Hepatitis Flashcards
HBsAg neg
Anti HBc neg
Anti HBs neg
Susceptible
HBsAg neg
Anti HBc pos
Anti HBs pos
Immune due to natural infection
HBsAg neg
Anti HBc neg
Anti HBs pos
Immune as vaccinated
HBsAg pos
Anti HBc pos
Anti HBc IgM pos
Anti HBs neg
Acutely infected
HBsAg pos
Anti HBc pos
Anti HBc IgM neg
Anti HBs neg
Chronic infection
HBsAg neg
Anti HBc pos
Anti HBs neg
1) recovering acute infection or
2) distantly immune and low level of anti HBs not detected
3) false positive anti HBc
4) chronic infection with rare circumstance of not detectable HBsAg
Infectious period for people with hep a
2 weeks before (prodrome) and 1 week of the jaundice phase
Hep A incubation period
15-45 days
Average 28 days
Percentage of adults that asymp with hep A or v mild non specific Sx with little or no jaundice
50%
Symptom phases of hep A
Pro dome phrase - flu like illness (malaise, fatigue, myalgia) often with RUQ pain. Lasts 3-10 days
Icteric phase - jaundice with anorexia, nausea and fatigue. Usually 1-3 weeks. Fever rare in this phase
Signs in the icteric phase of hep A
Jaundice with pale stools, dark urine, liver enlargement and signs of dehydration
Complications of hep A
Pregnancy - miscarriage and preterm but nil teratogenic
Mortality v low (<0.1%) except if ALFailure (40%)
Chronic infection >6/12 but small nos
0.4% acute liver failure
15% need hosp care (25% severe hepatitis) PT >3 secs and Bili >170nanomols/l
General Mx Hepa A
PHE inform avoid food handling until non infectious
Employment hx
PN for Hep A
At risk MSM within infectious period (oroanal, anal or digital rectal)
House hold contacts, those at risk from food or water contamination will be contacted by PHE
Rx for Hep A contacts
When to give vaccine up until?
Who to give HNIG to ans when up until?
Can give Hep A vaccine up to 14 days after exposure providing the exposure was within the infectious period of the source case
Human normal immunoglobulins (HNIG) 250-500mg IM to high risk contacts (hep b or c also, hiv, chronic liver disease or >50yo) only from PHE. Best when first few days post first contact, unlikely to work after 2 weeks, can use up to 28 days to reduce severity of disease
Hep A vaccine schedule
0 and then 6-12 months
95% protection for at least 10 years
If vaccinating Hep A an HIV positive patient with CD4< 300 at time?
Give further vaccine when CD4 over 500 if IgG still remains neg on testing
Active Hep A follow up plan
See every 1-2 weeks until ALT normal (usually 4-12 weeks)
Who to offer Hep A vaccine to routinely?
MSM visiting GUM - one off due to vaccine shortages
PWID
Chronic hep B and C
GP vaccinate those going to developing countries
Can check Hep A antibodies prior but can give dose whilst await results
Countries where Hep B common
South east Asia Africa South and Central America Southern Europe Western Europe
Routes of transmission for Hep B
Sexual contacts - MSM (multiple partners, anal sex, oro- anal sex. Heterosexuals also.
Sex workers
Vertical
Parenteral (blood products, needle sharing. Tattoo
Incubation period of Hep B
40-160 days
Symptoms of Hep B
Kids asymp
Adults 10-50% asymp
Chronic carriers - asymp but might have fatigue or loss of appetite
Prodromal and icteric phases similar to Hep A but more prolonged and severe
Signs of Hep B
Acute phase - as for Hep A
After many years of chronic - spider naevi, clubbing, jaundice, hepatospenomegaly
Ascites, liver flap, encephalopathy
Complications of Hep B
Acute -
Pregnancy- preterm del and miscarriage
ALF less than 1% but worse risk than Hep a
Chronic infection -
>6/12
5-10% of sumtpomayics but higher if HIV
Almost all infants born to infectious mother (e antigen pos) will be chronic carriers unless immunise at birth
5 phases of chronic Hep B infection
1) immune tolerant - HBeAg pos chronic HBV- HBeAg pos, HBV DNA high, normal ALT, no liver necro on biopsy
2) immune active - HSeAg pos, high but falling HBV DNA, raised ALT, significant necro inflam and fibrosis
3) inactive Hep B carrier - HBeAg neg, HBV DNA low and normal ALT
4) HBeAg neg chronic active hepatitis - HBeAg neg, fluctuate HBV DNA, inform and progressive fibrosis, ?genetic mutations
5) occult HBV infection - HBsAg neg, positive Anti HBc +/- Anti HBs, normal ALT no DNA
Chronic infection in Hep B - outcomes
Phases 2 and 4 may give progression to cirrhosis
Concurrent Hep C infection - more aggressivejnfevtion with higher risk of cirrhosis and liver Ca
Concurrent HIV infection - increased risk of death and cirrhosis
Acute Hep A infection with Hep B can be severe
Can go concurrent Hep D which can be severe
10-50% chronic carriers develop cirrhosis leading to pre death in 50%
General Mx of Hep B
Public health
No sex until not infectious (loss of HBsAg or partner successfully vaccinated)
Don’t donate blood/ semen/ organs
If chronic infection - liver USS and fibroscan or liver biopsy if needed
Management of Hep B
Acute icteric - supportive Mx
If severe acute infection - antivirals can prevent ALF
Refer all HBsAg pos to hepatology
Usually Rx adults with HBV DNA >2000i.u/ml with evidence of necro inflam and or fibrosis
Hep B drug options
(Nucleostide analogues) Tenofovir disoproxil fumarate (TDF) Tenofovir alafenamine (TAF) Entecavir (these three antivirals would risk ARV resistance if used as mono therapy) Pegylated interferon
Decision to Rx Hep B with drugs depends on…
Pattern of disease
HBV dna level
Prescense or abscence of necro inflam and fibrosis
What can you use to suppress HBV replication during HIV therapy?
Lamivudine
Emtricitabine
TDF (tenofovir disproxil fumatate)
TAF (tenofovir alafenamide)
Prevent liver damage if used as part of triple therapy
Lamivudine and Emtricitabine high resistance on own to HIV
Entecavir - do not use for HIV unless HIV suppressed
HBV follow up
6-12 monthly for those with significant fibrosis or cirrhosis to check for HCC with USS and alpha feta protein
Which patients are at high risk of HCC development regardless of cirrhosis status in HBV?
Africans over 20 Asian men over 40 Asian women over 50 Over 50 FHx HCC Give screening despite no cirrhosis
Hep B and vertical transmission perfectanges depending on e antigen positivity
E antigen pos - 90%
E antigen neg but surface antigen pos - 10%
What can be given to pregnant woman if highly infectious in acute HEp B?
Hep B specific immunoglobulin 200i.u IM
Reduces vertical transmission by 90%
When would you give tenofovir mono therapy to a pregnant woman with Hep B?
In third trimester if HBV DNA > 10 to power of 7 iu/ml
Reduces vertical transmission
Partner notification for Hep B
Sex or needle share partner during infectious time ( 2 weeks pre jaundice and until surface antigen neg)
Chronic infection - as far back as jaundice or when thought to acquired
Screen kids if needed
Public health
What can be given to a non immune contact of Hep B after a single UPSI or parenteral exposure and when does it work?
Hep B immunoglobulin 500i.u IM Works within 12 and ideally 48hours Won’t work after 7/7 From public health Give rapid vaccination also to all sexual and household contacts
Ultra rapid Hep B vaccination
0, 7 and 21 days
Booster at 12 months
Rapid Hep B vaccine course
0, 1, 2 months and booster at 12/12
Vaccination post exposure to Hep B
All sexual and household contacts
Rapid schedule
Theoretically protection when started within 6 weeks from first exposure
Single booster for those prev vaccinated with proven immunity
Post ultra rapid vaccine schedule - when to test and boost?
Test anti Hbs at 4-12 weeks post last dose
If >10i.u but ideally >100 - ok
If low risk then booster 12/12
If inadequate antibody response or high risk - repeat course
How long does Hep B vaccination last?
20 years at least
Hep B follow up schedule
Acute hep B - serology after 6/12 even if LFTs normal
Chronic - if untreated then yearly review
Immunity after recover i.e surface antigen neg - life long in over 90%
Who to test for Hep B?
MSM Sex workers PWID Hiv pos Sex assault Endemic countries Needle stick Heterosexuals with > 10 partners per year and pos or high risk partners
If positive Hep b from screening how to manage?
If not immune - vaccinate
Chronic carrier - ref to Hep
If anti HBc neg - vaccinate
If anti HBc pos - test HBsAg - if pos acute or chronic Hep B so check IgM anti HBc/ HBeAg/ HBeAb/HBV DNA
If anti HBc pos and HBsAg neg - naturally immune to Hep B. Check anti- HBs and if neg give booster
Standard Hep B vaccine schedule
0,1and 6/12
Hep B Vaccination regime for HIV pos patients
Reduced response
Loss of antibodies quicker post vaccine
Give high dose vaccine 50nanograms Engerix or HBVaxPro or use Fendrix 20mcg at 0,1,2 and 6/12
Only use single dose ultra rapid if CD4 > 500
Measure levels at 4-8 weeks post last dose ans give booster if >10 but less than 100
Boosters when <100
What to do if HB vaccine course not completed?
Can give outstanding doses at 4 or more years later without needing to restart
Hep D overview
RNA Only those HBV HBsAg positive Risk - infection from abroad, PWID, sex workers If Hep b acute phase severe or chronic carrier has further acute attack or rapidly progressive liver disease - suspect hep D High rate of cirrhosis and fulminant Check anti HDV antibody and HDV RNA Poor response to antiviral Ref to Hep
Hep E brief overview
Pigs Slaughterhouse and vets High mortality in pregnancy Faecal oral route Contaminated water Incubation 2-9 weeks Self limiting No chronic illness Serology, good hand sanitation, avoid high risk water
Hep C transmission
Parenteral - shared needles Transfusions Renal dialysis Needle stick Sharing razors Snorting kit Sexual Vertical
Risk of sexual transmission of Hep C
V low risk in heterosexuals
Increased risk if HIV pos also
MSM rising incidence of Hep C largely with HIV coinfection
Association with other STIs - sts/ LGV, traumatic anal sex, fisting, sharing sex toys, group sex
Sex workers
Former prisoners
Hep C transmission risk correlates with…
HCV RNA
Vertical transmission 5% but higher with HIV
HCV incubation
4-20 weeks
HCV serology positive for 3 months post exposure but can take 9 months
HCV antibodies often delayed in HIV pos
Percentage of Hep C that become chronic carriers
50-85%
Usually asymp
Chronic Hep C risk of liver disease
Increased risk liver ca
35% significant liver disease but normal ALT
30% severe liver disease 14-30 years post infection
Hep C seeology in acute infection
HCV RNA - pos after 2 weeks
HCV RNA pos but anti HCV antibody neg or they seroconvert to antibody pos
HCV core antigen marker of replication activity
Hep C serology if chronic infection.
HCV RNA pos after 6/12
Do EIA screening antibody/ antigen test
Do viral RNA and identify HCV genotype
General Mx hep C
Curable Public health Don’t donate blood/ semen/ organs Written info Ref to hepatology Sti screen Fibroscan
Definition of HCV cure?
Negative HCV RNA in blood at 12 weeks post Rx competed
Treating HCV during acute phase
Most asymp
Reduces progression
Spont resolution if RNA cleared in 6/12
4 weekly RNA - if less than 2 log 10 decline at week 4 give Rx
Or if greater than 2 log ten - check RNA 12 weeks. If remains pos at week 12 - Rx
If neg then monitor for 48 weeks
Treating Hep C with what drugs?
Direct acting antiviral agents Target HCV non structural proteins to prevent viral replication Target NS3/4A protease inhibitors Simiprevir Ritonavir boosted ombitasvir Grazoprevir Glecaprevir Can give DAAs to HIV pos Depends on viral load of HCV, liver disease stage Vaccinate against hep B and C
Hep c and breastfeeding and preggers
Breastfeed ok
Can’t rx in pregnancy - small vertical risk
PN for Hep C
Any needle share partners
Screen contacts for HCV
Avoid sex in acute infection
Chronic infection - condoms with partner but low risk transmission through sex (except HIV coinfect)
MSM and HIV - gloves fisting, no group set, single use sex toys
Hep C follow up
Chronic untreated - 6-12 monthly assessment
Cirrhosis fibrosis - 6/12 alpha and uss for HCC screen
Prev HCV doesn’t prevent future infection
Who screen for HCV?
PWID Hiv pos annual screen Blood pre 1990 Needle stick Annual test MSM at high risk Group sex Annual HCV RNA for those cleared HCV Other STI Traumatic sex hx - fisting etc
Hep B and HIV - peginterferon risks
Low response rate
Depression and myelotoxicity
Risk of CD4 decline
Hiv positive and Rx Hep B
Truvada good
If egfr <60 use TAF plus Emtricitabine
Protease inhibitors for treating Hep C (DAAs)
Ritonavir boosted:
Ombitasvir
Dasabuvir
Paritaprevir
NS5A inhibitors for treating Hep C
Daclatasvir
Elbasvir
Ledipasvir
Ombitasvir
NS5B polymerase inhibitor for treating Hep C:
Non nucleoside dasabuvir
Nucleotide sofosbuvir
Post exposure to Hep B when is the latest can give ultra rapid vaccine
6 weeks
