Acute Hepatitis + chronic hep B Flashcards
1
Q
What is hepatitis A
A
self-limiting viral illness spread through the faecal-oral route that primarily causes inflammation of the liver.
2
Q
How does hepatitis A present
A
Flu like symptoms
Right upper abdominal pain
Nausea, diarrhoea, vomitting
Jaundice can develop
3
Q
Incubation period hep A
A
Incubation - 28 days/4 weeks
4
Q
First line test for heatitis A
A
PCR test for hep A RNA
5
Q
Second line test for hep adn when repeat
A
IgM HAV + IgG HAV blood tests
Repeat in 1-2 weeks if within 10 days of symptom onset
6
Q
What does + IgM HAV antibodies mean
A
Acute hep A infection
7
Q
Negative IgM and + IgG HAV antibodies suggests
A
Past hep A infeciton or immunity (vaccination)
8
Q
Investigations for hep A
A
PCR/IgG/M HAV antibodies
LFTs
9
Q
LFTs in hep A
A
Significant raise ALT and AST (>1000)
Bilirubin and PT may be elevated
ALP may be elevated, less thna 2 x upper limit
Check INR <1.5 /albumin
10
Q
Diagnosis of hep A probabale
A
Acute illness + onset of suggestive features + jaundice OR raised ALT and confirmed contact with hep A case OR HAV IgM antibodies
11
Q
Confirmed case of hep A
A
Acute illness + suggestve features + raised ALT OR jaundice +
Hep A RNA etected
Asymptomatc but anti-HAVIgM and contact with confirmed case
12
Q
General management hep A
A
Manage at home unless severely unwell
Rest and hydrate
Pain relief as required
Anti emetics - metoclopramide/cyclizine
Itch - loose clothing, avoid hot baths + showers, use chlorphenamine
Avid alcohol
AVOID FOOD PREP AND SEX 7 days after onset
Off school or work 7 dyas after onset
13
Q
Monitoring f hep A
A
LFTs every 1-2 weeks and general follow up, repeat until ALT and AST in normal ranges
14
Q
Why is it important to identify hep A
A
Notifiable disease
15
Q
Rare complications of hep A
A
Relapsing course of illness over several months
Fulminant liver failure, acalculous choleccystitis, pancreatitis, aplastic anaemia, post viral encephalitis, reactive artheritis, AI haemolysus, TP, G6PD def, GBS, transverese myelitis, renal failure, cryoglubinaemia, mononeurtis multiples
16
Q
Routes of transmission of hep B
A
Vertical - transplacental, childbirth
Sexual
Percutaneous transmission - IVDU, tattoos, piercing etc
Blood transfusion or organ donation - v rare
17
Q
Hep B pathophysiology
A
cyctotoxic T cells target hepatocytes -> liver damage by inflammation, fibrosis
Cytotoxic direct damage in fibrosing cholestatic hepatitis
18
Q
4 phases of HBV
A
Immune tolerance
Immune clearance - symptoms and damage occur
Immune control - biochem tests normalise
Immune escape - HBV escapes and replicates again
19
Q
Problems with hep B presentation
A
Non specific - similar to many other causes of liver damage
Risk factors help differentiate
Massive clinical variation between individuals
20
Q
Acute hep B infection presentation
A
Majority asymptomatic - >90% asymptomatic in children, 70% in adults
Prodrome - N+V, anorexia, fever, abdo pain (Flu like = serum sickness like syndrome - malaise,chills, lethargy, arthralgia )
Acute hep - Jaundice,
Hepatomegaly, RUQ pain, dark uirne pale stools
Fulminatn acute liver failures
21
Q
Fulminnat acute liver failure presentation
A
Jaundice
Altered mental state (e.g. confusion, lethargy, drowsiness, stupor comatose)
Asterixis
Symptoms of raised intracranial pressure from cerebral oedema (e.g. headache, sluggish pupillary response, systemic hypertension and bradycardia, seizures)
22
Q
Chronic heo B presentation
A
Asymptomatic until complications often
Non specific symptoms eg fatigue, anorexia, wight loss, weakness, malaise
Symptoms of chronic liver disease
Cirrhosis and portal HPTN
Extra hepatic manifestations - serum sickness like syndrome
Polyarteritis nososa, membranous nephropathy
23
Q
Symptoms of chronic liver disease
A
Palmar erythema
Spider angiomas (the number and size of spider angiomata correlate with increasing severity of liver disease)
Asterixis
Easy bruising (reduced production of clotting factors in liver)
24
Q
Symptoms of cirrhosis and portal HPTN
A
Ascites
Hepatmogealy
Splenomegaly
Peripheral oedema
Caput medusae
25
Investigations for hep B
LFTs
Hepatitis serlogy - HBsAg (surface antigen), anti-HBs (surface antibody), anti-HBc (core antibou)
Serum HBV DNA
FBC, U+Es, creatinine, coag screen, albumin
Liver US
26
ALT+AST in hep B acute infection
>25 x upper limit of ALT+AST
27
ALT+AST in chronic HBV
Mildly raised - 2 x upper limit of normal
28
Active flares/exacerbations of chronic HBV AST/ALT
>10 x upper limit normal
29
AST/ALT in chronic HBV carriers
Usually normal
30
ALP+GGT in hep B
AST/ALT will be raised much further in hep B infection
31
What happens to AST:ALT ratio in cirrhosis from viral hepatitis
AST>ALT - ratio doesnt normally exceed 2
32
When will HBsAg be positive? acute vs chronic?
ONLY in current infection - acute or chronic
Acute - appears 1-10 weeks after exposure
Chronic - persistent raised over 6 months
33
When are anti-HBs positive
For life after infection, aslo after vaccination, confirms immunity
34
When are anti-HBc antibodies present
Only present in prev or current infective state, not post vaccination
IgM - acute infectin, IgG - chronic infection
35
What antibodies would you see in previously infected patient hep B
HBsAg - Negative
Anti-HBc - Positive
Anti-HBs - Positive
36
Acute HBV antibodies on serology
HBsAg - positive
AntiHBc - IgM postiive
Negative antiHBs
37
Chronic HBV antibodies on serology
Postiive HBsAg
IgG positive Antib-HBc
Negative AntiHBs
38
Prev vaccination antibodies
ONLY anti-HBs
39
What clinical use does serum HBV DNA testing have
Identify if patient -> antiviral therapy
40
Who is a candidiate for antiviral therapy hep B
Active liver disease, high HBV DNA titre
41
What can cause abnormal FBC in HBV?
Complications
Reduced Hb and microcytic aneamia- GIT bleed from portal HPTN
Normocytic anaemia - chronic disease
Reduced platelets - portla HPTN
42
What can cause U+e DISTURBANCE IN HBV
Hyponatremia - ascites dilutational
Hepatorenal syndrome from cirrhosis increases urea and creatinine
43
Synthetic liver function effect complications HBV
Reduced albumin
Elevated PT and INR
44
When use US in HBV
Chronic hepatitis B - evaluate fibrosis, cirrhosis and monitor for HCC
45
Monitoring in HBV
LFTs every 3-6 months when in crhonic state, more frequent if exacerbations
US every 6 monhts if chronic infection+/- cirrhosis or if high risk
46
Transmission of hep A
Faeco-oral route - contaminated food or water
Travel to places where virus ighly endemic
47
Risk factors for hep A transmission
Travel to endemi areas
Clotting factor disorders - factor VIII and IX concentrates can be sourecs
mEN WHO HAVE SEX WITH MEN/RISKY SECUAL BEHAVIOURS
IVDUs
Ocupational risk
48
High risk for hepatitis B
Exposue to virus
Sexually assaulted
Needle stick
HIV psotive
Babies of mothers with HBV
Risky sexual behaviour
Close family contacts with hep B
49
How is hep B prophylaxis given
Rapid immunisation schedule - 0,1 and 2 months or over 21 days
Can give immunoglobulins IM within 48 hrs of exposure alongside first vaccine
otherwise 0,1 and 6 months
50
Acute HBV management
Supportive - low risk of progression
Screen for other BBVs - HIV, hep C
Screen for hep D co-infection
51
What criteria need to be met before give active treatment for HBV acute infection
Sever coagulopathy (INR>1.5)
Persistent symptoms >4 weeks
Marked jaundice - bilirubin >3mg/dL
Presence of ascites or encephalopathy (acute liver failure)
52
What use in acute HBV infection
Entecavir
Tenofovir
Until HbSaG CONFIRMED ON SEROLOGY
Liver transplant for fulminnat hepatic failure - continue with drugs indeficitely
53
Chronic HBV indications for anti-viral therapy clincal criteria
Acute liver failure
Decompensated cirrhosis
Compensated cirrhosis + HBV DNA >2000IU/ml
Concurrent immunosupressive therapy
HCC
54
First line treatments anti viral therapy chronic HBV infection
Nucleotide analogues - Entecavir, tenofocir, Pegylated IFN-a
55
Nucleoside analogues vs nucloetide analogues
Nuceloside - entecavir, lamivudine
Nucleotide - tenofovir, adefovi
56
Goal of antiviral treatemtent
Reduce hepatic dysfunction and serocoversion HBsAg +-> negative , keep HBV DNA non detecetable in serum
Improved long term outcomes eg crrhosis/HCC developments
Reduce transmission HBV
57
Monitoring of treatment in chronic HBV
3 monthly HBV DNA until undetectable
LFTs 3 monthly
HBsAg yearly
58
High risk patietns foor HCC development
Cirrhosis
ASian men >40
asian Women 50 years old
FH HCC
Super infection hep D
59
Lifestyle with HBV
Avoid alcohol and hepatotoxc drugs eg paracetemo, amoxicllin-clavunate
Vaccinations- hep A + flu annually
60
3 main omplications of HBV
Fulminant liver failure
Liver irrhosis
HCC
61
What serum test direcely relates to risk of HCC from HBV infection
HBV DNA in serum
62
What is hep C
Slow progressive disease of liver caused by infection with hep C virus
63
What are most genotypes of hep C in england
1 + 3
64
How is hep C transmitted
Contact with infected blood or blood derived products
65
Those at risk of HCV
IVDUs most common (1/4)
Transufion of infected blood products before 1991
Re-use of medical equipment
Needelsticks and sharps injuries
Sharing razors, tattoo, piercings etc
Sexual trasnmission can occur in more risky behviours
Vertical trasmission mother lower risk than hepB, more if have HIV
66
What increases risk of fulminant liver failure in hep C
Co-infection with hep A
67
What increases risk of cirrhosis and HCC with HCV
Alcohol intake
Coinfection with hep B or HIV
IMmunosupression
68
What is the significance of HCV in pregnancy
Adverse foetal outcomes - FGR, low BW. Most chilren - chronic infection and liver damage
69
Most common comorbidities with HCV
Most to least common
Depression
DM
CKD
Sjrogens
Chronic renal disease
Symptomatic cryoglibulinaemia
Lichen planus
RA
70
What HCV genotupes are more responsive to anitbirals
2+3 -
1,4,5,6 less
71
Who do yuo offer HCV screening to
High risks:
IVDUs
Blood transfusion before 1991
Origin in country of med or high prevalence
Babies - HCV mothers
Prisoners
Cared for children
Hostels, homeless HIV+ men who have sex with men
Close contacts of known chronic infection with HCV
Also increased risk + clinical features, abnormal LFTs (ALT>10x upper limit)
71
What risks worsen prognosis of HCV
Infection at older age .40 decrease resonse to treatment as age
Genotype
Men more likely -> cirrhosis
Black african american and hispanic people lower susteained viral reponse rates to antivirals
Co infection hep A or B or HIV
BMI >25
Smoking
Alochol intake
Immunosupression
72
Clincial features of HCV
Non specific fatigue, myalgia, anxiety, depression, poor memory and conentration
N+V
RUQ abdo pain
Jaundice - cholestasis
Chronic liver disease if advanced
Majority asymptomatic in early stages of infection
72
Routine screening for HCV
People who intend to donate blood or organs/tissue.
People with end-stage chronic kidney disease requiring renal replacement therapy.
Healthcare workers who perform invasive or exposure-prone procedures (for example surgeons).
Mothers at higher risk of HV
73
Diagnosis of HCV
HCV RNA PCR/genotyping
for acute infection
antiHCV antibodies (if ever had, cat differentiate current)
74
Assessment before initiating treatment for Hep C
Confirm diagnosis - HCV RNA
Genotype
Liver disease stage - biopsy, elastography, erum markers
Co-infections - HIV, hepB, hepA
LFTs - ALT, AST, bilirubin, albumin
FBC, U+Es, clotting screen, HbA1c, TFTs, ferritin level
Assess for CIs to DAAs + drug interactions
75
What is sponteanous resolution of HCV defined as
Loss of serum HCV RNA in blood < 6 months
76
What is a DAA
Direct acting antivirals
77
What does regimen and treatment duratio =n of HCV depend on
HCV genotype
Whetehr cirrhotic
Treatment history
Renal unction
78
First line for HCV
8-12 weeks of once daily DAA eg daclatasvir + sofosbuvir or sofosbuvir+simeprevir with o without ribavirin
79
Monitoring of DAAs in HCV
HCV RNA LEVELS - assess response to therapy
adverse effects - rare
LFTs - ALT, AST, bilirubin
80
Post treatment monitoring of HCV
Sustained virological response - undetectable HCV RNA 12 weeks post treatment
SVR12 = cure
Liver disease - HCC and cirrhotic complications if already cirrhotic/fibrotic
81
How often monitor ALT in immune tolerant and clearnace phases of hep B Ag +
every 24 weeks
every 12 weeks at least 3 consecutive occassions if increase in ALT levels
82
How often monitor inactive chronic he B
every 48 weeks - ALT and HBV DNA levels
83
When can contract hep D
Only super infection if already have hep B
84
Which hepatitis especially accelerates alcohol related liver disease
hep C
85
When is hepatitis acute
<6 month duration of inflammation
86
Complications of acute hepatitis
Acute liver failure
Progression to chonic hepatitis
87
Causes of acute hepatitis
Drugs eg paracetamol
Infections esp viral hep
Autoimmune
Pregnancy related
Toxins
Ischaemia
Malignancy
Budd-chiari syndrome
Wilsons disease
88
What can cause acute hepatitis in immunocomp - rare/travel ass
immunocomp - VZV, HSV, adenovirus, invasive fungal eg candidiasis
Rare/travel - hep D, yellow fever, leptospira, typhoid, TB, Q fever (coxiella), malaria, liver flukes, schistosomiasis
89
Prodrome hep A how long and what causes
3-10 dyas - flu like, GI, low grade fever
90
Icteric period hep A (acute hepatitis)
Acute hep caused by own immune response After 10 dyas infection
Jaunduce, fatigue, anorexia, vomitting, RUQ pain, HEPATO/SPLENOMEGALY
Improve - 1-3 weeks, up to 12.
91
Convalescent phase - hep A
recovey 6 up to 6 months - muscle weakness, malasie, anorexia, heptaic tenderness
92
Different presentations of hep A
ASymtpomatic - younger children
Acute liver failure - rare - old/pre-exist liver disease
Death
93
How long is hep A infectious for
Approx 1 week after onset of jaundice - need to be in side room w own toilet in hospital
Dont handle food if at home
94
What give hep A close contacts
Hep A vaccine
Human normal immunoglobulin if immunosupressed
95
Prevention of hep A
Improved sanitation and hygeine
Education eg travellers
Hep A vaccination - purified, ina tivated
96
Hep A vaccination who give to
Travellers to endemic areas
Men who have sex w men
IVDU
Chronic liver disease
Haem
Haemophilia
Occupational risk eg lab workers, sewage workers
Following exposure to infected
>2 weeks before required, booster needed after 6-12 months
97
What are the two types of hep E infection
Classical - 1/2
Sporaduc - 3/4
98
Endemic countrie classical vs sporadic
Classic = resource limited countries
Sporadic - Resource ricj
99
Hep E routes of transmission calssical
faeco-oral, like hpe A, mainly enedemic country travel
100
Hep E routes of transmission sporadic
Zoonosis - undercooked meat esp pork
Faexo oral - contaminated water, shellfish
Blood transfusion
101
At risk groups for classical hep E
Travellers
Usually young adults 15-40 - asymptomatic in children
Pregnant women
102
At risk frous hep E sporadic
Increasing age
M>F
No increased mortality in pregnancy
103
Incubation period in hep E
40 dyas - 2-9 weeks
104
How does symptomatic hep E present
Prodrome - N+V, anorexia, fever, abdo pain
After 1 week -> acute hep - jaundice, dark urine pale stools, RUQ pain, hepatomegaly
105
What are possible outcomes of hep E
Acute liver failure
Extraheaptic manifestations eg neuro
Full clinical recovery <2/3 months
Chronic hep E
106
Who gets chronic hep E
Immunocompromised patients with genotype 3/4 - sporadic hep E
107
Death in hep E - who
Classical - 1/2 genotype
25% fatality in pregnancy
108
LFTs in hep E
Raised serum aminotransferases - ALT + AST >1000
Raised bilirubin + ALP
109
How differentiate hep A + E
Hep E serology
110
IgM vs IgG hep E serology - how test for chronic infection
IgM = acute
IgG = past infection
PCR + = current (confirm or test for chronic infection)
111
Management for hep E
Supportive care
Infection control
Prevention of secondary cases
112
What do for infection controlk hep E
Infectious for 3 weeks after jaundice onset
Side room, no handling food etc
113
Mortality in hep B
Higher than in hep A/E
114
Prognosis of hep B
Majority of adults clear hep B spontaneously without complication
115
Chronic hep B who does it progress into this in
>90% those infected perinatally
20-50% children
5% adults
116
Prognosis of chronic hep B
Majority still clear on own
May progress to chronic iver sdisease
117
Hep B incubation period
Incubation 60-90 days
118
What markers are present when patients are symptomatic with acute hep B
HBsAg
IgM Anti-HBc
HBeAg
ALT increase, jaundice
119
What markers are present after acute infection
Anti-HBe
IgG anti-HBc
Anti-HBs
120
Why need to contact sexual partners in hep B quickly
Can give hep B vaccine +/- HBIG to prevent infection within certain window
121
What test for to check hep B clearnance
Loss og HBsAg
antiHBs antibodies present
122
Prevention of hep B transmission
Education re modes of transmission - safe sex, needle exchange
Increased testing - antenatal screening, blood products
HepB immunoglobulin
HepB vaccines
123
Hep B immunoglobulins when give them
Neonates w highly infectious mothers, unvaccinated who have definitive exposure eg needlesitck/sexual to HBV positive source, HBV vaccine non responders who recieve possible exposure
124
What is hepB vaccine
Recombinant hepatitis B surface antigen
Safe and highly effective
Pre and post exposure to preevnt infection
125
Who is vaccinated against hep B
All neonates
Anyone at increased risk exposure to HBV - close contacts, travellers, risky sexual behaviour, IVDU, regular blood products, renal failure haemodialysis, residential accom learning difficulties, inmates, occupational risk
High risk complications disease eg HIV, chronic liver disease
Post exposure vaccination - needlesticj, sex, neonates Hb +
126
Hep B vaccination how give
Usually at least 3 doses
Neonates -8,12,16 weeks of age
0,1,6 months - healthcaer
0,1,2,12 months - rapid course
127
EBV + CMV hepatitis
Ass w glandualr fever/mononucleosis syndrome (fever, sore throat, lymphadenopathy, fatigue etc)
Mild hepatitis 90%, rest have clinical jaundice
Risk increased hepatitis
128
Pathogenesis of Hep B chronic infection
Host immune response to virus -> liver inflammation and heptitis
Persistent -> liver fibrosis and damage
Doesnt happen to everyone w hep B
129
Investigating chronic hep B
Lab markers LFT - ALT
HBsAg, HBeAg, Anti-HBe, HBV DNA, Anti-HBs
Liver imaging, biopsy, non invasive methods eg transient elastography
130
What is the E antigen
HBV specific protein secreted from virus infected cells
Supresses immune system
E antibodies reduces viral replication - reduces severity and infectivity
Seroconversion from E antigen to antibody does not equate to disease history
131
When does seroconversion from E antigen to E antibody occur in chronic hep B
End of stage 2 - after immune system triggered
132
Stages of chronic hep B
Stage 1 - infection - viral load high, liver function normal
Stage 2 - Immune system triggered after months - years, high ALT, decreased E antigen
Stage 3 - months/years, normal ALT, low HBV DNA levels
Stage 4 - HBeAg negative, mod to sev fibrosis, moderate raised ALT, can clear virus from blood
Stgae 5 - functional cure - past infection
133
What can persist in cells after clearnace of hep B infection
cccDNA
Can reactivate if then become immunosupressed, therefore screen before start drugs
134
General management of hep B
Referr to specialist for full assess
Prevent scondary cases - transmission, testing etc
Prevent further liver damage - other BBVs, vaccinate for hep A, reduce alcohol
Treatment w antiHBV durgs if needed
135
Function of treatment for hep B
Supresses hep B, doesnt clear - therefore long term
136
End points of treatment for hep B
Ideally loss of HBsAg but RARE
Loss of HBeAG/anti-HBe seroconversion
Supression of HBV DNA
ALT normalisation
137
Nucelotide analogues how work in chronic hep B
Inhibit viral DNA polymerase
Oral tablets long term
138
When is pegylated IFN-a used in chronic hep B, how is it iven and what does it do
If no cirrhosis
Long term immunological control
Finite duration of treatment
Injected
139
INdications for chronic hep B treatment
Prevent disease progression and development of cirrhosis/HCC
-cirrhosis, HIV, FH HCC or corrhosis, hepatitis, high HBV DNA or ALT or HBeAg + >30yrs
Reduce transmission
Pregnancy w high HBV DNA levels
HBV + health care workers >200
140
Co-infection vs super infection hep D
Co-infection = contracted at same time as hep B
Super infection = after hep B infection
141
Clinical presentation of hep D
Acute infection - suspect if fulminant acute HBV, acute hepatitis in HBV patient
Chronic HBV + HDV - more rapid prgression to corrhosis and HCC
142
Screen for hep D
Anti-HDV antibodies
HDV RNA for current infection
143
Treatment hep D
Treat hep B and its cleared
144
Why are genotypes of hep C important
Some are treatment specific
Can be co-infected with multiple genotypes or re-infected
145
Hep B vs Hep C acute -> chronic infection
Hep C much less likely acute spmtomatic (20%)
Hep C much more likely to c=cause chronic (55-85%), hep B (5%)
146
Development of cirrhosis in hep B
slow development - 20-30% over 20-30 years
147
What is beneficial about hep C and immunosupression
Cure is possible - CANNOT reactivate once immunosupressed
148
Wy is anti-HCV not that helpful in HCV diagnosis
Cant differentiate past and current infection
False negatives in immunocompromised patinets eg HIV
Negative in acute HCV infections
149
When use HCV RNA PCR
Immunocomp patients
Acute hepatitis
150
End goal of DAA treatmet of hep C
Clearance of hep C RNA from blood
151
WHO elimination of viral hep 2030
INcrease hep B vaccination
Prevent vertical trasnmission
Blood and injection safety
Screening
Haem rediction
Diagnosis improved
152
When can hep E be cause of chronic hepatitis
Immunosupressed paitents
Genotypes 3/4
153
What test need to do diagnose hep E in immunocomp cases
HEV PCR
other tests may be falsely negative
154
WHO elimination target for hepB and hepC
2030
