INTRODUCTION

• Liver is the largest organ in the body.

• It lies in the right upper quadrant of the

abdomen.

• In adult the liver weighs about 1500g.

• Liver is a complex organ central to the

maintenance of homeostatic.
FUNCTION OF LIVER

• The main function of liver include ;

• Protein synthesis
• Storage of vitamin and glycogen
• Metabolism of fat, carbohydrate,
• Detoxification of drugs and other toxins
• Excretion of bilirubin
• Metabolism of hormones
LIVER DISEASE

• DEFINATION;
• Liver disease is defined as acute or chronic on the basis of whether
the history of disease is less than or greater than 6 months .
• PATHOPHYSIOLOGY OF LIVER DISEASE;
• The hepatocytes is the functioning unit of liver .hepatocytes are
arranged in lobules and within a lobule hepatocyte perform different
function depending upon how close they are from the portal tract.
• The portal tract is the service network of liver and contain a artery
and a portal vein delivering blood to the liver and bile duct which
form apart of biliary drainage system
• Blood supply to liver is 30 percent arterial and remainder is from
portal system
• Blood passes from the portal tract through sinusoid that facilitate
exposure to hepatocyte before blood is drained by hepatic venues and
vein.
• There are number of cell in liver like Kuppfer cell and fixed monocytes
that phagocytes bacteria and particulate matter .
• Stellate cell responsible for the fibrotic reaction that lead to cirrhosis.
CAUSES OF LIVER DISEASE ;

• The main cause of liver disease is viral infection .

• VIRAL INFECTION ;
• Viruses affect the liver resulting in a transient and
innocuous hepatitis.
• Virus which target liver are called as hepatotropic
viruses these lead to clinical significant hepatitis or
in some cases to viral hepatitis with viral
persistence .
TYPES OF LIVER DISEASE

• ACUTE LIVER DISEASE;

• Acute liver disease is a self limiting episode of hepatocyte damage .
• This is a rare condition in which there is a rapid deterioration in liver
function with associated encephalopathy(altered mentation)and
coagulopathy.
• ALF carries a significant morbidity and mortality and may require
emergency liver transplant .
CHRONIC LIVER DISEASE

• Chronic liver disease occur when permanent structural changes within

liver develop that lead toward long standing cell damage with loss of
normal liver architecture.
• In many cases this progression lead toward cirrhosis .this process is
irreversible but therapeutic intervention in hepatitis and
hemochromatosis cause reversal of cirrhosis.
• Cirrhosis progresses to liver failure, portal hypertension and
hepatocellular carcinoma.
• Time period of cirrhosis is from 5 to 20 year or more.
TYPES OF HEPATITIS

• Five types of hepatitis virus are ;

1. Hepatitis A
2. Hepatitis B
3. Hepatitis C
4. Hepatitis D
5. Hepatitis E
HEPATITIS
A
 EPIDEMIOLOGY

• Account for upto 25% of clinical hepatitis in the

developed world.
• Globally, an estimated 1.4 million cases occur each
year . Hepatitis A can occur sporadically or in an
epidemic form
• Can cause ALF in less than 1 % of patients who are
typically older adults.
INTRODUCT CLINICAL MECHANISM OF RISK FACTORS INCUBATION
ION MENIFESTATIO TRANSMISSIO PERIOD
NS N
• HAV is a • The prodromal • HAV is an • Poor sanitation • Short incubation
member of phase is enteric virus. areas period (2-7
the genus characterized by • Fecal oral route • Often associated weeks).
Hepatovirus non-specific is the main with water- and • During this time
in the family symptoms, such as mechanism of food- borne virus replicates
Picornavirida fatigue, weakness, transmission. epidemics. and
e. anorexia, nausea, • Particularly • High-risk abnormalities in
• HAV virus is vomiting, prevalent in groups include liver function
a non- abdominal pain, areas of poor sewage workers, test can be
enveloped and, less sanitation. cleanin determined.
RNA virus. commonly, fever. personnel and
• Major cause • Headache, children in day-
of acute arthralgias, care centers.
hepatitis myalgias, rash
worldwide. and/or diarrhea are
• less common
symptoms
• The early signs and
symptoms are
followed by
jaundice typically
peaks within two
weeks.

•
HEPATITIS B
 EPIDEMIOLOGY
• Up to 500 million people worldwide are chronically infected
with the hepatitis B virus.

• In endemic areas of Africa and the Far East, up to 15-20% of the

population are chronic carriers of HBV and vertical transmission
is the major risk factor for development of chronic HBV.

• 15-40% of HBV carriers will develop serious illness during their

lifetime, namely liver cirrhosis and hepatocellular carcinoma.

• Infants and children are much more likely to develop a chronic

infection.
INTRODUCTION CLINICAL MECHANISM OF RISK FACTORS INCUBATION
MENIFESTATIO TRANSMISSION PERIOD
NS
• HBV virus, is a • Jaundice • Sexual contact • New borns • Acute HBV virus
DNA virus and • Joint pain • By parenterally whose mothers infection has a
member of the • Dark urine • Transfusion of are infected long incubation
family • Abdominal blood or blood with HBV. period of 3-6
Hepadnoviridae. pain especially products • Infants and months, which
• Hepatitis B around liver • Vertical children whose is generally self-
infection may be • Loss of transmission parents were limiting and
either acute — appetite • Needle sharing born in areas does not require
lasting less than where HBV antiviral
six months — or infection is therapy.
chronic. widespread.
• Chronic HBV is • Sharing of
defined as the needles and
presence of household with
hepatitis B surface the infected
antigens (HBsAg) person.
for a period of • Unprotected sex
more than 6
months.
Treatment of acute Hepatitis B
• If HBeAg beyond 12 week then nucleoside analogue
are recommended
• Lamuvudine for very ill patient
• Passive and active immunization for HBsAg positive
mother
• Adult dose: 500 IU HBIG
• New borne : 200 IU
• Dose regimen: 0,1, 6 m0nth
Treatment of Chronic HBV
• HBeAG, HBsAG, HBV DNA with abnormal serum
AlT Should be treated.
-ve HBeAg with HBV DNA level >20,000 IU/l
should also be treated.
Pegylated alpha-2a interferon 180 ug once a week
subcutaneously, 12 month treatment.
Give 25 -45% response to genotype Aand B.
Concomitant HIV respond poorly.
PT with cirrhosis shoud not receive interferon
 Side effects
• 6-8 hr after injection flu like illness
• Malaise
• Headache
• Myalgia
• Depression
• Reversible hair loss
• Bone marrow depression
• Platelet count may be lower
Treatment for chronic HBV
• Lamivudine 100mg/day given orally
• Entecavir is more effective than
lamivudine
• Effective againt viral DNA
• Serum HBV DNA become –ive in 67%
and 90% HBeAg negative by 48 week.
• Tenofir monotherapy 300mg/day
HEPATITIS C
 Introduction

• Single strand RNA virus of the flaviviridae

family.
• Acute infection are asymptomatic just 10% pt
having flu like illness,jaundace, raised
aminotransferase.
• Most pt will not be diagnosed upto years..
• Extrahepatic manifestation including arthritis
• Glomerulonephritis,are seen
 EPIDEMIOLOGY
• over 170 million people are chronically
effected by HCV
• 2.7 million people in USA are infected.
• 200,000 and 500,000 people in UK are
affected
• The vertical transmission rate from HCV
infected mother to child is less than 3%.
 Transmission
• HCV is a hepatotropic, noncytopathic,
predominantly blood borne virus with greater
infectivity than the human immunodeficiency virus .
• HCV is transmitted parenterally, most commonly
through intravenous drug use and the sharing of
contaminated needles.
• There remains a small risk of HCV infection
associated with tattooing, electrolysis, ear piercing,
acupuncture and sexual contact.
• The vertical transmission rate from HCV infected
mother to child is less than 3%.
 CONTINUED……..
• 85% of the subjects exposed to HCV develop
chronic disease

• Which can lead to progressive liver damage,

cirrhosis and hepatocellular carcinoma

• 20-30% of pt with chronic HCV infection progress

to end stage liver disease within 20 years, small %
develop hepatocellular carcinoma.
 Pathophysiology
• Incubation period Average 6-7 weeks.
• In chronic HCV infection immune response is
insufficient to remove the virus.
• Early phase of infection: natural killer cell are
activated.
• HCV specific CD4 and CD8 (T lymphocyte)
and interferon coexpression decreases viral
replication
• Liver damage is associated with high levels of
hepatocyte apoptosis.
 Treatment
• Pt with end stage liver disease require liver transplant

• HCV infection leading world wide indication for liver

transplantation.

• HCV recurrence in the graft underline the limitation of

transplantation.
• Aim of treatment: viral clearance, SVR(ABSENCE OF
VIREMIA 6 month after antiviral therapy has been
discontinued.
• This improve pt quality of life reduces risk of
progression to cirrhosis and hepatocellular carcinoma.
 Cont………
• Combination therapy pegylated interferon (180
ug/day) +ribavirin (1000 – 1200 mg/day) for
genotype 1 and duration is 6 month.
• Ribavirin 800mg/day for genotype 2 and 3 for
12 month.
• HCV RNA > 6, 00000 IU/L less likely to
respond
• Pt failing to achieve a significant reduction in
viral load after 12 weeks of treatment are
usually withdrawn from therapy.
 Liver transplantation
• patients with ALF, decompensated chronic liver
disease, inherited metabolic disorders and
primary liver cancer

• HCV and alcohol-induced end-stage liver

disease are the commonest indications for liver
transplantation

• Typical 1 year survival rates are around 90% for

elective transplants
 Immunosupressent used to prvent
rejection
• immunosuppressive therapy
• calcineurin inhibitors (CNIs)
• tacrolimus
• ciclosporin
• Corticosteroids are used first 3 months after
transplantation.
• drugs used regularly for long-term
immunosuppression include azathioprine,
mycophenolate, sirolimus and everolimus
INTRO- SOURC MODE OF SYMP- INCUB- PREVEN-
DUCTION E OF TRANSMISSION TOMS ATION TION
VIRUS PERIOD

 It is an Blood Percutaneous Malaise 1.5 to 6 Pre post

incomplete Blood exposures Weakness months. exposure
virus that can derived Injection drug use Anorexia immunizati
establish body Per mucosal exposure Progressi on
infection only fluids. Sexual contact ve liver
in patients damage
simultaneously Cirrhosis
infected by carcinoma.
HBV
Associated
with the
development
of recognized
episode of
acute
hepatitis .
 HEV
• HEV is endemic in India, Asia, the Middle East
and parts of Latin America.
• It is an RNA virus which is transmitted
enterically and leads to acute hepatitis.
• an average incubation period of 42 days. It was
previously thought that the risk of death was
increased in pregnancy, especially in the final
trimester, but more recent data do not support
this belief
 CLINICAL
INVESTIGATIONS
 INVESTIGATIONS

•Assessment regarding to liver disease- done in all patients.

Investigation done on
Aetiology may patient groups to
differ (acute, ensure no primary
chronic) cause or co-factor
overlooked
 CONT..

• Some tests are done:

BIOCHEMICA
• Biochemical tests L TEST- Not
used in
• Laboratory investigation of aetiology isolation for
• Imaging techniques diagnosis
making.
• Liver biopsy
BIOCHEMICAL PARAMETERS-
LIVER ENZYMES

Cholestatic - Alkaline phosphatase,

bilirubin elevation

Hepatocellular pathology-
Bilirubin
Aminotransferase, Bilirubin
elevation
elevation
=
50micro
mol/L
exceedin
Hepatocyte damage- AST and ALT
g

Acute hepatitis, end- stage chronic

diseases – Bilirubin elevation-
jaundice
 BIOCHEMICAL TEST
 In Acute liver disease-
value of transaminases ( in
thousands elevation)
e.g.: Viral hepatitis, paracetamol
overdosing
 Chronic hepatitis- serum
transaminases more than five
to eight times than normal
upper limit (elevated)
 Liver Injury: acute, chronic -
PT (prothrombin time) ,INR
(International normalized
ratio) test
 Albumin- for
hypoalbuminemia,
proteinuria
IMAGING TECHNIQUES
 ULTRASOUND
o non-invasive test
o Size, shape and texture of liver
assessment, dilatation of
biliary tract screening
o Detection of Portal
hypertension(
o ( spleen size) for chronic
liver disease patients
o Hepatocellular carcinoma
screening- routinely used.
 If Abnormalities found in
Ultrasound then proceeding to:
 Computed tomography (CT
scan)
 Magnetic Resonance (MR)
 LABORTARY
INVESTIGATION OF LIVER BIOPSY
AETIOLOGY
• Invasive procedure
• Liver disease screening • Gold standard- diagnosis
• routinely tested assessment of chronic liver
• (for Hep-A,B,C and liver disease
dysfunction)

• Fibro scan
• Auto-immune and • Liver fibrosis (non-invasive) test
Immunoglobulins screening • For HCV patients
• For auto-immune diseases
• Liver histology

• Standard Investigations • Initiation for anti-viral therapy

• Serum ferritin
• Lipid profile
• Caeruloplasmin (in patients • dysfunction- liver
In acute liver
under 40yrs) biopsy (unnecessary)- condition self
limited