QuestionSBA
QuestionChoice
This patient has positive IgG antibodies to the core antigen of hepatitis B virus and positive surface antigen antibodies. If this were an acute infection, we would expect positive IgM antibodies to the core antigen, as well as positive surface antigen due to the presence of virus particle production.
53004
c
Acute infection with hepatitis B
QuestionChoice
This patient has positive IgG antibodies to the core antigen of hepatitis B virus and positive surface antigen antibodies. Early acute infection would have a positive surface antigen present, without presence of antibodies. The first type of antibody to appear would then be IgM.
53006
e
Early acute hepatitis B virus infection
QuestionChoice
This patient has positive IgG antibodies to the core antigen of hepatitis B virus and positive surface antigen antibodies. This is in keeping with previous exposure to hepatitis B virus with recovery and the presence of current antibodies.
53002
a
Previous exposure and recovery to hepatitis B
QuestionChoice
This patient has positive IgG antibodies to the core antigen of the hepatitis B virus and positive surface antigen antibodies. Previous vaccination would mean only antibodies for the surface antigen would be present since there is no core antigen present in the vaccine. This patient has antibodies to both, indicating previous infection with immunity.
53005
d
Vaccination against hepatitis B
QuestionChoice
This patient has positive IgG antibodies to the core antigen of hepatitis B virus and positive surface antigen antibodies. If the infection were chronic, we would expect a positive surface antigen to be present due to ongoing virus particle production. The surface antigen is currently negative, indicating recovery from the infection.
53003
b
Chronic infection with hepatitis B
QuestionComment
Formatting the results would have been nice
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### Summary

Hepatitis is an inflammation of the liver caused by a variety of infectious and non-infectious factors. The most prevalent causes of viral hepatitis in the UK are hepatitis A, B, and C viruses. Hepatitis can present with symptoms such as fatigue, nausea, vomiting, and jaundice. The different hepatitis viruses can cause different spectra of disease, with some more likely to cause an acute hepatitis, and others a chronic hepatitic picture. The differential diagnosis includes conditions such as drugs, toxins, alcohol, EBV, CMV, leptospirosis, and malaria. Key investigations include serology for specific hepatitis types. The management of hepatitis is largely supportive, with some patients requiring antiviral treatment depending on the type of hepatitis.

### Definition

Hepatitis refers to the inflammation of the liver. It is typically caused by viral infection but can also result from non-infectious aetiologies such as toxins and alcohol. 

Hepatitis A and Hepatitis E can lead to acute liver failure, whereas Hepatitis B and Hepatitis C tend to lead to chronic liver failure. Hepatitis D only occurs in individuals who are infected with Hepatitis B. 

### Epidemiology

Viral hepatitis is common in the UK with the primary causes being hepatitis A, B, and C viruses. These can cause acute disease, but hepatitis B and C can also lead to chronic infection, liver fibrosis, and hepatocellular carcinoma. The prevalence of Hepatitis A is higher in developing countries, while Hepatitis B is the most common cause of hepatitis globally.

Other causes of acute hepatitis include drugs, toxins, alcohol, EBV, CMV, hepatitis E, leptospirosis, and malaria.

NB: All infectious hepatitis cases are notifiable diseases in the UK.

### Signs and Symptoms

#### Acute liver failure

- Predominantly caused by Hepatitis A and E
- Prodromal viral illness:
- Fever
- Malaise
- Anorexia
- Nausea and vomiting

#### Acute hepatitis

- Right upper quadrant pain
- Jaundice
- Tender hepatosplenomegaly (due to swelling of the liver capsule)

#### Chronic liver failure

- Hepatic encephalopathy
- Jaundice
- Ascites
- Coagulopathy due to abnormal clotting


### Hepatitis A

- RNA picornavirus, transmitted by faecal-oral route (occasionally through food sources or through anal sex)

#### Epidemiology 

- Prevalence is high in developing countries.
- Increasing age is the only real determinant of disease severity, with the greatest morbidity and mortality in those over 50 years old.
- Travellers and those at risk can be offered immunisation
- It is transmitted via the faecal-oral route (commonly through shellfish)

#### Presentation 

- Flu-like symptoms followed by jaundice, pale stools (in some), dark urine and abdominal pain
- Incubation period of 2-6 weeks, presents only as an **acute** hepatitis with no chronic phase
- Complete recovery can take up to 6 months.

#### Investigations 

- Hepatitic LFTs, with ALT/AST as high as in the 1000s
- IgM and IgG antibodies to HAV

#### Management 

- Management is largely supportive

#### Hepatitis E
- Similarly spread via faecal-oral route (commonly undercooked pork)
- It is **e**xtremely dangerous in pregnancy, with a mortality rate up to 20%
- Similar to Hepatitis A with only an acute presentation and no chronic phase, with management also supportive in nature

### Hepatitis B 

- dsDNA virus of Hepadnaviridae family
- Primarily causes an acute hepatitis, with the main and most severe complication being progression to chronic hepatitis infection

#### Epidemiology

- Most common cause of hepatitis globally
- High prevalence regions include sub-Saharan Africa, Asia and the Pacific Islands.
- Decline of disease in children and adolescents in the UK is due to **routine vaccination**
- Incubation period usually 60-90 days.

#### Transmission

- Transmission is via infected blood or body fluids
  - Vaginal/anal intercourse
  - Transfusion
  - Vertical transmission (in 90% of pregnancies where the mother is HBeAg positive, and 10% where this is negative).
  - In developing countries, infection is mostly in childhood through vertical or horizontal transmission. In areas of low endemicity (such as the UK), infections are mostly acquired in adulthood.

#### Presentation

- Children - Only 5% of children have jaundice and severe symptoms i.e. it is mostly an asymptomatic primary infection, but the majority (90%) develop chronic disease with only 10% able to clear the virus
- Adults - more likely to have an acute hepatitis picture with jaundice, fever, malaise, viral prodrome and occasionally darkening of urine and lightening of stool. Some develop fulminant liver failure with decompensation (ascites, encephalopathy etc.). 90% clear the infection, with only around 10% developing chronic disease
- Chronic features occur when the virus has been unable to be cleared for more than 6 months - development of cirrhosis, decompensated liver failure, and increased risk for **hepatocellular carcinoma**
- Rarer features of hepatitis B infection include glomerulonephritis, cryoglobulinaemia and polyarteritis nodosa

#### Investigations

- HBsAg is detected 3-5 weeks after infection. If present for >6 months, this defines carrier status (5-10% of infections).
- In carriers, HBeAg-positive patients are the most infectious. If HBeAg-negative (and anti-HBe-antibody positive), they have lower infectivity.
- Patients with chronic infection who are HBeAg -ve may get immune escape phase when the virus mutates despite anti-HBe antibodies being present. These patients are the main pool for the spread in the UK, and so all chronically infectious patients need yearly screens to identify this.

A summary table of the serology in Hepatitis B is below:


| Marker                      | Description                                     |
|-----------------------------|-------------------------------------------------|
| HBsAg (Hepatitis B Surface Antigen) | Indicates current infection; persists >6 months |
| Anti-HBs (Hepatitis B Surface Antibody) | Indicates immunity from past infection or vaccination |
| HBeAg (Hepatitis B e Antigen) | Indicates active viral replication; higher infectivity |
| Anti-HBe (Hepatitis B e Antibody) | Indicates lower infectivity; seroconversion is associated with reduced viral replication |
| HBcAb (Hepatitis B Core Antibody) | IgM indicates acute infection; IgG indicates past infection or vaccination |
| HBV DNA (Hepatitis B Virus DNA) | Quantifies viral load; used to monitor response to treatment |

- Biopsy of the liver in chronic hepatitis B infection will reveal 'ground-glass' hepatocytes on light microscopy

#### Management 

- There is no **cure** for chronic hepatitis B, but there is a *functional* cure as you can prevent liver disease with pegylated interferon
- Indications for antiviral treatment
- Adults aged 30 years and older who have HBV DNA greater than 2000 IU/ml and abnormal ALT on 2 consecutive tests conducted 3 months apart
- Adults who have HBV DNA greater than 20,000 IU/ml and abnormal ALT on 2 consecutive tests conducted 3 months apart regardless of age or the extent of liver disease
- Adults with cirrhosis and detectable HBV DNA, regardless of HBeAg status, HBV DNA and ALT levels
- Pegylated interferon alfa-2a is the first line, with tenofovir and entecavir as second-line alternatives
- Pegylated interferon can lead to viral suppression which leads to ALT normalisation and improved liver histology

If a patient with hepatitis B becomes suddenly very unwell with a worsening hepatitic picture, consider if they are now suffering co-infection with **Hepatitis D**

### Hepatitis C 

- RNA virus of the Flaviviridae family, with 6 major genetic types (genotypes 1 and 3 are most common in the UK, and genotype 1 is associated with longer treatment and worse prognosis)
- There is no vaccination for Hepatitis C, currently

#### Transmission

- Transmitted via exchange of blood and bodily fluids:
  - Intravenous drug use
  - Blood transfusion
  - Haemodialysis (rare in the UK)
  - Sexual transmission (less than 1% per year of relationship, but rate higher if co-infected with HIV)
  - Needlestick injuries in healthcare facilities - 3% risk of transmission.
  - Perinatal infection from infected mother.
- Incubation period of 6-9 weeks.

#### Presentation

- Most infections are asymptomatic, and only 15-25% clear the virus. 75% go on to develop chronic infection
- Patients with chronic infection have persistently high LFTs, and cirrhosis develops in 20-30%
- 1-4% of patients with cirrhosis develop hepatocellular carcinoma, and 2-5% develop liver failure
- Additional features – arthralgia/arthritis, Sjogren’s syndrome, cryoglobulinaemia, porphyria cutanea tarda, membranoproliferative glomerulonephritis

#### Investigations 

- Anti-HCV serology - 90% are positive 3 months after infection but it may take many months to become positive for some
- Even if the virus has been cleared, HCV antibodies can remain positive for months afterwards
- HCV RNA - if positive for more than two months then need to be treated.

#### Management 

- Symptomatic treatment in the early stages of the disease
- There is a **c**ure (Hepatitis **C** for **C**ure), unlike in Hepatitis B
- Drug therapy should be considered for all patients and depends on the genotype of the virus. Nucleoside analogs are generally preferred e.g. Sofosbuvir and often lead to undetectable viral loads
- Sofosbuvir and daclatsavir may be used as combination therapy
- Antivirals of proven benefit in basically every patient irrespective of the amount of cirrhosis and fibrosis
- Manage any underlying cirrhosis

### NICE Guidelines

[Click here for NICE CKS on hepatitis A](https://cks.nice.org.uk/topics/hepatitis-a/)

[Click here for NICE CKS on hepatitis B](https://cks.nice.org.uk/topics/hepatitis-b/#!references)

[Click here for NICE CKS on hepatitis C]([https://cks.nice.org.uk/topics/hepatitis-c/)
1867
2224
Hepatitis viruses
Topic
23
Gastroenterology
10661
Positive IgG anti-HBc and positive anti-HBs indicate previous hepatitis B infection with subsequent recovery and immunity.
A 42-year-old man has some blood tests conducted by his hepatology team in the outpatient department. The results are shown below:

Hepatitis B surface antigen - negative
Anti-hepatitis B surface antibody - positive
IgM anti-HBc - negative
IgG anti-HBc - positive

Which of the following is the most likely explanation for these results?
a