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Hepatitis C
Aka: Hepatitis C, HCV Infection
- See Also
- Hepatitis C Antiviral Regimen
- Viral Hepatitis
- Bloodborne Pathogen Exposure
- Epidemiology
- Mortality from Hepatitis C in the United States is more than any other infectious disease
- Effective treatment exists for those diagnosed, but many are undiagnosed
- Only 52% of estimated patients with Hepatitis C in U.S. have been diagnosed
- Only 37% of Hepatitis C patients have been diagnosed
- Worldwide, only 5% have been diagnosed, and <1% have been treated
- Chhatwai (2019) Aliment Pharmacol Ther 50(1): 66-74 [PubMed]
- Prevalence
- U.S. Population: 1.8% (4 to 6.5 million)
- Chronic hepatitis Prevalence is estimated at 3.7 million (2016)
- Prevalence is underestimated
- Undiagnosed patients infected in the 1960s and 1970s
- Opioid epidemic quadrupled acute infection rate ages 18-39 years from 2010 to 2018
- World Prevalence estimated at >185 million
- Associated with 350,000 deaths per year
- Intravenous Drug Abuse: 97% (some communities)
- Pathophysiology
- Incubation 7-8 weeks
- HCV RNA found in blood within 3 weeks post-exposure
- Transmission by Blood Products and blood exposure
- Intravenous Drug Abuse (43-60% of acute cases in U.S.)
- Intravenous Immunoglobulin
- Transfusion
- Accounts for 85% transfusion associated hepatitis
- Clotting Factor transfusion before 1987
- Blood Product transfusion before 1992
- Risk from transfusion low after July 1992
- Now <1 case per 1,000,000 units transfused (2015)
- Tattoo needles
- Organ transplant (before July 1992)
- Longterm Hemodialysis
- Vertical transmission from mother to child
- Delivery method does not alter transmission rate
- Average rate: 6%
- HIV coinfection: 17%
- Needle Stick injury (4-10% rate of Infectivity)
- Seroconversion in 2200 healthcare workers per year
- No apparent parenteral risk factor in 40% of cases
- Transmission by other body fluid is less common
- Transmission to simple household contacts is rare
- No association with Lactation
- Sexual transmission is much less common
- Prevalence 1.5% in longterm partners
- Higher risk behaviors that raise transmission (blood to blood transmission)
- Multiple partners
- Early sex
- Non-Condom use
- Sex with associated Trauma or open lesions
- Comorbid Sexually Transmitted Disease
- Men who have Sex with Men (esp. if HIV positive)
- Anal intercourse
- Sex during Menses
- Shared sexual paraphernalia
- Pathophysiology
- Similar to Flavivirus with RNA genome
- Similar viruses
- Yellow Fever virus
- DengueVirus
- Findings: Signs and Symptoms
- Acute infection
- See Viral Hepatitis
- Asymptomatic in up to 70-80% of cases
- Symptoms in up to 35% of acute HCV Infection cases (onset 2 to 12 weeks after exposure)
- Malaise
- Weakness
- Anorexia
- Minor Fatigue
- Jaundice (uncommon in acute infection)
- Right Upper Quadrant Abdominal Pain or ache
- Nausea
- Arthralgias
- Chronic disease
- Most patients are asymptomatic
- Observe for signs of Cirrhosis
- Differential Diagnosis
- Acute Hepatitis Causes
- History: Screening Indications
- Universal screening for Hepatitis C age 18 to 79 years old at least once, regardless of risk factors (U.S., 2019)
- Screen all pregnant patients
- Screen once all patients born between 1945 and 1965 for Hepatitic C
- Screen periodically (up to annually) for continued high risk behavior
- Intravenous Drug Abuse
- HIV positive Men who have Sex with Men (unprotected)
- Other screening indications
- Received blood Clotting Factor concentrate before 1987
- Received Blood Transfusion or transplant before 1993
- Received blood from donor later found with HCV
- Received Hemodialysis
- Symptoms or signs of liver disease, or persistently elevated serum transaminases
- Mother with HCV at the time of delivery
- Labs: Diagnosis
- See Hepatitis C Serology
- Hepatitis C Antibody Detection
- Detectable 4 to 10 weeks after exposure
- Positive in 97% of HCV Infections at 6 months
- Screening: EIA for Anti-HCVAntibody
- Third generation enzyme linked immunoabsorbent assay
- Test Sensitivity and Test Specificity: 99%
- Negative
- Consider False Negative if Immunocompromised
- Repeat in 12 weeks if HCV exposure in prior 6 months
- Alternatively, HCV RNA may be obtained every 4-8 weeks for 6 months
- Positive
- Confirm with HCV RNA (see below)
- Screening: OraQuick HCV Rapid Antibody Test
- CLIA Waved point-of-care test
- Test Sensitivity: 94.1%
- Test Specificity: 99.5%
- Negative Predictive Value: 99.9%
- Positive Predictive Value: 72.7%
- Confirmation of positive xHCV: RT-PCR for HCV RNA
- HCV RNA indicates acute infection (present as early as 2 weeks after exposure)
- Start with qualitative PCR (more sensitive)
- Positive EIA xHCV with negative PCR HCV RNA suggests resolved
- Repeat in 1-2 months if negative
- Also indicated before initiating HCV therapy
- Viral Genotype
- Indicated before initiating HCV therapy
- Of 6 HCV Genotypes, types Ia, Ib, 2 and 3 account for 97% of U.S. HCV Infections
- HCV Genotypes 2 and 3 have better prognosis than HCV Genotype 1
- Labs: Assessment of liver disease
- Liver Function Tests
- Serum Albumin
- ProTime (PT) with INR
- Partial Thromboplastin Time (PTT)
- Liver Transaminase (Indicate hepatocellular necrosis)
- Serum AST
- Serum ALT
- Increases by 8 to 10 weeks (range 2 to 21 weeks, mean 7 weeks) from onset
- Peak at 10 to 20 times normal upper limit
- Normal in up to one third of patients
- Comorbid Infections
- Human Immunodeficiency Virus Test (HIV Test)
- Anti-HAV (Hepatitis A VirusAntibody)
- Hepatitis B Surface Antigen (HBsAg)
- Other tests
- Serum Iron (for Hemochromatosis)
- Renal Function Tests
- Serum Creatinine
- Blood Urea Nitrogen (BUN)
- Labs: Post-exposure to Hepatitis C Virus
- Indications
- Blood-borne Exposure to Hepatitis C positive source (xHCV positive with detectable HCV RNA)
- Protocol
- Baseline (at time of exposure)
- Hepatitis C Antibody
- Hepatitis C RNA
- Alanine Transaminase (ALT)
- Week 4-6 post-exposure
- Hepatitis C RNA
- Month 4-6 post-exposure
- Hepatitis C Antibody
- Hepatitis C RNA
- Alanine Transaminase (ALT)
- Evaluation: Grading
- See Metavir Scoring System (liver fibrosis, Cirrhosis)
- Imaging (and advanced labs) to evaluate for fibrosis or Cirrhosis
- See Cirrhosis for interpretation
- Transient Elastography and AST to Platelet Ratio Index
- Fibrosis-4
- Fibrosure
- Management: General
- See Prevention of Liver Disease Progression
- Avoid Alcohol
- Alcohol and Hepatitis C work synergistically
- Alcohol decreases response to Interferon therapy
- Avoid Hepatotoxins
- Chemical Dependency treatment for injection drug use (if indicated)
- Avoid iron supplements
- Maintain a Low Fat Diet
- Maintain a target Body Mass Index <25 kg/m2
- Target a Low Sodium Diet <2000 mg/day
- Vaccination (decreases Hepatitis C progression risk)
- Hepatitis A Vaccine
- Hepatitis B Vaccine
- Pneumococcal Vaccine and PrevnarVaccine
- Prevent transmission
- Do not share razors or ToothBrushes
- Cover skin lesions
- Do not donate Blood Products
- Use Condom protection for intercourse (esp. for multiple partners, Men who have Sex with Men)
- Management: Antiviral Agents
- See Hepatitis C Antiviral Regimen
- Consider early treatment for Acute Hepatitis C (started within 4 weeks of onset)
- Improves prognosis and decreases risk of chronic infection
- Wiegand (2006) Hepatology 43(2): 250-6 [PubMed]
- Management: HCV-Related Cirrhosis
- Refer for consideration of liver Transplantation (see below)
- Hepatocellular Carcinoma monitoring
- Obtain RUQ Ultrasound and a-fetoprotein every 6-12 months
- Esophageal Varices monitoring
- Obtain upper endoscopy every 1-2 years
- Management: Liver Transplantation
- Hepatitis C is most common cause of liver transplant
- Post-transplant survival similar to other liver failure
- One year survival post-transplant: 84%
- Five year survival post-transplant: 68%
- Ten year survival post-transplant: 60%
- Predictors of poorer outcome
- Female liver donor
- Recipient over age 52 years
- Preoperative Serum Creatinine >1 mg/dl
- More urgent UNOS status
- Increased Serum AST and Serum ALT levels
- References
- Ghobrial (2001) Ann Surg 234:384-94 [PubMed]
- Complications
- Cirrhosis (20 to 30% in 25 to 30 years)
- Individualized risk can be calculated (see below)
- Decompensated Cirrhosis (Ascites, Hepatic Encephalopathy, Portal Hypertension, Varices)
- One Year: 3.9%
- Five Years: 18%
- Ten Years: 29%
- Hepatocellular Carcinoma
- Annual risk: 2-4% if Cirrhosis present
- Five Years: 7%
- Ten Years: 14%
- Other associated conditions (Extrahepatic Manifestations)
- Diabetes Mellitus (four fold increased risk)
- Membranoproliferative Glomerulonephritis
- Idiopathic Pulmonary Fibrosis
- Thyroid Disorders (Hypothyroidism, Hyperthyroidism, Thyroiditis)
- Vascular Disease
- Cardiovascular Disease (Coronary Artery Disease)
- Cerebrovascular Disease
- Rheumatologic and Autoimmune
- Sjogren's Syndrome
- Rheumatoid Arthritis
- Cryoglobulinemic Vasculitis
- Dermatologic conditions
- Porphyria cutanea tarda
- Lichen Planus
- Cutaneous necrotizing Vasculitis
- Raynaud Phenomenon
- Necrolytic Acral Erythema
- Malignancy
- B-Cell Non-Hodgkin Lymphoma
- Monoclonal Gammopathy
- Course
- Progression after acute HCV Infection
- Spontaneous resolution: 15-45% of cases
- HCV RNA undetectable at 6 months after acute HCV
- Decreased chance of spontaneous clearance in HIV Infection
- Factors favoring spontaneous clearance and resolution
- Younger age
- Jaundice
- Increase alanine transaminase level
- HBsAg positive
- Female gender
- HCV Genotype 1
- Specific host genes (e.g. IL28 gene)
- Chronic Hepatitis: 50 to 85% of cases
- HCV RNA present >6 months after acute HCV Infection
- Cirrhosis develops in 20% of chronic HCV after 20-30 years, with a 75% mortality
- Chronic HCV mortality is secondary to Cirrhosis, end-stage liver disease and hepatocellular cancer
- Survival
- One Year: 96%
- Five Years: 91%
- Ten Years: 79%
- Risk Factors for Progression to fibrosis and Cirrhosis
- Age over 40 to years at time of infection
- Duration of infection
- Median duration of infection to Cirrhosis: 30 years
- In up to one third, Cirrhosis delayed for >50 years
- Male gender
- Excessive Alcohol intake
- Marked risk at >50 grams/day
- Moderate risk
- Men: >40 grams/day
- Women: >20 grams/day (2 beers, 1 pint wine)
- Other risk factors
- HIV Infection
- Hepatitis BVirus Infection
- Immunosuppression
- Obesity
- Hepatotoxic Medications
- Nonalcoholic Steatohepatitis
- Resources
- IDSA HCV Management Guidelines
- http://www.hcvguidelines.org
- Probablility of Cirrhosis in Patients with Hepatitis C
- http://www.aafp.org/afp/20031101/poc.html
- References
- Gross (1998) Mayo Clin Proc 73(4):355-60 [PubMed]
- Maness (2021) Am Fam Physician 104(6): 626-35 [PubMed]
- Morton (1998) Ann Emerg Med 31:381-90 [PubMed]
- Heathcote (2000) N Engl J Med 343:1673-80 [PubMed]
- Ward (2004) Am Fam Physician 69(6):1429-40 [PubMed]
- Wilkins (2015) Am Fam Physician 91(12): 835-42 [PubMed]