Viral hepatitis Flashcards

Question

Healthy adults with vigorous immune response can clear virus rapidly, but suffer severe illness. 10% cannot clear, and become carriers What is definition of HBV carrier? Who is at risk of become chronic carrier HBV?

Answer 1

Detection of HBsAg in blood 6 months after exposure Immunodeficient - likely to be carrier, but wont suffer much disease If infected perinatally, have 95% carriage rate Males more likely to be carrier

Answer 2

Cirrhosis HCC - 20-30 years following initial infection

Answer 3

HBV DNA load become useful marker, as some virus strains have mutations in e antigen, which results in absence of HBeAg, although viable virion produced. Known as pre-core mutant virus This therefore means they can be HBeAg neg, and HBeAb positive but could be highly infectious.

Answer 4

Acute Hepatitis B ``` HBsAg - pos HB core antibody (total anti-HBc) - pos HB core IgM (anti-HBcIgM) - pos HBeAb - neg HBeAg - pos HB surface antibody (anti-HBs) - neg ``` HBsAg appears in serum during incubation period. If self-limiting, HBsAg will gradually reduce as HB core IgM is produced. HB core IgM then reduces and is replaced with HB core IgG If persisting infection, HBsAG remains high. HBeAg begins to icnrease. HB core antibodies are produced, IgM reduces, and is replaced by IgG. But this is ineffective at clearing the virus

Answer 5

Past Hepatitis B ``` HBsAg - neg HB core antibody (total anti-HBc) - pos HB core IgM (anti-HBcIgM) - neg HBeAb - pos HBeAg - neg HB surface antibody (anti-HBs) - pos ```

Answer 6

Hepatitis B carrier high infectivity ``` HBsAg - pos HB core antibody (total anti-HBc) - pos HB core IgM (anti-HBcIgM) - neg HBeAb - neg HBeAg - pos HB surface antibody (anti-HBs) - neg ``` Hepatitis B carrier low infectivity ``` HBsAg - pos HB core antibody (total anti-HBc) - pos HB core IgM (anti-HBcIgM) - neg HBeAb - pos HBeAg - neg HB surface antibody (anti-HBs) - neg ``` anti-HBs only turns positive upon vaccination, or after approx 36 weeks after infection

Answer 7

Hepatitis vaccine response ``` HBsAg - neg HB core antibody (total anti-HBc) - neg HB core IgM (anti-HBcIgM) - neg HBeAb - neg HBeAg - neg HB surface antibody (anti-HBs) - pos ```

Answer 8

Three injections over 6 months 0, 1, 6 months - routine 0, 1, 2 months - accelerated ``` Healthcare workers IVDU Transfusion dependent Dialysis patient Sex worker ``` Now all neonates recommended to be vaccinated

Answer 9

Give HepB vaccination - - if already immunised - give booster dose - if not previously immunised - accelerated course 3 injections 3 months - if vaccine non-responder - boost dose an HBIG Consider HBIG Check green book - depends on vaccine status of recipient, and risk form source

Answer 10

``` DNA DNA polymerase HBcAg HBsAg with glycoproteins Envelope ```

Answer 11

All 10 genotypes (A-J) all contain four long open reading frames (ORFs) C - core. Encodes HBcAg and HBeAg. Mutations in pre-core region result in lack of HBeAG S - surface. Encodes pre-S1/ pre-S2/ s region - encode HBsAG P - polymerase. Encodes DNA polymerase and ribonuclease H. Encompasses 75% of whole genome. Also responsible for reverse transcription. X gene - encodes polypeptide with several functions

Answer 12

1. False-positive anti-HBc, thus susceptible 2 Resolved infection (most common) - not devleoped anti-HBs yet 3. “Low level” chronic infection 4. passive transfer of maternal anti-HBc – in children up to 3 years of age

Answer 13

Phase 1 - high replicative, low inflammatory state. HBeAg positivity, high viral load, normal aminotransferases Phase 2 - HBeAg positive chronic hepatitis B phase, fluctuating aminotransferases, high HBV DNA, inflammation on liver biopsy Phase 3 - HBeAg negative phase, low levels HBV DNA, and normal aminotransferases. If persists, has lower rate of progression towards cirrhosis

Answer 14

Phase 4 - HBeAg negative, representing late immune reactive phase, with periodic fluctuating levels of aminotransferases and HBV DNA. Virus may have nucleotide substitutions in pre-core or basal core promoter region, explaining lack of HBeAg Phase 5 - HBSag negative phase, HBV DNA usually undetectable

Answer 15

Can locate origin - different genotypes more prevalent certain regions Tailor treatment to patient Certain genotypes have different modes of transmission e.g vertical/ horizontal, useful for epidemiology Genotype influences disease outcomes and development of HCC

Answer 16

Antiviral drug resistance mutations Antiviral drug-associated potential vaccine escape mutants Immune escape mutants - evade B cells Deletion mutants unable to express non-essential HBV proteins e.g HBeAg

Answer 17

genotype A found in North America, Europe, South-East Africa and India; genotypes B and C in Asia and Oceania; genotype D, the most widespread, in North America, North Africa, Europe, the Middle-East and Oceania; genotype E in West Africa; genotype F in South America; genotypes G and H in Central and South America UK - ADG

Answer 18

Vertical - A2 B C ``` Horizontal - A1 D E F G H I ```

Answer 19

A2 - early seroconversion C - late seroconversion

Answer 20

HAV Ab HCV DNA/ Ab HIV Ab STIs Chlamdyia Gonorrhoea Syphilis ``` FBC U+Es LFTs Coag AFP ``` USS liver/ fibroscan

Answer 21

- initial 48-week course of peginterferon alfa-2a as first-line treatment (cannot be continued past this date. So if treatment to continue e.g lifelong, switch to other agent - Offer entecavir or tenofovir disoproxil as second-line treatment to people with detectable HBV DNA after first-line treatment with peginterferon alfa-2a.

Answer 22

- initial 48-week course of peginterferon alfa-2a as first-line treatment. NICE guidelines. Other countries suggest straight to tenofovir/ entecavir - tenofovir disoproxil as second-line treatment to people who do not undergo HBeAg seroconversion or who relapse (revert to being HBeAg positive following seroconversion) after first-line treatment with peginterferon alfa-2a. - entecavir as an alternative second-line treatment to people who cannot tolerate tenofovir disoproxil or if it is contraindicated.

Answer 23

tenofovir disoproxil in the third trimester to reduce the risk of transmission of HBV to the baby Avoid peginterferon alfa-2a in pregnancy. Must use contraception if on treatment and not pregnant

Answer 24

immunomodulatory - acts by binding to human type 1 interferon receptors. Activation and dimerization of this receptor induces the body's innate antiviral response by activating the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway

Answer 25

tenofovir - NRTI - selectively inhibits viral reverse transcriptase by causing DNA chain termination entecavir - NRTI - guanosine analgoue, cause DNA chain termination

Answer 26

- Refer hepatology/ transplant - pegylated interferon contraindicated - entecavir first line (if no history lamivudine resistance) - tenofovir second line (if history lamivudine resistance)

Answer 27

Mild - 2.5 -7.5 kPa Severe - 7.5 - 12.4 kPa Cirrhosis - >12.5 kPa Treatment usually initiated if LSM >11.0 kPa. If above 11, this is highly suggestive of cirrhosis, and USS is not required. If between 6-11, cirrhosis cannot be determined. So biopsy may be required.

Answer 28

1. Any patient with cirrhosis - regardless of HBV DNA/ ALT levels 2. adults aged 30 years and older - - HBV DNA >2000 IU/ml - ALT >30 male, >19 female on 2 consecutive tests, conducted 3 months apart 3. adults younger than 30 years - - HBV DNA >2000 IU/ml - ALT >30 male, >19 female on 2 consecutive tests, conducted 3 months apart - must have necroinflammation or fibrosis on liver biopsy or a transient elastography score greater than 6 kPa. - if HBV DNA >20 000 treat irregardless

Answer 29

Review adherence to treatment Stop treatment if - - If HBV DNA level has decreased by less than 2 log10 IU/ml or - HBsAg is greater than 20,000 IU/ml or - If do not udnergo HBeAg seroconversion/ relapse Offer tenofovir second line therapy Offer entecavir alternative second line if tenofovir not tolerated/ contra-indicated

Answer 30

No cirrhosis - stop after 12 months after achieving undetectable HBV DNA and HBsAg seroconversion Cirrhosis - Do not stop treatment after achieving undetecable HBV DNA and HBsAg seroconversion

Answer 31

Mother - - tenofovir in third trimester to reduce risk transmission to baby - stop treatment 4-12 weeks after birth, unless meets criteria for long term treatment - no risk transmitting via breast milk. Can breast feed on anti-virals Baby - - HepB immunisation - HBIG

Answer 32

peginterferon alfa and ribavirin

Answer 33

48-week course of peginterferon alfa-2a if evidence significant fibrosis Stop treatment after HBsAg seroconversion.

Answer 34

HBV DNA >2000 IU/ml - - entecavir or tenofovir HBV DNA < 2000 IU/ml - lamivudine if treatment lasting <6 months - entecavir or tenofovir if treatment lasting >6 months Start prophylaxis before beginning immunosuppressive therapy and continue for a minimum of 6 months after HBeAg seroconversion and HBV DNA is undetectable

Answer 35

lamivudine start prophylaxis before beginning immunosuppressive therapy and continue for a minimum of 6 months after stopping immunosuppressive therapy.

Answer 36

monitor HBV DNA monthly and offer prophylaxis (lamivudine) to people whose HBV DNA becomes detectable

Answer 37

Do not offer prophylaxis

Answer 38

- immune-tolerant phase (defined by active viral replication and normal ALT levels [less than 30 IU/L in males and less than 19 IU/L in females]). Check every 24 weeks. Check every 12 weeks if rise in ALT - chronic hepatitis B infection (defined as HBeAg negative on 2 consecutive tests with normal ALT [less than 30 IU/L in males and less than 19 IU/L in females] and HBV DNA less than 2000 IU/ml). Check every 48 weeks

Answer 39

Weeks 4, 12, 24

Answer 40

Routine bloods - week 4 then every 3 months HBV serology - week 12 week 24 week 48

Answer 41

Significant fibrosis - every 6 months with USS/ AFP no fibrosis - - if HBV DNA >20 000 - consider USS - if HBV low, no follow up

Answer 42

In HBeAg-positive disease, HBeAg seroconversion is a predictor of durable response to antiviral treatment and can be used as a milestone after which treatment can be stopped no marker exists for HBeAg negative disease

Answer 43

Hep A-E CMV EBV HSV Brucellosis Leptospirosis

Answer 44

HAV vaccination Avoid sexual intercourse Avoid alcohol Avoid sharing razors HepB vaccination close contacts Contact trace

Answer 45

- HBeAg seroconversion, and HBV DNA undetectable - continue treatment for 12 months after this point. - 50% seroconvert by 5 years - If HBeAG negative - continuee lifelong treatment to prevent cirrhosis/ HCC

Answer 46

HDV single stranded RNA HDV Ag HBsAg acquired when buds from hepatocyte Once inside hepatocyte, uses host RNA polymerases to replicate

Answer 47

HDV antigen HDV IgM/IgG HBsAg

Answer 48

Treat as HBV guidelines HBV vaccination is reducing incidence of HDV

Answer 49

Blood Needles Tatto/ piercing/ accupuncutre Dialysis Uncommon vertical transmission

Answer 50

90% of infections in Europe are genotype 1, 2, 3 (1 + 3 most common) Americas - genotype 1/2 Northeast/central Africa - genotype 4 Asia - genotype 6

Answer 51

Predictive of antiviral therapy response Genotype 1 associated with poor response Being infected with one genotype does not protect against other. Therefore making vaccine more difficult

Answer 52

80% become chronically infected 20% spontaenosuly clear virus by 6 months (90% in HBV) 2-4 months. Mean 7 weeks

Answer 53

Most have subclinical infection 25% develop jaundice, as opposed to 90% seen in acute HBV infection

Answer 54

25% spontaneously clear (90% in HBV) 80% HCV infected will develop cirrhosis 10% will progress to HCC

Answer 55

HCV RNA - shows if current infection | HCV Ab - shows if ever had infection or current infection

Answer 56

Initial tests same as HBV 8 - 12 weeks treatment which costs approx £40 000 90% will be cured by end of treatment

Answer 57

Genotype Liver disease - Child-Pugh score If HCV viral load dose not reduce by 4 weeks, then spontaneous clearance unlikely. Consider starting treatment HCV can become resistant to anti-virals. On stopping treatment this reverses backto "wild-type". Restarting treatment does not trigger resistance again, because RNA virus cannot store resistance genes

Answer 58

1a sofosbuvir + ledipasvir (8-12 weeks) 1b sofosbuvir + ledipasvir (8-12 weeks) 2 sofosbuvir + ledipasvir 3 sofosbuvir + ledipasvir 4 grazoprevir plus elbasivir 5/6 sofosbuvir + ledipasvir

Answer 59

1a sofosbuvir + ledipasvir 1b sofosbuvir + ledipasvir 2 sofosbuvir + ledipasvir 3 sofosbuvir + ledipasvir 4 grazoprevir plus elbasivir 5/6 sofosbuvir + ledipasvir Difference from non-cirrhotic, is all must be 12 weeks treatment

Answer 60

1a sofosbuvir + ledipasvir + ribavirin 1b sofosbuvir + velpatasvir + ribavirin 2 sofosbuvir + velpatasvir + ribavirin 3 sofosbuvir + velpatasvir + ribavirin 4 grazoprevir + elbasvir + ribavirin All for 12 weeks Primary treatment is liver transplant, so should be managed by gastroenterologist

Answer 61

NS3/4A PI NS5A inhibitor Nucleotide/ nucleoside NS5B polymerase inhibitor Non-nucleoside NS5B polymerase inhibitor

Answer 62

Binds to viral protease inhibiting it Grazoprevir Simeprivir

Answer 63

Blocks NS5A virus protein required for replication Elbasvir Ledipasvir Velpatasvir

Answer 64

Prevents HCV replication in hepatocyte Sofosbuvir

Answer 65

Binds to polymerase preventing further viral replication Dasabuvir

Answer 66

Fatigue - anaemia GI symptoms Headache Insomnia

Answer 67

Weeks 2, 4, 8, 12 Assess for SVR - absence of HCV RNA by PCR at 6 months on completing treatment An increase in viral load from on-treatment nadir of greater than 1 log is indicative of poor adherence and virological breakthrough and treatment will be discontinued. Discontinuation avoids futile therapy and minimises the development of drug resistance.

Answer 68

C - core protein E1/E2 - envelope proteins NS2a - envelope protein NS2, NS3, NS4a, NS4b, NS5a, NS5b -non-structural

Answer 69

``` lichen planus Mixed cryoglobulinaemia Membranoproliferative glomerulonephritis porphyia cutanea tarda pulmonary fibrosis Sjogren's syndrome Thyroid disease ```

Answer 70

HCV Ab - detectable after 6 weeks (HIV may have false-negative result) HCV RNA - detectable after few days Genotype testing Fibroscan/ USS or liver biopsy

Answer 71

CD4 count less than 200 cells/mm3, it may be advisable to first initiate antiretroviral therapy and defer HCV therapy until the person is stable on antiretroviral therapy with suppressed HIV RNA levels Most clinical trials evaluating the efficacy of HCV therapy in persons with HIV have enrolled those with suppressed HIV RNA levels and CD4 counts greater than 200 cells/mm3. ART will slow HCV progresison towards liver cirrhosis

Answer 72

If treatment for both HIV and HCV is indicated, the selected treatment regimens should consider potential drug interactions and whether the recommended duration for persons with HCV monoinfection should be given for a longer duration because of the confection with HIV. LFTs may raise substantially more if co-infected, and may be attributed to immune reconstitution inflammatory syndrome

Answer 73

5x upper limit of normal However, if develops rising bilirubin, and symptoms such as nausea, weakness. Need to evaluate treatment/ other causes e.g HBV, alcohol, If blood tests show raised LFTs, then perform more frequent monitoring

Answer 74

NRTIs: avoid tenofovir + sofosbuvir NNRTIs: avoid efavirenz and etravirine INSTIs: avoid with tenofovir PIs - avoid all CCR5 - maraviroc safe

Answer 75

HIV Ag/Ab, RNA HBsAg, HBV DNA HCV Ab, HCV RNA HTLV Ab CMV IgG EBV VCA (viral capsid antigen) IgG - only organ donor Treponema pallidum Ab Toxoplasma IgG - only organ donor Travel histroy dependent: West Nile Virus Trypanosoma cruzi IgG Malarial Ab Individuals who receive blood products, particularly pooled blood products, could have false positive serology tests due to passively acquired antibodies from donor

Answer 76

Treat ever patient as potentially infectious Training on how to deal with sharps Sharps bins Gloves Mask/ eye shield if splash exposure Vaccinate HBV

Answer 77

If viral load >200 copies/ ml, not allowed to practice exposure prone procedures

Answer 78

HBeAg positive - cannot practice exposure prone procedures HBeAg negative - if HBV DNA >1000 genome copies/ml HBeAg negative - if HBV DNA <1000 genome copies/ml can return to exposure prone procedures HCV - RNA undetectable HIV - RNA <200 copies

Answer 79

Not allowed exposure prone procedure if HCV RNA detectable Can return to work is sustained virological response to antiviral therapy

Answer 80

HCV IgG Pooled immunoglobulins contain large variety of immunoglobulins to various organisms, so patient will test positive to lots of organisms. In UK, blood is screened for HIV, HTLV, HCV, so not expected to be present in immunoglobulin preparations. CMV/ EBV/ toxoplasma/ HepB core antigen are not routinely screened for, and could appear as passive antigens

Answer 81

Exposure Prone Procedures (EPP) are invasive procedures where there is a risk that injury to the worker may result in the exposure of the patient’s open tissues to the blood of the worker (‘bleed-back’). These include procedures where the worker’s gloved hands may be in contact with sharp instruments, needle tips or sharp tissues (e.g. spicules of bone or teeth) inside a patient’s open body cavity, wound or confined anatomical space where the hands or fingertips may not be completely visible at all times.

Answer 82

Venepuncture Other procedures are exposure prone procedures. They carry risk of injury to worker, which may result in exposure of patient's open tissues to the blood of the worker Can perform EPP once viral load <1000 copies/ml

Answer 83

Blood tests suggest previous HBV exposure through infection. This means risk of possible reactivation. Give 6 monts entecavir or tenofovir Lamivudine would also be suitable, but resistance develops if used for longer periods such as 6 months

Answer 84

False positive HBsAg - need to repeat on another platform, and perform neutralisation False negative antibody test Recent vaccination, but nor produced anti-HBs yet Newly recently acquired HBV infection, and has not yet sero-converted Patient with immunodeficiency or on chemotherapy - so produces inadequate antibody response. May have been infected at any time

Answer 85

Acute HBV infection High viral replication, prior to immune response/ sero-conversion

Answer 86

Check inherent resistance before treatment Assess risk of cirrhosis/ HCC Assess source of infection - certain genotypes associated with vertical or horizontal transmission Epidemiological studies

Viral hepatitis Flashcards

(112 cards)