Professional Documents
Culture Documents
FUNCTION OF HEPATOCYTES
1. synthesis of most essential serum proteins:
albumin, carrier proteins, coagulation factors,
hormonal and growth factors
2. Production of bile and its carriers: bile acids,
cholesterol, lecithin and phospholipids
3. Regulation of nutrients: glucose, glycogen, lipids,
cholesterol, amino acids
4. Conjugation of lipophilic compounds: bilirubin,
cations drugs for excretion in bile or urine
LIVER
Clinical History:
- Laboratory Tests
- Diagnostic Imaging
- Liver Biopsy : gold standard
LIVER
Biochemical Tests useful in evaluation and
management of patients with hepatic dysfunction:
Agents:
Hepatitis A virus - HAV
Hepatitis B virus - HBV
Hepatitis C virus - HCV
Hepatitis D virus - HDV or
HBV associated delta agent
Hepatitis E virus - HEV
Hepatitis G virus - HGV
ACUTE VIRAL HEPATITIS
HAV
Virus Particle : 27 nm
Morphology : Icosahedral
Genome : 7.5-kb RNA, linear, ss, +
Classification : Hepatovirus
Antigen(s) : HAV
Antibodies : anti-HAV
Features : Early fecal shedding
Diagnosis: IgM anti-HAV
Previous infection: IgG anti-HAV
Clinical and Epidemiologic Features
HAV
Incubation : 15-45, mean 30
Onset : Acute
Age preference : Children, young adults
Transmission
Fecal-oral : +++
Percutaneous : Unusual
Perinatal : -
Sexual : +
Clinical
Severity : Mild
Fulminant : 0.1%
Progression to
chronicity : None
Carrier : None
Cancer : None
Prognosis : Excellent
Prophylaxis : IG, Inactivated vaccine
Therapy : None
Scheme of typical clinical and laboratory
features of viral hepatitis A
Jaundice
ALT IgG Anti-HAV
IgM Anti-HAV
Fecal HAV
0 4 8 12 16 20
Commonly = self-limited
Complications and Sequelae:
1. Relapsing Hepatitis
- weeks to months after recovery
- recurrence of symptoms, amino-transferase
elevations, jaundice, fecal excretion HAV
2. Cholestatic variant
- protracted cholestatic jaundice + pruritus
3. Rare fulminant cases: older adults, underlying
CLD
Nomenclature and Features of
Hepatitis Viruses
HBV
Virus Particle : 42 nm
Morphology : Double shelled virion (surface and
core spherical)
Genome : 3.2-Kb DNA, circular, ss/ds
Classification : Hepadna virus
Antigen(s) : HBsAg, HBcAg, HBeAg
Antibodies : anti-HBs, anti-HBc, anti-HBe
Features : Bloodborne virus, carrier state
Acute diagnosis: HBsAg, IgM anti-HBc
Markers of replication: HBeAg, HBV DNA
Liver, lymphocytes, other organs
Nomenclature and Features of
Hepatitis Viruses
HBV
Virus Particle : 27 nm
Morphology : Nucleocapsid core
Genome :
Classification :
Antigen(s) : HBcAg, HBeAg
Antibodies : anti-HBc, anti-HBe,
Features : Nucleocapsid contains DNA and DNA
polymerase; present in hepatocyte
nucleus’ HBcAg does not circulate,;
HBeAg (soluble, nonparticulate) and
HBV DNA circulate-correlate with
infectivity and complete virions
Nomenclature and Features of
Hepatitis Viruses
HBV
Virus Particle : 22 nm
Morphology : Spherical and filamentous; represents
excess virus coat material
Genome :
Classification :
Antigen(s) : HBsAg
Antibodies : anti-HBs
Features : HBsAg detectable in >95% of patients
with acute hepatitis B; found in serum,
body fluids, hepatocyte cytoplasm; anti-
HBs appears following infection-
protective antibody
HEPATITIS B VIRUS: HBV
Pre-S2
Pre-S1 S
Jaundice
ALT
HbeAg Anti-HBe
IgG Anti-
HBc
HBsAg
Anti-HBs
IgM
Anti-HBc
0 4 8 12 16 20 24 28 32 36 52 100
Fulminant Hepatitis
- terminal events:
Cerebral edema - common
Brainstem compression
GIT bleeding
Sepsis
Respiratory Failure
Cardiovascular collapse
Renal Failure
ALT
HBeAg Anti-HBe
HBV DNA
HBsAg
Anti-HBc
IgM anti-HBc
0 1 2 3 4 5 6 12 24 36 48 60 120
CHRONIC HEPATITIS B
HCV
Virus Particle : Approximately 40-60 nm
Morphology : Enveloped
Genome : 9.4-kb, RNA, linear, ss, +
Classification : Flavivirus-like
Antigen(s) : HCV, C100-3, C33c, C22-3, NS5
Antibodies : anti-HCV
Features : Bloodborne agent, formerly labeled
non-A, non-B hepatitis
Acute diagnosis: anti-HCV (C33c,
C22-3, NS5)
Chronic diagnosis: anti-HCV (C100-3,
C33c, C22-3, NS5) and HCV RNA;
cytoplasmic location in hepatocytes)
Clinical and Epidemiologic Features
HCV
Incubation : 15-160, mean 50
Onset : Insidious
Age preference : Any age, but more common in adults
Transmission
Fecal-oral : -
Percutaneous : +++
Perinatal : +
Sexual : +
Clinical
Severity : Moderate
Fulminant : 0.1%
Progression to
chronicity : Common (50-70% chronic hepatitis;
80-90% chronic infection)
Carrier : 1.5-3.2%
Cancer : +
Prognosis : Moderate
Prophylaxis : None
Therapy : Interferon plus ribavirin
HEPATITIS C VIRUS
2. Chronic Hepatitis C
Scheme of typical clinical and laboratory features
during acute hepatitis C progressing to chronicity
Anti-C100
Anti-C22/C33
HCV RNA
ALT
0 1 2 3 4 5 6 12 24 36 48 60 120
Nomenclature and Features of
Hepatitis Viruses
HDV
Virus Particle : 35-37 nm
Morphology : Enveloped hybrid particle with HBsAg
coat and HDV core
Genome : 1.7-kb RNA, circular, ss, -
Classification : Resembles viroids and plant satellite
viruses
Antigen(s) : HBsAg, HDV antigen
Antibodies : anti-HBs, anti-HDV
Features : Defective RNA virus, requires helper
function of HVB (hepadnaviruses); HDV
antigen present in hepatocyte nucleus
Diagnosis: anti-HDV, HDV RNA;
HBV/HDV coinfection-IgM anti-HBc and
anti-HDV; HDV superinfection - IgG anti
HBc and anti HDV
Clinical and Epidemiologic Features
HDV
Incubation : 30-180, mean 60-90,
Onset : Insidious or acute
Age preference : Any age (similar to HBV)
Transmission
Fecal-oral : -
Percutaneous : +++
Perinatal : +
Sexual : ++
Clinical
Severity : Occasionally severe
Fulminant : 5-20%
Progression to
chronicity : Common
Carrier : Variable
Cancer : +
Prognosis : Acute, good
Chronic, poor
Prophylaxis : HBV vaccine (none for HBV carriers)
Therapy : Interferon +
HEPATITIS D VIRUS
1. Fulminant Hepatitis
2. Mild disease
3. Asymptomatic carriers
Nomenclature and Features of
Hepatitis Viruses
HEV
Virus Particle : 32-34 nm
Morphology : Nonenveloped icosahedral
Genome : 7.6-kb RNA, linear, ss, +
Classification : Alphavirus-like
Antigen(s) : HEV antigen
Antibodies : anti-HEV
Features : Agent of enterically transmitted
hepatitis; rare in USA, occurs in Asia,
Mediterranean countries, Central
America
Diagnosis: IgM/IgG anti-HEV (assays
being developed) virus in stool,
bile, hepatocyte, cytoplasm
Clinical and Epidemiologic Features
HEV
Incubation : 14-60, mean 40
Onset : Acute
Age preference : Young adults, (20-40 years)
Transmission
Fecal-oral : +++
Percutaneous : -
Perinatal : -
Sexual : -
Clinical
Severity : Mild
Fulminant : 1-2%
Progression to
chronicity : None
Carrier : None
Cancer : None
Prognosis : Good
Prophylaxis : Unknown
Therapy : None
ACUTE VIRAL HEPATITIS
CLINICAL FEATURES
Prodromal Symptoms
- systemic and quite variable
Clinical Jaundice:
- constitutional prodromal symptoms usually diminish
- mild weight loss ≈ 2.5-5 kg in some
- enlarged, tender liver + RUQ pain and discomfort
- cholestatic feature infrequently extrahepatic biliary
obstruction
- 10-20%: (+) splenomegaly
cervical adenopathy
- few spider angiomas
ACUTE VIRAL HEPATITIS
CLINICAL FEATURES
Recovery Phase:
- constitutional symptoms disappear
- some liver enlargement and biochemical
abnormalities evident
- duration variable: 2-12 weeks
Complete biochemical and clinical recovery expected:
1-2 months: Hepatitis A and E
3-4 months: 3/4 uncomplicated cases
Hepatitis B and C
ACUTE VIRAL HEPATITIS
LABORATORY FEATURES
- + - - - 1. Immunization with
HBsAg (after
vaccination)
2. Remote past
infection (?)
3. False-positive
ACUTE VIRAL HEPATITIS
Differential Diagnosis:
1. Viral diseases: Infectious Mononucleosis
CMV
Herpes simplex
Coxsackievirus
Toxoplasmosis
2. Drug hepatotoxicity
3. Alcoholic hepatitis
4. Biliary tract disease: acute cholecystitis, CBD stone,
cholangitis
5. Carcinoma: pancreas
metastatic
6. Pregnancy: HELLP syndrome
ACUTE VIRAL HEPATITIS
TREATMENT:
Prophylaxis:
HEPATITIS A immunization
Passive - immune globulin
Active - killed vaccine
Pre-exposure immunoprophylaxis
- vaccine preferred
TREATMENT
HEPATITIS B PROPHYLAXIS
HEPATITIS B PROPHYLAXIS
c. Sexual Contact
- single IM dose HBIG 0.06 ml/kg within 14 days of
exposure followed by complete course Hepatitis
B vaccine
HEPATITIS B IMMUNIZATION
IG role - undetermined
vaccine - in progress
CHRONIC HEPATITIS
Classification by cause:
Chronic Viral hepatitis caused by
Hepatitis B, B + D, C
Autoimmune hepatitis types 1,2,3 based on
serologic distinctions
Drug-associated chronic hepatitis
Cryptogenic chronic hepatitis = unknown cause
CHRONIC HEPATITIS
Classification by grade:
- based upon examination of liver biopsy
- include:
a. Degree of periportal necrosis
b. Disruption of limiting plate of periportal
hepatocytes by inflammatory cells:
piecemeal necrosis or interface
hepatitis
CHRONIC HEPATITIS
c. Bridging necrosis
- degree of confluent necrosis tract
links or form bridges between
vascular structure:
between portal tract and portal tract
between portal tract and central vein
d. Degree of hepatocyte degeneration and focal
necrosis within lobule
e. Degree of portal inflammation
Histologic Activity Index
Histologic Feature Severity Score
Classification by stage:
- reflects level of progression of disease
- based on degree of fibrosis
0 = no fibrosis
1 = mild fibrosis
2 = moderate fibrosis
3 = severe fibrosis, including
bridging fibrosis
4 = cirrhosis
CHRONIC VIRAL HEPATITIS B
Infection at birth 90% chance chronic Hepatitis B
Degree of Hepatitis B virus replication
- divided into 2 phases
a. Replicative phase
- (+) HBeAg
- (+) HBV DNA
- presence in liver of detectable intrahepatocyte
nucleocapsid antigens
- high infectivity
- accompanying liver injury
- HBV DNA detected in liver but extra
chromosomal
- more severe chronic hepatitis
CHRONIC VIRAL HEPATITIS B
b. Nonreplicative phase
- characterized by the absence of
conventional markers HBV
replication (-) HBeAg
(+) anti-Hbe
- absence of intrahepatocytic HBcAg
- limited infectivity
- minimal liver injury
- HBV DNA detected in liver but integrated
in host genome
- minimal or mild chronic B or
asymptomatic carriers
- 10-15% conversion replicative to
nonreplicative
Diagnostic Criteria of HBV
Infection
• Chronic Hepatitis B
- HBsAg(+)>6 months
- Serum HBV DNA >20,000 IU/ml.
Lower values 2,000-20,000 IU/ml
are often seen HBeAg(-)chronic
hepatitis B
- Persistent or intermittent elevation in
AST/ALT levels
- Liver biopsy showing chronic hepatitis
with moderate or severe
necroinflammation
Diagnostic Criteria of HBV
Infection
• Resolved Hepatitis B
- Previous known history of acute or chronic
hepatitis B or the presence of
anti-HBC ± anti-HBs
- HBsAg(-)
- Undetectable serum level HBV DNA
- Normal ALT levels
Asian-Pacific Guidelines For
Treatment of Chronic Hepatitis B
Algorithm Management of
HBeAg(+) Carriers
Algorithm Management of
HBeAg(-) Carriers
Recommendations for Treatment
of Chronic HBeAg(-) Patients
Recommendations for Treatment of
Chronic Hepatitis B Patients with
Cirrhosis
CHRONIC HEPATITIS C
TREATMENT:
Two approaches to antiviral therapy:
1. Monotherapy with interferon
2. Combination therapy with interferon + ribavirin
RETREATMENT RECOMMENDED
2. Idiosyncratic
- Halothane
- Isoniazid
- Chlorpromazine
3. Cholestatis
- Oral Contraceptives
Principal Alterations of Hepatic Morphology Produced
by Some Commonly Used Drugs and Chemicals
Principal
Morphologic
Change Class of Agent Example
Principal
Morphologic
Change Class of Agent Example
Clinical Symptomatology
• Gastric lavage
• supportive measures
• oral administration of activated charcoal or cholestyramine to
prevent drug absorption
• N - acetylcysteine
1. Alcoholic steatosis
(alcoholic fatty liver)
2. Alcoholic steatonecrosis
3. Alcoholic cirrhosis
ALCOHOLIC CIRRHOSIS
CLINICAL FEATURES:
Alcoholic : asymptomatic or
hepatitis = viral/toxic hepatitis:
anorexia,vomiting, malaise,
weight loss, fever, jaundice,
tender hepatomegaly,
1/3 splenomegaly
ALCOHOLIC CIRRHOSIS
CLINICAL FEATURES:
Supportive
Treat Encephalopathy
CARDIAC CIRRHOSIS
• Etiology: prolonged severe right sided
congestive heart failure
• Clinical features: tender enlarged liver
severe RUQ pain
AST
albumin and protime
• Diagnosis: usually clinical
(+) valvular heart disease
(+) cor pulmonale
• Treatment: treat underlying disorder
BILIARY CIRRHOSIS
PRIMARY BILIARY CIRRHOSIS
• Clinical Features
early: asymptomatic
marked alkaline P04tase
pruritus
jaundice
osteopenia 20%
xanthomas 10%
(+) association with Sjogren’s syndrome 75%
rheumatoid arthritis 5%
CREST syndrome 3%
PRIMARY BILIARY CIRRHOSIS
• Diagnosis:
serum cholesterol
4-6x elevation Alkaline P04tase
direct bilirubin
(+) antimitochondial antibodies 90%
• Treatment:
Supportive
Antipruritic = Cholestyramine
Vit. B/K supplements
Dietary supplements - MCT
SECONDARY BILIARY CIRRHOSIS
• Portal Hypertension
• Variceal bleeding
• Splenomegaly
• Spontaneous bacterial peritonitis
• Hepatorenal syndrome
• Coagulopathy
• Hepatocellular carcinoma
MAJOR COMPLICATION OF
CIRRHOSIS
PORTAL HYPERTENSION
results from increased resistance
to portal blood flow
(> 30 cm saline)
increased resistance can occur at
3 levels:
1. Presinusoidal
2. Sinusoidal
3. postsinusoidal
PORTAL HYPERTENSION
• Clinical Features:
- hemorrhage from : gastroesophageal
varices
- splenomegaly with hypersplenism
- ascites
- acute and chronic encephalopathy
• Diagnosis: clinical
endoscopic findings
• Treatment: directed toward a specific
complication
TIPS
Surgery
HEPATIC ENCEPHALOPATHY
Pathogenesis:
most important: severe hepatocellular
dysfunction and/or intrahepatic and
extrahepatic shunting of portal venous
blood into the systemic circulation
bypassing the liver
Incriminated substances:
1. Ammonia
2. Mercaptans
3. Short chain fatty acids
4. Phenol
5. False neurochemical
transmitters: octopamine
GABA
Common Precipitants of Hepatic Encephalopathy
Protein restriction
Inadequate response?
Inadequate response?
- asymptomatic
ETIOLOGIC FACTORS:
• Previous HEPATITIS B infection
90-95% HCC: (+) HBV infection
60-70% Chronic hepatitis/cirrhosis
• Mycotoxins
• Humoral factors
androgen
• Schistosomiasis (?)
Clonorchiasis (?)
PRIMARY HEPATOCELLULAR
CARCINOMA
CLINICAL FEATURES:
• Hepatomegaly
• Hepatic bruit or friction rub
• ascites - bloody 50%
• nonspecific symptoms
- malaise - weight loss
- anorexia - abdominal pain
• clinical deterioration or sudden increase in
transaminases in a stable cirrhotic patient
PRIMARY HEPATOCELLULAR
CARCINOMA
DIAGNOSIS:
TREATMENT:
• No effective treatment
Survival rate < 6 months
• Surgery : 5-year survival rate < 10%
• Radiotherapy
rare response
• Chemotherapy
METASTATIC HEPATIC
MALIGNANCY
• More common than primary
• Source:
GIT carcinomas
malignant melanoma
CA - pancreas
lung
breast
kidney
ovary
Lymphoma
METASTATIC HEPATIC
MALIGNANCY
• Clinical features:
fever
RUQ pain
hepatomegaly
friction rub
jaundice
• Diagnosis
liver biopsy; CT or UTS guided
aspiration biopsy
METASTATIC HEPATIC
MALIGNANCY
TREATMENT:
Pulmonary TB
Normal
Pneumonia
Pulmonary Congestion
Elevated (R) hemidiaphragm
HEPATOBILIARY TUBERCULOSIS
• Sonographic findings
Biliary obstruction
intrahepatic duct
common bile duct
common hepatic duct
unspecified
Hepatomegaly
with calcification
without calcification
Contracted Gall Bladder
HEPATOBILIARY TUBERCULOSIS
• Sonographic findings
Cholecystitis
Choletithiasis
Choledocholithiasis
TB liver
Pancreatic head mass
Pancreatitis
Portal HPN
Splenomegaly
HEPATOBILIARY TUBERCULOSIS
TREATMENT:
Anti-TB therapy
12-18 months triple/
quadruple treatment
Surgery
LIVER ABSCESS
• Amoebic
• Pyogenic
AMOEBIC LIVER ABSCESS
• Etiology
Entamoeba histolytica
• Clinical features
RUQ pain
fever
chills
pleuritic pain
night sweats
intestinal amoebiasis 50%
AMOEBIC LIVER ABSCESS
• Laboratory
leukocytosis 50%
transaminases
serum bilirubin
alkaline Po4tase 80%
AMOEBIC LIVER ABSCESS
• Diagnosis
Ultrasound = complex mass
solitary
right lobe 90%
CT scan
Gallium scan - filling defect
Aspiration Biopsy
- “anchovy paste” fluid with trophozoites
Serologic test : (+) 95%
- indirect hemagglutination gel diffusion
AMOEBIC LIVER ABSCESS
• Therapy
Amoebicides : Metronidazole
Chloroquine
• Complications
cyst rupture pleural space
lung
bowel
retroperitoneum
PYOGENIC LIVER ABSCESS
70% mixed flora
commonly: Anaerobes
- E. coli
- Klebsiella
- Staphylococcus aureus
- Streptococcus
PYOGENIC LIVER ABSCESS
• ETIOLOGY:
• CLINICAL FEATURES:
- fever
- chills
- RUQ pain
- anorexia
- nausea
- tender hepatomegaly 50%
PYOGENIC LIVER ABSCESS
• DIAGNOSIS:
Laboratory:
80% elevated Alkaline P04tase
33% jaundice = bilirubin
40% (+) Blood Culture
Diagnostic Procedures:
Ultrasound
CT Scan
UTS guided aspiration
PYOGENIC LIVER ABSCESS
• TREATMENT
- aspiration:
percutaneous or surgical drainage