Other liver diseases

CIRRHOSIS

It is a pathological description of the liver in which there is:

·         Diffuse hepatic fibrosis

·         Nodular regeneration

·         A disturbance of normal hepatic architecture.

It is end result of all chronic liver disease that are usually, not always associated with recurrent episodes of necrosis, cell death and attempts by liver to regenerate. It consists of wide variety of complications:

Hepatic encephalopathy: 

This occurs in patients with advanced cirrhosis which is precipitated by sedative and large protein intake. Here blood ammonia is raised which can cross BBB and can cause encephalopathy. But his also occurs in urea cycle enzyme defect.

Ascites:

Excess accumulation of extracellular fluid in peritoneal cavity is another complication of cirrhosis. This occurs due to portal hypertension, sodium and water retention. Increased resistance to portal flow and increased hydrostatic pressure within sinusoids favour transudation of tissue fluid into peritoneal cavity. Sodium and water retention from kidney is another cause of ascites, due to increased aldosterone secretion or increase tubular sensitivity to low level of aldosterone. Hypoalbuminemia also lead to ascites as there is loss of plasma oncotic pressure.

The standard LFT are normal in ascites. There is low urea level in blood since hepatic ureagenesis is impaired during cirrhosis.

Measurement of plasma ascetic albumin gradient, ascetic LDH or ascetic cholesterol concentration, ADA in different conditions like cirrhotic ascites and malignant ascites and other conditions.  

Renal failure: 

The onset of renal failure is indicated by rising plasma concentrations of creatinine and urea and usually, but not always reduced GFR <30 ml/min. There is hyperkalaemia which can precipitate encephalopathy during liver disease. The major clinical problem is an idiopathic form of renal failure known as hepatorenal syndrome and associated with advanced liver disease, ascites and encephalopathy.

Hepatorenal failure: 

The condition is known as functional renal failure (FRF). There is disturbance in function but not structure in kidney. This occurs due to vascular abnormalities in cirrhosis which leads to renal vasoconstriction resulting in decreased renal blood flow and reduced GFR.

Relation between liver disease and renal disease.

During cirrhosis this condition can be diagnosed by reduced urine flow and rising urea and creatinine are features of renal failure, but characteristic feature of FRF is the dramatic degree of sodium retention and urinary sodium is <12 mmol/L. This is in contrast with acute tubular necrosis (ATN) in whom urinary sodium is >12 mmol/L.

Differential diagnosis of renal failure in cirrhosis:

                                                           

Prerenal failure   Functional renal failure    ATN

Urinary sodium (mmol/L)                 <12                       <12                                >12

Urine:plasma osmolality                  >1.15                 1.1-1.15                            1.1

Response to volume expansion       yes                       No                                  No

Alcohol consumption and sexual dysfunction

Liver function during pregnancy: 

Liver disease leading to acute liver failure is a rare complication of pregnancy. There is tendency towards cholestasis in the last trimester. Plasma level of GGT and ALP are increased. But there may be presence of acute fatty liver of pregnancy, the ‘hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome and liver impairment in eclampsia.

Liver function test and HELLP during pregnancy, in different trimesters. 

Hepatocellular carcinoma and α-fetoprotein:

Hepatocellular carcinoma (HCC) is one of the commonest and most rapidly progressive malignant neoplasma. It arises in most of the cases as complication of hepatic cirrhosis and is identified by AFP whose normal value is <10 ng/ml. Value more than 500 ng/ml are virtually diagnostic of HCC but there is gray area between 10-500 ng/ml where similar value is seen in chronic liver disease. AFP is widely used to monitor treatment. AFP originating from malignant cells is hyperfucosylated, and routine test for this fraction may be important.

REYE’S SYNDROME:
 

This is a rare disease of children that occurs during recovery from mild viral illness particularly when aspirin and NSAID have been used. There is encephalopathy, cerebral oedema, vomiting and biochemical evidence of hepatic involvement indicated by increased aminotransferase, hyperammonaemia, hypoglycemia and prolonged PT. Bilirubin is normal.

The cause is unknown but there are presence of inherited metabolic defects. These includes urea cycle disorder, organic acidaemias, disorder of fatty acid oxidation. 

DRUGS AND THE LIVER:

Biochemical test plays an important role in recognition and monitoring of adverse effects of therapeutic drugs. Agreed criteria for classification of drug induced liver damage:

Hepatocellular:

ALT>2ULN

ALT/ALP >2

E.g. paracetamol, isoniazid

Cholestatic

ALP>2ULN

ALT/ALP<2

E.g. anabolic steroids

Mixed:

ALT and ALP >2ULN

ALT/ALP>2 and <5

E.g. chlorpromazine. 

(ULN: Upper limit normal)