II. 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

III. Pathophysiology

  1. Similar to Flavivirus with RNA genome
  2. Similar viruses
    1. Yellow Fever virus
    2. DengueVirus

IV. 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

V. Differential Diagnosis

VI. History: Screening Indications

  1. Universal screening for Hepatitis C for age of 18 years old at least once, regardless of risk factors (U.S., 2019)
  2. Screen once all patients born between 1945 and 1965 for Hepatitic C
  3. Screen periodically (up to annually) for continued high risk behavior
    1. Intravenous Drug Abuse
    2. HIV positive Men who have Sex with Men (unprotected)
  4. 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

VII. 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 HCV Genotype 1

VIII. 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)

IX. 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)

X. Grading

  1. See Metavir Scoring System (liver fibrosis, Cirrhosis)

XI. 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

XII. 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

XIII. 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]

XIV. 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]

XV. 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

XVI. 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)

XVII. 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

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Ontology: Hepatitis C (C0019196)

Definition (NCI) A viral infection caused by the hepatitis C virus.
Definition (MSH) INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally, and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.
Definition (CSP) viral disease caused by hepatitis C virus; most common form of post transfusion hepatitis, also is a common acute sporadic hepatitis; may also follow parental drug abuse.
Concepts Disease or Syndrome (T047)
MSH D006526
ICD9 070.7
ICD10 B19.2 , B19.20
SnomedCT 123324009, 154349000, 186643004, 50711007, 186634008
LNC LA19423-5
English Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted, Parenterally-Transmitted Non-A, Non-B Hepatitis, PT-NANBH, HEPATITIS C, HEPATITIS NON-A NON-B, PT NANBH, nonA nonB hepatitis, viral hepatitis C infection, hepatitis C infection (diagnosis), hepatitis C infection, Hepatitis C Infection, Hep non-A non-B, Non-A non-B hepatitis, Unspecified viral hepatitis C, Viral hepatitis C NOS, Hepatitis C [Disease/Finding], hepatitis c viral, hepatitis C, hepatitis non-a non-b, viral hepatitis c, hepatitis viral c, non b hepatitis, Parenterally Transmitted Non A, Non B Hepatitis, Viral hepatitis, non-A, non-B, Hepatitis C (disorder), Viral hepatitis, non-A, non-B (disorder), Hepatitis (non-A non-B), Viral hepatitis C (disorder), Viral hepatitis type C (disorder), Viral hepatitis type C, Type C viral hepatitis, Viral hepatitis C, Hepatitis non-A non-B, Hepatitis non-A non-B (disorder), hepatitis nonA nonB, hepatitis non A non B, hepatitis; virus, non-A, non-B, hepatitis; virus, type C, non-A non-B-hepatitis, virus; hepatitis, non-A, non-B, Non-A, non-B hepatitis, Viral hepatitis, non-A, non-B -RETIRED-, Hepatitis C, NANBH, Non-A, Non-B Hepatitis, Unspecified viral hepatitis C NOS
Portuguese HEPATITE C, Hepatite a vírus C, Hepatite não A não-B, HEPATITE NAO-A NAO-B, Hepatite não A não B de Transmissão Parental, Hepatite Viral não A não B de Transmissão Parental, Hepatite Viral C, Hepatite não-A não-B, Hepatite C
Spanish HEPATITIS C, Hepatitis (no A no B), Hepatitis vírica C, hepatitis viral, no A, no B, hepatitis vírica tipo C, hepatitis NANB, hepatitis C (trastorno), hepatitis viral, no A, no B - RETIRADO -, hepatitis viral, NANB, hepatitis viral, no A, no B - RETIRADO - (concepto no activo), hepatitis C, hepatitis ni A ni B (trastorno), hepatitis ni A ni B, hepatitis no A no B, hepatitis viral tipo C (trastorno), hepatitis viral tipo C, Hepatitis no A no B, Hepatitis C, Hepatitis no-A no-B de Transmisión Parental, Hepatitis Viral no-A no-B de Transmisión Parental
Italian Epatite non-A non-B, Epatite (non-A non-B), Epatite virale C, Epatite virale non A non B trasmessa per via parenterale, Epatite C
Dutch hepatitis (non-A non-B), non-A-non-B-hepatitis, virale hepatitis C, hepatitis; virus, non-A, non-B, hepatitis; virus, type C, virus; hepatitis, non-A, non-B, hepatitis C, hepatitis non-A non-B, Hepatitis C, Hepatitis, non-A-non-B-, Non-A-non-B-hepatitis
French Hépatite (non A non B), Hépatite non A non B, Hép non-A non-B, HEPATITE NON-A NON-B, HEPATITE VIRALE C, Hépatite virale non A-non B, Hépatite C, Hépatite virale C, Hépatite virale non-A non-B transmise par voie parentérale
German Hep non-A non-B, Hepatitis (non-A non-B), virale Hepatitis C, HEPATITIS NON-A NON-B, Hepatitis non-A non-B, Hepatitis C, Hepatitis, virale, Non-A, Non-B, parenteral übertragene, Parenteral übertragene Non-A, Non-B-Hepatitis
Japanese 非A非B型肝炎, 肝炎(非A非B), C型肝炎, カンエンヒAヒB, Cガタカンエン, ヒAヒBガタカンエン, Cガタウイルスセイカンエン, C型ウイルス性肝炎, 肝炎-C型, C型肝炎, PT非A非B肝炎, 非経口性非A非Bウイルス肝炎, 肝炎-ウイルス性-非A非B非経口性, 肝炎-ウイルス性-非経口性非A非B
Swedish Hepatit C
Czech hepatitida virová non-A, non-B, hepatitida C, Hepatitida non A non B, Hepatitida C, Hepatitida (non A non B), Hepatitida non-A non-B, Virová hepatitida C
Finnish Maksatulehdus C
Polish Zapalenie wątroby wirusowe nie A nie B, Zapalenie wątroby wirusowe C, Zapalenie wątroby C
Hungarian Viralis hepatitis C, hepatitis non-A non-B, non-A non-B hepatitis, hepatitis C, Hepatitis (non-A non-B), Hepatitis non-A non-B
Norwegian Hepatitt C