Hepatitis caused by the hepatitis C virus. It shares some similarities with Hepatitis B, but although it is less infectious, there is no vaccine available. It can be asymptomatic for many years, but if the virus is not spontaneously cleared, chronic hepatitis eventually leads to cirrhosis and hepatocellular carcinoma.
Hepatitis C infection is caused by the hepatitis C virus (HCV). HCV is an RNA virus. It is a flavivirus. There are 6 main genotypes of HCV, with distinct geographical distributions. Unlike Hepatitis B, it only appears to be transmitted by blood, sexual contact or vertically.
HCV can cause an acute hepatitis with fever and jaundice. This is a relatively rare presentation. Most cases in the UK are asymptomatic, and only diagnosed after an incidental finding of deranged LFTs. Infection may be cleared spontaneously (sometimes even antibody is lost, eventually), but most go on to have chronic infection. Years may go by before there is progression to cirrhosis or hepatocellular carcinoma.
- Hepatitis C serology - seroconversion occurs 2-6 months after initial infection.
- Hepatitis C RNA PCR qualitative or quantitative - shows on-going viral replication.
- HCV Genotype
Blood tests will differentiate:
- acute infection (PCR positive without antibody), which requires referral for specialist treatment.
- chronic infection (PCR and antibody positive)
- previous infection (PCR negative but antibody positive) -care is needed after initial infection, where RNA levels may oscillate. Hence a negative PCR should always be confirmed with a second sample, especially since the date of infection may not be known. If persistently negative, no further treatment is required.
Biochemical and radiological tests are poorly predictive of liver fibrosis, and can only really differentiate mild disease from cirrhosis. So liver biopsy may be required to establish severity, especially when treatment is being considered. Where a patient has genotype 2 or 3, pre-treatment biopsy may not be necessary given the high rates of response.
Sustained viral response (SVR) is more common in individuals with the C/C genotype on a single nucleotide polymorphism near the IL28β gene, a finding initially identified through a few independent whole genome association studies.
Persistent infection carries a risk of progression to cancer or cirrhosis which is difficult to quantify on an individual basis. Age and sex seem to be relevant, with older patients and men having a higher risk, but studies have addressed different populations. Moderate or higher alcohol intakes, smoking and HIV or HBV co-infection all increase risk. Genotype, surprisingly, does not appear to make a difference.
- Vaccination against hepatitis A (increased risk of acute fulminant liver failure) and B (increased risk of progression)
Anti-viral treatment of hepatitis C should be initiated and supervised by a hepatologist, gastroenterologist or infectious diseases physician. Duration of treatment is determined by the HCV genotype - genotype 1 requires a longer course than those with types 2 or 3. Treatment can continue for between 6 to 12 months (e.g. for PEG-interferon and ribavarin), but shorter courses have been used with newer drugs which are also easier to tolerate. However these new drugs might not be able to be used alone in patients co-infected with another virus that they are not active against.
The objective of treatment is sustained viral response i.e. undetectable RNA at 6 months. Various combinations of the below are used:
- Pegylated interferon alpha, specifically:
- Simeprevir (protease inhibitor)
- Sofosbuvir (RNA polymerase inhibitor)
- Patients with hepatitis C virus and concurrent operable hepatocellular carcinoma should be offered liver transplantation.
- Patients with HCV associated chronic liver failure should be offered liver transplantation.
Surveillance and follow up of cases
Standards for surveillance and follow up of hepatitis B & C have been published by the Health Protection Agency. Screening for hepatocellular carcinoma with alpha feto protein levels and ultrasound is only really of value in patients with established cirrhosis, and probably needs to be done 6 monthly.
There is currently no vaccine for HCV. Prevention occurs on a population level by the screening of donated blood/blood products for HCV. See maternal hepatitis C for vertical transmission.
Post exposure prophylaxis
Early treatment of new infections where spontaneous clearance does not take place has been validated, but is not yet standard practice.
All forms of viral hepatitis are notifiable diseases.
- SIGN guideline (2005) website
- Hepatitis C information at the Health Protection Agency website
- US CDC website.
- Viral hepatitis prevention board
- ↑ Hutchinson SJ, Roy KM, Wadd S, Bird SM, Taylor A, Anderson E, Shaw L, Codere G, Goldberg DJ. Hepatitis C virus infection in Scotland: epidemiological review and public health challenges. Scottish medical journal. 2006 May; 51(2):8-15.
- ↑ Health Protection Agency, Health Protection Scotland, National Public Health Service for Wales, CDSC Northern Ireland, CRDHB, and the UASSG. Shooting Up; Infections among injecting drug users in the United Kingdom 2004. An update. London: Health Protection Agency, October 2005. (http://www.hpa.org.uk/infections/topics_az/injectingdrugusers/shooting_up.htm)
- ↑ EMEA investigation of risk of direct acting antivirals used to treat hepatitis C. Accessed 30 April 2016
- ↑ Health Protection Agency. Standards for surveillance and follow up of hepatitis B & C. April 2006.
- ↑ Santantonio T, Fasano M, Sinisi E, Guastadisegni A, Casalino C, Mazzola M, Francavilla R, Pastore G. Efficacy of a 24-week course of PEG-interferon alpha-2b monotherapy in patients with acute hepatitis C after failure of spontaneous clearance. Journal of hepatology. 2005 Mar; 42(3):329-33.(Link to article – subscription may be required.)