Introduction to liver diseases

Indika Gawarammana
(MBBS, MD, MRCP, FRCPE, PhD)
• Largest Organ in the body
• Two lobes
• 25% of cardiac output goes to liver
• 25% from hepatic artery
• 75% from portal vein
 Functions of the liver:
Protein metabolism

• All circulating protein except gamma globulins

• Plasma contains 60-80g/L of protein: mainly
alb, glob and fibrinogen
• Alb maintains intravascular pressure and
transports bili, hormones and drugs
• Coagulation factors
 Protein metabolism:
degradation

• Ammino acids are degraded to ammonia

 Carbohydrate metabolism
• Glucose homeostasis: stores 80g of glycogen
• Releases glucose during fasting
 Lipid metabolism
• It synthesizes VLDL,HDL ect
 storage
• Iron
• Copper
• Vitamins A,D and B12
 Other functions
• Bile secretion, hormone and drug inactivation
• Kupffer cells – phagocytosis
• Stellate cells- regulate blood flow
Clinical assessment of liver disease

• History
• Physical examination
• Investigations
 Acute liver diseases- symptoms
• Fever
• loss of appetite, vomiting,
• upper abdominal pain,
• abdominal distension,
• discolouration of urine
• encephalopathy
 history
• Onset, prodromal illness
• Contact history of liver diseases
• Alcohol abuse
• Myalgia
• Tattooing
• Dietary history
• Drug history, IV drug abuse
• Recent travel
 signs
• Jaundice
• Tender enlarged liver
• Scratch marks
• Myalgia
• Encephalopathy
• Acsites
• Splenomegaly
 Chronic liver diseases

• With obvious signs of liver disease

• With abnormal biochemistry

 Chronic liver diseases
• Symptoms: may be NONE
• Non specific:
lethargy
abdominal discomfort
abdominal distension
leg odaema
gynaecomastia
altered mental functions
 contd
• May present for the first time with a
complication:
bleeding
encephalopathy
severe abdominal distension
prolonged bleeding after minor surgery
other diseases such as diabetes and
movement disorders
 Important factors in the history
• Risk factors for Hep B and C ( drug , blood,
tatooing)
• Alcohol history
• Drug history, herbal medicines
• Family history
 Physical examination
• Spider naevi
• Palmar erythema
• Clubbing
• Dupuytren’s contracture
• Leuconychia
• Jaundice
• Ascites and oedema
• Hepatic encephalopathy
• Hepato- splenomegaly
• Caput Medusae
• Abdominal masses
 Investigations
• Assesses liver function
• To detect structural abnormalities
• Detect complications
• To determine the underlying cause
 Blood tests
• Liver function tests: albumin and prothrombin
time
• Liver biochemistry: aspartate and alanine
aminotransferases( liver damage)
• Alkaline phosphatase and gamma glutamyl
transpeptidase( cholistasis)
• Viral markers
• Urine bilirubin and urobilinogen
 Assess the following:
• Pattern: hepatocellular or cholestatic
• Magnitude of elevation
• Duration of abnormality
• Associated symptoms
• Clinical evidence of cirrhosis
 Clinical clues:
Alcohol abuse ALD
Incresed BMI, lipid NAFLD
Type 2 Diabetes
IV drugs, blood Hep B,C
New drugs, herbs Drug induced
F/H of CLD Haemochromatosis
Wilson’s
Other autoimmune PBC,autoimmune
diseases hepatitis
Recent travel Hep A,E
Diarrhoea PSC
 Degree of elevation
Minor < 100 Chronic hep B,C
Haemochromatosis
Fatty liver
Moderate 100-300 Above
Alcoholic hepatitis
NAFLD,Autoimmune
hepatitis, Wilson’s
Major >1000 Drug, acute viral hep,
Acute autoimmune hep
Ischaemic liver
 Cholestasis: elevated ALP
• ALP is produced by bone,intestine and
placenta
 Associated symptoms
• Pain: biliary obstruction
• Itching in the absence of jaundice suggests
intrahepatic disease: PBC, PSC
• In elderly, biliary obstruction can present with
confusion and elevated ALP
 Degree of elevation
• Very high ( >1000-2000) in the absence of
jaundice : hepatic infiltration
Chronic liver disease screen
Hepatitis C antibody,RNA Chronic Hep C
Hep B Santigen Chronic HepB
Transferrin saturation Haemochromatosis
>55%, HFE genotype
AMA PBC
Anti Sm muscle ab,ANA Autoimmune hepatitis
Immunoglobulin:
IgG Autoimmune hepatitis
IgM PBC
IgA ALD
Low caeruloplasmin level Wilson’s disease
 Other investigations
• Ultrasound examination
• Computed tomography
• MRI
• UGIE
• ERCP( outlines the biliary and pancreatic
ducts)
• Liver biopsy
Liver cirrhosis
• 6000 deaths a year in UK
• Liver fibrosis is the final pathological pathway
in many CLD
• Cirrhosis is the irreversible state of liver
fibrosis
 Definition
• Histologically: diffuse process characterized by
by fibrosis and a conversion of normal
architecture into structurally abnormal
nodules
• Histological classification micro, macro and
mixed
• Aetiological classification
 Pathogenesis
• Regardless of the aetiology, the cellular
mechanisms are common
• Site of origin may be different: viral hepatitis-
periportal,
alcohol- pericentral
 Hepatic stellate cell ( HSC)
• Major cell in matrix synthesis and metabolism
• Plays the pivotal role in cirrhosis
• In the normal liver HSC is situated in the
subendothelial space of Disse and are involved
in retinoid storage
Proliferative, fibrogenic and contractile
• After injury HSC proliferates, loose the retinoid
droplets and are activated to a myelofibroblast
like cell: “ activated HSC”
• Activated HSC acts as the major source of
collagen, and non collagenous matrix proteins
• HSC also secrete matrixmetalloproteinases
• Kupffer cells too have a role HSC activation
 Contd.
• Parenchymal cell necrosis also aid activation
• Possibly via release of lipid peroxidases and
insulin like growth factors
 Once activated
• HSC expresses numerous cytokines and their
receptors: TGF and PDGF
• They sustain activation, proliferation and
fibrogenesis
• Activated HSC lays down the matrix, initially in
the spaces of Disse
• Fibrous septae form which distort the liver
parenchyma
• The vascular structures get linked and the
architecture is distorted
• With advanced fibrosis parenchymal
dysfunction and portal HT develops
• Insight of this process offers hope of
treatment: blocking the fibrogenic cascade
 Aetiology of cirrhosis
Drugs and toxins Alcohol, methotrexate, isoniazid, methyldopa

infections Hepatitis B and C , Schistosoma japonicum

autoimmune PBC, autoimmune hepatitis, PSC

metabolic Wilson’s disease, haemochromatosis, alpha 1 antitrypsin,

porphyria
Biliary obstruction Cystic fibrosis, atresia, strictures, gall stones

vascular Chronic right heart failure,Budd Chiari syndrome

miscellaneous Sarcoidosis, intestinal by- pass surgery for obesity

unknown cryptogenic
 Clinical presentation
• Non specific symptoms: lethargy, malaise, abd
pain
• Specific: pruritus, jaunndice, ascites ect.
• Signs of CLD
• Most present when they develop
complications
 investigations
• Routine
• Ast/alt, albumin , PT
 Aetiological diagnosis

Viral hepatitis Hepatitis B and C serology

PBC AMA, serum IgM level

Autoimmune Anti LKM antibody, anti smooth muscle antibody, IgG

hepatitis
Alpha 1 Alpha 1 antitrypsin level, phenotype testing
antitrypsin
deficiency

Wilson’s disease Reduced serum Cu and Caeruloplasmin; increased 24

hr Cu excretion
haemochromatos s. ferritin, HFE
is
Hepatocellular Alpha feto protein level
carcinoma
 diagnosis
• Ultimately a histological diagnosis
• Ultrasound cheap, accurate, non invasive
• CT complements US/S, in Haemochromatosis
there is a dramatic increase in hepatic density
• Liver biopsy : cornerstone
A score of 10 or greater is associated with a 50% chance of death within 1 year. (Child Class
A=5-6 points, Child Class B=7-9 points, Child Class C=10-15 points)

Clinical variable 1 point 2 points 3 points

Encephalopathy None Stages 1-2 Stages 3-4

Ascites Absent Slight Moderate

Bilirubin (mg/dL) <2 2-3 >3

Bilirubin in PBC or PSC (mg/dL) <4 4-10 10

Albumin (g/dL) >3.5 2.8-3.5 <2.8

Prothrombin time(seconds prolonged or INR) <4 s or INR <1.7 4-6 s or INR 1.7-2.3 >6 s or INR >2.3
 treatment
• Stop alcohol
• Treat specific aetiology when possible
• Treat complications