Liver diseases

Waseem Hamoudi, MD
Internal Medicine
Gastroenterology & Hepatology
Jordanian Friend of Liver Patients Society
Karak 2013
 Hepatitis A virus
First reference to epidemic jaundice has been
described to Hippocrates.
It accounts for 20-25% of clinical hepatitis in the
developed world.
It is due to a small 27-nm cubically symmetrical RNA
Picorna virus.
The virus is absorbed from the
gastrointestinal tract and reaches
the liver where it is engulfed.
Viral proteins are synthesized and packed into
vesicles to be released into bile.
 The virus is not directly cytopathic
and damage is caused by T cell
mediated immune responses.
The serum antibody appears as the stool becomes
negative for virus
IgG anti-HAV gives immunity from further infection
with hepatitis A.
IgM anti-HAV demonstrate recent infection with HAV
and they persist only for 2-6 months and rarely up to
1 year.
 Epidemiology
The disease occurs sporadically or in epidemic form
and has an incubation time of 15-50 days.
Spreading way is fecal-oral route.
Most affected group is aged 5-14 years and adults
are usually infected by spread from children
Spread is related to overcrowding and to poor
hygiene and sanitation.
Fulminant hepatitis in less than 1%.
Over 99% will be cured within few days to weeks.
 Hepatitis E virus
This accounts for sporadic and major epidemics of
viral hepatitis in developing countries.
Disease is enterically transmitted (fecal-oral route),
usually by sewage-contaminated water.
The virus is a 32-34-nm RNA virus, unenveloped.
It resembles calciviruses but has not be classified yet,
and has been placed in a new group called
herpesviridae.
It is direct cytopathic virus and cause minimal
immunological injury.
 It is secreted in the bile, but fecal excretion is low,
that is why there is low secondary spread.
Immunity is weak in this infection and longevity of
protective antibody is uncertain.
Clinical picture of this hepatitis resembles hepatitis
A, with incubation period of 22-46 days for blood
and 34-46 days for feces.
Onset is abrupt, jaundice in majority of the cases,
but there is no chronic course.
Acute fulminant hepatitis occurs in 1-2% and up to
10-20% for pregnant women.
 Diagnosis of HEV
HEV IgM can be detected by ELISA within 10-12 days
of acute illness, and it disappears within 6 months.
HEV IgG appears at 10-12 days also of acute illness
and remains positive for a long period of time.
Prevention by better sanitation and hygiene
education, clean water supply.
There is a vaccine for this virus.
 Hepatitis B virus
First discovered in 1965 in Philadelphia by Blumberg
from an Australian Aborigine (named at that time
Australia Antigen), then it was recognized as a viral
hepatitis virus. In 1977 Blumberg was awarded with
a noble prize for his discovery.
Australia antigen is now named surface antigen
known as HBsAg.
Over 2 billion people alive today have been infected
with HBV and over 350 million of them are
chronically infected carriers who have no significant
liver disease.
 The worldwide prevalence of HBV infection is falling due to
vaccination and better hygiene regarding shared syringes and
needles and sterilization.
Contamination occurs vertically (from mother to child during
labor) or horizontally( shared needle drug abuser,
contaminated blood products transfusion, needle-stick injury,
sexual transmission, shared toothbrushes and razors, dentist
instrumentation and barber instrumentation).
Kissing and blood-sucking arthropods such as mosquitoes or
bed bugs may have a role mainly in the tropics (not will
documented).
 The virus integrate in the genome of the hepatocytes and
replicate within them and expose the HBsAg upon the
external membrane if the hepatocytes.
The immune system of the infected person recognize the
infected cells and Ab against infected HBsAg and infected
hepatocytes are formed, and damage occurs.
Viral persistence is related to specific failure of cytotoxic T
lymphocytes (CTL) to recognize HBV antigen.
Normally self limited infection is mild to moderate and
termination of viral infection and resolution of the infection
occurs (90%)=acute hepatitis B.
If the destruction of hepatocytes is high (exaggerated immune
response) fulminant hepatitis occurs.
 Acute hepatitis B
Acquired by contact with blood or body fluids containing HBV.
Infectivity only for blood, genital secretions and occasionally
saliva.
Incubation period ranges from 6-26 weeks (Average 12
weeks).
HBS appear first in the incubation period, and disappears
within 3 months from the onset usually.
HBV DNA and HBeAg appear also at the same period.
Symptoms appear when the concentrations of bilirubin and
ALT are high and this coincide with the appearance of HBV Ab
(>4weeks).
 Chronic hepatitis B
1-10%.
> 85-95% of newborns and children infected under
age of 3 years, born to HBeAg positive mother,
become chronic carriers. (Due to immunological
immaturity in the children).
Persistence of HBsAg > than 6 months.
If HBV DNA and HBeAg persist high, it is a marker of
chronic active infection.
Long standing infection may enter low level of
replication (HBeAg cleared and produce HBeAb and
low level of HBV DNA) called carriers.
 Acute hepatitis, HBS Ag < 6 months
Chronic hepatitis, HBS Ag > 6 months.
Evolution of HBV infection: 5% of infected have
acute hepatitis (from that 1% have fulminante
hepatitis, and 99% heal).
65% have sub clinical infection, which heals 100%.
10% have chronic hepatitis B, which evolve in
cirrhosis in 10-30% and develop in HCC.
Rest of 70-90% is carrier of HBS Ag.
 Treatment
Acute hepatitis will not necessitate any treatment.
Acute fulminant hepatitis will necessitate admission
in ICU, with strict monitoring of vital signs, P.T, etc,
with strong indication of liver transplantation (90%
mortality).
Chronic hepatitis needs treatment ( Pegylated
interferon, lamuvidine, Adefovir, Entacavir etc)
Carrier state does not need treatment (low infectivity
and low replication), only close monitoring of LFT
and viral markers periodically.
 Hepatitis C virus
150 - 200 million infected worldwide.
USA: 3-4 million.
Americas: 12-15 million.
Africa: 30-40 million.
Fareast Asia: 60 million.
Southeast Asia: 30-35
million
Australia: 0,2 million.
 Genotypes
Six genotypes and multiple subtypes.[ based on
analysis of NS5 region nucleotide sequence]
Genotype 1: with subtypes a and b: common in USA
and West Europe
Genotype 2: Also in USA and W.Europe, second
place.
Genotype 3: same.
Genotype 4: Egypt (Middle East)
Genotype 5: S.Africa and Australia.
Genotype 6: Southeast Asia. (Hong Kong).
 Clinical course
Hepatitis C virus acute hepatitis C (anti-HCV)
Resolved spontanously(20%) [HCV -RNA negative,
ALT normal].
Chronic hepatitis C (80%) [HCV-RNA positive, ALT
increased] Cirrhosis (20%) HCC (25%).
 Course of the disease
74-86% are chronic (persistent viremia, asymptomatic)
15-25% resolves the infection.
The interval between infection and the development of
cirrhosis can exceed 30 years.
Cirrhosis develop from chr.hep.C (15-20%)
Factors that accelerate clinical progression: Alcohol intake,
co-infection with HIV or HBV, male, older age at infection.
Risk of HCC for the cirrhotic C patient is 1-4% / year.
HCC without cirrhosis can occur but more rare than HBV
infection
 Clinical features
Clinical manifestation can occur within 7 to 8
weeks (2 to 26) after exposure to HCV.
Majority do not have /or have mild symptoms.
Fulminant hepatitis very rare (not known).
Symptoms if exists are jaundice,
malaise and nausea .
 Treatment
Acute hepatitis C (if diagnosed), treatment with regular
Interferon (IFN) 5 MU e.o.d for 4 months or Pegylated
interferon alone (monotherapy) weekly for 4 months.
Chronic hepatitis C treat with Pegylated interferon weekly and
Ribavirin (combination therapy).
Chronic inactive carriers do not treat but close monitor.
Compenstaed active cirrhosis treat with combination therapy.
Decompensated cirrhosis do not treat.
 Liver cirrhosis
Is a complication of chronic hepatitis.
Causes of hepatitis may vary from viral
infections, autoimmune hepatitis, metal
disorders, NASH, PBC, PSC , Alcohol, and
others.
Golden standard of diagnosis by liver biopsy
(blind or guided by US or CT).
Clinical signs and symptoms and Para clinical
tests may diagnose the disease.
 Laboratory diagnosis
Etiological tests: HBsAg, HCV Ab, ANA, ASMA,
LKM1Ab, AMA, serum and urine cupper,
ceruloplasmine, Iron, Ferritin.
Prothrombin time(P.T), serum Albumin.
Liver function tests: AST, ALT, Bilirubin.
Alfa Feto protein (AFP).
Kidney function tests for H-R syndrome.
CBC (hypersplenism).
 Complication of liver cirrhosis
Hepato-renal syndrome.
Hepato-pulmonary syndrome.
Spontaneous bacterial peritonitis.
Upper gastrointestinal bleeding due to
esophageal varices rupture.
Encephalopathy.