Viral Hepatitis (C)

Question 1

Define Hepatitis C. What % progress to chronic infection?

Answer 1

Hepatitis caused by infection with hepatitic C virus (HC), often following a chronic course:

• 70% become chronic hepatitis C (females 60% but 80% males)
• 30% spontaneous clearance

Question 2

What type of virus is hepatitis C? How does HCV replicate?

Answer 2

HCV is an 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 patinet many viral quasi-species may be present.

Question 3

How is HCV transmitted?

Answer 3

Bloodborne

Sexual and vertical transmission is not common (1-5%, increased risk for those co infected with HIV)

Question 4

What are the risk factors for HCV?

Answer 4

• Receiving blood or blood products prior to screening
• IV drug use
• non-sterile acupuncture and tattooing
• haemodialysis
• health care workers

Question 5

What is the pathophysiology of HCV?

Answer 5

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

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 6

How common is HCV?

Answer 6

• Common
• Prevalence 0.5-2% in developed countries and higher in certain areas e.g. Middle East because of poor sterilisation practices
• Different HCV genotypes have different geographical prevalence

Question 7

What is the typical presentation of HCV?

Answer 7

• 90% of acute infections are asymptomatic and <10% become jaundiced with a mild “flu-like” illness
• May be diagnosed after incidental abnormal LFT or in older individuals with complications of cirrhosis

Question 8

What are the features of HCV on examination?

Answer 8

May be no signs or signs of chronic liver disease in long-standing infection. Less common extra-hepatic manifestations include:

• skin rash, caused by mixed cyroglobulinaemia causing small-vessel vasculitis and
• renal dysfunction, caused by glomerulonephritis

Question 9

What investigations would you do for HCV?

Answer 9

NB: cannot check anti-HCV during acute hepatitis – check the viral load (HCV RNA) instead because anti-HCV antibodies only develop after the transaminitis/acute infection

Bloods:

HCV serology - anti-HCV antibodies, either IgM or IgG in 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 raised AST and ALT, mild elevated bilirubin. Chronic causes 2-8 times elevation of AST and ALT fluctuating over time. Sometimes normal

Invasive.

Liver biopsy - assess degree of inflammation and liver damage as transaminase levels bear little correlation with histological change. Also useful in diagnosing cirrhosis as patients with cirrhosis require regular monitoring for hepatocellular carcinoma.

Question 10

How do you manage HCV?

Answer 10

Prevention - screen blood products and organ donors, needle exchange schemes for IV drug users, instrument sterilisation

NO VACCINE available at present

Medical:

Acute - mainly supportive (e.g antipyretics, antiemetics, cholestyramine). Specific antiviral treatment may be delayed for 3-6 months.

Chronic - combined treatment with pegylated interferon-alpha (cytokine augmenting natural antiviral mechanisms) and ribavirin (guanosine nucleotide analogue). Type of HCV dictates treatment length:

• HCV genotype 1 or 4: 24-48 weeks
• HCV genotype 2 or 3: 12-24 weeks

Question 11

Which drugs are used to treat HCV?

Answer 11

• Peginterferon-alpha2b - cytokine which augments bodily antiviral response → once weekly depot injection
• AND ribavirin - guanosine nucleotide analogue

→ 90% curerate

Question 12

How long is the treatment for genoype 4 HCV?

Answer 12

24-48 weeks

Question 13

How often should you monitor HCV viral load?

Answer 13

Recommended after 12 weeks of treatment to determine efficacy

Regular US of liver mau also be necessary if patient has cirrhosis

Question 14

What are the complications of HCV?

Answer 14

• Fulminant hepatic failure in acute phase in 0.5%
• Chronic HCV carriage
• Cirrhosis
• Hepatocellular carcinoma

Less common: porphyria cutanea tarda, cryoglobulinaemia, glomerulonephritis

Question 15

What is the prognosis with HCV?

Answer 15

Early treatment with interferon has high success rate

80% of those exposed progress to chronic HCV infection and of these 20-30% develop cirrhosis over 10-20 years

Question 16

Answer 16

D

Question 17

Answer 17

C – thalassaemia suggests blood transfusions (which probably caused the Hep C which then caused hepatic carcinoma)

Question 18

Answer 18

B

Question 19

What is the incubation time of HCV?

Answer 19

2-6 weeks

Question 20

Describe the virology of HCV.

Answer 20

• Single stranded RNA virus
• Consists of components for the Core (C), Envelope (E) and Non-Structural (NS) components
• Most antivirals are protease inhibitors and inhibitors of non-structural components

Question 21

What is SVR12 and its use?

Answer 21

Sustained viral response at 12 weeks after stopping treatment, if the virus is gone then “cured”.

Question 22

What are the genotypes of HCV and what is their significance to treatment?

Answer 22

Genotype 1 - longer duration and higher doses

Non-genotype 1 = shorter duration and lower doses

Question 23

Name 3 targets of new HCV drugs.

Answer 23

• NS3/4 serine protease = ‘-revir’
• NS5a RNA (unknown action) = ‘-asvir’
• NS5b RNA dependent RNA polymerase = ‘-buvir’

2 regimens:

• Pan-genotypic regimen
• Single-tablet regimen