Hepatology

Division C

Cambridge University Hospitals NHS Foundation Trust Page 1 of 11

Hepatology referral pathways for GPs Version 14; Approved November 2020

Hepatology referral pathways for GPs

1 Scope

For use within hepatology

Contents 2. Liver blood tests and what they mean p2

Acute and chronic liver screen p2

3. Hepatology A&G FAQs p3

Common reasons for referral

4. Raised ALT +/- GGT p4

5. Non alcoholic fatty liver disease (NAFLD) pathway p5

6. Alcohol-related liver disease (ArLD) pathway p6

7. Isolated asymptomatic raised bilirubin p7

8. Raised ALP and normal ALT p7

9. Combination of LFT abnormalities p8

10. Raised ferritin p8

11. Abnormal liver imaging p9

12. Hepatitis B p10

13. Hepatitis C p10

14. Referral pathways p11

Hepatology

Division C

Cambridge University Hospitals NHS Foundation Trust Page 2 of 11

Hepatology referral pathways for GPs Version 14; Approved November 2020

2 Liver blood tests and what they mean

Test Normal range

What does it mean? Actions if abnormal

ALT 7-40 Hepatocellular injury

Raised ALT

Bilirubin isolated raised Bilirubin with abnormal LFT

<21 Gilberts Haemolysis Liver or biliary pathology

Isolated asymptomatic raised bilirubin Refer (routine vs urgent acc to values)

Alkaline Phosphatase (ALP)

30-130 Biliary disease (if raised GGT) Bone disease Pregnancy (placenta) Acute phase response

Raised ALP and normal ALT

Gamma glutamyl transferase (GGT)

Male 0-73 Female 0-38

Non-specific – can reflect alcohol intake, non-alcoholic fatty liver or biliary disease if associated with raised ALP

Follow relevant pathway

Prothrombin time (PT) Elevated with impaired synthetic function or biliary obstruction

Refer if could be liver related

Albumin 35-50 Non-specific, but may represent impaired synthetic function if low

Refer if could be liver related

Ferritin Not necessarily iron overload Raised ferritin

Reduced platelets Can be a feature of cirrhosis with portal hypertension

Refer if could be liver related

Chronic liver screen U/E, LFT, FBC, PT, FIB-4 if suspected NAFLD Hepatitis B & C serology Liver autoantibodies Serum immunoglobulins Ferritin Alpha-1 antitrypsin level Random glucose, HBA1c, lipids if ?NAFLD If under 50 caeruloplasmin

Acute liver screen LFT, FBC, PT Hepatitis A, hepatitis B and hepatitis E serology (IgM & IgG), EBV and CMV Liver autoantibodies Serum immunoglobulins If under 50 caeruloplasmin

Hepatitis B screen Chronic liver screen plus: HBV DNA Hepatitis A IgG HIV screen

Hepatitis C screen Chronic liver screen plus: HCV RNA and genotype Hepatitis A IgG HIV screen

Hepatology

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Hepatology referral pathways for GPs Version 14; Approved November 2020

3 Hepatology A&G FAQs

Result What it means

BLOOD

ALP raised with normal GGT

Not likely to relate to liver, more likely bony origin

Bilirubin (isolated raised ) Likely Gilbert’s if nil else to suggest liver disease, normal Hb, ‘split’ bilirubin predominantly unconjugated. NB may have family history

Caeruloplasmin 0.17-2.0 Unlikely to be significant if no other pointers to Wilson’s disease

Ferritin raised/normal tf sat

Common in NAFLD, Alcohol-related liver disease (ArLD)

FIB4 <1.3 (<2.0 over age 65)

Can be requested on T-Quest. Use for NAFLD assessment only. Means low risk of significant fibrosis. Not valid < age 35 or > age 75

FibroScan < 7 kPa (NAFLD)

Means low risk of significant fibrosis in NAFLD

FibroScan < 8 kPa (Alcohol)

Means low risk of significant fibrosis in Alcohol-related liver disease

Hepatitis C Ab positive Past exposure - requires HCV RNA to assess for active infection

HepBcAb +ve /HepBsAg –ve

Previous exposure, natural immunity, not chronic infection

IgA raised Common in NAFLD, ArLD – not concerning in itself

SmA/ANA Weak positive This will always be non-specific, common in NAFLD. Not a concern if IgG normal.

IMAGING

Focal lesion on US If likely benign but report not definitive – repeat at CUH if done elsewhere otherwise A&G

Gallbladder polyps Refer to ‘HPB surgery’ for advice/ follow their guidance

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Hepatology referral pathways for GPs Version 14; Approved November 2020

4 Isolated raised ALT (+/- GGT)

Reinforce lifestyle advice/ monitor

Alcohol related liver disease pathway

YES

NO

ALT <150

ALT >300 at any stage Acute liver screen , urgent CUH USS

ALT normal

ALT >150

Repeat 2/52

ALT <150 Repeat

4/52

ALT remains >150 USS and Chronic liver screen

USS and Chronic liver screen

Do all the features below apply?

NO hepatomegaly/splenomegaly NO cirrhosis/portal hypertension

Normal chronic liver screen

Routine referral

Features of significant liver disease at any stage (eg possible cirrhotic appearance, splenomegaly, raised

bilirubin/PT, low platelets)

Routine referral

THINK about and address Risk Factors

• Metabolic syndrome • Diabetes • Alcohol • Risks for viral hepatitis (ethnicity, IV drug use) • Medication • Vigorous exercise (check CK)

> 14 units alcohol per week NAFLD pathway

NO

YES

Routine referral

Urgent referral

Hepatology

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Hepatology referral pathways for GPs Version 14; Approved November 2020

5 Non Alcoholic Fatty liver Disease (NAFLD) pathway

From Pathway 4 (raised ALT +/- GGT) OR Type 2 diabetic or morbid obesity with BMI >35 kg/m2 (often with isolated elevated

GGT)

Age <35 or >75 with no significant comorbidities

Age 35 to 75

Intermediate Risk Intermediate values

High Risk > 2.67

RISK Stratification with FIB-4 to assess risk of significant fibrosis (available on T-QUEST)

Low Risk < 1.3 (age 35-64) < 2.0 (age ≥65)

Lifestyle advice Re-stratify in 2 years

FIBROSCAN REFERRAL

Unless BMI >40 when

for ROUTINE REFERRAL

If BMI <40 otherwise routine referral

NO

Hepatology will arrange a clinic

appointment

YES

Score ≥ 8 kPa

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Hepatology referral pathways for GPs Version 14; Approved November 2020

6 Alcohol-related Liver Disease (ArLD) pathway

Reinforce lifestyle advice for

heavy alcohol intake

metabolic syndrome

Score ≥ 8 kPa:

Lifestyle advice for heavy alcohol intake and metabolic syndrome

Dependent drinkers should seek advice from CGL FIBROSCAN REFERRAL

From Pathway 4 (raised ALT +/- GGT)

Repeat FibroScan 3-5 years according to lifestyle success/LFTs

Repeat fibroscan 3-5 years according to lifestyle success/LFTs

Repeat fibroscan 3-5 years according to lifestyle success/LFTs

Repeat fibroscan 3-5 years according to lifestyle success/LFTs

Score < 8 kPa:

Hepatology will arrange a clinic

appointment

Hepatology

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Hepatology referral pathways for GPs Version 14; Approved November 2020

7 Isolated asymptomatic raised bilirubin

8 Raised ALP and normal ALT

Ultrasound

Chronic liver screen

ROUTINE REFERRAL

YES

YES

Haemolysis screen: reticulocytes

lactate dehydrogenase (LDH) haptoglobin level

Direct Antiglobulin Test (DAT)

Blood film

+/- refer haematology

NO

YES

NO

NO

YES

NO Predominantly unconjugated hyperbilirubinemia,

normal albumin and platelet count

Anaemia?

Likely Gilbert’s syndrome (inherited defect in ability to conjugate bilirubin that is benign and requires reassurance and no

follow up)

Split bilirubin and FBC

Bilirubin > 2x ULN URGENT/2WW

REFERRAL

Check GGT Is it raised? ROUTINE

REFERRAL

Tests for bone pathologies Consider bone profile, vitamin D, ESR/CRP

PSA, PTH, myeloma screen

Ultrasound

Chronic liver screen

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Hepatology referral pathways for GPs Version 14; Approved November 2020

9 Combination of LFT abnormalities

10 Raised ferritin

Bilirubin > 2x upper limit normal

(not isolated)

URGENT/2WW

REFERRAL

ALT >300 and/or ALP > 500 URGENT REFERRAL

Other USS

Chronic Liver screen ROUTINE

REFERRAL

If CRP elevated – exclude inflammatory cause / repeat after interval. Exclude anaemia (haem ref)

Check fasting transferrin saturation (tf sat) and LFTs / family history

Low/normal tf sat +/- raised ALT Borderline/raised tf sat or family history

HFE genotyping (EDTA to Molecular Genetics for simple

HFE1 genotype – see form at end of document or click here)

Consider: NAFLD pathway ArLD pathway

Lifestyle advice

Refer if not improving or

>1000 mcg/l

Refer to Bill Griffiths, Consultant Hepatologist

through CAS

Hepatology

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Cambridge University Hospitals NHS Foundation Trust Page 9 of 11

Hepatology referral pathways for GPs Version 14; Approved November 2020

11 Abnormal liver imaging

Hepatomegaly Chronic liver screen ROUTINE REFERRAL

Cyst/s

Simple cyst/s No referral required unless >10

(?polycystic liver disease)

Complicated cysts thick-walled /septated

US CUH → A&G referral US not CUH → rpt US CUH

Suspected haemangioma

Small (< 2cm) incidental haemangioma No referral required

Large (> 2 cm)/complex/complicated

US CUH → A&G referral US not CUH → rpt US CUH

Focal fat sparing on background of “fatty liver” NAFLD/fibroscan pathways

Suspected cancer 2WW referral

Ultrasound scan shows gall bladder polyp(s)

Referral to HPB surgery

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Hepatology referral pathways for GPs Version 14; Approved November 2020

12 Hepatitis B

13 Hepatitis C

* Pre-clinic workup: (see T-Quest Groups) For HBV and HCV: Chronic liver screen plus HIV and hepatitis A immunity serology For HCV: HCV RNA and genotype (large EDTA tube) For HBV: HBV DNA (large EDTA tube)

Refer to hepatitis clinic for assessment of the need for treatment, contact tracing and

cancer surveillance *

Exposed to and cleared hepatitis B. Contact tracing with GP.

Referral only required if patient takes immunosuppression or chemotherapy (or

does so in the future)

Hepatitis B surface antigen (HBsAg) positive

Hepatitis B core antibody (anti-HBcAb) positive

Hepatitis B surface antigen (HBsAg) negative

Hepatitis C antibody positive

+ve -ve

Exposure and clearance Contact tracing

Confirm with repeat HCV RNA and if negative no further action required.

Refer to hepatitis clinic for highly effective treatment, contact tracing and

cancer surveillance *

HCV RNA test (large EDTA)

Hepatology

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Cambridge University Hospitals NHS Foundation Trust Page 11 of 11

Hepatology referral pathways for GPs Version 14; Approved November 2020

14 Referral pathways

Urgency Conditions Proforma

2WW REFERRAL

Jaundice >40 yrs Suspected liver cancer

2WW proforma

URGENT REFERRAL

Jaundice <40 yrs Tense ascites ALT > 300 and/or ALP > 500 Suspected cirrhotic decompensation

Urgent CAS referral with hepatology proforma

ROUTINE REFERRAL (please review guidance first)

Abnormal LFTs Suspected chronic liver disease Raised ferritin Hep B or C new diagnosis FibroScan- include ultrasound scan

Routine CAS referral with hepatology proforma

Benign abnormal liver imaging Referral according to guidance

ADVICE & GUIDANCE

A&G CAS referral with hepatology proforma

Addenbrookes Hepatology Webpage

Further information: https://easternliver.net

Equality and diversity statement This document complies with the Cambridge University Hospitals NHS Foundation Trust service equality and diversity statement.

Disclaimer It is your responsibility to check against the electronic library that this printed out copy is the most recent issue of this document.

Document management Approval: Dr Bill Griffiths, Clinical Lead, 11 November 2020

Owning department: Hepatology

Author(s): Dr Will Gelson, Dr Bill Griffiths, Dr Mike Allison

File name: Hepatology referral pathways for GPs Version14 November 2020

Supersedes: Version 13, October 2019

Version number: 14 Review date: November 2023

Local reference: Document ID: 100137

REGIONAL GENETICS LABORATORIES TEST REQUEST All tests requested will be reviewed against departmental criteria. If testing is not arranged, the samples will be stored and the referring clinicians informed. After testing, samples may be used anonymously for the development of new tests and for quality monitoring.

Venous blood samples: Adult: 5ml; Children: 1-5ml

☐ DNA test: EDTA tube

☐ Chromosomes: Lithium Heparin tube

☐ Microarray: Lithium Heparin and EDTA tubes

Other samples:

☐ Cord/Placenta/insertion site/skin

☐ Products of Conception (whole specimen in sterile pot)

☐ Amniotic Fluid

☐ CVS

☐ Other (please contact the laboratory)

Sample obtained by (Signature)……………………………

Printed Name ……………………………………………..

Date………………………………………………………….

Clinical Synopsis Please provide clinical synopsis and pedigree with relevant family history to help the team generate a laboratory

report Tests Required:

Storage Only (no testing at this time): ☐

Gestation in weeks (If pregnant): Partners Name and DOB: Index Case (if not this patient):

The Laboratory does NOT report results via the telephone

Surname Date of Birth Age at Presentation

First Names Sex

NHS Number

Ethnicity

Hospital Number Family Number

Home Address Postcode Patient email address

GP Name (Printed) GP Address Postcode GP email address (nhs.net preferred)

Consultant (PRINT) Hospital

Speciality/Dept/Ward Contact telephone number Email address (nhs.net preferred)

Results to (if different from above) inc email address (nhs.net preferred)

Billing to:

Private Patient: ☐

In Submitting this sample, the clinician confirms that consent has been obtained for:

a) Testing and Storage

☐ Yes ☐No

b) The use of this sample and the information generated from it to be shared with members of the patient’s family and their health professionals (if appropriate)

☐Yes ☐No

All samples MUST be labelled with FULL name, date of birth and NHS number Processing of samples will be delayed if information is incomplete

Send samples at room temperature by 1st

class post or courier to:

East Anglian Medical Genetics Service, Genetics Laboratories, Box 143

ATC Level 6, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ

CUH Laboratory Use Only:

Receipt date and time:

Tube type: Volume:

No of tubes:

Shire Only ☐

Patient Demographics Checked:

Other Information:

Send out approved by:………………………………….. Signature:…………………………………………………

Date:……………………………………………………

Laboratory opening hours: 8.30am - 5.30pm Monday to Friday

Telephone: 01223 348866 Fax: 01223 348712

E-mail: geneticslaboratories@nhs.net

For further information about sample requirements and tests available see: www.cuh.org.uk/genetics-labs Indication for Genetic Testing:

1. To establish a diagnosis ☐

2. Guide clinical management ☐

3. Information regarding prognosis/recurrence risk ☐

4. Predictive testing ☐

5. PGD/Prenatal diagnosis ☐

Has the test been discussed at a clinical meeting? If so, please provide information on clinical meeting (I.e.: Neurology meeting, cancer meeting)

☐

Is the test urgent? (i.e. pregnant or will alter management)

☐

Please confirm that your department will fund the test* Has the test been approved by patient’s consultant

☐

☐

* Please see UKGTN website (http://ukgtn.nhs.uk/) for approximate cost or contact the duty scientist (tel: 01223 348866)