Dr Derek LuoConsultant Gastroenterologist

Director

Greenlane Medical Specialists

Auckland

14:00 - 14:55 WS #37: Interpreting LFTs

15:05 - 16:00 WS #49: Interpreting LFTs (Repeated)

Dr Alasdair PatrickGastroenterologist and General Physician

Middlemore Hospital

Auckland

The only fully comprehensive

Gastroenterology center in Auckland

Opened in 2009

Largest Gastro practice in NZ

12 Gastroenterologists

1 Paediatric Gastroenterologist

1 Hepatologist

4 Surgeons

Dietician

Full diagnostic facilities on site

Dr Alasdair PatrickGastroenterologist

Case 1: AS23♀

• Unwell 2 days• Abdominal pain, Jaundiced and drowsy• Depressed otherwise well• OE: Jaundiced, No signs of CLD• LFTs Bil 250

ALP 160GGT 200ALT 2380AST 1960

• Thoughts?

Case 1: AS23♀

• Other Bloods:– INR 2.3, Cr 85, pH 7.40, Paracetamol 120

• Liver Screen– Negative (HAV and HBcoreIgM – Negative)

• Imaging– USS: Normal

• Pattern of LFT Disturbance– Hyperbilirubinaemia, Hepatitic Picture ALT>1000

• Diagnosis– Paracetamol Overdose

Case 1: AS23♀

x

Paracetamol Treatment Nomogram

Paracetomol overdose

• More than 250mg/kg likely severe liver damage

• 12g total potentially fatal– Less if low glutathione or p450 induction

• When taken in excessive amounts conjugation becomes inundated giving rise to alternate metabolism and toxic metabolite– Gives liver and renal tubule necrosis

• NAC 100% effective in first 8 hours

Paracetomol overdose

• Liver Transplant Criteria (Kings College)• Paracetamol

– Arterial pH < 7.3; or– All three: INR>6.5, Cr>300, G3-4 Encephalopathy

• Non Paracetamol– INR >6.5; or – Three of the following five criteria

• Patient age <11 or >40; • Bilirubin >300; • Time from onset of jaundice to enceph. greater than 7 days; • INR >3.5; or, • Drug toxicity

Paracetomol overdose

• Follow up

– Gradual improvement of LFT’s and synthetic function

• Treatment

– Close Observation

– Frequent Blood test repeat

– Rx – n-acetyl cysteine (NAC)

– Psychiatry

Case 2: GH66♀

• Gradual Itch• Previous autoimmuine thyroid disease• Abnormal LFT’s on routine GP testing• OE: Normal apart from scratch marks• LFT’s Bil 15

ALP 502GGT 438ALT 65AST 48

Thoughts?

Case 2: GH66♀

• Other Bloods:– INR 1.0, Alb 40

• Liver Screen– AMA Positive, ANA 1:80

• Imaging– USS: Normal

• Pattern of LFT Disturbance– Choleststatic picture with preserved synthetic function

• Diagnosis– Primary Biliary Cirrhosis (Cholangitis)

Primary biliary cirrhosis

• Auto-immune disease of the liver

– Slow progressive destruction of small bile ducts

• Female to male ratio 9:1

• Prevalence 1:4000

Primary biliary cirrhosis

• Treatment– Ursodeoxycholic acid

• Reduce the cholestasis - improves LFT’s results

• Minimal effect on symptoms

• Whether it improves prognosis is controversial

– Cholestyramine (bile acid sequestrant)• Absorb bile acids in the gut

• Alternative agents: Naltrexone & Rifampicin

– Ongoing follow up• T bili best indicator of prognosis

Case 3: GF 56♂

• Heavy alcohol consumption – Many years• Stopped 4 weeks ago• Gradual jaundice, confusion and lethargy• OE: Jaundiced, Spider Naevi, Small liver• LFTs Bil 406

GGT 198ALP 137AST 126ALT 52

Thoughts?

Case 3: GF 56♂

• Other Bloods:– INR 1.8, Albumin 30

• Pattern of LFT Disturbance– Mixed, significant hyperbilirubinaemia, AST>ALT

• Liver Screen– Negative

• Imaging– USS: Coarse Liver Echotexture

• Diagnosis– Alcoholic Hepatitis

Alcoholic hepatitis

Alcoholic hepatitis

• Treatment

– Abstinence from Alcohol

– Monitor for withdrawal

– Vitamin K

– In Hospital 3 weeks

• Good improvement

– Prednisone 30mg Daily for 4 weeks

– Cirrhosis follow up

Case 4:

• 22 lady Chinese who says she has Hep B

– ALT normal

– sAg +ve, eAg +ve, anti HBE –ve

• HBV DNA 10*9

• What would you do?

• Watch 6/12ly and get flare and

seroconverts

Case 5

• 47 year old Indian man– Ex boozer

• ALT 55

• What else would you check?– HBsAg positive

• HBe Ag-ve, anti HBe +ve

• Rpt 6/12 ALT 127

• What would you do now?– Fibroscan- cirrhosis

Case 5

• Asymptomatic 40 year old man

• Screening LFTs– Bili 38

– ALT 15 IU/ml

– ALP 85

– GGT 30

– Alb 36

• What other information would be helpful?

Case 5

• Otherwise well– No alcohol

– No family history

• What bloods would you check?

• Diagnosis: Gilberts syndrome

• How could you confirm this?– unconjugated hyperbilirubinaemia

• Often increases in infections but also on starving

Case 6

• 46 year old European man– Feeling tired

– Gaining weight• Wt 120kg, BMI 32

– Occasional alcohol

• LFTs– T bili 20

– GGT 198

– ALP 88

– AST 40

– ALT 65

Thoughts?

Non-alcoholic fatty liver disease (NAFLD)

• Spectrum of severity– Mild fatty infiltration

– Non-alcoholic steatohepatitis

– Fibrosis, cirrhosis

• Most common cause of abnormal LFT’s in primary care

• Hepatic manifestation of metabolic syndrome

NAFLD

• Associated with

– Obesity - central

– Type-2 diabetes

– Hypertension

– Hypertriglyceridaemia

– FHx of type-2 DM common in absence

NAFLD

• Thought to affect up to 24% population

• 70% of obese

• 50% of type-2 DM

• Mostly benign….

– Cirrhosis and hepatocellular carcinoma?

• Cirrhosis risks - age, obesity, DM

NAFLD - Clinical

• Symptoms

– Usually none

– Fatigue, RUQ discomfort

• Laboratory

– Elev GGT and ALT• If AST > ALT suspect ETOH, or cirrhosis if denied

– Elev TG/Chol, glucose

– USS (CT also)

Ultrasound

• Hepatomegaly

• Altered echogenicity

• Can’t distinguish mild form from steatohapatitis/cirrhosis

Differential• Should exclude other causes

– Viral hepatitis

– Drugs - esp alcohol

– Autoimmune (ANA, SMA)

– Metabolic (iron, copper)• High ferritin with normal transferrin saturation common in

NAFLD

• If saturation >45% ---> HH studies in Caucasians

• Investigate for metabolic syndrome if not known– Almost always assoc with insulin resistance

• High risk of type 2 diabetes

Role of SWE

• Not clearly elucidated

• Consider in

– Pts at risk severe disease

– Concerning lab studies

• AST>ALT, low platelets

Management

• Not really known

• Evidence accumulating that reducing BMI and improving insulin resistance with diet/exercise can reverse

• Endoscopic weight loss options or Bariatric surgery?

Weight loss

• Aim 0.5-1kg/wk

• Faster can precipitate steatohepatitis or gallstones

• Decrease refined sugars

• Increase fibre

• Cholesterol improving and DM diet

Exercise

• Increases oxidative capacity of myocytes

• Increases insulin sensitivity

• Check LFTs monthly

• Should see improvements in 2-3/12

Weight Loss in NASH

• Randomized 2:1 ratio to receive intensive lifestyle intervention (LS) or structured education (control) for 48 weeks.

• LS group lost an average of 9.3% TBW versus 0.2% in the control group (p=0.003).

• LS group reduction of NAS of at least 3 points or had post treatment NAS ≤ 2 compared with the control group (72% versus 30%, p=0.03).

• Participants who achieved the study weight loss goal (>7%), had significant improvements in NAS (P < 0.001).

Pomrat et al. Hepatology 2010

Helpful points

• Fatty liver can lead to cirrhosis

• Females and elderly do worse

• Often asymptomatic

• USS usually sufficient for diagnosis

• No established treatment

– Steady weight loss first line if obese

– Rapid weight loss may be dangerous

Take home messages: Patient care

• Jaundice and evidence of liver failure– Immediate discussion and consider admission

• Jaundice, no liver failure– Immediate discussion ?admission– Urgent USS, (haemolysis screen)

• Major elevation ALT/ AST (10 X ULN)– Immediate discussion ?admission– Repeat and review within 24 hours with synthetic function

Take home messages: Patient care

▪ Moderate elevation LFTs (5 X ULN)

– INR, Bilirubin, early

– Repeat with 48 hours with liver screen

– Early referral

• Evidence of cirrhosis, no liver failure

– Abnormal LFTs, abnormal USS, low platelets

– Early referral with liver screen

Take home messages: Patient care

• Mild Elevation of LFTs (2-3x ULN)

– Repeat

– Liver screen

– USS

– Referral

• A methodical approach will usually yield the diagnosis!

Dr Alasdair Patrick

Gastroenterologist