GI & Hepatology JC054: Jaundice After Raw Oysters: Acute Hepatitis Flashcards

1
Q

Acute + Chronic Viral Hepatitis A-E

A

Large proportion may not have symptoms at all, esp. young
- ***Exacerbation of Chronic hepatitis B will have symptoms

Clinical features (same for acute hepatitis / exacerbation of chronic hepatitis):

  1. Pre-jaundice / Pre-icteric phase:
    - low grade fever (usually <39oC)
    - **severe LOA (smoker may even stop smoking)
    - **
    severe fatigue, myalgia
    - **diarrhoea (enteric type of viral hepatitis)
    - **
    RUQ dull ache due to liver capsule distension (if large HCC: occasionally pain)
    - **darkening of urine colour (∵ death of hepatocytes —> leakage of bile into blood)
    - **
    transient pruritis (∵ transient obstruction of bile ducts —> bile salt in skin)
  2. Jaundice / Icteric phase:
    - ***jaundice
  3. Convalescent phase:
    - whole cycle 2-4 weeks
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2
Q

***Biochemistry of Hepatitis

A
  1. ↑ AST (SGOT)
  2. ↑ ALT
    —> reflect amount of ***hepatocyte damage
    —> patients with fulminant hepatitis may have falling AST / ALT as disease progresses

Best index for progress / prognosis:
3. Factor 7 (short t1/2: 12 hours) (not usually done)

  1. ***Prothrombin time (check daily / BD)
  2. Bilirubin (mainly Conjugated / Direct):
    - may be ↑ for a long time after clinical / essential histological recovery (cholestatic phase)
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3
Q

Management of Symptomatic hepatitis

A
  1. None needed
    - no known drugs / herbs will hasten recovery of course of hepatitis —> TCM may cause liver damage / failure
  2. Rest (if extremely tired)
    - but do not alter course of hepatitis
  3. Diet
    - no alcohol for ***6 months for acute hepatitis / for life for chronic hepatitis
    - eat anything
    - glucose drip does not help (fatty liver if too much glucose)
    - fatty diet harmless
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4
Q

***Comparisons of Viral hepatitis A-E

A

HAV:

  • Pico-rna
  • 27nm
  • SS +RNA
  • 7400 nucleotides
  • no envelop
  • endemic-epidemic
  • ***oral-faecal
  • ***2-4 weeks incubation
  • ***no chronicity (once you get Hep A you will be immune forever)

HBV

  • Hepa-dna
  • 42nm
  • DS DNA (only DNA virus)
  • 3200 nucleotides (small)
  • have envelop (***i.e. surface Ag HBsAg)
  • endemic
  • blood
  • 4-24 weeks incubation (i.e. need to trace sexual history up to 24 weeks)
  • ***chronicity varies with age (>90% if acquired before 2 yo, never if acquired in adult e.g. sexually)

HCV

  • Flavi
  • 30-60nm
  • SS +RNA
  • ***9400 nucleotides (largest)
  • ***have envelop
  • endemic
  • ***blood
  • 2-25 weeks incubation
  • ***70-85% chronicity

HDV

  • Satellite (∵ require HBsAg to survive, if no Hep B you cannot have Hep D)
  • 35nm
  • SS circular RNA
  • 1700 nucleotides
  • ***no envelop
  • endemic
  • ***blood
  • ***chronicity depends on HBV population (acute / chronic Hep B)

HEV

  • Calici
  • 27-34nm
  • SS +RNA
  • 7600 nucleotides
  • ***no envelop
  • endemic-epidemic
  • ***oral
  • ***2-7 weeks incubation
  • ***no chronicity except in transplant patients
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5
Q

Hepatitis A transmission + epidemiology

A

Oral-Faecal transmission:

  • virus shed into faeces during incubation, not excreted 7-10 days after onset of jaundice (i.e. ***dangerous period: incubation period)
  • not well-cooked shellfish (bivalve e.g. clamps, oyster X fish / prawns) from infected water (esp. clamps, valves trap HAV)
  • ingestion of infected water e.g. uncooked vegetable
  • faecal contamination (e.g. children, sex, health care workers)

Parenteral transmission (rare but possible):

  • transfusion
  • acupuncture, tattoo
  • outbreak in Italian haemophiliacs in 1994 (∵ factor 8 concentrate contamination)

Epidemiology:

  • low in clean countries (USA, Europe, Australia, NZ)
  • high in dirtier countries (Africa, South America)
  • intermediate in HK, China
  • ***↓ incidence in HK over last decade
  • % change of notifications in 2009 over preceding 5 years: -21.3%
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6
Q

Hepatitis A clinical course

A

Clinical course:

  • ***Self-limiting
  • ***Anicteric (often only mildly symptomatic in children)
  • Icteric in some adults
  • ***Diarrhoea comparatively common in early stage (∵ enteric viral hepatitis)
  • Recovery within 4-6 weeks

Atypical clinical course:
- Prolonged cholestasis
—> **High bilirubin (10x above normal)
—> **
AST, ALT ↓
—> Last 12-24 weeks (6 months)
—> **Centrilobular cholestasis with **Periportal inflammation (may mimic CAH: Copper‐Associated Hepatitis)
—> Always complete resolution
—> Steroid quickly “whitewashes” but ↑ relapse (i.e. ***DO NOT give steroids!!!)
(Steroid can reduce jaundice by enhancing liver uptake / storage of bilirubin —> ↓ serum bilirubin concentration)

Relapse (Related to immune reaction of patient):

  • 6-10%
  • Biphasic (2 attacks) / Polyphasic
  • ***AST / ALT ↑↑ (> 1000)
  • Last 3-12 months
  • ***IgM anti-HAV remains positive
  • **HAV in stool, **HAV RNA in serum
  • Steroid ↑ relapse
  • ***Always resolves

Extrahepatic manifestations:

  • ***Rash (Purpuric), Arthralgia, Cryoglobulinaemia
  • Apparent triggering of Autoimmune chronic hepatitis (Type 1) in predisposed subjects
  • probably related to Immune complex disease
  • Usually rare (<15%)
  • More common in prolonged disease
Fatality rate:
- variation with age (CDC 1990)
—> <=14 years 0.1%
—> 15-39 years: 0.4%
—> >=40 years: 1.1%
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7
Q

***Hepatitis A serology

A

Pre-icteric phase:

  • ***Virus excretion
  • Histopathology (damage to hepatocytes)
  • ***Symptoms

Icteric phase:

  • Jaundice
  • ***Viral load ↓
  • ***IgM starts to ↑

Convalescent phase:

  • ***IgM ↑ (anti-HAV) first (already at high level), after 3-4 months ↓
  • IgG ↑ later (last probably for life)
  • IgA ↑ (smaller degree)
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8
Q

***Hepatitis A diagnosis

A

**IgM anti-HAV
- for acute infection
- peaks at acute stage / early convalescent stage
- detected:
—> **
2-3 weeks after ↑ AST / ALT
—> 1-2 weeks after jaundice
—> occasionally delayed (
recheck if IgM anti-HAV negative in first time)

  • persists:
    —> **3-4 months (usually)
    —> over 6 months (25%)
    —> over 12 months (very rarely) (i.e. IgM anti-HAV +ve does **
    not necessarily mean acute infection)

IgG anti-HAV:

  • persists for ***decades
  • protected probably ***for life from Hep A
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9
Q

Hepatitis A prevention

A
  1. Careful cooking of shelled seafood
    - Virus killed by:
    —> Dry heat at 100oC in 1 min
    —> Wet heat at 100oC in 5-10 mins
    —> ***Not killed at 60oC even in 12 hours
  2. Chlorination of drinking water
  3. Passive immunisation (IVIG)
    - up to 90% efficacy
    - prevent / reduce severity of infection
    - dose-dependent efficacy
    - ***<6 months efficacy
    - mainly for travellers with no time for vaccination
  4. Vaccine
    - **Inactivated whole virus from cell cultures
    - 2 doses IM (2nd dose **
    6 months apart as booster)
    - Effective protection within 3-4 weeks after 1st dose
    - Immunogenicity 99%
    - Protective efficacy 100%
    - Unknown duration of protection (probably ***lifelong)
    - Primary target non-immune adult travellers (HAV occurs 40x more common than typhoid, 800x than cholera)
    - Use in areas of moderate - high endemicity? However:
    —> cost
    —> low mortality of Hep A
    —> no chronic carriers
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10
Q

Hepatitis E

A
  • previously known as Enteric NANB hepatitis (Non-A, Non-B)
  • commonly affects adults in 3rd decade

Epidemiology:

  • known epidemics in India, Burma, Nepal, Pakistan, China, Central Russia, Mexico (dirty areas)
  • ***↑ incidence in HK: 26% in 1992, 33.6% in 2016
  • % change of notifications in 2009 over preceding 5 years: +39.8% (***記住: Hep A跌, Hep E升)
  • slightly higher mortality than Hep A
  • now ***more common than Hep A in HK
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11
Q

Hepatitis E transmission

A

4 common genotypes:

  • 1, 2 from Humans —> Waterborne
  • 3, 4 **Zoonotic —> esp. **Swine (first described in Japan, USA) (ingestion of pig’s liver) (more common in HK) (other animals: Snakes, ***Rats)
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12
Q

Hepatitis E clinical course

A

Almost identical to Hep A

  • Incubation 2-7 weeks (slightly longer than Hep A: 2-4 weeks)
  • ***~20% prominent cholestasis
  • Major difference: ***NO permanent protection against re-infection (∵ many genotypes + Ab probably not long-lasting)

Mortality:
- normal patients 1-2% (vs 0.2% for HAV)
- **pregnant woman up to 20%
—> ∵ HEV damages Kupffer cells —> **
endotoxin damage to liver (pregnant woman more sensitive to endotoxin effects)

Post-transplant HEV:

  • getting infected with HEV after liver transplantation
  • some can become ***chronic with ↑ ALT + +ve HEV RNA
  • 5 cases of post-transplant chronic HEV identified as Rat HEV
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13
Q

Hepatitis E diagnosis

A
  1. **IgM anti-HEV
    - coincide with symptoms
    - persists for **
    ~3 months
  2. IgG anti-HEV
    - follows ↑ of IgM
    - can persists for ***several years
  3. PCR assay for **HEV RNA (esp. for **chronic infection)
    - may be important for chronic infection to check whether patient still carrying the virus e.g. transplant patients who are immunocompromised (cannot clear the virus)
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14
Q

***Hepatitis E serology

A

~ Hep A

Pre-icteric phase:

  • Virus excretion (mostly before symptoms appear)
  • Histopathology (damage to hepatocytes)
  • Symptoms

Icteric phase:

  • Jaundice
  • ***IgM starts to ↑ then after 3 months ↓

Convalescent phase:

  • ***IgM ↑ (anti-HEV) first (already at high level)
  • IgG ↑ later
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15
Q

Hepatitis E prevention

A
  1. Better sanitation
  2. Immunoglobulin for passive immunisation
    - efficacy unknown?
  3. Vaccine
    - Recombinant vaccine containing genotype 1 + 4 (from China)
    - 3 doses at 0, 1, 6 months
    - protective efficacy 100% after 3 doses
    - not licensed in other places
    - shows protective effects after 4.5 years —> protective efficacy 86.8%
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