Specific Liver Disease

Question 1

Hepatitis B/C risk factors? (6)

Answer 1

From high prevalence areas: South-East Asia, Egypt, Italy

IVDU

Multiple transfusions

Vertical (from mother)

MSM

Multiple sexual partners

HCP

Question 2

Interpret following Hep-B serology.

HBsAg +

Persistently or intermittently elevated AST & ALT

HBeAg -

HBV DNA +

Answer 2

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.

Question 3

Interpret following Hep-B serology.

HBsAg +

HBcAg +

Normal AST & ALT

HBeAg -

eAb +

HBV DNA -

Answer 3

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.

Question 4

What is this patient’s Hepatitis B status?

s-Ag: +

Anti-HBs: -

core-IgM: +

core-IgG: -

e-Ag: +

Anti-HBe: -

HBV DNA: +

Answer 4

Active infection.

Question 5

Pre-core mutant infection of HBV is diagnosed by… (which serology findings?)

Answer 5

HBeAg -ve

HBeAb +ve

However HBV-DNA raised

ALT raised.

Question 6

What are indications of treatment for hepatitis B? (5) - state general principles

Answer 6

• 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.

Question 7

What is your approach in pharmacological Mx of Hepatitis B? (treatment goal, drug choices and follow-up)

Answer 7

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)

Question 8

What are the two major side effects of Tenofovir?

Answer 8

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

Question 9

Hep B drug of choice in a) renal dysfunction (2), b) pregnancy (2)?

Answer 9

Renal impairment - use TAF (tenofovir AlaFenamide) or Entecavir

Tenofovir is drug of choice in pregnancy (TDF, class B) or Lamivudine (C)

Question 10

Which antiviral is contraindicated in decompensated liver cirrhosis?

Answer 10

PEG-IFN is contraindicated.

Question 11

How would you minimise recurrence of HBV in patient undergoing liver transplant? (2)

Answer 11

Strategies include

Tx with antiviral to minimise HBV DNA, followed by large dose of Hep B Igs

Question 12

Major advantage of PEG-IFN for Hep B and problems (3)?

Answer 12

No resistance.

Side FX: Depression, contraindicated in decompensated liver disease or pregnancy.

Question 13

How would you manage Hepatitis B patient undergoing pregnancy? (3)

Answer 13

Aim is to prevent vertical transmission.

1. Treat mother with Tenofovir or Lamivudine in the 3rd trimester.
2. Give passive Hep B Immunoglobulins
3. Vaccinate infant

Question 14

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?

Answer 14

1. The main concern is the reactivation of Hep B, which sometimes can result in fulminant hepatic failure.
2. The risk is higher if HBsAg+ve, but even HBsAg -ve HBcAb +ve patients can reactivate.
3. 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.
4. Monitor DNA,sAg, ALT 1-3 monthly

Question 15

What are extrahepatic manifestations of Hepatitis C?

Answer 15

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

Question 16

How would you interpret Fibroscan?

Answer 16

It gives E score.

3 = normal

9 = fibrosis

20 = cirrhosis

Question 17

What is your approach in Mx of new Hepatitis C? (treatment goal, drug choices and follow-up)

Answer 17

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.

Question 18

Indications for HCC surveillance?

Answer 18

Any cirrhotics.

Any Hep B (as they can be non-cirrhotic but still develop HCC). Basically anyone above age of 40, FH, African.

Question 19

Blood findings suggestive of Haemochromatosis? How would you proceed to establish diagnosis?

Answer 19

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.

Question 20

Haemochromatosis Mx in brief? (3)

Answer 20

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.

Question 22

Principle of Mx of NASH?

Answer 22

Treat underlying disease like DM.

Strict control of hyperglycaemia and dyslipidaemia.

Consider Statin

Avoid alcohol