Case studies Abnormal LFTs

Enoka Gonsalkorala

Caboolture, RBWH

Case 1 – Ms BG

– 19F, Caucasian

– 3/12 of worsening lethargy

– PHMx

– Hay fever, acne

– BMI 30

– Medication – nil

– Work – apprentice hairdresser

– No EtOH

Bloods

– Bili 40, Alb 34, ALT 640, AST 410, ALP 220, GGT 74

– Hb 130 Plt 237 INR 1.7

– Cr 150 Ur 5

What else?

– Previous bloods?

– Other symptoms – joints, skin, pain, weight loss

– Drug history

– Lymecycline – completed 4mths prior to presentation

– No herbs, OCP, over the counter meds, gym supplements, NSAIDs

– Travel

– Camping, ?water ?party drugs ?tattoos

– Returned home 1mth prior to jaundice

– Sexual history

– Not sexually active

– Family history

– Uncle ankylosing spondylitis, great-aunt phemphigoid, uncle scleroderma

Back to bloods…

– Bili 40, Alb 34, ALT 640, AST 410, ALP 220, GGT 74

– Hb 130 Plt 237 INR 1.7

– Cr 150 Ur 5

What are the differentials?

1. Drug Induced Liver Injury (DILI)

2. Infection – biliary, leptospirosis, HBV

3. Autoimmune hepatitis

4. Fatty liver disease

Where to now?

What’s the next step?

Liver ultrasound

Referral pathway

Progress

– ANA 1/640, smooth muscle anti-body positive

– Liver biopsy – autoimmune hepatitis

Normal AIH

Management

– Prednisolone – 40mg daily for two weeks, then wean. Initially weekly blood tests

– Excellent biochemical response

– Commenced 6-mercaptopurine 8 weeks post as steroids sparing agent

Autoimmune Hepatitis

– Multifactorial aetiology – genetics, immune dysregulation, environment

– Insidious onset, F >M

– Diagnostic criteria

– Treatment – Prednisolone

– Taper steroids, add steroid sparing agent – azathioprine, 6-mercaptopurine

– AZA/6MP side effects – Cholestatic hepatitis, pancreatitis, infections, rash, N+V, opportunistic

infections – 10%

– Cytopaenia 5%

Case 3 – Mr ND

– 50M, Caucasian

– New patient to your practice

– PMHx

– T2DM

– Dyslipidaemia

– Ischaemic heart disease

– Medication

– EtOH – 6 units/wk

– Exam – BMI 27, central adiposity

Routine blood tests

– Alb 33, Bili 4, ALT 60, AST 67, GGT 300, ALP 250

– Hb 120, Plt 95, INR 1.1

– HbA1c 8%

– Choles – within normal range

– Concerns?

– Further tests → Health Pathways

– Liver screen negative

Interpretation

1. Alcoholic liver disease

2. Fatty liver disease

3. Advanced liver disease

4. Drug induced liver disease

5. Autoimmune hepatitis

What next?

- Liver US – nodular liver, splenomegaly, 3cm lesion

Low albumin Low platelets

Tertiary management

– Reviewed as Cat 1 pt

– No symptoms of hepatic decompensation (jaundice, ascites, peripheral oedema, variceal bleed, muscle wasting)

– Multi-phase CT confirmed 3cm hepatocellular carcinoma (HCC) without extra hepatic spread

– Discussed at hepatoma MDT

– Not suitable for locoregional curative therapy

– Referred for consideration of liver transplantation – listed

NAFLD

– Definition – hepatic steatosis on imaging or biopsy in the absence of:

– Significant EtOH (<21std for men, <14std for women)

– Medication

– Hereditary disorders

– NASH is a histological diagnosis

– Global prevalence 25%

– Associated conditions – obesity, diabetes, HTN, dyslipidaemia

NAFLD natural history

– Increased mortality – driven by cardiovascular disease

– Cancer related mortality

– Likely to take over as the most common indication for liver transplantation

– Role for bariatric surgery

What to do with the NAFLD patient in the community?

– Lose weight – portion size, exercise

– Control metabolic risk factors

– Diabetes

– HTN

– Lipids (statins can be used safely)

– Cardiovascular health

– Alcohol – limit to safe levels (14units per wk)

– Chronic Disease Management plan

Who to refer with abnormal LFTs?

– ALL patients with cirrhosis (decompensation, bloods, imaging)

– Patients at risk of developing NASH cirrhosis

– High ALT

– Insulin resistance / diabetes

– Metabolic syndrome

– Atypical NAFLD – fatty liver PLUS:

– Drugs – methotrexate, other

– Drug induced liver injury

– Hereditary disorder

Case 3 – Mr ED

– 45M

– General check up

– PMHx – HTN, T2DM

– Medication – perindopril, metformin

– EtOH – 20 units/wk

– Exam unremarkable

Investigations

– Hb 160, WBC 4, Plt 300

– Alb 40, Bili 3, ALT 50, AST 60, ALP 300, GGT 250

– Liver screen

– Ferr 1300, Transferrin saturation 75%

– What is the role of serum iron?

Causes of raised ferritin

– HBV/HCV

– NAFLD

– EtOH

– Hereditary haemachromatosis

– Thalassaemia major

– Non-HFE hereditary iron overload

What would you do next?

– HFE gene test

– Ultrasound liver

– Modify cofactors

– HbA1c

– Reduce/stop alcohol

– Blood pressure

Interpreting HFE results

– HFE Gene panel – which of the following mutations can cause hereditary iron over load? – H63D homozygous

– C282Y : H63D

– C282Y : C282Y

– H63D heterozygous

– Patient – C282Y homozygous

– What next?

– Screen family

– Refer

Hereditary haemochromatosis

– C282Y – homozygous, heterozygous, compound heterozygous (H63D)

– Other organ involvement – Diabetes

– Arthropathy

– Cardiomyopathy

– Hypogonadism

– Hypothyroidism

– 70% of homozygous will have abnormal LFTs, only 10% will have severe liver disease

Management

– Liver biopsy given cofactors – confirmed iron overload, fibrosis stage 2

– Commence venesection (Australian Red Cross, private lab)

– 1 unit 1-2 weekly, check Hb prior – aim <80% drop from baseline

– Check ferritin 3 mthly, aim 50-100

– Avoid vitamin C supplementation

– Do not need to regulate dietary iron intake

Take home…

– Framework to tackle abnormal LFTs – Health Pathways

– Include as much history as possible in referral – CPC guidelines

– Recognise the cirrhotic patient

– Metabolic syndrome and the liver

– Aggressive risk factor modification