: 2-4% if Cirrhosis present
       2. Five Years: 7%
       3. Ten Years: 14%
    4. Other associated conditions
       1. Diabetes Mellitus
       2. Sjogren's Syndrome
       3. Lymphoma
       4. Glomerulonephritis
       5. Dermatologic conditions
          1. Porphyria cutanea tarda
          2. Lichen Planus
          3. Cutaneous necrotizing Vasculitis
16. Course
    1. Progression after acute HCV infection
       1. Spontaneous resolution: 15-50% of cases (undetectable HCV at 6 months after acute HCV)
       2. Chronic Hepatitis: 50 to 85% of cases
          1. Cirrhosis develops in 20% of chronic HCV after 20-30 years, with a 75% mortality
          2. Chronic HCV mortality is secondary to Cirrhosis, end-stage liver disease and hepatocellular cancer
    2. Survival
       1. One Year: 96%
       2. Five Years: 91%
       3. Ten Years: 79%
    3. Risk Factors for Progression to fibrosis and Cirrhosis
       1. Age over 40 years at time of infection
       2. Duration of infection
          1. Median duration of infection to Cirrhosis: 30 years
          2. In up to one third, Cirrhosis delayed for >50 years
       3. Male gender
       4. Excessive Alcohol intake
          1. Marked risk at >50 grams/day
          2. Moderate risk
             1. Men: >40 grams/day
             2. Women: >20 grams/day (2 beers, 1 pint wine)
17. Resources
    1. IDSA HCV Management Guidelines
       1. http://www.hcvguidelines.org
    2. Probablility of Cirrhosis in Patients with Hepatitis C
       1. http://www.aafp.org/afp/20031101/poc.html
18. References
    1. Gross (1998) Mayo Clin Proc 73(4):355-60 [PubMed]
    2. Morton (1998) Ann Emerg Med 31:381-90 [PubMed]
    3. Heathcote (2000) N Engl J Med 343:1673-80 [PubMed]
    4. Ward (2004) Am Fam Physician 69(6):1429-40 [PubMed]
    5. Wilkins (2015) Am Fam Physician 91(12): 835-42 [PubMed]