Makindo Medical Notes

PEG stands for polyethylene glycol - a water-soluble polymer attached to the molecule and makes it longer acting. The aim is to prevent fibrosis and eradicate HCV. There is a reduction in the incidence of HCC

About

• Viral infection causing a chronic viral hepatitis
• Chronic hepatitis seen in 185 million worldwide
• May lead to cirrhosis, liver failure, hepatocellular carcinoma
• Genotypes 1a and 1b are the most common in the US but also the least likely to respond to treatment

Incidence

• In UK 200,000-400,000 are infected with HCV
• Many are asymptomatic and unaware

Aetiology

• Hepatitis C infection is due to a RNA flavivirus.
• There are 6 genotypes with similar disease
• Genotype 1 commoner in Europe is harder to treat
• RNA virus - 6 genotypes (Genotype 1 responds least to treatment)
• 80% go on to have chronic infection with abnormal LFT's
• 30% get cirrhosis and 5% go on to develop Hepatocellular carcinoma

Pathophysiology of Hepatitis C infection

• Acute becomes chronic infection in 50-80%
• Th1 response ? gamma interferon and interleukin 2 clears the virus
• Th2 response ? interleukins 4,5,6,10,13 leads to chronic infection

Virus from

• Blood transfusion pre-screening
• Blood products pre-screening
• IV drug use
• Maternal (vertical transmission)
• Sex (uncommon)
• Needlestick injuries in healthcare workers

Clinical

• Acute infection is very rarely symptomatic.
• Chronic infection 80% (inflammation more than 6 months) - The infection is only symptomatic in 20% of carriers - acute infection may cause jaundice, fatigue, dark urine, abdominal pain, loss of appetite, nausea.
• Chronic infection presents with malaise and fatigue. Many however are picked up with screening for the virus after finding deranged LFTs
• Rash (purpura, hives, leukocytoclastic vasculitis), neuropathy, and membranoproliferative glomerulonephritis.
• Cryoglobulinemia can be severe and lead to end-stage renal disease or severe neuropathies,
• Chronic HCV can trigger the symptoms of porphyria cutanea tarda

Investigations

• Anti-HCV antibody test result is positive
• Hepatitis C RNA is the first detectable marker measured with PCR.
• HCV genotype testing
• There is usually a mildly raised transaminase of 50-200. Types 2 and 3 do best.
• Liver transaminases do not give a good guide to the degree of liver damage so a biopsy is preferred in some cases.
• Monoclonal rheumatoid factor and cryoglobulins are found
• Low titres of ANA, anti-smooth muscle and low complement levels
• Screening for liver fibrosis and cirrhosis to identify those needing treatments or at risk of Hepatocellular carcinoma
• Liver biopsy may be needed in some cases

Cirrhosis is more common in these groups.

• Male sex, Alcohol, HIV
• Older than 40 at time of infection
• Hepatitis B, Immunosuppression

Hepatitis C is associated with

• Sporadic Porphyria cutanea tarda
• Arthritis, Glomerulonephritis, Diabetes
• Sicca syndrome, Non-Hodgkin's lymphoma
• Lichen planus, Cryoglobulinaemia
• Mooren's corneal ulcer, Idiopathic lung fibrosis

Management: The disease is now curable

• In the past 10 years there has been a move away from interferon-based therapies to antivirals which have allowed HCV to be eradicated. There are now agents which work on all the HCV genotypes. These are often combined and these are constantly changing but effectiveness is over 90%.
• Sofosbuvir (400 mg/day PO), which is a nucleotide analogue inhibitor of the HCV RNA-dependent RNA polymerase. It is active against all genotypes.
• Simeprevir (150 mg/day PO), which is an inhibitor of the HCV protease
• Velpatasvir is an NS5A inhibitor that is used together with sofosbuvir in the treatment of hepatitis C infection of all six major genotypes
• Voxilaprevir is a hepatitis C virus (HCV) nonstructural (NS) protein 3/4A protease inhibitor (by Gilead) that is used in combination with sofosbuvir and Velpatasvir.
• These drugs are expensive. Course are up to 24 weeks.
• The response to treatment is assessed by using PCR to measure Hepatitis C virus RNA levels (it is an RNA virus). Successful treatment can be shown by a fall in ALT and evidence of reduced hepatic inflammation and fibrosis.