HEPATOLOGY

Gatot Sugiharto, MD,

Internist
Faculty of Medicine, UWKS
Lecture - 2013

1
GSH - Gastro - 2010

Hepatitis, introduction(1)
Generic term for inflammations of the
liver
Caused by a number of viruses, other
infectious agents, and toxins

Viral Hepatitis
There are 7 hepatitis viruses : A, B, C, D, E, F, G
Hepatitis A and E are transmitted primarily by
contaminated food and water, high-risk areas :
poor sanitation contamination of water.
Hepatitis B and C are spread by sexual contact,
exchange of body fluids, injections from
contaminated needles and syringes, and
unscreened blood transfusions.
Percutaneous exposure and risk of infection
HBV
6-30%
HCV 0-7%
HIV 0.3

Symptoms
Can vary, some cases completely unnoticed.
Because the liver is involved with so many
metabolic functions, the symptoms is
generalized
Most common : fever, fatigue, loss of appetite,
jaundice (yellow skin), dark urine, abdominal
pain, and aching joints.
May occur weeks to months after exposure and
typically last from 2 to 6 weeks. .
Complete recovery (most cases A and E), but

Laboratory test
A definite diagnosis : viral-specific hepatitis test
(serologic markers)
Viral hepatitis assays : detect the presence of
specific Vi antigens and/or antibodies in serum.
The purposes of serologic marker test :
Diagnose, differentiate between virus,
differentiate stage & resolution of the infection
Screening to prevent spreading, to test sex
partner etc
Monitor & evaluate seroconversion, success of
prophylaxis

Hepatitis
A
Vaccine-preventable viral illnesses and the most
frequently diagnosed form of hepatitis in developing
countries.

Very widespread and close to 100% of people in less

developed countries are infected by 10 years of age, in
contrast in US, about 33% has serologic evidence of
previous HAV infection
Accounts for 20-40% of all viral hepatitis
Spread fecal-oral route, results in acute, self-limited
illness or asymptomatic infection (majority of cases)
Fulminant disease when co-infected with HBV or HCV,
especially when older
Labs
ALT > AST usually >1000 IU/dl

Hepatitis A (Contd)
Treatment supportive 85% full

clinical/biochemical recovery in 3 month

Prevention handwashing, good

sanitation
Postexposure propylaxis
Immune globulin and HAV vaccination
Immune globulin effective within 2
weeks of exposure
Vaccine recommended for higher risk
groups
GI 9

Hepatitis B

The double-stranded circular

Hepadnaviridae family consists of a
central core nucleocapsid containing
viral DNA and a surrounding
envelope containing the surface
protein antigen
Global public health problem
300 million HBV carriers
250,000 deaths yearly
GI 10

Routes of Transmission
Percutaneous :
Contaminated needle stick (injecting drug use and
occupational exposure/nosocomial) more common
from patient to health care provider
Hemodialysis, Human bite, Transplant or transfusion,
Sharing razors

Permucosal
Sexual intercourse (50% of cases in U.S)
Perinatal-infant born (infection at or after birth)
90% if mother HBeAg positive (30% if negative)
C/S doesnt prevent & breastfeeding doesnt
increase risk
Contact with infected household objects (toothbrush
or razor)

Individual at Risk
Sexual contacts, multiple sex partners,
Injecting drug users
Infants born to HBV infected mother
Individual who have occupational contact
with blood (medical workers, laboratory
personnel, public service employees
Recipients of unscreened blood
Hemodialysis patients
Household contacts of HBV infected
individuals
Institutionalized populations (i.e.

Clinical Course
Incubation period averages 60-90
(range 45-180 days)
Onset is often insidious
HBV causes clinical illness in 30-50 % of
all individuals age five and older, but
less than 10 % of those aged under five
years
Symptoms may include anorexia,
fatigue, nausea, vomiting, abdominal
pains, muscle or joint aches, mild fever,
dark urine, skin rases, and jaundice

Clinical Course (cont)

Jaundice develops in 25-35 % of patients
with symptoms
Most of HBV-infected adults will recover
within six months and develop immunity
Of those infected with HBV, 30-90 % of
chlidren less than 5 years of age and 2-10
% of the population over 5 years of age
will progress to chronic infection
Among all age groups, 15-25 % of those
who become chronically infected with HBV
die prematurely as a result of chronic liver
disease

Diagnostic panels
Consists of 5 markers: HBsAg, HBeAg, anti-HBe
anti-HBc and anti-HBs
If HBSAg and anti-HBc IgM is positive Acute
Hepatitis B serial testing with the
monitoring panel is indicated
Hepatitis B monitoring panels :
Determine the persistence of HBsAg (chronic
HBV infection)
Determine relative infectivity (HBeAg)
Monitor seroconversion from HBeAg to antiHbe resolution of the disease
Monitor seroconversion from HBsAg to anti

Chronic HBV Infection

Determine the stage of chronic
infection: HBsAg, HBeAg, Anti-HBc total
HBsAg and anti-HBc total will always be
present, HBe Ag may be positive or
negative depending on the stage of
disease progression or the existence of
pre- core mutant.
Two types of chronic HBV infection:
1. No seroconversion
2. Late seroconversion

Testing to Determine Immunity:

Anti-HBs

Recommended for: Healthcare workers, Babies

born to HBV infected mother, Sex partners of
persons with chronic HBV infection,
Immunocompromised individuals
The purposes of quantitative levels of anti-HBs are:
To determine the need for initial vaccination
To establish an initial level of anti-HBs after the
vaccination
To determine whether revaccination is needed
Prevention/Prophylaxis
To assess recovery from HBv infection

Screening of blood and blood products

Destruction of disposable needles, and
adequate sterilization of reusable medical
equipment
Universal precautions and barrier techniques

Treatment for chronic HBV

infections

Considered when HBsAg >6 months, evidence

of active virus replication (HBeAg and HBV
DNA positive) and active liver disease
(chronic hepatitis on biopsy, elevated ALT)

Interferon/Pegylated interferon Therapy

12-24 weeks in doses of 5 MU/daily or 10
MU 3x/week
Pegylated interferon may be helpful
Results
Supresses HBV replication ( HBV-DNA,
HBeAg)
GI 20
Improvement in liver disease (normal

Hepatitis C
Acute process often asymptomatic;
80% develop chronic hepatitis liver
transplant cirrhosis10-15%, 10% may
develop decompensated disease or
hepatocellular carcinoma
Six genotypes (1 to 6 ) and multiple subtypes
(a,b,c etc)
Genotype 1 and 4 are more resistant to therapy
than genotype 2 and 3
Genotype 1b : more severe & agresive liver,
GI 21

HEPATITIS C VIRUS
Single, positivestranded
Flaviviridae RNA
virus
Individual at Risk
Injecting drug users
Persons
occupationally
exposed to blood
Hemodialysis patients
Tranfusion and

Diagnostic Testing for Hep

C
HCV is diagnosed serologically by:

Detecting anti-HCV does not distinguish

between an acute, chronic or resolved
infection
Ruling out other viruses such as HAV or HBV
If initial result is negative, but clinical signs
& symptoms suggest a HCV infection
retesting for anti-HCV
A supplemental test, RIBA (recombinant
immunoblot assay) confirm a positive EIA
anti-HCV test
HCV RNA test (Quantitative/Qualitative)
confirm acute or chronic infection +

Developments in HCV Testing

(HCV RNA)

Assess circulating virus

Evaluate suspect HCV infection before
seroconversion occurs
Asses viral load before & monitor the effectiveness
of antiviral therapy
Detect HCV infection in cases with ambiguous
Hepatitis C transmission
serology
Exposure to infected blood before 1992(Screening
started in 1992)
Heterosexual monogamous relationships (Risk low
0-0.5%/year
Perinatal
2% when EIA positive, 7% when HCV RNA positive
NO data on preventive by C/S

Routes of Transmission

Percutaneous
Contaminated needle stick (injecting drug use and
occupational exposure)
Hemodialysis
Human bite
Transplant or transfusion of unscreened blood or
blood products
Acupuncture, tattooing, and body-piercing with
unsterilized needles
Permucosal
Sexual intercourse
Perinatal-infant born to an HBV infected mother
Contact with infected household objects (i.e
toothbrush or razor that may have blood on it)

Hepatitis C Treatment
Highest response with Pegylated
Interferon and Ribavirin
Genotype 1
Treat for 48 weeks if minimum of 2 log
decrease detected at 12 weeks
Ribavirin 1000-1200 mg usual dose

Genotype 2,3 : Ribavirin 800 mg (24

weeks)
Prognosis : Hepatitis C and cirrhosis
GI 28

HEP D & E
HDV depends on HBs-Ag for replication and
expression. Without the HBs-Ag coating
cannot infect on its own.
HEV : non enveloped virus, similar with HAV,
in pregnant woman mortality reaches 15-25%
(2nd & 3rd trimester)
Large outbreaks occur through contaminated
drinking water
More than 50% of the patients with acut
Hepatitis E develop a cholestatic form

Hepatic injury

Patterns of Hepatic Injury

Inflammation = hepatitis
Degeneration (ballooning ) : swelling and edema of
hepatocytes
Necrosis - coagulative necrosis (ischemia), less common
( liver has dual blood supply)
Apoptosis = councilman body ( apoptotic bodies in the
liver caused by viral hepatitis)
Regeneration : possible in all but not in fulminate diseases
Fibrosis : seen in cirrhosis
Hepatic failure : fulminate damage (80 to 90% of liver is
damaged)

 Portal HTN = 12 mm Hg or >, clinically :

1. Ascites (peritoneal fluid)
2. Varicosities
3. Congestive splenomegaly
4. Hepatic encephalopathy
Cholestasis = retention of bilirubin , bile salts & cholesterol
Jaundice =Bilirubin production > hepatic clearance
Total bilirubin = conjugated + unconjugated.
Conjugated bilirubin is more soluble
Result from Hepatocellular dysfunction (Intrahepatic)
or Biliary obstruction (Extahepatic)
Symptoms ; jaundice- (Bilirubin), pruritus - retention
of bile acids, Xanthomas (skin accumulations of
cholesterol),

Jaundice

Unconjugated Hyperbilirubinemia

Bilirubin overproduction hemolytic anemias,

resorption of major hemorrhages, ineffective Erythropoiesis
in the bone marrow

Hepatic uptake of bilirubin = drugs rifampin

Impaired hepatic conjugation of bilirubin
Physiological jaundice of newborns (neonatal jaundice)
Genetic diseases : Gilbert syndrome, Crigler-Najjar
syndrome type I-II
Conjugated hyperbilirubinemiaassociated with cholestasis
Dubin-Johnson syndrome :defective canalicular secretion of
bilirubin
Rotor syndrome :

Cholestasis - Types

Intrahepatic
Hepatocellular dysfunction
or intrahepatic bile duct
disease
Congenital
Transplantation is only the
treatment
if uncorrected- becomes
cirrhotic

Extrahepatic
resulting from obstruction

Acquired
amenable to surgical
correction
if uncorrected- becomes
cirrhotic

Liver Cirrhosis
Liver Cirrhosis : histopathologic term (xirros =
shrunken & hard)
Major causes:
Alcohol (ASH)
Cryptogenic cirrhosis called NASH
Viral hepatitis B & C (tropical countries)

Diagnosed based on two clinical syndromes:

Hepatocellular failure, or
Portal Hypertension syndrome

Three characteristics
Fibrosis irreversible and result in Portal HTN
Nodules - regeneration of hepatocytes
GILoss
of architecture of the entire liver
35

Clinical features

Jaundice, hypoalbuminemia, hyperammonemia

Fetor hepaticus
Hyperestrogenemia : palmar erythema, spider
angiomas of the skin (one or two are normal esp. in
pregnancy), hypogonadism, gynecomastia
Complications
Coagulopathy ( hepatic synthesis of clotting factors)
Multi- organ failure, hepatic encephalopathy ( excess
ammonia)
Hepatorenal syndrome

Patterns of Hepatic Injury

Normal Liver

Inflammation
(Hepatitis)

Fibrosis
(Cirrhosis)

Hepatocellular Failure Syndrome

(HFS)
Consists of : loss of hair, hyperpigmentation,
Jaundice, Spidernaevi, gynaecomastia, testis
atrophi, disturbance of periodicity, liver palm,
white nail
Portal Hypertension Syndrome (PHS)
Consists of:
Varices of the esofagoes and rectum
(haemorrhoid)
Hematemesis melena
Rectal bleeding (haematochezia/enterorrhagia)
Vascular collateral in the abdominal wall
Splenomegali , Ascites
Oedema of the lower extremeties

palmar erythema

Spider
angiomas

The Complications of
Liver Cirrhosis

Hematemesis-melena
Ascites per magna
Peritonitis bacterial spontanea
Hepatorenal syndrome
Hepatic encephalopathy
Hepatoma

Ascites
In patients with cirrhosis and
Ascites:
Ascites is the most common form of
clinical decompensation
Carries a poor prognosis, 50% mortality
within 2 years
Prone to spontaneous bacterial
peritonitis (diagnostic tap is mandatory
if suspect infection)
Patients with new-onset ascites or
clinical deterioration should undergo
GI 44

Ascites (Contd)
Follow a sodium-restricted diet
Diuresis, with spironolactone (Aldactone)
as first-line therapy and occasional use of
a supplemental loop diuretic
Diagnosis of spontaneous bacterial
peritonitis (SBP) heralds advanced liver
disease
Antibiotic prophylaxis for SBP as a
preventive strategy cannot be definitely
recommended
TIPSS (Transjugular intrahepatic portalGI 45

Hepatic Encephalopathy
Disorder of CNS & neuromuscular transmission
Disturbances of consciousness & sleep, (behavioral
abnormalities, confusion, stupor, coma, death)
EEG changes, limb rigidity and Hyperreflexia,
Seizures & asterixis (a flapping tremor of outstretched
hands)
Pathogenesis : Severe loss of Hepatocellular function &
Exposure of the brain to excess ammonia levels

Hepatorenal Syndrome

Renal insufficiency (Urea and creatinine)

secondary to severe liver disease
Decreased renal perfusion pressure renal
vasoconstriction
Oliguria with a hyperosmolar urine without
Proteinuria
Low urinary sodium (though kidney can still
concentrate Urine)
Kidney function promptly improves if hepatic
failure is reversed

Hepatoma
Hepatocellular carcinoma is a leading
cause of death in patients with
cirrhosis
Once cirrhosis has developed, hepatitis
C is the most common cause of
hepatocellular Ca
Screening with alpha-fetoprotein and
ultrasonography every six months
GI 48

Gallbladder Disease
Acute Cholecystitis
90% of cases - gallstone obstructs the
cystic duct,10% of cases - absence of
gallstones (acalculous cholecystitis)
Diagnostic tests: Ultrasound (most
useful), Cholescintigraphy, Abdominal
CT scanning
Management: definitive therapy
-cholecystectomy
Pregnant patient -conservative therapy
GI 49

Gallbladder Disease (Contd)

Choledocholithiasis
15% of patients with gallbladder stones
have stones in common bile duct
Tests: ERCP (gold standard),
cholangiography
Ultrasound visualizes about 50% of
common bile duct stones, can detect CBD
dilatation in 75% of cases
Complications: cholangitis, acute
pancreatitis
Management: stone removal by ERCP,
GI 51
early cholecystectomy

Cholangitis
85% of cases due to impacted stone in duct
Charcots Triad (RUQ abdominal pain, fever
and jaundice) present in 70% of cases
Diagnosis: increased WBC, increased LFTS,
blood cultures, ERCP(gold standard),
cholangiogram, ultrasound, MRCP
Management: ERCP with stone removal,
Antibiotics that cover gram-negative
organisms, consider cholecystectomy
GI 53