Hepatitis C Infection

an updateDr.T.V.Rao MD

04/10/2023 1

Hepatitis C virus (HCV)

Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States; approximately 3.2 million persons are chronically infected. Although HCV is not efficiently transmitted sexually, persons at risk for infection through injection drug use might seek care in STD treatment facilities, HIV counselling and testing facilities.

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What is Hepatitis C Infection

Infection with Hepatitis C causes

1 Chronic hepatitis

2 Cirrhosis 3

Hepatocellular Carcinoma 04/10/2023 3

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HCV - Virology

Family – Flaviviridae Genus – Hepacivirus A small ( 50 nm ) virus ss RNA virus, positive senstive RNA sequence analysis into at least six major genotypes (Clades) There are 100 subtypes.

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Genome - HCV

Clades differ from each other by 25-30% at the nucleotide level:The genome is 9.4kb in size and encodes a core protein

The expression of cDNA clones of HCV in yeast led to the development of serological tests for antibodies to HCVHCV displays genomic diversity.The genomic diversity is not correlated to difference in clinical disease

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Why Hepatitis C is an important Disease

WHO estimates 170 million ( 3 % ) world population is infected with HCV.Highest in Egypt.Lowest in Sweden.In USA 2.7 to 3.4 million people infected.In USA there is a decline since 1990.Those born between 1940 and 1965 had highest incidence reaching a peak between the age of 20 to 35 yearsIn USA 25,000 persons die of cirrhosis and chronic liver disease

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How Hepatitis C is transmitted

Blood transfusions

Drug absue – Injections

Tattooing

Contamination of Medical equipment.

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HCVMother to Child transmission Vertical transmission occurs in 3 -10% Mother with higher HCV viral loads or co infection with HIV transmit in higher rates.No risk of transmission is associated with breast feeding.

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Transmission of Infection in Spouses

Sexual transmission of HCV can occur, with much lower frequency than that of HIV, and HBVLong term partners of HCV infected patients have higher rates of infection than the general population.May be associated with shared use of Razors and tooth brushes.

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CDC on Spouse Transmission

CDC on the basis of current evidence does not recommend use of barrier precautions among the heterosexual monogamous couples, to prevent HCV transmission.04/10/2023 12

Higher incidence of HCV Infections

Increased prevalence in

Sexually transmitted diseases.

HIV co infection.

Injecting drug use.

High risk sexual practices.

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Health care devices and HCV

WHO calculates that unsafe health care devices account for 2.3 million new HCV infections per year, and 200 000 HCV related premature deaths, mostly in Developing countriesThe re-use of injection equipment's without sterilization contributes to major spread.WHO estimates that about 40% of injection related equipment is reused in Devloping countries.

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HCV and Blood Transfusions

Blood transfusions from unscreened donors and unsafe therapeutic procedures are major modes of transmission in Developing countries.Paid donors are grave risk

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Trends of Change in Transmission

Education among the drug abusers, blood donor screening needle exchange programmes have remarkably reduced the incidence.

Sexual, and Perinatal transmission has gained importance.

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Needle Stick Injuries

A CDC report suggested risk of HCV transmission is about six times higher per needle stick exposure than is the risk with HIV infection

( 1.8% vs 0.35 )

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Onset of Infection in HCV

The average incubation period for HCV is 6-7 days

The period for exposure to seroconversion is 8-9 weeks.

About 90% of the infected are anti HCV positive in 5 months

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How Virus C replicates in Hepatocytes

Depends on cellular factors and shared by viral proteins.

Replicates with viral and host proteinsMultiplication rate is very high a Trillion particles are produced every day.

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Pathology of HCV infection

Virus causes inflammation of Liver

Microscopically spotted parenchymal cell degeneration

Necrosis of Hepatocytes

Causes diffuse lobular inflammatory reaction

Disruption of liver cell cords

Accumulation of Macrophages near degenerating Hepatocytes.

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Pathology

Both Hepatitis B and C are cytopathogenicCellular damage is immune mediatedBoth HBV and HBC have significant roles in in the development of Hepatocellular carcinomaCarcinoma may appear 15 – 60 years after the beginning of infection.

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Viral clearance from Hepatocytes

Virus clears either spontaneously or by treatment

May lead to cure, even fibrosis is regresses

Normalization of enzymes liver enzymes on clearance of virus

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Clinical course of Hepatitis C Infection

Acute HCV infection is asymptomatic in most patients.

Natural history and chronicity rate varies much between the population groups.

Persistence of virus has been defined as detectable HCV RNA for more than 6 months from the time of presumed infection04/10/2023 23

Progress of HCV infections

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How Acute Infection Manifests

Symptomatic infection in only 15 % of the infectedSpontaneous clearance is higher in patients present with symptomatic than an asymptomatic acute HCV infectionsMajor studies suggest that chronicity rates might depend on the mode of infection, and the age at which patient acquire infection.04/10/2023 25

Acute manifestations

Only 10-20% of all acutely infected patients develop Jaundice, Higher incidence of Jaundice is in injecting drug usersFatigue,myalgia,low grade fever.Right upper quadrant pain,nausea or vomiting

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Other clinical Manifestations

Influenza like illnessDark colored urineClay colored stoolJaundice is more indicative of disease

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Progress of events in HCV Infection

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Bio Chemical marker

Concentration of Alanine aminotransferase greater than ten times the upper limit of normal are uncommon.

Even few cases symptomatic HCV infection have reported increase up to 20 times

The presence of jaundice might be an indicator of an effective host immune response, leads to spontaneous viral clearance.

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Diagnosis of HCV Infection

No definitive pathological test to diagnose acute HCV infection.Diagnosis is supported by,

Identifiable exposure to HCV Recent seroconversion Marked increased concentration of

liver enzymes

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Serology in Diagnosis

Detection of antibodies against HCV immunoassay is unreliable to identify acute infectionsAntibodies may be absent in acute stageThe appearance of antibodies against HCV could be delayed in as many as 30% of patients at the onset of symptoms, particularly in Immunosuppressed.IgM antibodies against HCV have not proven useful in diagnosis of acute HCV infections, as their concentration remain fairly constant in both acute and chronic infections.

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RNA estimation in HCV infections

HCV RNA levels could fluctuate ( may be undetectable ) up to a year after the infection, necessitating serial measurements of HCV RNA for a period of 1 year.As many as 10% of acutely infected patients might eventually lose serological markers.04/10/2023 32

Sensitive methods of Diagnosis of HCV infection

Qualitative and quantitative methods of detection of HCV RNA by

1 Reverse transcriptase RT-PCR,

2 Branched DNA (bDNA)

3 Transcription mediated amplification (TMA )

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CDC guidelines for testing HCV infection.

Testing for antibodies Measuring Analine

aminotransferase concentration

Testing for HCV RNA by PCR at 4 -6 weeks after exposure and again for antibodies against HCV and analine aminotransferase concentration at 4- 6 months

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Prevention and Control

There is no vaccine for HCV infection

Control measures focus on prevention activities that reduce risks for contracting HCV

Major guidelines are

1 Screening and testing blood,plasma,organ, tissue,and semen donors.

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Counseling and Educative measures

Counseling of persons with high drug or sexual practices

Implementation of infection control practices in health care and other settings.

Professional and Public education

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Treatment in HCV

Optimum timing of treatment is critical to avoid unnecessary treatment of those who will clear the infection spontaneouslyThe evidence suggests that it is prudent to wait for at least 12 weeks before initiating antiviral treatment in patients with acute Hepatitis C, especially when they present with symptomatic hepatitis CPhysicians select the regimes depending on the clinical experience and to suit the circumstances.

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Treatment Regimen

With advent of newer pegylated Interferons and use has improved

efficacy in patients with chronic HCV infection, clinicians now use

pegylated interferon as first line therpay,high sustained Virological

response rates have been reported.

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New Improvements in HCV Treatment

HCV treatment improved again in 2001 with FDA approval of pegylated interferon. Attaching the polyethylene glycol (PEG) molecule to interferon (a process called pegylation) keeps the drug in the bloodstream longer and makes it more effective against HCV.

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Pegylated Interferons replaces…

Replacing standard interferon with pegylated interferon has significantly improved response to HCV treatment and requires a dosing regimen of only one injection per week . Currently, therapy with pegylated interferon plus ribavirin is the standard treatment of HCV in HIV-positive people and the only FDA-approved treatment for coinfection.

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Preventive strategies in HCV Infection

As there is no effective vaccine ,preventive aspects should carry priority on

Universal screening of Blood and Blood products

Sterilization of medical and dental equipment.

Mandatory used of disposable needles, avoidance of unnecessary injections or

surgical procedures. Health workers, and public should be educated about the risk of infection from

unsafe practices. Dr.T.V.Rao MD 04/10/2023 41

Created by Dr.T.V.Rao MD for Medical and Health

Workers in the Developing World

Email

doctortvrao@gmail.com

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