Hepatitis C virus hepatitis

Hepatitis C infection is a slowly progressive disease of the liver caused by the hepatitis C virus. It is a highly variable and unpredictable condition with effects of the infection varying from asymptomatic disease to liver failure or primary liver cancer (1).

Prior to 1991 hepatitis C virus was an important cause of post-transfusion hepatitis. It accounts for most cases of viral hepatitis previously designated as non-A, non-B viral hepatitis.

• unlike hepatitis A and B, there is no vaccine for hepatitis C but infection is avoidable through strategies that reduce transmission.
• HCV is a single stranded, enveloped RNA virus. It is structurally similar to the flaviviruses and is 30-38 nm in size has a genome of 9379-9481 base pairs.
• the incubation period of 15-150 days which is broadly comparable to that of HBV.

The patient may be asymptomatic. About 10% develop jaundice. Fulminant hepatitis is rare. Patients who are HIV positive may have a rapidly progressive course.

Serum diagnosis is usually by detecting anti-HCV. HCV RNA may be detected by PCR 1-2 weeks after infection. PCR is a supersensitive technique but is not routinely available.

Hepatitis C virus is a highly variable agent and there are 6 recognised genotypes with numerous subtypes.

• genotype 1 is the most common in the UK, accounting for about 40-50% of cases. Genotypes 2 and 3 contribute another 40-50%; and genotypes 4, 5 and 6 constitute the remainder, about 5%
• antiviral treatment of hepatitis C, previously interferon-based, has become interferon-free, with resulting improvements in sustained virological response rates, safety, and tolerability and a shorter duration of treatment
• available drugs for interferon-free antiviral treatment of hepatitis C include inhibitors of the RNA-dependent RNA polymerase, NS3/4A protease, and NS5A protein of the hepatitis C virus (HCV), and ribavirin
  • typically, two specific inhibitors are given in combination; the usual duration of treatment is 12 weeks
  • the antiviral drugs differ in their genotypic antiviral effectiveness and resistance barriers - appropriate drug(s) should be chosen in consideration of the patient’s hepatic and renal function and potential drug interactions
  • patients with hepatitis C, whatever their disease stage, can derive a sustained eradication of HCV from a combination of drugs with direct antiviral activity

In England, an estimated 89,000 people are chronically infected with hepatitis C (HCV)

• in 2018 sentinel surveillance data suggests that, of all individuals testing positive for anti-HCV
  • 85% were tested for HCV RNA. Among persons who were HCV RNA tested after a positive anti-HCV test
  • 52% were RNA positive, of whom 42% had an HCV genotype recorded; 49% were genotype 1, with a further 43% genotype 3
• Drug injection continues to be the most important documented risk factor for HCV infection in 2018, being cited as the risk in 93% of all laboratory reports where risk factors were disclosed
• Of those participating in the Unlinked Anonymous Monitoring (UAM) Survey
  • proportion of people who inject drugs (PWID) who test HCV antibody (anti-HCV) positive has increased in recent years, from 45% in 2011 to 55% in 2018, however, chronic prevalence has remained relatively stable over this period (28% in 2018);
  • prevalence of cleared infection (anti-HCV positive, RNA-negative) has increased from 19% in 2011 to 27% in 2018

By 2018, the number of liver transplant registrations and transplants undertaken in those where post-HCV cirrhosis and hepatocellular carcinoma (HCC) is given as the indication for transplant, fell by 44% and 29% respectively when compared to pre-2015 levels, although both showed a rise over the previous year (by 19% and 13% respectively).

Deaths from HCV-related end stage liver disease (ESLD) and hepatocellular cancer (HCC) have been falling since 2014, with a decline of 20% by 2018 from the 2015 World Health Organization (WHO) baseline (3)

WHO guidance proposes impact targets for validation of HCV elimination that are absolute, namely reducing incidence to equal to or less than 5 per 100,000 persons (equal to or less than 2 per 100 PWID) and HCV-related annual mortality to a rate of equal to or less than 2 per 100,000 persons (4)

• absolute impact targets are proposed in combination with a set of programmatic targets toimprove HCV testing (equal to or greater than 90% of people with HCV diagnosed) treatment(equal to or greater than 80% of people diagnosed with HCV are treated) and prevention of infection (0% unsafe injections, 100% blood safety, and 300 needles or syringes per PWID/year)

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• advice from the UK National Screening Committee on antenatal screening for hepatitis C..click here

Reference:

• (1) Royal College of General Practitioners (RCGP) 2007. Guidance for the prevention, testing, treatment and management of hepatitis C in primary care
• (2) PHE (2020). Hepatitis C in England 2020 - Working to eliminate hepatitis C as a major public health threat
• (3) Zeuzem S. Treatment Options in Hepatitis C -The Current State of the Art. Dtsch Arztebl Int. 2017 Jan; 114(1-2): 11-21.
• (4) the Hepatitis C Trust. 'Hepatitis C: Risk Factors' 2020