Makindo Medical Notes

Related Subjects: | Chronic liver disease | Cirrhosis | Alkaline phosphatase (ALP) | Liver Function Tests | Ascites Assessment and Management | Budd-Chiari syndrome | Autoimmune Hepatitis | Primary Biliary Cirrhosis | Primary Sclerosing Cholangitis | Wilson disease | Hereditary Haemochromatosis | Alpha-1 Antitrypsin (AAT) deficiency | Nonalcoholic steatohepatitis (NASH) | Spontaneous Bacterial Peritonitis | Alcoholism and Alcoholic Liver Disease |Hepatitis C

PEG stands for polyethylene glycol - a water-soluble polymer attached to the molecule that makes it longer-acting. The aim is to prevent fibrosis and eradicate HCV, reducing the incidence of hepatocellular carcinoma (HCC).

About Hepatitis C

• A viral infection that causes chronic viral hepatitis.
• Affects approximately 185 million people worldwide.
• May lead to cirrhosis, liver failure, and hepatocellular carcinoma.
• Genotypes 1a and 1b are most common in the US but respond less to treatment.

Incidence

• In the UK, between 200,000 and 400,000 individuals are infected with HCV.
• Many remain asymptomatic and unaware of the infection.

Aetiology

• Caused by the Hepatitis C virus, an RNA flavivirus with six genotypes.
• Genotype 1 is common in Europe and more challenging to treat.
• About 80% of infections progress to chronic infection with abnormal liver function tests (LFTs).
• Approximately 30% develop cirrhosis, and 5% go on to develop HCC.

Pathophysiology

• Acute infections progress to chronic in 50-80% of cases.
• A Th1 immune response involving gamma interferon and interleukin-2 may clear the virus.
• A Th2 response involving interleukins 4, 5, 6, 10, and 13 may lead to chronic infection.

Transmission

• Blood transfusion (prior to screening protocols).
• Use of blood products before screening.
• IV drug use.
• Maternal (vertical transmission).
• Sexual transmission (rare).
• Needlestick injuries in healthcare workers.

Clinical Features

• Acute infection is rarely symptomatic.
• Chronic infection in 80% of cases involves inflammation lasting more than 6 months.
• Symptoms in chronic infection include malaise, fatigue, jaundice, dark urine, abdominal pain, loss of appetite, and nausea.
• May present with rash (purpura, hives, leukocytoclastic vasculitis), neuropathy, and membranoproliferative glomerulonephritis.
• Cryoglobulinemia can lead to end-stage renal disease or severe neuropathies.
• Chronic HCV can trigger symptoms of porphyria cutanea tarda.

Investigations

• Anti-HCV antibody test (first line for detection).
• Hepatitis C RNA (first detectable marker via PCR).
• HCV genotype testing to determine treatment approach.
• Usually presents with mildly raised transaminase levels (50-200).
• Liver biopsy may be needed to assess liver damage in some cases.
• Monoclonal rheumatoid factor and cryoglobulins may be found.
• Low ANA and anti-smooth muscle antibodies with low complement levels.
• Screening for liver fibrosis and cirrhosis is essential to identify high-risk patients.

Higher Risk of Cirrhosis in:

• Male patients, those consuming alcohol, or with co-infections (e.g., HIV, Hepatitis B).
• Individuals over 40 at the time of infection.
• Patients who are immunosuppressed.

Associated Conditions

• Sporadic porphyria cutanea tarda.
• Arthritis, glomerulonephritis, diabetes.
• Sicca syndrome, Non-Hodgkin's lymphoma.
• Lichen planus, cryoglobulinemia.
• Mooren's corneal ulcer, idiopathic lung fibrosis.

Management

• HCV is now curable with direct-acting antivirals (DAAs) that achieve a >90% success rate.
• Sofosbuvir: A nucleotide analogue inhibitor of HCV RNA-dependent RNA polymerase, effective across all genotypes.
• Simeprevir: An HCV protease inhibitor.
• Velpatasvir: An NS5A inhibitor combined with sofosbuvir for all major genotypes.
• Voxilaprevir: An NS3/4A protease inhibitor used with sofosbuvir and velpatasvir.
• These medications are costly, and treatment duration can be up to 24 weeks.
• Treatment efficacy is assessed using PCR to measure HCV RNA levels, aiming for undetectable levels and normalized ALT.

• Liver transplantation may be necessary for advanced liver disease; however, re-infection and cirrhosis may recur in the new liver.
• There is currently no vaccine for HCV, but research continues. High-risk groups include IV drug users, hemophiliacs, and those at risk of sexually transmitted infections.
• Chronic HCV-related liver failure is a leading cause of liver transplantation in the US.

Response to therapy is determined by normalization of hepatic transaminases and undetectable hepatitis C RNA levels in plasma.

References

• EASL Recommendations on Treatment of Hepatitis C 2018
• Hepatitis C: Diagnosis and Treatment