hepatitis

Question 1

pathophysiology of hepatitis

Answer 1

1) hepatropic virus infect hepatocytes
2) hepatocytes present MHC I molecules
3) CD8+ T cells recognise MHC I molecules
4) cytotoxic killing & apoptosis (@ portal tract of liver lobules)
5) liver inflammation -> damage

Question 2

symptoms of hepatitis

Answer 2

1) fever
2) anorexia, N&V
3) malaise
4) pain in right hypochondria
5) elevated AST/ALT (ALT > AST, takes longer time to return to normal): leak out from liver into bloodstream
6) hepatomegaly: abnormally large liver due to inflammation -> pain
7) increase in abnormal lymphocytes (lymphocytosis): increase in size due to antigen stimulation
8) jaundice
- yellow discolouration of skin, sclera, mucous membranes due to excess amount of bilirubin
- conjugated bilirubin leak from bile duct that is damaged because hepatocytes die
- hepatocytes die = lesser ability to conjugate = increase in unconj
- conjugated excreted in urine = darker pee
- darker pee, paler shit
- increase in urobilinogen (UBG) in urine: UBG produced when bilirubin reduced in gut by microbes, reabsorbed & transported back to liver to be converted into bilirubin/bile, when hepatocytes die UBG transported to kidneys to be excreted in urine

Question 3

acute vs chronic hepatitis

Answer 3

. acute < 6 months, chronic > 6 months
. chronic = inflammation
. persistent inflammation & cirrhosis = postnecrotic cirrhosis

Question 4

routes of transmission for hepatitis

Answer 4

. A: faecal-oral
. B: blood & body fluids, parenteral, perinatal, sexual
. C: blood & body fluids, parenteral (uncommon), perinatal, sexual (not well defined)
. D: coinfection with B
. E: faecal oral

Question 5

risk factors for the different routes of transmission for hepatitis

Answer 5

. faecal oral: ingestion of contaminated food and water
. parenteral: unsafe needle practices, IV drug users, tattos @ unregulated shops, needle prick injury for healthcare workers
. perinatal: infected mother
. sexual: man - man/multiple sex partners

Question 6

diagnosis of hepatitis - biochemical markers

Answer 6

leukopenia, urobilin, UBG, increase in transaminases (ALT > AST), increase in GGT

Question 7

diagnosis of hepatitis - viral markers

Answer 7

. A: anti HAV IgM, anti HAV IgG
. E: anti HEV IgM, anti HEV IgG
. C: anti HCV IgG +ve -> HCV PCR confirmation test
. B: Hep B surface antigen (HBsAg) +ve, Hep B e surface antigen (HBeAg) +ve/-ve, Hep B core antigen (anti HBc IgM) +ve, HBV PCR +ve
. D: anti HDV IgM, anti HDV IgG

Question 8

complications of hepatitis

Answer 8

. A&E: recover safely with no clinical consequences
. B&C:
- cirrhosis
- chronic active hepatitis (CAH)
- chronic persistent hepatitis (CPH)
- HCC
. B: superinfection with D
. C: extrahepatic manifestations: cryoglobulinemia: deposits of immune complex that cause vasculitis, skin and internal organ damage (predominantly kidney -> renal damage)

Question 9

prevention of hepatitis

Answer 9

. vaccination
- A: for susceptible individuals travelling to/working in countries with high/intermediate Hep A population endemicity
- B: routine for newborn, healthcare workers, population at risk

Question 10

treatment goals of hepatitis B

Answer 10

. eradication impossible
. chronic: detection of HBsAg > 6 months + liver inflammation
. goals of therapy:
1) suppression of viral HBV
- loss of HBsAg w/wo anti HBs seroconversion
- loss of HBeAg w/wo anti HBe seroconversion for patients +ve for HBeAg
2) prevent progression of complications to cirrhosis & HCC

Question 11

implications to treat for hepatitis B

Answer 11

. ALT & cirrhosis
. cirrhosis = treat
. no cirrhosis = see severity before deciding if treat

Question 12

pharmacotherapy for Hep B

Answer 12

1) immune mediated therapy
. pegylated INF-alpha, INF-alpha
- injectables
- defined duration
- S/E: bone marrow suppression, flu-like symptoms, GI (nausea, abdominal pain, diarrhoea), CNS (depression, suicidal thoughts)

2) nucleotide/nucleoside agents (NAs)
- +ve effect for HIV: adefovir, adefovir t, lamivudine, telbivudine
- others: tenofovir, tenofovir alafenamide, diprovoxil
- oral, use until achieve set end point
- SE: generally well tolerated

Question 13

non-pharmacologic therapy for Hep B

Answer 13

. prevent transmission
- sexual & household contacts vaccinated, protection when having sex
. lifestyle modification
- lesser alcohol & smoking to prevent progression

Question 14

treatment goals for Hep C

Answer 14

1) prevent transmission
2) improve QoL

Question 15

pre-diagnostic tests before initiating therapy for Hep C

Answer 15

1) quantitative test & genotyping
- affect choice of therapy & pre-treatment resistance testing
2) underlying liver disease
- concomitant ribavirin use and duration
3) Screening for Hep B
- prevent reinfection

Question 16

pharmacotherapy for Hep C

Answer 16

1) direct acting agents (DAAs)
- N3/4A inhibitors (-previr), NS5A inhibitors, (-asvir), NS5B polymerase inhibitors (-buvir)
- oral
- combination therapy of 2/> that act on different targets for 8-12 wks
- S/E: well tolerated but significant DDI

2) nucleoside agents (NAs)
- ribavirin
- + DAA for decompensated cirrhosis or Hep C type 3
- oral
- S/E: haemolytic anaemia, fatigue, teratogenic

Question 17

patient education for Hep C

Answer 17

• prevent transmission
• Hep A & B vaccination
• lifestyle mod: stop drinking & weight loss (diet & exercise)

Question 18

when to treat Hep B

Answer 18

1) liver cirrhosis: prevent progression
2) ALT > 2x ULN
3) HBV DNA >/= 2000 copies
4) undergoing immune therapy: prevent reactivation of Hep B