Liver disorders and related conditions Flashcards
Cholestasis is
an impairment of bile formation and/or bile flow, which may clinically present with fatigue, pruritus, dark urine, pale stools and, in its most overt form, jaundice and signs of fat soluble vitamin deficiencies.
Ursodeoxycholic acid can be used
• to dissolve gallstones (mineral or fatty deposits in the gallbladder). It can also be used to treat primary biliary cirrhosis (autoimmune disease of the liver, which progressively destroys the small bile ducts of the liver causing bile and other toxins to build up in the liver).
Cholic acid
• (predominant primary bile acid in humans) can be given to patients born with deficiencies in bile acid synthesis. The liver produces bile hence these diseases occur due to liver enzyme deficiencies.
Treatment of cholestatic pruritus
Colestyramine is the drug of choice for treating cholestatic pruritus. It is an anion-exchange resin that is not absorbed from the GI tract. It relieves pruritus by forming an insoluble complex in the intestine with bile acids and other compounds—the reduction of serum bile acid levels reduces excess deposition in the dermal tissue with a resultant decrease in pruritus.
- Ursodeoxycholic acidp has a small and variable impact on cholestatic pruritus.
- Rifampicin [unlicensed indication] can be used as an alternative treatment for pruritus, but should be used with caution in patients with pre-existing liver disease because of possible hepatotoxicity.
- Where previous therapy has proved ineffective or was not tolerated, other drugs including sertraline [unlicensed indication] and naltrexone hydrochloride [unlicensed indication], may be used to treat cholestatic pruritus. However, their use is limited due to significant side-effects.
Intrahepatic cholestasis in pregnancy
- Ursodeoxycholic acid is effective for the treatment of pruritus associated with intrahepatic cholestasis in pregnancy
- Intrahepatic cholestasis usually occurs in late pregnancy and is associated with adverse fetal outcomes. There is no evidence that ursodeoxycholic acid used in late pregnancy affects birth weight in the infant or the risk of preterm delivery. There is limited data about the effect of fetal exposure during the first trimester.
Gallstones (cholelithiases) occur when
hard mineral or fatty deposits form in the gallbladder. Gallstone disease is a general term that describes the presence of one or morestones in the gallbladder or in the bile duct, and the symptoms and complications that they may cause.
- The majority of patients with gallstones remain
asymptomatic. When the stones irritate the gallbladder or block part of the biliary system, the patient can experience symptoms such as pain, or infection and inflammation that if left untreated, can lead to severe complications such as biliary colic, acute cholecystitis, cholangitis, pancreatitis, and obstructive jaundice.
Gallstones Non-drug treatment
Asymptomatic gallbladder stones do not need to be treated unless symptoms develop.
The definitive treatment of symptomatic gallstones (and all bile duct stones) is surgical removal by laparoscopic cholecystectomy.
Gallstones Drug treatment
Analgesia should be offered to control pain symptoms. Paracetamol or a NSAID is recommended for intermittent mild-to-moderate pain. Intramuscular diclofenac sodium can be given for severe pain or, if not suitable, an intramuscular opioid (such as morphine or pethidine hydrochloride).
- Although ursodeoxycholic acid has been used for the management of gallstone disease, there is no evidence to support its use.
Inborn errors of primary bile acid synthesis are a group of diseases in which
the liver does not produce enough primary bile acids due to enzyme deficiencies. These acids are the main components of the bile, and include cholic acid and chenodeoxycholic acid.
Inborn errors of primary bile acid synthesis - treatment
- Cholic acid is licensed for the treatment of inborn errors in primary bile acid synthesis due to an inborn deficiency of two specific liver enzymes. It acts by replacing some of the missing bile acids, therefore relieving the symptoms of the disease.
- Chenodeoxycholic acid is licensed for the treatment of inborn errors of primary bile acid synthesis due to a deficiency of one specific enzyme in the bile acid synthesis pathway when presenting as cerebrotendinous xanthomatosis.
- Ursodeoxycholic acid [unlicensed indication] has been used to treat inborn errors of primary bile acid synthesis, but there is an absence of evidence to recommend its use.
Primary biliary cholangitis (or primary biliary cirrhosis) is
a chronic cholestatic disease which develops due to progressive destruction of small and intermediate bile ducts within the liver, subsequently evolving to fibrosis and cirrhosis.
Primary biliary cholangitis (or primary biliary cirrhosis) - treatment
Ursodeoxycholic acid is recommended for the management of primary biliary cholangitis, including those with asymptomatic disease. It slows disease progression, but the effect on overall survival is uncertain. Liver transplantation can be considered in patients with advanced primary biliary cholangitis.
Chenodeoxycholic acid monitoring requirements
Manufacturer advises to
monitor serum cholestanol levels and/or urine bile alcohols every 3 months during the initiation of therapy and dose adjustment, and then at least annually; liver function should also be monitored during initiation of therapy and then at least annually; additional or more frequent investigations may need to be undertaken to monitor therapy during periods of fast growth or concomitant disease.
Cholic acid monitoring requirements
Manufacturer advises
monitor serum and/or urine bile-acid concentrations every 3 months for the first year, then every 6 months for three years, then annually; monitor liver function tests at the same or greater frequency.
Obeticholic acid MHRA alert
RISK OF SERIOUS LIVER INJURY IN PATIENTS WITH PRE-EXISTING MODERATE OR SEVERE HEPATIC IMPAIRMENT; REMINDER TO ADJUST DOSING ACCORDING TO LIVER FUNCTION MONITORING
