Supot Nimanong, MD.

Reviews in Internal Medicine

for 2nd Year Resident 2017

Division of Gastroenterology Siriraj Hospital, Mahidol University

Liver Diseases

Liver diseases

Level 1 • Cholestasis• Portal hypertension• Alcoholic liver diseases• Acute hepatitis• Chronic viral hepatitis• Drug /toxin induced hepatitis• Cirrhosis• NAFLD

Level 2 • Hepatorenal syndrome• Immunologic hepatitis• Hemochromatosis• Liver abscess

Level 3 • Dubin-Johnson syndrome• Gilbert’s disease• Crigger-Najjar syndrome• Rotor syndrome• Cystic diseases of the liver• Veno-occlusive disease• Budd-Chiari syndrome• Osler-Weber syndrome• PBC• Alpha1 antitrypsin deficiency• Wilson disease

Liver diseases

Normal liver

CirrhosisAcute Hepatitis

Chronic Hepatitis

HCC

• Virus• ALD / NAFLD• Wilson disease• Hemochromatosis• Autoimmune • Drugs, toxin• Vascular

• Esophageal varices• Ascites / SBP / hepatic

hydrothorax• Hepatorenal syndrome• Hepatic encephalopathy• HPS / PPHT• HCC

Normal

Cirrhosis

Acute Hepatitis

Chronic Hepatitis

HCCFulminant hepatitis

• HAV, HEV• EBV, CMV, HSV• Ischemic hepatitis• SOS• Hemophagocytosis

• HCV• NASH• Hereditary hemochromatosis

• HBV, HDV• Alcoholic liver diseases • Wilson disease • AIH• Drugs • Budd-Chiari syndrome

HAV HEV HBV HDV HCV

Transmisssion Feco-oral Feco-oral Blood, SexualVertical

HBsAg-dependent

Blood

Presentation Acute AcuteChronic*

AcuteChronic

AcuteChronic Chronic

Risk factors Travel Travel IVDU, tattoo, blood Tx, unsafe sex, family Hx

IVDU IVDU, tattoo, blood Tx

Diagnosis Anti HAV IgM Anti HEV IgMAnti HEV IgG

Anti HBc IgMHBsAg

Anti HDV IgG Anti HCVHCV RNA

Treatment Supportive Ribavirin PegIFNNUCs

IFN IFN + RBVDAAs

Prevention Vaccine 0,6 mo. Vaccine 0,6 mo. Vaccine 0,1,6HBIG

Hepatotrophic viral hepatitis

*AIDS, post organ transplantation

EBV HSV CMV

Host Adolescent ImmunocompromisedPregnancy

Immunocompromised

Symptoms & signs

Mononucleosis-like Skin lesions (50%) Retinitis, colitis, pneumonitis

Diagnosis Blood smearAnti EBV IgM

HSV PCRLiver biopsy

CMV viral loadHistology

Treatment Supportive Acyclovir Ganciclovir

Non-hepatotrophic viral hepatitis

Hepatitis B serology

Interpretation of HBV serology

Setting Anti HBc HBsAg Anti HBs Interpretation

Acute hepatitis

IgM + + - Acute or flared hepatitis B

IgM + - -/+ Severe hepatitis B with spontaneous “S” loss / seroconversion

IgM - + - Flared hepatitis B orCHB with other causes of hepatitis

IgM - - any Other causes of hepatitis

Chronic hepatitis

or check up

IgG + + - Chronic hepatitis B

IgG + - + Prior HBV infection

IgG - - + Post HBV vaccination

IgG + - - Occult HBV, prior HBV infection, pre “S” seroconversion, passive immunization

Phases of chronic HBV infection

0 20 40 60Years

Immune tolerantImmune clearance

HBeAg-positive chronic hepatitis

Inactive carrier state

HBV DNA

Reactivation HBeAg-negative chronic hepatitis

ALT

HBeAg

Anti-HBe

Evaluation of HBsAg+ patient

• HBeAg, anti HBe, (HBV DNA)

• AST, ALT, alb, globStage of disease

• anti HCV, anti HIV, (anti HDV)

• anti HAV IgG

Co-infection &

vaccination

• Ultrasound

• (AFP)Screening

for HCC

Indication for HBV treatment

1. Chronic hepatitis B (both HBeAg+ and HBeAg-)• DNA > 2000 IU/mL, persistent ALT elevation* or significant fibrosis**

*ALT >2x more than 3 months**liver biopsy: F>2 (Metavir), F>3 (Ishak) or fibroscan >7.0 kPa

2. Cirrhosis• Compensated : detectable HBV DNA• Decompensated : HBsAg +

3. HCC: decrease recurrence after curative treatment 4. Prophylaxis

• TACE: HBsAg+• CMT : HBsAg+• Rituximab, SCT : antiHBc IgG+• Post liver transplantation: NUCs + HBIG

5. Decrease vertical transmission: LdT or TDF (GA 24-32 wk until delivery)• Pregnant women : HBV DNA > 2,000,000 IU/ml

Adapted from THASL guideline 2015

HBsAg + HBsAg -, anti HBc +

HBV DNA +

NUCs: LAM, (ETV, TDF) LAM

HBV DNA -

Monitor ALT & HBV DNA

q 1-3 months

RituximabSCT

*After cessation of CMT

HBV DNA < 2000 IU/ml

Pre-emptive treatment for HBV

Adapted from THASL guideline 2015 and EASL guideline 2012

Start

Stop* 6-12 months 12 months

Post exposure prophylaxis for HBV infection

Status Schedule

Unvaccinated HBIG (0.06 ml/kg) + HBV vaccine (3 doses)

Vaccinated• +anti HBs >10 mIU/ml• +anti HBs <10 mIU/ml• -anti HBs

No treatmentHBIG + vaccine 1 dose (booster dose)HBIG 2 doses or HBIG + vaccine 3 doses

Anti HCV

HCV RNA

Interpretation

+ + Chronic hepatitis C

+ - False positiveSVR (post Rx)

- + Acute hepatitis CImmunocompromised host

- - No HCV infection

Hepatitis C serology

Evaluation of anti-HCV+ patients

• HCV RNA (for confirmation)

• HCV genotype (for treatment)HCV

• AST, ALT, alb, glob, CBC

• Liver stiffness, histology, U/SStage of disease

• HBsAg, anti HBs, anti HIV

• Anti HAV IgG

Co-infection

& vaccination

THASL guideline 2015

HBV

• PAN• Glomerulonephritis

Membranous nephropathy MPGN IgA nephropathy

Extrahepatic manifestations

HCV

• Mixed cryoglobulinemia• MPGN• NHL• Porphyria cutanea tarda• Lichen planus• Sjogren syndrome

Risk factors for cirrhosis• Dose: women > 20 g/d, men > 60-80 g/d• Duration: > 10 yearsPE• Common signs: parotid enlargement, Dupuytren’s

contracture, spider neviInvestigations• Megaloblastic anemia• AST > ALT 3x• AST< 500 in alcoholic hepatitis• Imaging: fatty change

Alcoholic liver diseases (ALD)

Alcohol abstinence

Rx alcoholic withdrawal symptoms

Nutritional support

Folic and vitamin supplement

Prednisolone or pentoxifylline for severe alcoholic hepatitis

Management of ALD

Suspected ASH

Severe ASH Mild ASH

mDF* > 32

Lille score at D7

Prednisolone(40 mg daily x 1 wk)

Pentoxifylline*(400 mg tid x 4 wk)

Continue Rx for 3 wk

Stop RxConsider LT

*Severe sepsisActive GI bleeding

Renal failurePancreatitis

or

*mDF, Maddrey’s discriminant function = 4.6 x (PTpatient – PTcontrol) + TB

Non-alcoholic fatty liver disease (NAFLD)

Diagnosis• Metabolic syndrome

: DM, HT, hypertriglyceridemia, obesity• Imaging: fatty liver• Alcohol intake < 20 g/d• Exclude other causes + liver biopsy

NAFLD

Treatment• Rx Comorbid: DM, HT, dyslipidemia• Quit smoking / alcoholic drinking• Weight reduction: goal > 10%

Diet control Exercise Medication Bariatric surgery

• Vitamin E, pioglitazone

Autoimmune hepatitis (AIH)

Clues • Female• Autoimmune diseases

Autoimmune thyroiditis Sjogren syndrome Scleroderma

• High globulin (no cirrhosis)• Responded to steroid treatment

Revised original scoring system of the International Autoimmune Hepatitis Group

Simplified scoring system

Features Score

ANA or SMA 1:40ANA or SMA > 1:80 or anti LKM > 1:40 or SLA +

12

IgG > UNLIgG > 1.1 UNL

12

Viral hepatitis: absence 2

Histology: compatible with AIHtypical AIH

12

• Probable AIH > 6• Definite AIH > 7

Treatment for naïve AIH

Prednisolone• Severe cytopenia• TPMT deficiency• AIH with ALF• Pregnancy• Active malignancy

Prednisolone + Azathioprine• Postmenopausal state• Uncontrolled DM• Severe HT• Obesity• Osteoporosis

Prednisolone < 10 mg/d and/or

Azathioprine 1-2 MKD

Induction

Maintenance

Induction

Maintenance

or

Primary biliary cirrhosis (PBC)

Clues• Middle-aged women• Pruritus, fatigue, scratch marks, (jaundice)• Elevated cholesterol, xanthoma, xanthelasma• Associated autoimmune diseases

: sicca syndrome, autoimmune thyroiditis, RA, scleroderma

Diagnosis of PBC

Elevation of ALP and GGT

Positive AMA(> 1:40)

Histology:Non-suppurative

destructive cholangitis

+

or

Management

Specific treatment• UDCA

Treatments of symptoms and complications• Pruritus• Fatigue• Osteopenia and osteoporosis• Hypercholesterolemia• Fat soluble vitamin supplementation• Portal hypertension

Primary sclerosing cholangitis (PSC)

Clues• Middle-aged men• Recurrent cholangitis, fatigue, pruritus• Associated with IBD (UC > CD)

Diagnosis of PSC

Elevation of ALP and GGT

AbnormalCholangiogram(ERCP, MRCP)

Exclude 2o cause

+

Cause of 2o sclerosing cholangitis

• AIDS cholangiopathy

• Ischemic cholangiopathy

• IgG4 associated cholangitis

• Choledocholithiasis

• Biliary tract neoplasm

• Congenital abnormality of biliary tract

• Biliary tract injury / surgery

Management of PSC

Specific treatment• Dilatation of dominant stricture• No proven medical therapy• Liver transplantation

PBC vs PSC

Features PBC PSC

Sex F M

Chronic cholestasis + +

Associated diseases Sicca, RA, scleroderma,Autoimmune thyroiditis

IBD (UC > CD)

Autoantibody AMA (pANCA)

Cholangiogram Normal Bead-like appearance

Histology Florid duct lesion Onion skin fibrosis

Treatment UDCA Dilation of dominant stricture

Wilson disease (WD)

Clues• Age < 40-50 yr• Acute hepatitis, ACLF, cirrhosis in young

patients• Neurological involvement

Parkinsonism Neuropsychiatric

• KF ring (50-95%), sunflower cataract• Family Hx (AR)

Diagnosis of WD

• Ceruloplasmin

• 24-hr urine copper

• Hepatic copper

• Liver histology

• Brain imaging

• Genetic studies

Diagnostic tests of WD

Tests Normal WD False positive False negative

Ceruloplasmin > 20 mg/dl < 20 mg/dl (S > 90%)

< 5 mg/dl (high Sp)

• Infant, childhood

• End-stage cirrhosis

• NS / PLE

• Copper deficiency

• Menkes disease

• Aceruloplasminemia

• Heterozygote (20%)

• General population (1%)

• Acute inflammation

• Severe liver injury

• Hyperestrogenemia

: pregnancy, pills

Diagnostic tests of WD

Tests Normal WD False positive False negative

Ceruloplasmin > 20 mg/dl < 20 mg/dl (S > 90%)

< 5 mg/dl (high Sp)

• Infant, childhood

• End-stage cirrhosis

• NS / PLE

• Copper deficiency

• Menkes disease

• Aceruloplasminemia

• Heterozygote (20%)

• General population (1%)

• Acute inflammation

• Severe liver injury

• Hyperestrogenemia

: pregnancy, pills

24-hr urine copper < 40 μg > 100 μg (S 77-84%)

• Chronic liver diseases

• Heterozygote (40-70 μg)

• Renal failure

WD with acute liver failure

Tools Sensitivity (%) Specificity (%)

ALP:bilirubin < 4 94 96

AST:ALT > 2.2 94 86

Both 100 100

• F:M = 2:1• Coombs-negative hemolytic anemia: 5-15%• AST&ALT (< 2000 IU/L), AST > ALT• Normal or low ALP (typically < 40 IU/L)

Avoid high copper diet

Medication; D-penicillamine and/or zinc

Rx cirrhotic & neuropsychiatric complications

Consider OLT; ALF, decompensated cirrhosis

Genetic counseling and family screening

Management of WD

Hereditary hemochromatosis (HH)

Clues• Onset: M > 40-50 yr, F > 50-60 yr• Hepatomegaly• Arthropathy (specific: 2nd, 3rd MCP),

diabetes, restrictive cardiomyopathy• Family Hx (AR, AD)

Enterocyte

Macrophage

Ferroportin

Transferrin

HFETfR2HJV

BMPs

Hepcidin

Classification of HH

Type Gene Gene product Inheritance Comment

Type 1HFE-related HH

HFE HFE AR Classic HH

Type 2AJuvenile HHType 2BJuvenile HH

HJV

HAMP

Hemojuvelin

Hepcidin

AR

AR

Younger ageMore severe

Cardiac complicationsHypogonadism

Type 3TfR2-related HH

TfR2 Transferrin receptor2

AR Similar to classic HH

Type 4Ferroportin disease

SCL40A1 Ferroportin AD Less severeAnemia with phlebotomy

Iron study

Transferrin saturation (TS)• Diagnosis: TS > 45% (Sens 98%, NPV 93%)• False positive

22% of heterozygote Secondary iron overload

Serum ferritin (SF)• Diagnosis, marker of fibrosis (>1000 μg/L), monitoring

Diagnosis

HFE geneExclude

secondary HC

Tissue/organ iron overload

Iron study

Liver biopsy

MRI liver

Avoid high ferrous diet

Phlebotomy, (deferoxamine)

EV and HCC surveillance

Consider OLT; decompensated cirrhosis, HCC

Genetic counseling and family screening

Management of HH

WD vs HH

Features WD HH

Mutation ATP7B HFE(C282Y), others

Inheritance AR AR, AD

Penetrance Complete Incomplete (10-15%)

Onset Before 40-50 After 40-50

Hepatic manifestations

Acute on chronic hepatitiscirrhosis

Chronic hepatitiscirrhosis

Other organs involvement

Brain, eye Pancreas, heart, joints

Drug-induced liver injury (DILI)

Mechanisms• Dose dependent: paracetamol• Idiosyncrasy

Immunologic reaction: most drugs Hypersensitivity: allopurinol Autoantibodies (AIH like): minocycline, methyldopa,

diclofenac, atorvastatin

Diagnosis of DILI

1. Temporal relationship

2. Biochemical injury pattern

– Signature drug

– Prior reports / cases

3. De-challenge

4. Re-challenge

5. Exclude other causes

Types of Injury Drugs

Acute hepatocellular injury Isoniazid, rifampicin, ketoconazole, diclofenac etc.

Mononucleosis-like Sulfonamides, phenytoin, dapsone

Bland cholestasis Anabolic/ androgenic steroids

Cholestatic hepatitisChlorpromazine, erythromycin, amoxiclllin-clavulanate,

clarithromycin

Chronic hepatitis Methotrexate, lisinopril

Autoimmune hepatitis Nitrofurantoin, minocycline, methyldopa, diclofenac, atorvastatin

Macrovesicular hepatitis Corticosteroids, methotrexate, asparaginase, alcohol, halothane

Microvesicular hepatitis Valproic acid, tetracyclines, amiodarone, tamoxifen

Cirrhosis Methotrexate, amiodarone

Granulomatous hepatitis Allopurinol, rosiglitazone, sulfonamide, phenylbutazone, quinidine

Primary biliary cirrhosis-like Chlorpromazine, erythromycin, amoxiclillin-clavulanate, haloperidol

Peliosis hepatitis Anabolic steroids, oral contraceptives

Portal vein thrombosis Oral contraceptives

Sinusoidal obstructive syndrome Pyrrolozidine alkaloids, adriamycin, floxuridine, oncotherapy

Hepatic adenoma Anabolic and contraceptive steroids

Pattern• Single overdose – exceed 20 g• Therapeutic misadventure

Risk factors• Malnourished• Heavy alcoholic drinkers• CYP P450 inducers: phenobarbital, phenytoin, isoniazid, zidovudine

Antidote: N-acetylcysteine (NAC)

Paracetamol poisoning

Statins

Features Frequency Comment

Asymptomatic ALT elevation

0.1-3% Dose dependent, class effect

Significant hepatitis Very rare May be seen in combination with other medications

Fulminant hepatitis Extremely rare Risk: 2 in 1 million

AIH like Case report Risk: genetically susceptible individuals

• Compensated cirrhosis is not contraindicated• Can be prescribed safely to NAFLD patients

Antituberculous drugs

Onset: 2 weeks – 14 months

Prevalence • Mild elevation of transaminase 10%• Jaundice 1%

INH, PZA• Idiosyncratic: hepatocellular injury

Rifampicin• Physiologic: indirect hyperbilirubinemia• Hypersensitivity• CYP P450 inducer: enhance INH toxicity

Amoxicillin clavulanate

Onset: 1-3 weeks, may be later than 6 weeksHepatocellular injury (1/3)

• Younger patients• Shorter duration of drug use (1 week)• HLA A*3002, HLA B*1801

Cholestasis (1/3) + mixed pattern (1/3)• Older patients• Longer duration of drug use (2 weeks)• HLA DRB1*1501-DQB1*0602

Lucena MI, et al. Hepatology 2006

Portal Vein Thrombosis

Budd-Chiari Syndrome

Sinusoidal ObstructionSyndromex

x

x

Acute PVT Chronic PVT

Portal biliopathy

Varicealbleeding

Recurrent thrombosis

Complete recanalization

Death

SMV thrombosis

Bowel ischemia

abdominal pain fever

Acute PVT Chronic PVT

CT scan

Causes of PVT

Prothrombotic disorders %

Myeloproliferative diseasesAntiphospholipid syndromePNHBehcet’s diseaseFactor V Leiden mutationFactor II mutationProtein C deficiencyProtein S deficiencyAnti-thrombin III deficiencyPlasminogen deficiencyPregnancyOral contraceptive useHyperhomocysteinemiaTT677 MTHFR genotype

30-406-190-2

0-316-32

14-400-262-300-260-6

6-4012

12-2211-50

Local factors %

CancerCirrhosisInfection / inflammationSurgeryTrauma

2417-225-175-300-3

2/31/3

Causes of PVT

• Malignant tumors of liver1

• Cirrhosis2

• Pylephlebitis3

• Prothrombotic states4

Investigations for prothrombotic stateProthrombotic Investigations

Myeloproliferative neoplasm V617F JAK2 mutation (80% in PV, 50% in ET and PMF)

BM biopsy (normal CBC 40%)

PNH CD55- and CD59-deficient clone at flow cytometry

Ham–Dacie and sucrose tests

Behcet’s disease Conventional criteria + IVC thrombosis

Antiphospholipid syndrome Anticardiolipin Ab or LA or antiß2 glycoprotein 1 Ab

Antithrombin deficiency Antithrombin level

Protein C deficiency Protein C level

Protein S deficiency Protein S level

*Pills, preganancy; cofactors

• Start with LMWH

• Change to warfarin, keep INR 2-3

• Duration: – At least 3-6 months

– long term* in prothrombotic state, SMV thrombosis

Anticoagulation

ATBSurgery

Thrombolytic, TIPS

(Warfarin)

ERCP

BB, EVL

Acute PVT Chronic PVT

Portal biliopathy

Varicealbleeding

Recurrent thrombosis

Complete recovery

Death

xAsymptomatic20%

Acute BCS20%

Chronic BCS60%

IVC thrombosis Fulminant BCS

Budd-Chiari syndrome (BCS)

x x• Jaundice• Tender hepatomegaly• Ascites: wide SAAG, high protein

Cirrhotic complications

CT scan

• Heterogeneous enhancement***

• Caudate lobe hypertrophy

• Thrombus, collateral circulation

• Splenomegaly, ascites

Early central enhancement Delayed peripheral enhancement

Flip flop phenomenon

Causes of BCSProthrombotic disorders %

Myeloproliferative diseasesAntiphospholipid syndromePNHBehcet’s diseaseFactor V Leiden mutationFactor II mutationProtein C deficiencyProtein S deficiencyAnti-thrombin III deficiencyPlasminogen deficiencyPregnancyOral contraceptive useHyperhomocysteinemiaTT677 MTHFR genotype

40-504-250-4

0-336-325-7

10-307-200-230-4

6-126-6037

12-22

Local factors

IVC webMalignancies• HCC• RCC• Adrenal carcinoma

Acute phase

Treatment of BCS

AngioplastyLocal thrombolysis

Stent

Rx prothromboticcondition

Malignant transformation

LMWH

Warfarin

TIPS

Liver transplantation

Rx cirrhotic complicationsSurveillance for EV & HCC

Long term

Sinusoidal obstruction syndrome (SOS)

Drugtoxic agents

TNF

IL1 IL2

• Jaundice• Tender hepatomegaly• Ascites, edema, weight gain

CT scan

• Hepatosplenomegaly

• Ascites

• Patchy liver enhancement

• Patent hepatic vein & IVC

Treatment of SOS

• Symptomatic treatment Low salt diet Diuretics Renal & respiratory support

• Defibrotide• t-PA + heparin• Liver transplantation

Laurie D. DeLeve, et al. Hepatology 2009

Summary

PVT BCS SOS

Presentation• Acute

• Chronic

Abdominal pain + fever

EV, portal biliopathy

Jaundice, ascites,tender hepatomegalyCirrhotic complications

Tender hepatomegaly, ascites, edema, wt. gain, (jaundice)

Common Causes HCC, cirrhosisProthrombotic states

Prothrombotic states PBSCT, CMT

Investigations Doppler US, CT, (Prothrombotic states)

Treatment Anticoagulant• Acute symptomatic PVT• Chronic PVT

(Prothrombotic state, SMV involvement)

Long term anticoagulant Symptomatic Rx

Liver diseases unique to pregnancy

Features Hyperemesis gravidarum

Intrahepaticcholestasis

HELLP Acute fatty liver of pregnancy

Trimester 1 2, 3 3 3

Symptoms N/V, weight loss Pruritus N/V, RUQ pain Hepatitis with coagulopathy

Elevated AST & ALT < 10x 2-10x Severe Moderate to severe

Jaundice Rare < 5 mg/dl Uncommon > 5 mg/dl

Treatment Supportive UDCA Prompt delivery Prompt delivery

Recurrence Possible 60-70% ? 20-70%

Features Hemangioma FNH Adenoma

Prevalence 1-2% 0.01% 0.001%

Sex Female

OCP use - ? Yes

Size Small Small May be large

Number Single

U/S Hyper Slightly hyper/hypo

Slightly hyper/hypo/iso

Arterial enhancement

Peripheral nodular Homogeneous Heterogeneous

Venous Progressive enhancement

Isodensity Isodensity

Other feature - Central scar Fat, hemorrhage

Association Osler-Weber-Rendudisease

Klippel-Trenaunay Type I glycogen storage disease

Characteristics of benign liver tumors

Zakim and Boyer’s Hepatology 6th Edition 2012,Schiff’s Diseases of The Liver, 11th edition 2012Clinical Gastroenterology and Hepatology, 2nd edition 2012

Hemangioma

Incontinuous, peripheral

nodular enhancement

Progressive enhancement

with centripetal filled-in

Kim T et al. Radiology 2001

FNH

Homogeneous arterial

enhancement, sparing the central scar

Isodensity to liver parenchyma

Hepatic adenoma

Heterogeneous arterial enhancement

Heterogeneous mass:fat, hemorrhage

HCC

Arterial enhancement Venous wash out

sensitivity 90%, specificity 95%: Cirrhotic liver or HBsAg+

Risk factors for HCC in Asia

60%

5%

15%

20%HBV

Others

Alcohol

HCV

Bosch FX, et al. Gastroenterology 2004.

Pathogenesis of HCC

Chronic hepatitis

Cirrhosis

HCC

Hepaticadenoma

HBV

Aflatoxin

NASH Wear & tear

HBx

p53

PNPLA3?

Beta catenin

HCC surveillance

Bruix J, Sherman M. Hepatology 2010

EASL-EORTC guidelines 2012

High risk group

Cirrhotic patients• Child-Pugh A and B• Child-Pugh C awaiting liver transplantation

HBV• Age; M>40, F>50• Family history of HCC

HCV• F3 fibrosis

Mass on surveillance ultrasound*

No

Arterial enhancement AND venous wash out

4-phase MDCT/dynamic contrast enhanced MRI

Repeat U/S next 3 months

Growing/changingcharacter

Stable

< 1 cm > 1 cm

No

Yes

BiopsyYesHCC

Other study(CT or MRI)

Arterial enhancementAND venous wash out

Bruix J, Sherman M. Hepatology 2010*in a cirrhotic or HBsAg+ liver

HCC

Compensated Decompensated

Early Intermediate Early

Supportive

Main PV Metastasis

Resection

RFA, OLT

TACE TARE

Sorafenib

PF 0-2

No PHT PHT

OLT

Cirrhosis

No cirrhosis

Early Intermediate Main PV Metastasis

TARE

SorafenibResection

RFA TACE

Early HCC• 1 lesion < 5 cm • 3 lesions < 3 cm

Normal Cirrhosis HCCChronic hepatitis

Prevention of HCC

EASL-EORTC guidelines 2012

Recurrence

HBV & HCV: antiviral treatment (1A)NASH: metformin, statin

HBV : NUCs • HBV vaccination: newborn & high risk groups (1A)

• Avoid risk factors: HBV, HCV, obesity, alcohol (1A)

• Control metabolic conditions : i.e. DM (2A)

Good Luck