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Hepatitis C
Aka: Hepatitis C
- See Also
- Viral Hepatitis
- Bloodborne Pathogen Exposure
- Epidemiology
- Prevalence
- U.S. Population: 1.8% (4 to 6.5 million)
- Chronic hepatitis Prevalence is estimated at 2.7 million
- Prevalence is underestimated due to as yet undiagnosed patients infected in the 1960s and 1970s
- Mortality from Hepatitis C in the United States is more than any other infectious disease
- World Prevalence estimated at >185 million
- Associated with 350,000 deaths per year
- Intravenous Drug Abuse: 97% (some communities)
- 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
- Risk from transfusion low after July 1992
- Now <1 case per 1,000,000 units transfused (2015)
- Tattoo needles
- Organ transplant (before July 1992)
- 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
- Anal sex
- Sex during Menses
- Shared sexual paraphernalia
- Pathophysiology
- Similar to Flavivirus with RNA genome
- Similar viruses
- Yellow Fever virus
- DengueVirus
- Signs and Symptoms
- Acute infection
- See Viral Hepatitis
- Jaundice is uncommon in acute infection
- Constitutional symptoms in up to 35%
- Malaise
- Weakness
- Anorexia
- Minor Fatigue
- Right upper quadrant abdominal 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 for age of 18 years old at least once, regardless of risk factors (U.S., 2019)
- 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
- Screening: EIA for Anti-HCVAntibody
- 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)
- Confirmation of positive xHCV: RT-PCR for HCV RNA
- 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 2-21 weeks from onset (mean 7 weeks)
- 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)
- Grading
- See Metavir Scoring System (liver fibrosis, Cirrhosis)
- Management: General
- See Prevention of Liver Disease Progression
- Avoid Alcohol
- Alcohol and Hepatitis C work synergistically
- Alcohol decreases response to Interferon therapy
- Avoid Hepatotoxins
- Avoid iron supplements
- Maintain a Low Fat Diet
- Vaccination (decreases Hepatitis C progression risk)
- Hepatitis A Vaccine
- Hepatitis B Vaccine
- Prevent transmission
- Do not share razors or ToothBrushes
- Cover skin lesions
- Do not donate Blood Products
- Use protection for intercourse
- 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: 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: 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% in 20 years)
- Individualized risk can be calculated (see below)
- Decompensated Cirrhosis
- 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
- Diabetes Mellitus
- Sjogren's Syndrome
- Lymphoma
- Glomerulonephritis
- Dermatologic conditions
- Porphyria cutanea tarda
- Lichen Planus
- Cutaneous necrotizing Vasculitis
- Course
- Progression after acute HCV infection
- Spontaneous resolution: 15-50% of cases (undetectable HCV at 6 months after acute HCV)
- Chronic Hepatitis: 50 to 85% of cases
- 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 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)
- 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]
- 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]