Maruf Aberra(MD)

HEPATITIS C VIRUS

VirologyRNA virus that belongs to the family

flaviviruses; sole member of the genus hepacivirus.

Enveloped, 55-65 nm in diameter.Circulates in various forms in the

serum (1)Lipo - Viro-Particles ,

represent the infectious fraction (2)Bound to immunoglobulin (3)Free virions

Viral replication and Life Cycle

Hepatocytes are major sites of replication. Mononuclear cell, dendritic cells also support replication.

Viral binding Entry Inside hepatocytes viral packaging and

release infect adjacent

hepatocytes or enter circulation

Genotypes and quasispecies

Genetic heterogeneity

Six distinct but related HCV genotypes and multiple subtypes have been identified.

Genotype 1 is common (60 to 70 percent of isolates) in the United States and Europe followed by genotypes 2 and 3

Genotype 3 is most common in India, the Far East, and Australia

Genotype 4 is most common in Africa and the Middle East Genotype 5 is most common in South Africa Genotype 6 is most common in Hong Kong, Vietnam and

Australia

Quasispecies-closely related yet heterogeneous sequences of HCV within a single infected person

EpidemiologyWorldwide seroprevalence - 3%>170 million people infected chronicallyPrevalence of anti-HCV antibody in Ethiopians Healthy Blood donors -1.4%. urban/rural communities(1993) -2% patients with chronic hepatitis -21%. cirrhosis of liver -36% HCC -

46%

TransmissionSources of Infection

Injecting Drug Use and HCV Transmission Highly efficient

Contamination of drug paraphernalia, not just needles and syringes

Rapidly acquired after initiation 30% prevalence after 3 years >50% after 5 years

Four times more common than HIV

Posttransfusion Hepatitis C

0

5

10

15

20

25

30

1965 1970 1975 1980 1985 1990 1995 2000

Year

% o

f Rec

ipie

nts I

nfec

ted

All volunteer donors

HBsAg

Donor Screening for HIV Risk Factors

Anti-HIV

ALT/Anti-HBc

Anti-HCV

Improved HCV Tests

Adapted from HJ Alter and Tobler and Busch, Clin Chem 1997

Occupational Transmission of HCV

Inefficient by occupational exposures Average incidence 1.8% following needle

stick from HCV-positive source Associated with hollow-bore needles

Case reports of transmission from blood splash to eye; one from exposure to non-intact skin

Prevalence 1-2% among health care workers Lower than adults in the general population 10 times lower than for HBV infection

Perinatal Transmission of HCV Transmission only from women HCV-

RNA positive at delivery Average rate of infection 6% Higher (17%) if woman co-infected with

HIV Role of viral titer unclear

No association with Delivery method Breastfeeding

Infected infants do well Severe hepatitis is rare

Sexual Transmission of HCV Partner studies

Low prevalence (1.5%) among long-term partners

infections might be due to common percutaneous exposures (e.g., drug use), BUT

Male to female transmission more efficient more indicative of sexual transmission

Occurs, but efficiency is low Factors that facilitate transmission between

partners unknown (e.g., viral titer) Accounts for 15-20% of acute and chronic

infections in the United States

Natural History of HCV InfectionNatural History of HCV Infection

Incubation periodIncubation period Average 6-7 Average 6-7 weeksweeks

Range 2-26 Range 2-26 weeksweeks

Acute illness (jaundice)Acute illness (jaundice) Mild (Mild (<<20%)20%)

Case fatality rateCase fatality rate LowLow

Chronic infectionChronic infection 60%-85%60%-85%

Chronic hepatitisChronic hepatitis 10%-70%10%-70%

CirrhosisCirrhosis <5%-20%<5%-20%

Mortality from CLDMortality from CLD 1%-5%1%-5%

Age-related

Serologic Pattern of Acute HCV Infection with Recovery

Symptoms +/-

Time after Exposure

Tite

ranti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4YearsMonths

HCV RNA

Serologic Pattern of Acute HCV Infection with Progression to Chronic Infection

Symptoms +/-

Time after Exposure

Tite

ranti-HCV

ALT

Normal

0 1 2 3 4 5 6 1 2 3 4YearsMonths

HCV RNA

Chronic Hepatitis C Factors Promoting Progression or Severity

Increased alcohol intake

Age > 40 years at time of infection

HIV co-infection

Other Male gender Chronic HBV co-infection

Clinical FeaturesAcute Hepatitis (20%) Jaundice - 10-20% Non specific sx- 20-30% Chronic hepatitis Most patients are asymptomatic mild nonspecific symptoms most frequent complaint is fatigue;

other less common manifestations include nausea, anorexia, myalgia, arthralgia, weakness, and weight loss

Extrahepatic manifestation of HCV HEMATOLOGIC DISORDERS

Essential mixed cryoglobulinemia

Monoclonal gammopathies

Lymphoma DIABETES MELLITUS AUTOIMMUNE DISORDERS

Autoantibodies

Thyroid disease

Sialadenitis

Autoimmune idiopathic thrombocytopenic purpura

Myasthenia gravis

Sarcoidosis

Extrahepatic Manifestations of HCV

OCULAR DISEASE RENAL DISEASE DERMATOLOGIC DISEASE Porphyria cutanea tarda Leukocytoclastic vasculitis Lichen planus Necrolytic acral erythema

MUSCULOSKELETAL MYOCARDITIS AND CARDIOMYOPATHY NEUROCOGNITIVE DYSFUNCTION

Diagnosis

Indirect assay (EIAs) Anti-HCV Direct Assays Qualitative- HCV RNA Quantitative- HCV RNA levels HCV Core Antigen Assay- EIA HCV genotyping

Histopathology

Considered as the gold standard for establishing the severity of the disease.

Two components-

Necroinflammatory changes

Stage of structural alterations Exclusion of coexisting Disease Determination of Rate of Progression Guidance in Treatment decision-making Scoring systems

Histology Activity Index(HAI)

METAVIR scoring system