Approach to Chronic Liver

Disease
Nu’man AS Daud
Gatroentero Hepatology Division
Departement of Internal Medicine
Hasanuddin University
November 12, 2016
 History

• Usually nonspecific
• Constitutional-malaise, listless, weight loss, nausea
• Alcohol ingestion
• Drugs-all of them, including IVDU
• Herbals
• Family history
• Transfusion
 Physical exam

• HEAD: parotid, enlargement, JVP elevation

• HANDS: muscular wasting, palmarerythema, dupuytren’s
• CHEST: Spider nevi, gynecomastia, R pleural effusion
• Abdomen / pelvis : caput medusae, testicular atropy, lymphadenopathy,
ascites, splenomegaly, liver size, texture and tenderness, mass
Palmar erythema
Spider
Caput
 Abnormal Liver Chemistry

• ALT (alanineaminotransferase)
• AST (asparateaminotransferase)
• SAP / ALP (serum alkaline phosphatase)
• GGTP (gamma glutamyltranspeptidase)
• Bilirubin (conjugated or not)
• Albumin (produced)
• INR
 Liver injury / Hepatocellular

• AST and ALT released

• High levels with acute injury
• AST also from heart and skeletal muscle
 Cholestatic injury

• Anything that impairs bile flow

• SAP, GGTP raised when chronic,

• Transaminas eselevated with acute obstruction, e.g., passing a stone

• Bilirubinrises with biliary obstruction.

• Mixed conjugated and unconjugated.
• Nearly pure unconjugated with hemolysis or Gilbert’s syndrome
 Liver function

• Albumin decreased with advanced liver failure. Remember losses of albumin

from kidney and gut and malnutrition also decrease
• INR/prothrombintime. Also correlates with liver function
 Liver function

• Albumin decreased with advanced liver failure.

• Remember losses of albumin from kidney and gut and malnutrition also decrease

• INR / prothrombin time.

• Also correlates with liver function.
 Approach to Liver disease

• Start with pattern, degree and duration of enzyme changes.

• Hepatocellular vs. cholestatic

Hepatocellular
Viral heptitis
 Type of Hepatitis
A B C D E

Source of feces blood/ blood/ blood/ feces

virus blood-derived blood-derived blood-derived
body fluids body fluids body fluids

Route of fecal-oral percutaneous percutaneous percutaneous fecal-oral

transmission permucosal permucosal permucosal

Chronic no yes yes yes no

infection

Prevention pre/post- pre/post- blood donor pre/post- ensure safe

exposure exposure screening; exposure drinking
immunization immunization risk behavior immunization; water
modification risk behavior
modification
 Hepatitis A

• Never chronic
• IgM HAV positive (IgG positive = previous infection)
• AST>ALT
 Typical Serological Course
Symptoms Total anti-HAV

Titre ALT

Fecal
HAV
IgM anti-HAV

0 1 2 3 4 5 6 1 2
2 4
Months after exposure
 Hepatitis B

• Contact with blood/body fluids

• Incubation 1-4 months
• 90% acute only, and 10 % chronic
• Chronic (IT, IC,LR dan Reactvasion)
 Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Symptoms
HBeAg anti-HBe

Total anti-HBc
Titre

HBsAg IgM anti-HBc anti-HBs

0 4 8 12 16 20 24 28 32 36 52 100

Weeks after Exposure

Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
Acute Chronic
(6 months) (Years)
HBeAg anti-HBe
HBsAg
Total anti-HBc
Titre

IgM anti-HBc

0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
 Outcome of Hepatitis B Virus Infection
100 by Age at Infection 100

80
Chronic Infection (%) 80

Symptomatic Infection (%)

60 60
Chronic Infection

40 40

20 20

Symptomatic Infection
0 0
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
Age at Infection
Clinical Characteristics of HBV chronic
Serologic test of HBV IgM Anti-
HBcAg

HBsAg 1st AB to appear; acute infection

Anti HBcAg
HBsAg
appears before not found in blood test
symptoms; used to resolution of acute
screen blood donor; disease & immunity (sole
negative = viral marker after vaccination) IgG Anti-
clearence HBcAg

previous (HBsAg-) or chronic (HBsAg

+) HBV infection
HBeAg HBV DNA

by product (evidance) of viral active viral replication

replication (↑ infectivity/acute
infection)

waning viral
Anti
replication, 
HBeAg infectivity
Natural history of chronic hepatitis B.
 Hepatitis C

• Rarely see acute infection

• 80% become chronic and of these only 20% develop end stage liver disease
and/or HCC
• Screen with HCV Ab
• HCV RNA to confirm active infection
 Typical Serologic Course
anti-
HCV
Symptoms

Titre

ALT

Normal
0 1 2 3 4 5 6 1 2 3 4
Month Years
s Time after
Exposure
Serologic test of HCV
acute infection/ resolving infection/false positive
Anti-HCV (confirm HCV qualitative)

in serum, livertissue, peripheral blood lymphocytes

HCV RNA

quantitative
qualitative

viral load ( high >800.000 IU/ml), (+) 2 weeks, marker active infection (< 50IU/ml), order
along with genotyping determination to define with HIV & hemodyalisis
treatment schedule & evaluate response therapy
 Clinical Course HBV & HCV
HCV 20-30%
neonatus approaching Hepatic
100%, children 70%, syntetic
healthy adult 1%;
failure

HBV 2-5% of HCV

cirrhotics/year
(usually after 20-30
Chronic Infection years)

HCV Portal
hypertension
70-85%

HBV
10-39 x increase risk even
without cirrhosis
(highest: perinatal acquired
and HBeAg+/↑viral load)
 Alcoholic Liver Disease

• Starts with fatty liver and progresses to cirrhosis

• Need 60 gms/day in males and 30 gms/day in females. One drinks is 10 gms.
• Not everyone is susceptible
• Acute alcoholic hepatitis-AST>ALT.
• If severe consider corticosteroids for 1 month in consult with IM/Hepatology.
 Drug / Toxic Hepatitis

• Acetaminophen (esp. with ethanol)

• INH, rifampin
• Minocycline, trimethaprim, clavulinicacid
• Diclofenac, phenytoin, valproic acid, DDI, tamoxifen, methotrexate,
amiodarone
• MANY herbals
 Autoimmune Hepatitis

• Mostly female and middle aged

• High gammaglobulins (IgG increase for Girls)
• Raised AST/ALT
• Low SAP/ALP
• Positive ANA and ASM (smooth muscle)
• Treatable
Metabolic Liver Disease
 Metabolic Liver Disease

• NASH/NAFLD

• 20% of obese, 2-3% cirrhosis

• assoc. with metabolic syndrome
• biopsy is AST/ALT>2ULN
• Statins
• treatment is weight loss
• similar biopsy to alcoholic liver disease
 Metabolic Liver Disease

• Alpha 1 antitrypsin deficiency

• Protein electrophoresis
• Hemachromatosis sceenwith Fe / TIBC
• If >45% consider genetic testing and liver biopsy
 Metabolic Liver Disease

• Metabolic: Wilson’s Disease

• acute or chronic,
• < 40 years
• association neurological disease and KF rings.
• Abnormal Cu excretion in bile
• Screen with ceruloplasmin
Cholestatic Liver Disease
 Cholestatic Liver Disease

• SAP/ALP elevates with age-esp in females

• GGTP/5’NT as elevated with liver disease
• Rule out extrahepatic obstruction/infiltrative with US, MRCP, or ERCP
• Primary BiliaryCirrhosis (PBC)
• AMA (mitochrondrial)
• Improved with Ursodiol.
The End
Questions?