This document provides an overview of the approach to chronic liver disease. It discusses the history, physical exam findings, and abnormal liver chemistry patterns seen in various liver diseases. It then describes the characteristics of hepatocellular and cholestatic liver injury. Specific liver diseases covered include viral hepatitis A, B, C, alcoholic liver disease, drug/toxic hepatitis, autoimmune hepatitis, and metabolic/cholestatic liver diseases. Testing and clinical course are outlined for each condition.
NO1 Top Black Magic Specialist In Lahore Black magic In Pakistan Kala Ilam Ex...
Chronic_Liver_Disease.pptx
1. Approach to Chronic Liver
Disease
Nu’man AS Daud
Gatroentero Hepatology Division
Departement of Internal Medicine
Hasanuddin University
November 12, 2016
2. History
• Usually nonspecific
• Constitutional-malaise, listless, weight loss, nausea
• Alcohol ingestion
• Drugs-all of them, including IVDU
• Herbals
• Family history
• Transfusion
7. Abnormal Liver Chemistry
• ALT (alanineaminotransferase)
• AST (asparateaminotransferase)
• SAP / ALP (serum alkaline phosphatase)
• GGTP (gamma glutamyltranspeptidase)
• Bilirubin (conjugated or not)
• Albumin (produced)
• INR
8. Liver injury / Hepatocellular
• AST and ALT released
• High levels with acute injury
• AST also from heart and skeletal muscle
9. 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
10. 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
11. 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.
12. Approach to Liver disease
• Start with pattern, degree and duration of enzyme changes.
• Hepatocellular vs. cholestatic
15. Source of
virus
feces blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
blood/
blood-derived
body fluids
feces
Route of
transmission
fecal-oral percutaneous
permucosal
percutaneous
permucosal
percutaneous
permucosal
fecal-oral
Chronic
infection
no yes yes yes no
Prevention pre/post-
exposure
immunization
pre/post-
exposure
immunization
blood donor
screening;
risk behavior
modification
pre/post-
exposure
immunization;
risk behavior
modification
ensure safe
drinking
water
Type of Hepatitis
A B C D E
16. Hepatitis A
• Never chronic
• IgM HAV positive (IgG positive = previous infection)
• AST>ALT
17. Fecal
HAV
Symptoms
0 1 2 3 4 5 6 1
2
2
4
Total anti-HAV
Titre ALT
IgM anti-HAV
Months after exposure
Typical Serological Course
18. Hepatitis B
• Contact with blood/body fluids
• Incubation 1-4 months
• 90% acute only, and 10 % chronic
• Chronic (IT, IC,LR dan Reactvasion)
19. Symptoms
HBeAg anti-HBe
Total anti-HBc
IgM anti-HBc anti-HBs
HBsAg
0 4 8 12 16 20 24 28 32 36 52 100
Acute Hepatitis B Virus Infection with Recovery
Typical Serologic Course
Weeks after Exposure
Titre
20. IgM anti-HBc
Total anti-HBc
HBsAg
Acute
(6 months)
HBeAg
Chronic
(Years)
anti-HBe
0 4 8 12 16 20 24 28 32 36 52 Years
Weeks after Exposure
Titre
Progression to Chronic Hepatitis B Virus Infection
Typical Serologic Course
21. Symptomatic Infection
Chronic Infection
Age at Infection
Symptomatic
Infection
(%)
Birth 1-6 months 7-12 months 1-4 years Older Children
and Adults
0
20
40
60
80
100
100
80
60
40
20
0
Outcome of Hepatitis B Virus Infection
by Age at Infection
Chronic
Infection
(%)
23. Serologic test of HBV
HBsAg
appears before
symptoms; used to
screen blood donor;
negative = viral
clearence
Anti
HBeAg
HBeAg
IgM Anti-
HBcAg
HBcAg
Anti
HBsAg
HBV DNA
resolution of acute
disease & immunity (sole
marker after vaccination)
not found in blood test
1st AB to appear; acute infection
previous (HBsAg-) or chronic (HBsAg
+) HBV infection
IgG Anti-
HBcAg
by product (evidance) of viral
replication (↑ infectivity/acute
infection)
waning viral
replication,
infectivity
active viral replication
25. Hepatitis C
• Rarely see acute infection
• 80% become chronic and of these only 20% develop end stage liver disease
and/or HCC
• Screen with HCVAb
• HCV RNA to confirm active infection
27. Serologic test of HCV
Anti-HCV
acute infection/ resolving infection/false positive
(confirm HCV qualitative)
quantitative
HCV RNA
qualitative
in serum, livertissue, peripheral blood lymphocytes
(+) 2 weeks, marker active infection (< 50IU/ml), order
with HIV & hemodyalisis
viral load ( high >800.000 IU/ml),
along with genotyping determination to define
treatment schedule & evaluate response therapy
28. Clinical Course HBV & HCV
HC
V
HB
V
Chronic
Infection
Portal
hypertension
Hepatic
syntetic
failure
HBV
10-39 x increase risk even
without cirrhosis
(highest: perinatal acquired
and HBeAg+/↑viral load)
neonatus approaching
100%, children 70%,
healthy adult 1%;
70-85%
HCV 20-30%
2-5% of HCV
cirrhotics/year
(usually after 20-30
years)
29. 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.
30. Drug /Toxic Hepatitis
• Acetaminophen (esp. with ethanol)
• INH, rifampin
• Minocycline, trimethaprim, clavulinicacid
• Diclofenac, phenytoin, valproic acid, DDI, tamoxifen, methotrexate,
amiodarone
• MANY herbals
31. 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
33. 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
34. Metabolic Liver Disease
• Alpha 1 antitrypsin deficiency
• Protein electrophoresis
• Hemachromatosis sceenwith Fe /TIBC
• If >45% consider genetic testing and liver biopsy
35. 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
37. 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.
