Case 13: Hepatitis Flashcards
1
Q
How is sporadic Hep E transmitted
A
- consumption of undercooked meat esp pork
- faeco oral route: water, shellfish
- blood transfusion
- Zoonosis: direct contact
2
Q
How does acute Hep E present: timeline
A
- prodrome: N/V, anorexia, fever, abdo pain, fatigue
- hepatitis after 1 week: jaundice, pale stools, dark urine, RUQ pain, hepatomegaly
- may be asymptomatic esp in young children
- Takes 2-3 months for full recovery
- Incubation period: 40 days
3
Q
Complications of acute Hep E
A
- ALF (rare)
- Death: up to 25% die with genotypes 1/2 in pregnancy
- Extrahepatic manifestations: more common than hepatitis A i.e. neurological
- Chronic hep E: Occurs in immunocompromised patients and sporadic (genotype 3/4- not travel associated)
4
Q
Chronic Hep E
A
- If a patient with acute hepatitis E is immunocompromised, they should be followed up to ensure clearance.
- Occasionally treatment may be required (Ribavirin).
- Hepatitis E serology may be falsely negative in immunocompromised patients – diagnosis needs HEV RNA PCR.
5
Q
Investigations for Hep E
A
- LFT’s: raised ALT/AST (in the 1000’s), raised bilirubin, raised ALP
- Hep E serology of serum (IgG or IgM). IgM is acute and IgG is chronic
- Hepatitis E PCR: confirming current or chronic infection
6
Q
Management of Hep E
A
- Supportive care
- Infection control: infectious during incubation period and 3 weeks after jaundice onset. I.e. side room, no food handling
- Notify PHE and contact tracing
- No vaccine
7
Q
Hepatitis B transmission
A
- Vertical transmission, blood born transmission i.e. sexually or needles.
- Small risk of transmission in houshold contacts
- Type of DNA (all other viral hepatitis are RNA)
- Vertical transmission is the most common cause worldwide
8
Q
Hepatitis B risk factors
A
- Risk factors: MSM, unprotected sex, sex workers, IV drug use
- Globally biggest cause of chronic hepatitis especially Sub-Saharan Africa, Asia and Pacific islands
9
Q
Hepatitis B timeline
A
- Incubation period: 60-90 days
- Acute hepatitis B: Majority of people are asymptomatic especially children. Tends to be spontaneously cleared
- Chronic hepatitis B: can occur from asymptomatic and symptomatic acute hepatitis B. Higher risk of developing in infants, children and immunosuppressed.
- NOT all patients with chronic hepatitis B infection have active inflammation and hepatitis
- NOT all patients with hepatitis B develop cirrhosis
- Liver damage is mainly immune-mediated
10
Q
Acute hepatitis B: clinical features
A
- Asymptomatic: majority
- Jaundice, RUQ pain, N+V, Hepatomegaly, fever/chills, Malaise, Lethargy, Arthralgia
- Fulminant acute liver failure (extremely rare): altered mental state and raised ICP
- Hepatitis forms 1 week after prodrome
- Can develop ALF and death
11
Q
Chronic Hep B: clinical features
A
- Asymptomatic: majority, may have no previous history of acute hepatitis. Will remain asymptomatic till complications develop (hepatocellular carcinoma, cirrhosis)
- Non specific: fatigue, malaise, weight loss
- Chronic liver disease symptoms: palmar erythema, spider angioma, asterixis, easy bruising
- Cirrhosis: Ascites, Hepatomegaly, Splenomegaly, Caput medusae
- <5% of acute progresses to chronic
12
Q
Hep B antibodies and antigens
A
- HBsAg: current infections either acute or chronic
- Anti-HBs (Hepatitis B surface antibody): past infection or vaccination
- Anti-HBc Ab: previous or current infections (IgM in acute, IgG in chronic)
- Serum HBV DNA (by PCR): help identify if a patient is a candidate for anti-viral therapy, detects viral load. Shows current infection (acute or chronic)
- Anti Hbe IgG: detected when there’s past, cleared infections
- In vaccination you inject HBsAg and Anti-HBs forms
- HbeAg: correlates with activity of virus and how infectious it is. Present in acute and chronic
13
Q
5 stages of Hepatitis B infection (1-2)
A
- HBeAg positive chronic infection: lots of viral replication, no inflammation/fibrosis. High levels of HBV DNA and HBsAg.
- HBeAg positive chronic hepatitis: active inflammation and increase ALT, reduced HBV DNA. Seroconversion to anti-Hbe IgG. Variable degree of fibrosis (progressing). Active hepatitis
14
Q
5 stages of hepatitis B infection (3-5)
A
- HBeAg negative chronic infection: minimal hepatitis. Last months- years. Normal ALT but low levels of Hepatitis B replication and HBV DNA. Variable degree of fibrosis (progressing). Not active
- HbeAg negative chronic hepatitis: moderate inflammation and raised ALT. Fluctuating HBV DNA levels. Seroconversion of HBsAg to Anti-HbS and clearance of the virus from the blood. Moderate to severe fibrosis (resolving). Active hepatitis
- Functional cure: cleared the virus so no active replication. cccDNA from Heb B stays in the cell lifelong, normally causes no issues but can reactivate if immunosuppressed.
15
Q
Hep B investigations
A
- LFT: ALT and AST rise the most
- Hepatitis serology: HBsAg, HBeAg, Anti-HBe, HBV DNA, Anti-HBs
- FBC, U&E
- Liver US: if chronic hep B
- Assessment for fibrosis/Cirrhosis: Liver biopsy, transient elastography
- Monitor: LFT’s every 3-6 months when chronic. Liver US every 6 months if chronic infection +/- cirrhosis
16
Q
Management of Hepatitis B
A
- Referral to Hepatology or infectious disease for specialist management
- Supportive treatment in majority
- Only adults who are HBsAg-positive, have compensated liver disease, are pregnant or of young age may be referred for treatment
- Nucleotide analogues i.e. Entecavir or Tenofovir monotherapy taken long term PO (first line).
- Pegylated IFN-a injected used for less time, rarely used
17
Q
Goals of Hepatitis B treatment and endpoint
A
- Goals: prevent disease progression and reduce transmission
- Endpoints of treatment: Ideally loss of HBsAg +/- anti-HBs seroconversion but rare. Loss of HBeAg/anti-HBe seroconversion. Suppression of HBV DNA. ALT normalisation
- Medications: tends to be long term, suppresses infection but rarely causes clearance
18
Q
Criteria for Hepatitis B treatment
A
- Severe acute hepatitis (active hepatitis) i.e. INR >1.5, protracted course (persistent symptoms/ marked jaundice >4 weeks), signs of acute liver failure
- Pregnant women with high HBV DNA start at 24-28 weeks gestation and continue till 12 weeks after delivery
- Health care works performing exposure prone procedure
- All patients with Cirrhosis, HIV, family history of HCC or Cirrhosis
- Patients age >30 who are e-Ag positive, high HBV DNA, persistently normal ALT
19
Q
Complications of chronic Hep B
A
- Periods of active hepatitis which may eventually cause liver fibrosis and cirrhosis
- Fibrosis: virus replication in hepatocyte causes immune response which helps clear the virus but causes liver inflammation and fibrosis
- Extrahepatic manifestations
- From cirrhosis can form HCC or decompensated liver disease
20
Q
Risk factors for development of Cirrhosis from chronic Hep B
A
- Active inflammation
- Co-infection with other hepatitis viruses (C/D) or HIV
- Other liver damage i.e. alcohol consumptions
21
Q
Conservative management of Hep B
A
- Education about reducing transmission
- Contact tracing and informing potential at-risk contacts
- Notify PHE
- Screen for Hep D co-infection and other blood born viruses
- Prevent further liver damage: vaccination against hepatitis A, avoid alcohol
- Follow up blood tests to demonstrate clearance
22
Q
What is given to close contacts of patients with Hep B
A
- hep B vaccine
- Hep B immunoglobulin (HBIG): i.e. neonates to infectious mothers, unvaccinated and definite exposure
23
Q
How can clearance of Hep B infection be demonstrates
A
- loss of hep B surface antigen
- hep B surface antibody seroconversion
24
Q
Prevention of Hep B
A
- education on modes of transmission i.e. needle exchange
- Increased testing: antennal testing, testing of blood products and increased testing of high risk groups
- hep B vaccination and immunoglobulin: Hep B vaccine should be given to high risk groups or with high risk of complications. Can be given pre or post exposure.
25
Q
Hep B vaccine: who gets it
A
- All new-borns: part of childhood immunisation
- Anyone at increased risk: close contacts with HBV, Travelling to high prevalence areas, lots of sexual contacts, IVDU, health workers, in prison, Have HIV
- Post exposure: after sexual contact, Neonate of HBV positive women, post needle stick injury
- 3 doses of vaccine required
26
Q
End goal of Hep B infection based on lab results
A
- loss of surface antigens
- loss of e antigens/ presence of antibodies against e antigens
- suppression of hep B DNA
- ALT normalisation
27
Q
Hepatitis C
A
- RNA flavavirus
- Transmitted through blood and bodily fluids: main risk is parenteral through shared needles and blood products. Sexual and vertical transmission but lower risk than HBV
- Breast feeding is contraindicated in Hep C
- Incubation period of 6-9 weeks
- Increased prevalence in Africa, Russia and Eastern Europe
28
Q
Different genotypes of Hep C and where are they most commonly found
A
- 1,2 and 3: Northern hemisphere
- 4: Middle East
- 5: South Africa
- 6: South Asia
- Most common genotypes in the UK: genotype 1 and 3
29
Q
Acute and chronic Hep C
A
- Acute → Chronic → Cirrhosis → HCC
- Most acute infections are asymptomatic (only 20% symptomatic)
- 75% go on to develop chronic infection
- Patients with chronic infection have persistently high LFTs, and cirrhosis develops in 20-30%. Cirrhosis develops slowly over 20-30 years
- 1-4% of patients with cirrhosis develop hepatocellular carcinoma, and 2-5% develop liver failure.
30
Q
Hepatitis C: Investigations
A
- Anti-HCV serology - 90% are positive 3 months after infection
- HCV RNA - if positive for more than two months then need to be treated. (gold standard for diagnosis). PCR- positive in current infection, used when immunocompromised or acute infection.
- Hep C antibody: screening (cant distinguish current vs past). May have false negatives if immunocompromised i.e. HIV or in acute infection.
- Hepatitis C genotyping: differentiate different strains
- At end of treatment test Hep C RNA (PCR)
31
Q
Management of Hepatitis C
A
- Symptomatic treatment in the early stages of the disease
- Drug therapy should be given to all patients and depends on the genotype of the virus.
- Nucleoside analogues are preferred (e.g. daclatasvir + sofosbuvir or sofosbuvir + simeprevir). Examples of DAA’s
- Older drugs are Ribaviron and Pega-interferon
- Direct Acting Anti-virals (DAAs). Given for 8-12 weeks: for example- sofosbuvir, a combination of ledipasvir and sofosbuvir
32
Q
Choice of which DAA to use
A
- DAA’s: Cause regression of fibrosis and cirrhosis
- HCV genotype
- Drug interactions
- Treatment history
- Prescence of cirrhosis
- Cost
- National/local guidelines
33
Q
Why do we carry out Hep C genotyping
A
- no cross protection
- can be co-infected by more than one genotype
- some treatments are genotype specific
- different genotypes respond differently to treatment
34
Q
Chronic hepatitis
A
- Liver inflammation for more than 6 months
- Causes: Hep B, Hep C, Hep D, Hep E
35
Q
Important differences between Hep B and C
A
- acute hep C is often asymptomatic whereas acute hep B is often symptomatic
- most hep C cases progress to chronic infection whereas only a small % of hep B cases progress
- there is no reactivation of hep C (cure is possible)
- there are multiple genotypes of hep C (reinfection is possible)
- there is no vaccine for hep C but there is a vaccine for hep B
36
Q
Ways to eliminate viral hepatitis
A
- Aim to eliminate Hep B and C by 2030
- Increased screening and testing
- Reduced stigma
- Increased education and awareness around modes of transmission
- Public health: needle exchange, safer sexual practises, sterile medical equipment
- Screening blood products
- Increased HBV vaccination
- Obstetric services
- Increased access to treatment i.e. reduce cost of DAA’s
37
Q
Hepatitis D
A
A single stranded RNA virus transmitted parenterally. Needs hepatitis B surface antigens for replication and transmission. Transmitted in same way as Hep B (exchange of body fluids)
38
Q
How is Hep D transmitted
A
- Co-infection: Hepatitis B and Hepatitis D infection at the same time.
- Superinfection: A hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection.
39
Q
Diagnosis and treatment of Hepatitis D
A
- Diagnosis: via PCR
- Screen for anti hep D antibodies and confirm diagnosis with Hep D RNA
- Treatment: Interferon and treating Hep B
40
Q
Presentation and treatment for Hepatitis D
A
- Acute infection: suspect if acute hepatitis in HBV patient or fulminant acute HBV (rapid progression of liver failure)
- Diagnosis: Anti-HDV antibodies (screening), HDV RNA through PCR (current infection)
41
Q
Complications of chronic Hep B and D co-infection
A
Results in more rapid progression to cirrhosis and HCC
42
Q
Lyme disease: how its spread and where is it prevalent
A
- Causes by the Spirochete bacterium Borrelia burgdorferi through Ixodes ticks
- Prevalent in North America, Europe and Asia in heavily wooded and grassy area i.e. Highlands. Tends to be late Spring/early summer
- Transmission occurs 36-48hrs after tic attachment
43
Q
Lyme disease species
A
- B.burgdorferi sensu lato: US
- B.garninii, B.afzelii (Europe)
44
Q
Early clinical features of Lyme disease (within 30 days)
A
- Erythema migrans: bulls eye rash, develop 1-4 weeks after initial bite. Painless and >5cm in diameter, slowly increases in size. Lasts several weeks. Not itchy, painful or hot
- Systemic: headache, lethargy, fever, arthralgia
45
Q
Non specific symptoms of Lyme disease
A
- fever and sweats
- swollen glands
- malaise, fatigue
- neck pain or stiffness
- migratory joint or muscle aches and pain
- cognitive impairment i.e. memory problems and difficulty concentrating (sometimes described as ‘brain fog’)
- headache
- paraesthesia
- Can occur at any stage of disease
46
Q
Less common features of early Lyme disease
A
- Cardiovascular: heart block (1st but can progress to 3rd), peri/myocarditis
- Neurological- weeks to months after exposure: facial nerve palsy (can be bilateral), other cranial nerve palsies, radicular pain (Mononeuritis multiplex), lymphocytic meningitis
- Neurological issues are rare but classical of Lyme and so should be suspicious
47
Q
Late clinical features of Lyme disease (after 30 days)
A
- Lyme arthritis (more common with US strains): inflammatory arthritis affecting 1 or more joints, fluctuating and migratory. Knee always affected
- late cutaneous features (more common with European strains): Acrodermatitis chronica atrophicans, Lymphocytoma
- non specific symptoms such as fever, lymphadenopathy, fatigue etc
48
Q
What are the late cutaneous features of Lyme disease
A
- acrodermatitis chronica atrophicans (rash with skin thickening on extremities)
- lymphocytoma (flesh coloured nodular lesion esp near earlobe)
49
Q
How to remove a tick bite
A
fine tipped tweezers, grasping tick as close to the skin as possible and pulling upwards
50
Q
Management of Lyme disease
A
- Doxycycline in early disease i.e. ECM rash for 21 days (Amoxicillin if contraindicated i.e. pregnancy)
- IV Ceftriaxone if disseminated disease for 21 days (meningitis, radiculopathy or CN palsy)
51
Q
Lyme disease investigations
A
- If erythema migrans is present its a clinical diagnosis
- ELISA test for IgG and IgM antibodies (takes 6 weeks to be positive)
- If ELISA positive confirm with Immunoblot test
- If ELISA negative but symptoms persist for >12 weeks then Immunoblot test
- Can only do PCR in joint disease
52
Q
Lyme treatment outcomes
A
- Successful treatment- resolution of symptoms after 12 months. Symptoms can persist for a couple months
- There is no test for ‘active infection’
- Re-treatment: can give another antibiotic for 7 days
- No role for long term antibiotics
