Specific Liver Disease Flashcards
Hepatitis B/C risk factors? (6)
From high prevalence areas: South-East Asia, Egypt, Italy
IVDU
Multiple transfusions
Vertical (from mother)
MSM
Multiple sexual partners
HCP
Interpret following Hep-B serology.
HBsAg +
Persistently or intermittently elevated AST & ALT
HBeAg -
HBV DNA +
Chronic Hepatitis B.
Key to remember
s-Ag: 1st to appear, lasts 1-6 months. If >6 months, indicates chronic disease.
Anti-HBc implies previous (or current) infection.
IgM anti-HBc appears during acute or the recent infection lasts ~6 months.
HBeAg results from breakdown of core Ag from infected liver cells and hence indicates marker of ACTIVE replication.
Interpret following Hep-B serology.
HBsAg +
HBcAg +
Normal AST & ALT
HBeAg -
eAb +
HBV DNA -
Inactive carrier state. Most important for this type: HBeAb is positive
Key to remember
s-Ag: 1st to appear, lasts 1-6 months. If >6 months, indicates chronic disease.
Anti-HBc impplies previous (or current) infection.
IgM anti-HBc appears during acute or recent infection, lasts ~6 months.
HBeAg results from breakdown of core Ag from infected liver cells and hence indicates marker of infectivity.
What is this patient’s Hepatitis B status?
s-Ag: +
Anti-HBs: -
core-IgM: +
core-IgG: -
e-Ag: +
Anti-HBe: -
HBV DNA: +
Active infection.
Pre-core mutant infection of HBV is diagnosed by… (which serology findings?)
HBeAg -ve
HBeAb +ve
However HBV-DNA raised
ALT raised.
What are indications of treatment for hepatitis B? (5) - state general principles
- General principle: tx is indicated when there is evidence of inflammation (elevated ALT > 2 ULN or active inflammation or advanced fibrosis on biopsy) combined with elevated HBV DNA.
- The guideline suggests (AASLD) that all cirrhotics (including compensated) should be treated to prevent decompensation.
- If not treated, they should have LFTs and VL checked 3-6 monthly.
What is your approach in pharmacological Mx of Hepatitis B? (treatment goal, drug choices and follow-up)
Goals
- Negative DNA and HBeAg (seroconversion) by week 48
- Normalise ALT and histology.
Treatment
- Entecavir or Tenofovir (=1st line and have high resistance barrier) = oral
- Lamivudine (cheaper)
- Peg IFN-alpha (S/C, 3/week)
Follow-up
- HBV DNA, eAg, eAb, LFTs 3-6 monthly
- If HBV DNA -ve at 6 months, continue, otherwise consider switching to other drugs
- Monitor for side effects of drugs - e.g. Fanconi syndrome (renal dysfunction) and Osteoporosis with Tenofovir (DEXA, CMP, EUCs)
- HCC surveillance
- Consider testing for resistance if patient has virologic breakthrough (>10-fold increase in DNA during treatment in a patient who had initial virologic response)
What are the two major side effects of Tenofovir?
Fanconi syndrome (type II RTA) - inadequate reabsorption at PCT (it is responsible for 80% reabsorption of phosphate so results in phosphate wasting)
Osteoporosis
Monitor with EUC, CMP and DEXA
Hep B drug of choice in a) renal dysfunction (2), b) pregnancy (2)?
Renal impairment - use TAF (tenofovir AlaFenamide) or Entecavir
Tenofovir is drug of choice in pregnancy (TDF, class B) or Lamivudine (C)
Which antiviral is contraindicated in decompensated liver cirrhosis?
PEG-IFN is contraindicated.
How would you minimise recurrence of HBV in patient undergoing liver transplant? (2)
Strategies include
Tx with antiviral to minimise HBV DNA, followed by large dose of Hep B Igs
Major advantage of PEG-IFN for Hep B and problems (3)?
No resistance.
Side FX: Depression, contraindicated in decompensated liver disease or pregnancy.
How would you manage Hepatitis B patient undergoing pregnancy? (3)
Aim is to prevent vertical transmission.
- Treat mother with Tenofovir or Lamivudine in the 3rd trimester.
- Give passive Hep B Immunoglobulins
- Vaccinate infant
Hepatitis B patient who is about to undergo chronic immunosuppression e.g. chemotherapy or steroids. What is your concern and what would you do about it?
- The main concern is the reactivation of Hep B, which sometimes can result in fulminant hepatic failure.
- The risk is higher if HBsAg+ve, but even HBsAg -ve HBcAb +ve patients can reactivate.
- I would consider giving prophylaxis, such as Lamivudine a week before starting chemo and continue treating for 6-12 months in conjunction with Gastro advice.
- Monitor DNA,sAg, ALT 1-3 monthly
What are extrahepatic manifestations of Hepatitis C?
HCV - CRYOPL
Cardiomyopathy / Cryoglobulinaemia
Renal - GN (membranoproliferative)
Rheumatologic - polyarthralgias/polyarthritis
Cutaneous - cutaneous Porphyria (porphyria cutanea tarda)
Haematologic: B-cell Lymphoma, Hashimoto’s thyroiditis
Vasculitis (cutaneous necrotising vasculitis)
Other: Lichen planus
How would you interpret Fibroscan?
It gives E score.
3 = normal
9 = fibrosis
20 = cirrhosis
What is your approach in Mx of new Hepatitis C? (treatment goal, drug choices and follow-up)
Goal: to achieve SVR (sustained virologic response) - that is, undetectable HCV RNA at 6 month after completion of therapy (=cure). Minimise progression of cirrhosis and prevent complications.
Baseline investigations
- Rule out coexistent HIV and Hep B. All should be tested for Hep A/B and vaccinate if Ab -ve.
- Baseline blood as some DAAs are contraindicated in certain situations - Sofosbuvir (renal impairment) and some are metabolised by liver hence cannot be used in decompensated disease (e.g. Simeprevir)
- Baseline HCV RNA, Genotype (type 3 is a/w more severe, rapidly progressive disease)
Non-pharm
- Manage other contributory factors - obesity, ETOH, smoking, marijuana - all contributes to fibrosis
- Counsel about routes of HCV transmission (no donation, no sharing of tooth brushes, razors or needles, minimise sexual contact)
- Screen & treat depression (especially if IFN considered)
- Cease Hepatotoxins.
Pharm
- DAA if detectable HCV RNA /VL or fibrosis. All cirrhotics. Check latest guidelines / Gastro advice regarding choice of DAAs - but depends on a) genotype, b) presence of decompensated cirrhosis, c) renal impairment, d) hx of prior treatment, e) other medications given interactions.
- Extra-hepatic manifestations also may respond to therapy - consider additional ImmSx
Follow-up as per CLD.
Indications for HCC surveillance?
Any cirrhotics.
Any Hep B (as they can be non-cirrhotic but still develop HCC). Basically anyone above age of 40, FH, African.
Blood findings suggestive of Haemochromatosis? How would you proceed to establish diagnosis?
Ferritin >300
Transferrin saturation >50%
Proceed to HFE mutation analysis if Ferritin >200 women/300 in men who have no other causes of inflammation or Tsat >40%.
Liver biopsy is indicated to determine degree of cirrhosis/fibrosis in known HH patient whose ferritin >1000 and LFTs are derranged.
Haemochromatosis Mx in brief? (3)
Regular venessection (initially weekly for 2 years then 3 monthly) - aim tSat <50%, Ferritin <50.
Genetic counselling + screen 1st degree relatives for HFE mutation
Otherwise as per Chronic Liver disease.
Principle of Mx of NASH?
Treat underlying disease like DM.
Strict control of hyperglycaemia and dyslipidaemia.
Consider Statin
Avoid alcohol
