Hepatitis C

Question 1

Define hepatitis C

Answer 1

Hepatitis caused by infection with hepatitis C virus (HCV), often following a chronic course (around 80% cases).

Question 2

Describe the Hepatitis C virus.

Answer 2

HCV is a small, enveloped, single-stranded RNA virus of the flavivirus family.

As it is an RNA virus, fidelity of replication is poor and mutation rates are high, resulting in different HCV genotypes, and even in a single patient, many viral quasi-species may be present.

Question 3

Describe the pathogenesis of HCV.

Answer 3

Transmission:
•Occurs via the parenteral route, and at-risk groups include:
—recipients of blood and blood products prior to blood screening,
—IV drug users,
—non-sterile acupuncture and tattooing,
—those on haemodialysis
—health care workers.

•Sexual and vertical transmission is uncommon (1–5%, ⬆️ risk in those co-infected with HIV).

Pathology/Pathogenesis:
•Although HCV is hepatotropic, it is not thought that the virus is directly hepatotoxic, rather that the humoral and cell-mediated response leads to hepatic inflammation and necrosis.
•Virus affects the hepatocytes and produces virirons.
—This phase is symptomatic in 90%, others have non-specific/typical hepatitis symptoms.
•Immune response results in clearance in 20-40% individuals
—Majority go on to have detectable HCV RNA in blood.

•Those that fail to clear the virus suffer ongoing liver inflammation and fibrosis (degree of this is variable).

• On liver biopsy, chronic hepatitis is seen and a characteristic feature is lymphoid follicles in the portal tracts.
• Fatty change is also common and features of cirrhosis may be present.

Question 4

Describe the epidemiology of HCV?

Answer 4

Common.

Prevalence is 0.5–2% in developed countries, with higher rates in certain areas (e.g. Middle East) because of poor sterilisation practices.

Different HCV genotypes have different geographical prevalence.

Question 5

What would a patient with HCV complain of in their history?

Answer 5

Ninety per cent of acute infections are asymptomatic with

Question 6

What would be found on examination of a patient with HCV?

Answer 6

There may be no signs or may be signs of chronic liver disease in long-standing infection.

Less common extra-hepatic manifestations include:
•skin rash, caused by mixed cryoglobulinaemia causing a small-vessel vasculitis;
•renal dysfunction, caused by glomerulonephritis.

Question 7

What investigations would you perform on a patient with suspected HCV?

Answer 7

Blood:
•HCV serology:
—Anti-HCV antibodies, either IgM (acute) (debated) or IgG (past exposure or chronic).

•Reverse-transcriptase PCR:
—Detection and genotyping of HCV RNA. Used to confirm antibody
testing; also recommended in patients with clinically suspected HCV infection but negative serology.

•LFT:
—Acute infection causes ⬆️ AST and ALT, mild ⬆️ bilirubin.
—Chronic infection causes 2–8 times elevation of AST and ALT, often fluctuating over time.
—Sometimes normal.

Liver biopsy:
To assess degree of inflammation and liver damage as transaminase levels bear little correlation to histological changes.
Also useful in diagnosing cirrhosis as patients with cirrhosis will require monitoring for hepatocellular carcinoma.

In chronic HCV infection both IgG antibodies to HCV and HCV RNA remain positive.
Those who clear the virus remain positive for IgG antibodies to HCV but become negative for HCV RNA.

Question 8

How would you manage a patient with HCV?
•prevention
•Acute
•Chronic

Answer 8

Prevention:
•Screening of blood, blood products and organ donors,
•needle exchange schemes for IV drug abusers,
•instrument sterilization.
•No vaccine available at present.

Medical:
Acute:
•No specific management and mainly supportive
—(e.g. antipyretics, antiemetics, cholestyramine).
Specific antiviral treatment can be delayed for 3–6 months.

Chronic:
•Combined treatment with pegylated interferon-a (cytokine which augments natural antiviral mechanisms) and ribavirin (guanosine nucleotide analogue) is the treatment strategy of choice:
—HCV genotype 1 or 4: 24–48 weeks
—HCV genotype 2 or 3: 12–24 weeks

Monitoring of HCV viral load is recommended after 12 weeks of treatment to determine efficacy of treatment.

Regular ultrasound of liver may be necessary if the patient has cirrhosis.

Question 9

What complications are associated with HCV?

Answer 9

• Fulminant hepatic failure in acute phase (0.5%)
• chronic HCV carriage,
• cirrhosis
• hepatocellular carcinoma.

Less common are
•porphyria cutanea tarda,
•cryoglo- bulinaemia
•glomerulonephritis.

Question 10

What prognosis would you expect for a patient with HCV?

Answer 10

Approximately eighty per cent of exposed progress to chronic HCV infection, and of these, 20–30% develop cirrhosis over 10–20 years.

Those who clear the virus are thought to have prognosis similar to uninflected individuals.

Progression to chronic infection is more likely in:
•Males
•Those >40yrs
•Those with ongoing alcohol excess.

Patients with cirrhosis related to HCV infection have a 2-4% risk of developing hepatocellular cancer.