Liver diseases

Anatomy , Physiology & Investigations
?Acute Paranchymalliver diseases
?Chronic Paranchymalliver diseases
?Cirrhosis & portal hypertension
?Immunological LD& IntrahepaticCholestasis
?Vascular LD
?Pregnancy & liver
?NASH & ALD
?Liver tumors & focal liver lesion
?Metabolic & inherited LD
?Liver Transplantation
?Drugs, Toxins & liver

Stigmata of Liver diseases :
HANDS:
Palmar Erythema
Clubbing
Dupytrens , Parotids Enlargement
Leuconychia
FLAPPING TREMOR,
S/C bleeding
HEENT/UPPER BODY
Jaundice
Spider Angiomata
Gynaecomastia and scant body hair
Scratch marks
Pigmentation
Fetor Hepatics
Eye KFR , Xanthelasma
ABDOMEN
Ascites
Hepatosplenomegally
Caput Medusa
Hemorrhoids on PR
Small testes
FUNCTIONS OF THE LIVER Protein metabolism Carbohydrate metabolism Lipid metabolism Formation of bile (Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and conjugated bilirubin. ) Hormone and drug inactivation Immunological function

Immunological function of the Liver :
The reticuloendothelial system of the liver contains many immunologically active cells.The liver acts as a sieve for the bacterial and other antigens carried to it via the portal tract from the gastrointestinal tract. These antigens are phagocytosed and degraded by Kupffer cells, which are macrophages attached to the endothelium.Kupffer cells have specific membrane receptors for ligands and are activated by several factors, such as infection. They secrete interleukins, tumour necrosis factor (TNF), collagenase and lysosomal hydrolases.Antigens are degraded without the production of antibody, as there is very little lymphoid tissue. They are thus prevented from reaching other antibody-producing sites in the body and thereby prevent generalized adverse immunological reactions
INVESTIGATIONS Investigative tests can be divided into:

Blood tests
(a) Liver function tests: (i) serum albumin (ii) prothrombin time ( Reflecting synthetic function of the liver )
(b) Liver biochemistry: (i) serum aspartate and alanine aminotransferases - reflecting hepatocellular damage (ii) serum alkaline phosphatase, ?-glutamyl transpeptidase - reflecting cholestasis (iii) total protein
(c) Viral markers
(d) Additional blood investigations; haematological, biochemical, immunological and genetic

Urine tests - for bilirubin and urobilinogen

Imaging techniques - to define gross anatomy

Liver biopsy - for histology

Useful blood tests for certain liver diseases
Test Disease
Antimitochondrial antibody Primary biliary cirrhosis
Antinuclear, smooth muscle (actin), Autoimmune hepatitis
liver/kidney microsomal antibody
High serum Immuoglobulin IgGAutoimmunehepatitis IgM PBC
Viral markers Hepatitis A, B, C, D andE
?-Fetoprotein Hepatocellular CA
Serum iron, transferrin saturation, serum ferritin In Hereditary haemochromatosis
Serum and urinary copper, serum caeruloplasmin Wilson s dise
?1-Antitrypsin Cirrhosis (± emphysema)
Antinuclear cytoplasmic antibodies Primary sclerosing cholangitis
Genetic analysese.g. HFE gene (hereditary haemochromatosis)

LFT
Synthetic function: Albumin, PT The International Normalized Ratio (INR) is used in many countries .
Hepatic Enzyme: AST, ALT, LDH
(Aspartate aminotransferase (AST) is primarily a mitochondrial enzyme (80%; 20% in cytoplasm) and is also present in heart, muscle, kidney and brain. High levels are seen in hepatic necrosis, myocardial infarction, muscle injury and congestive cardiac failure.
Alanine aminotransferase (ALT) is a cytosol enzyme, more specific to the liver so that a rise only occurs with liver disease.

Cholestatic enzymes: Alkaline Phosphatase( ALP ), ?GT (inducible e.g alcohol,anticonvulsants)
Gamma-GT – hepatocytes and biliary epithelial cells, pancreas, renal tubules and intestine
Very sensitive but Non-specific Raised in ANY liver discease hepatocellular or cholestatic Usefulness limited
Confirm hepatic source for a raised ALP

Markers of Cholestasis
ALP –Alkaline Phosphatase : liver and bone (placenta, kidneys, intestines or WCC)
Hepatic ALP present on surface of bile duct epithelia and accumulating bile salts increase its release from cell surface. Takes time for induction of enzyme levels so may not be first enzyme to rise and half-life is 1 week. ALP isoenzymes, 5-NT( Nucleotidase ) or gamma GT may be necessary to evaluate the origin of ALP.

Albumin and Prothrombin time (INR): Useful indicators of liver synthetic function

Acute hepatitis (ALT>10x upper limit of normal seen in :
Viral ,Ischaemic ,Toxins ,Drugs & Autoimmune hepatitis

What are the PRINCIPLES in investigation of LFTs? :
2.5% of population have raised LFTs , Normal LFTs do not exclude liver disease ,Interpret LFTs in clinical context Take a careful history for risk factors, drugs (inc OTCs), alcohol, comorbidity, autoimmunity & Physical examination for liver disease If mild abnormalities and no risk factors or suggestion of serious liver disease , repeat LFTs after an interval (with lifestyle modification) .
What is the Value of Liver Biopsy in Abnormal LFTs?
The most accurate way to grade the severity of liver disease
Aminotransferase levels correlate poorly with histological activity
Narrows the diagnostic options, if not diagnostic

Radiology:
Abdominal Ultrasound
MRCP
ERCP PTC
CT Abdomen MRI MRA , (DVI), Radionuclide Imaging
Endoscopy Upper GI endoscopy is used for the diagnosis and treatment of varices, for the detection of portal hypertensive gastropathy, and for associated lesions such as peptic ulcers. Colonoscopy may show portal hypertensive colopathy. Endoscopic ultrasound (EUS)
Ultrasound in Liver Disease
Detects Fatty Liver , Increased echogenicity may not be specific for fat
Unable to detect Inflammation or cirrhosis (unless advanced) Therefore unable to discriminate between NASH and simple fatty liver or identify other types of liver disease (which may include fatty change) Liver biopsy is the only way to make an accurate diagnosis It may be worth treating fatty liver for 6 months before considering referral for biopsy
Abdominal ultrasound is useful in: a jaundiced patient , hepatomegaly/splenomegaly ,the detection of gallstones ,focal liver disease - lesions > 1 cm ,general parenchymal liver disease ,assessing portal and hepatic vein patency ,lymph node enlargement , Colour Doppler ultrasound will demonstrate the vascularity of a lesion and the direction of blood flow in the portal and hepatic veins

Cholestatic Jaundice
Intracellular ( Causes ):Primary Biliary Cirrhosis ,Primary Sclerosing Cholangitis ,Sepsis ,Hepatocellular Disease &Drugs
Extracellular( Causes) Gallstones Cholangiocarcinoma Biliary Stricture ( Benign/ Malignant) Carcinoma Head of Pancreas
& Enlarged Porta Hepatis.