GI & Hepatology JC054: Jaundice After Raw Oysters: Acute Hepatitis Flashcards
Acute + Chronic Viral Hepatitis A-E
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):
- 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) - Jaundice / Icteric phase:
- ***jaundice - Convalescent phase:
- whole cycle 2-4 weeks
***Biochemistry of Hepatitis
- ↑ AST (SGOT)
- ↑ 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)
- ***Prothrombin time (check daily / BD)
- Bilirubin (mainly Conjugated / Direct):
- may be ↑ for a long time after clinical / essential histological recovery (cholestatic phase)
Management of Symptomatic hepatitis
- None needed
- no known drugs / herbs will hasten recovery of course of hepatitis —> TCM may cause liver damage / failure - Rest (if extremely tired)
- but do not alter course of hepatitis - 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
***Comparisons of Viral hepatitis A-E
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
Hepatitis A transmission + epidemiology
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%
Hepatitis A clinical course
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%
***Hepatitis A serology
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)
***Hepatitis A diagnosis
**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
Hepatitis A prevention
- 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 - Chlorination of drinking water
- 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 - 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
Hepatitis E
- 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
Hepatitis E transmission
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)
Hepatitis E clinical course
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
Hepatitis E diagnosis
-
**IgM anti-HEV
- coincide with symptoms
- persists for **~3 months - IgG anti-HEV
- follows ↑ of IgM
- can persists for ***several years - 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)
***Hepatitis E serology
~ 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
Hepatitis E prevention
- Better sanitation
- Immunoglobulin for passive immunisation
- efficacy unknown? - 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%