Describing liver dysfunction
Liver disease is a major cause of morbidity and mortality and is rated as one of the top 5 commonest causes of premature death in the UK. However, not all liver problems are related to underlying liver disease. Many patients have liver dysfunction which may be secondary to drug therapy, infections or sepsis, gallstones or trauma.It is important to differentiate between liver disease and liver dysfunction to understand how significant it might be when considering how it affects drug handling. For example, a transient rise in transaminases (ALT or AST) in someone newly started on a statin is an established side effect and doesn’t reflect any change in the liver’s ability to metabolise other drugs. Conversely, a rise in ALT in someone with autoimmune hepatitis is likely to indicate worsening liver disease.
Common terminology used to describe liver disease/ dysfunction is explained below. Fitting your patient into one (or more) of these categories can help you think about how their medicines might be affected:
Hepatocellular injury
This describes damage to the hepatocytes which are the main cells responsible for most liver functions. It is subdivided by severity:
✦ Hepatitis. Inflammation of the hepatocytes.
✦ Fibrosis. Early scar tissue is formed around the hepatocytes if the inflammation continues. Fibrosis is reversible if the cause is removed or treated.
✦ Cirrhosis. This is where scar tissue has built up and permanently damaged the architecture of the liver. It is not reversible. Cirrhosis can be subdivided into:
✦ Fibrosis. Early scar tissue is formed around the hepatocytes if the inflammation continues. Fibrosis is reversible if the cause is removed or treated.
✦ Cirrhosis. This is where scar tissue has built up and permanently damaged the architecture of the liver. It is not reversible. Cirrhosis can be subdivided into:
✧ Compensated cirrhosis – where there is sufficient hepatocyte function remaining for the majority of the liver’s roles to continue satisfactorily.
✧ Decompensated cirrhosis – there is insufficient hepatocyte function remaining and the patient develops signs of endstage liver disease or liver failure (e.g. encephalopathy and ascites).
✧ Decompensated cirrhosis – there is insufficient hepatocyte function remaining and the patient develops signs of endstage liver disease or liver failure (e.g. encephalopathy and ascites).
Cholestasis
This means the patient has impaired bile flow. It can be intrahepatic if it originates within the liver (e.g. caused by erythromycin), or extrahepatic (e.g. as a result of gallstones or biliary atresia).