Liver disease and how to manage it!

Liver disease and how Liver disease and how to manage it!to manage it!

Dr Allister J GrantDr Allister J GrantConsultant HepatologistConsultant Hepatologist

Leicester Liver UnitLeicester Liver UnitUniversity Hospitals Leicester NHS TrustUniversity Hospitals Leicester NHS Trust

Anatomy &PhysiologyAnatomy &Physiology

Hepatic Artery

IVC

Splenic Vein

SMVGallbladder

Portal Vein

CBD

Anatomy &PhysiologyAnatomy &Physiology

Liver FunctionsLiver Functions

Nutrition/MetabolicNutrition/Metabolic– – stores glycogen (glucose chains)stores glycogen (glucose chains)– – releases glucosereleases glucose– – absorbs fats, fat soluble vitaminsabsorbs fats, fat soluble vitamins– – manufactures cholesterolmanufactures cholesterol

Bile SaltsBile Salts– – lipids derived from cholesterollipids derived from cholesterol– – dissolves dietary fats (detergent)dissolves dietary fats (detergent)

BilirubinBilirubin– – breakdown product of haemoglobinbreakdown product of haemoglobin

Liver FunctionsLiver Functions

Clotting FactorsClotting Factors– – manufactures most clotting factorsmanufactures most clotting factors

Immune functionImmune function– – Kupfer cells engulf antigens (bacteria)Kupfer cells engulf antigens (bacteria)

DetoxificationDetoxification– – drug excretion (sometimes activation)drug excretion (sometimes activation)– – alcohol breakdownalcohol breakdown

Manufactures ProteinsManufactures Proteins– – albuminalbumin– – binding proteinsbinding proteins

Liver Function TestsLiver Function Tests

Different cells have different enzymes inside them, Different cells have different enzymes inside them, depending on the function of the cell.depending on the function of the cell.

AST and ALT are associated with AST and ALT are associated with hepatocytehepatocyte damage damage

GGT and ALP are associated with GGT and ALP are associated with cholangiocytecholangiocyte damage ie biliary diseasedamage ie biliary disease

AminotransferasesAminotransferases

1. Alanine aminotransferase (ALT) and 1. Alanine aminotransferase (ALT) and

Aspartate aminotransferase (AST) Aspartate aminotransferase (AST)

These are enzymes that help to process These are enzymes that help to process proteins.proteins.

ALT is more specific for liver disease than AST ALT is more specific for liver disease than AST as AST is found in more types of cell (e.g. heart, as AST is found in more types of cell (e.g. heart, intestine, muscle). intestine, muscle).

Alkaline PhosphataseAlkaline Phosphatase This enzyme level is elevated in a large number of disorders that affect the This enzyme level is elevated in a large number of disorders that affect the

drainage of bile e.g.drainage of bile e.g.

• Gallstones damaging the bile ductGallstones damaging the bile duct• Tumor blocking the common bile ductTumor blocking the common bile duct• Drug-induced cholestatic hepatitis, blocking the flow of bile in smaller bile Drug-induced cholestatic hepatitis, blocking the flow of bile in smaller bile

channels within the liverchannels within the liver

The alkaline phosphatase is also released from damagedThe alkaline phosphatase is also released from damaged

• bone, bone, • placenta, andplacenta, and• intestine (isoenzymes)intestine (isoenzymes)

For this reason, the GGT is utilized as a supplementary test to be sure that For this reason, the GGT is utilized as a supplementary test to be sure that the elevation of alkaline phosphatase is indeed coming from the liver or the the elevation of alkaline phosphatase is indeed coming from the liver or the biliary tractbiliary tract

Other Liver “Enzymes”Other Liver “Enzymes”

3) 3) AlbuminAlbumin is a major protein which is produced by the liver is a major protein which is produced by the liver

In more advanced liver disease, the level of the serum albumin is In more advanced liver disease, the level of the serum albumin is reduced.reduced.

4)4) Bilirubin Bilirubin is the main bile pigment in humans. is the main bile pigment in humans.

Bilirubin is formed primarily from the breakdown of called "haem” Bilirubin is formed primarily from the breakdown of called "haem” from red blood cells from red blood cells

When elevated, bilirubin causes the yellow discoloration of the skin When elevated, bilirubin causes the yellow discoloration of the skin and eyes- jaundice and maybe associated with dark urine.and eyes- jaundice and maybe associated with dark urine.

The bilirubin may be elevated in many forms of liver or biliary tract The bilirubin may be elevated in many forms of liver or biliary tract disease, and thus it is also relatively nonspecific.disease, and thus it is also relatively nonspecific.

Other Liver EnzymesOther Liver Enzymes

5) 5) Gamma Glutamyl Transpeptidase Gamma Glutamyl Transpeptidase is often elevated in liver is often elevated in liver disorders but disorders but notnot in diseases of bone, placenta, or intestine. in diseases of bone, placenta, or intestine.

HoweverHowever the high sensitivity and very low specificity of this test the high sensitivity and very low specificity of this test seriously hampers its usefulness.seriously hampers its usefulness.

GGT is elevated in a whole host of liver diseases GGT is elevated in a whole host of liver diseases

BUT also in BUT also in

• obesityobesity• hyperlipidaemiahyperlipidaemia• diabetesdiabetes• congestive cardiac failurecongestive cardiac failure• diseases of the kidney, pancreas and prostate.diseases of the kidney, pancreas and prostate.

ALT elevated? (>53)ALT elevated? (>53)

Hepatitic illnessHepatitic illness

AcuteAcute AgeAge SexSex DrugsDrugs AlcoholAlcohol TravelTravel ContactsContacts Risky behaviourRisky behaviour AutoimmunityAutoimmunity FeverFever AF/BP/CCFAF/BP/CCF Pregnant?Pregnant?

ChronicChronic Age/sexAge/sex EthnicityEthnicity BMIBMI LipidsLipids DiabetesDiabetes AlcoholAlcohol TravelTravel Risky behaviourRisky behaviour FHxFHx

• AutoimmunityAutoimmunity• Unexplained CirrhosisUnexplained Cirrhosis

The majority of abnormal LFTs in The majority of abnormal LFTs in asymptomatic people occur in those with:asymptomatic people occur in those with:

Diabetes or metabolic syndrome Diabetes or metabolic syndrome (increased risk of NAFLD) (increased risk of NAFLD)

Excessive alcohol intake Excessive alcohol intake Chronic hepatitis B or CChronic hepatitis B or C DrugsDrugs

ALT elevatedALT elevated

Hepatitic illnessHepatitic illness

AcuteAcute Hep A,B,C,EHep A,B,C,E EBV, CMV, TOXOEBV, CMV, TOXO Drugs screen?Drugs screen? ImmunoglobulinsImmunoglobulins Autoimmune profileAutoimmune profile Caeruloplasmin (<50)Caeruloplasmin (<50)

ChronicChronic TFTTFT Diabetic screenDiabetic screen Hep B, CHep B, C LipidsLipids ImmunoglobulinsImmunoglobulins Autoimmune profileAutoimmune profile FerritinFerritin Caeruloplasmin (<50)Caeruloplasmin (<50) αα-1 antitrypsin-1 antitrypsin TTGTTG (ACE)(ACE)

ALP Elevated? (>130)ALP Elevated? (>130)

Cholestatic IllnessCholestatic Illness((With or without jaundice)With or without jaundice)

AcuteAcute

Age/SexAge/Sex Drugs/AntibioticsDrugs/Antibiotics FHx gallstonesFHx gallstones Abdo PainAbdo Pain Red flag symptomsRed flag symptoms Jaundice?Jaundice?

Differentiate from bonyDifferentiate from bony

ChronicChronic

Family HxFamily Hx Metabolic syndromeMetabolic syndrome Recurrent FeverRecurrent Fever Itch/lethargyItch/lethargy Dry eyes/mouthDry eyes/mouth ColitisColitis PainPain SOB/Resp symptomsSOB/Resp symptoms CCFCCF

Liver ALP ElevatedLiver ALP Elevated Cholestatic IllnessCholestatic Illness

AcuteAcute

CBD stones/GallstonesCBD stones/Gallstones Tumours 1Tumours 1ºº or 2 or 2ºº Pancreatic pathologyPancreatic pathology DrugsDrugs InfiltrationInfiltration SODSOD

ChronicChronic

PBCPBC Sclerosing CholangitisSclerosing Cholangitis

• 11ºº or 2 or 2ºº NASHNASH αα-1 antitrypsin-1 antitrypsin SarcoidSarcoid AmyloidAmyloid HIVHIV

Drug Induced CholestasisDrug Induced Cholestasis Intrahepatic Hepatocellular Intrahepatic Hepatocellular

Cholestasis Cholestasis

Intrahepatic Ductular cholestasisIntrahepatic Ductular cholestasis

DuctopenicDuctopenic

GranulomatousGranulomatous

AllopurinolAllopurinolAntithyroid agentsAntithyroid agents

AugmentinAugmentinAzathioprineAzathioprineBarbituratesBarbituratesCaptoprilCaptoprilCarbamezepineCarbamezepineChlorpromazineChlorpromazineChlorpropamideChlorpropamideClindamycinClindamycin

ClofibrateClofibrateDiltiazemDiltiazem

Erythromycin estolateErythromycin estolateFlucloxacillinFlucloxacillin

IsoniazidIsoniazid

LisinoprilLisinoprilMethyltestosteroneMethyltestosterone

Oral contraceptives (containing estrogens)Oral contraceptives (containing estrogens)Oral hypoglycemics Oral hypoglycemics PhenytoinPhenytoinTrimethoprim-sulfamethoxazole Trimethoprim-sulfamethoxazole

Investigation of CholestasisInvestigation of Cholestasis

Dilated bile ducts

Non-dilated bile ducts

Full liver screen

Raised ALP

Check GT if isolated rise

1) Stop alcohol

2) Stop hepatotoxic drugs

3) Advise weight loss if BMI>25

4) Recheck LFT’s after an interval

Persistently raised ALP

ConsiderMRCPERCP

Other imaging

Diagnosis made-Treat disease

Non diagnostic Ix-consider

Liver biopsy

Isolated raise in Bilirubin (>22)Isolated raise in Bilirubin (>22)

DifferentialDifferential Gilberts vs HaemolysisGilberts vs Haemolysis

Gilberts- Gilberts- Unconjugated hyperbilirubinaemiaUnconjugated hyperbilirubinaemia

Haemolysis-Haemolysis-Unconjugated hyperbilirubinaemiaUnconjugated hyperbilirubinaemia

splenomegaly, anaemia , splenomegaly, anaemia , DCT, haptoglobin, reticulocyte count, filmDCT, haptoglobin, reticulocyte count, film

Disease ProgressionDisease ProgressionL

iver

fu

nct

ion

100%

Cirrhosis

Liver Failure

Years

A

B

CD

Mrs WMrs W 48 year old 48 year old ♀ admitted from a surgical clinic with ♀ admitted from a surgical clinic with

jaundice and unwelljaundice and unwell

Unwell for 6 wks after holiday in MexicoUnwell for 6 wks after holiday in Mexico

Hx of xs alcohol 30u/wkHx of xs alcohol 30u/wk

No previous jaundiceNo previous jaundice

USS normal size liver and spleen – biliary tree normalUSS normal size liver and spleen – biliary tree normal

OEOE

JaundiceJaundice DrowsyDrowsy Agitated/IrritableAgitated/Irritable Doesn’t obey Doesn’t obey

commandscommands No stigmata of CLDNo stigmata of CLD Asterixis (Liver Flap)Asterixis (Liver Flap)

No spleenNo ascites

Mrs WMrs W

U&EU&E normalnormal

ALPALP 107107 ALTALT 736736 Bili Bili 363363 Alb Alb 2424

FBC FBC NormalNormal

INRINR 3.73.7

Causes of Acute Liver FailureCauses of Acute Liver Failure

DrugsDrugs• Paracetamol (UK)Paracetamol (UK)• INHINH• HalothaneHalothane• EcstacyEcstacy

ViralViral• Hepatitis AHepatitis A• Hepatitis BHepatitis B• Hepatitis EHepatitis E• Non-A Non-BNon-A Non-B

Wilsons DiseaseWilsons Disease

Autoimmune HepatitisAutoimmune Hepatitis

Reye’s SyndromeReye’s Syndrome

CardiovascularCardiovascular• Ischaemic hepatitisIschaemic hepatitis• Budd ChiariBudd Chiari

Acute Fatty Liver of PregnancyAcute Fatty Liver of Pregnancy

Cirrhosis

Expanded Portal Tracts(Blue)

Signs of Chronic Liver DiseaseSigns of Chronic Liver Disease

NoneNone Asterixis/FlapAsterixis/Flap Relative hypotensionRelative hypotension OedemaOedema Jaundice/No jaundiceJaundice/No jaundice Large/Small liverLarge/Small liver SplenomegalySplenomegaly GynecomastiaGynecomastia Testicular atrophy-loss of secondary sexual Testicular atrophy-loss of secondary sexual

characteristicscharacteristics ImpotenceImpotence

Decompensation in CirrhosisDecompensation in Cirrhosis

Means the development of-Means the development of-

AscitesAscites

Hepatic EncephalopathyHepatic Encephalopathy

Portal hypertension (variceal haemorrhage)Portal hypertension (variceal haemorrhage)

The Development of AscitesThe Development of Ascites

50% of compensated cirrhotics develop ascites over 10yrs

50% of cirrhotics with ascites will die within 2 yrs

EncephalopathyEncephalopathy

Grade 1Grade 1• Constructional apraxiaConstructional apraxia• Poor memory – number connection testPoor memory – number connection test• Agitation/ irritabilityAgitation/ irritability• Reversed sleep patternReversed sleep pattern

Grade 2Grade 2• Lethargy, disorientationLethargy, disorientation• AsterixisAsterixis

Grade 3Grade 3• Drowsy, reduced conscious levelDrowsy, reduced conscious level

Grade 4Grade 4• ComaComa

Decompensation in CirrhosisDecompensation in Cirrhosis

Means the development of-Means the development of-

AscitesAscites

Hepatic EncephalopathyHepatic Encephalopathy

Portal hypertension (variceal haemorrhage)Portal hypertension (variceal haemorrhage)

Portal Portal CirculationCirculation

Oesophageal varicesOesophageal varices

Management of Bleeding VaricesManagement of Bleeding Varices

PreventionPrevention

Prophylactic AntibioticsProphylactic Antibiotics

ResuscitationResuscitation

Endoscopy -Endoscopy - Band LigationBand LigationSclerotherapySclerotherapy

Pharmacotherapy- TerlipressinPharmacotherapy- Terlipressin

Balloon TamponadeBalloon Tamponade

TIPSTIPS


PreventionPrevention

Prophylactic AntibioticsProphylactic Antibiotics





TIPSTIPS

Oesophageal varicesOesophageal varices

Bleeding Gastric VaricesBleeding Gastric Varices

Variceal BanderVariceal Bander

Variceal Band LigationVariceal Band Ligation




Pharmacotherapy- Pharmacotherapy- Terlipressin 2mg qds i.vTerlipressin 2mg qds i.v


TIPSTIPS






TIPSTIPS

The ENDThe END

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Liver disease and how to manage it!