Prevention and treatment of liver disorders

Question 1

Hepatitis

Answer 1

(inflammation of the liver)

Question 2

what causes hepatitis

Answer 2

Infectious (caused by viral, bacterial, fungal, and parasitic organisms)
or * Non-infectious (triggered by alcohol, drugs, autoimmune diseases,
and metabolic diseases) causes.

Question 3

Functions of hepatic parenchymal cells and their
disturbances in liver disease

Answer 3

Heme catabolism ↑Bilirubin
Carbohydrate metabolism ↓Glucose
Protein synthesis ↓Albumin
(coagulation factors) Prolonged prothrombin time
Protein catabolism ↑Ammonia
↓Urea
Lipid metabolism ↑Triglycerides, ↑cholesterol
Drug metabolism Altered biological half-life of a drug
Bile acid metabolism ↑Bile acid

Question 4

Non-viral hepatitis

Answer 4

Any form of hepatitis not caused by the common hepatotropic viruses. * * Notifiable medical condition if caused by agricultural chemicals or insecticides

Question 5

management

Answer 5

If the patient is bleeding, check INR and correct coagulopathy with: * Lyophilised plasma or FFP
* (Parenteral Vitamin K should be provided and the INR reassessed).
Hepatitis due to infections
* Antibiotic therapy based on culture, serology or suspected aetiology e.g. leptospirosis.
Alcohol-induced hepatitis
* Thiamine, oral, 300 mg daily. Other vitamins if indicated.
Drug-induced hepatitis
* Stop all potentially hepatotoxic medication immediately, in consultation with a specialist.
Auto-immune hepatitis
* Patients with persistent hepatitis, negative viral markers and no hepatotoxins. Biopsy and/or various parameters are required to make the diagnosis. * If autoimmune hepatitis: Corticosteroids (Prednisone) AND Azathioprine

Question 6

Drug-induced liver disease (DILD) / injury (DILI

Answer 6

Most common drugs causing DILD/DILI: * Alcohol * Antibiotics (TB & HIV medication) * Antiseizure medications
* Paracetamol * Complementary and alternative medicines (herbal remedies

Question 7

Mechanisms of DILD

Answer 7

• Stimulation of autoimmunity
• Idiosyncratic reactions
• Cytochrome P450 Enzymes as Agents of Liver Damage
• Disruption of Calcium Homeostasis and Cell Membrane Injury
• Liver Transport Proteins and Liver Cell Communities as Agents of Liver
  Damage
• Stimulation of apoptosis
• Mitochondrial injury
• Liver neoplastic disease

Question 8

Autoimmune injuries involve antibodymediated cytotoxicity or direct cellular toxicity

Answer 8

stimulation of autoimmunity.

often associated with fulminant
presentations. * Halothane, sulfamethoxazole, carbamazepine, nevirapine, fluoroquinolones,
and antitumor necrosis factor (TNF) alpha inhibitors are associated with
autoimmune injuries

Question 9

Chronic active hepatitis

Answer 9

periods of symptomatic hepatitis followed
by periods of convalescence, progressive disease with a high
mortality rate: * Dantrolene, isoniazid, phenytoin, nitrofurantoin, trazodone, and methyldop

Question 10

Idiosyncratic reactions DILD: Allergic

Answer 10

They are usually dose-related and have a
short latency period (less than 1 month).
On re-exposure to the offending agent, there is a rapid recurrence of
hepatotoxicity.

• Human leukocyte antigen (HLA) phenotypes mediate a patient’s susceptibility and severity of inflammatory reactions in the liver.
• HLA type B*5701 has separately been associated with antibiotic-associated
  idiosyncratic reactions for drugs such as flucloxacillin and abacavir

Question 11

Idiosyncratic reactions DILD: Non-allergic

Answer 11

Usually have a long latency period (several months), and are not associated with rapid reinjury with rechallenge.
* Amiodarone, isoniazid, and ketoconazo.

Question 12

Cytochrome P450 enzymes as agents of liver damage.

Answer 12

liver damage involves the production of high-energy reactive metabolites by the CYP450 system, these metabolites form covalent bonds with cellular proteins and nucleic acids.

lead to adduct formation. In case of acute toxicity enzyme- drug adduct can cause cell injury lysis

Question 13

Categories of DILD/DILI

Answer 13

• Hepatocellular damage
• Cholestatic damage
• Mixed hepatocellular cholestatic damage

Question 14

Hepatocellular injury

Answer 14

Characterized by significant elevations in the serum aminotransferases
(alanine aminotransferase (ALT), aspartate aminotransferase (AST)), which
usually precede elevations in total bilirubin (TBL) levels in serum and
alkaline phosphatase levels
* Hy’s law defines hepatocellular injury as an increase in ALT that is at least
three times above the upper limit of normal (UNL) with concurrent rise in
TBL to a point at least 2 UN

Question 15

Cholestatic injury (biliary obstruction

Answer 15

Also known as cholestatic jaundice or cholestasis
* Cholestatic disease is more often seen in patients over the age of 60
(compared with underage 60) and is slightly more common in males. *

Question 16

• In cholestatic disease: what happens to bile

Answer 16

e, disturbance of the subcellular actin filaments
around the canaliculi prevents the movement of bile through the
canalicular system. The inability of the liver to remove bile causes
intrahepatic accumulation of toxic bile acids and excretion products.

Question 17

• Alkaline phosphatase

Answer 17

is the predominant elevated enzyme with
cholestatic injury. Cholestatic injury is defined by an Alk Phos > 3 UNL
plus TBL > UNL.

Question 18

Mixed hepatocellular cholestatic injury

Answer 18

Common example: first line TB treatment * Rifampicin
* Isoniazid
* Pyrazinamide

Question 19

Causes may include

Answer 19

• Viral hepatitis (most common), * Drug-induced liver injury (most common), * Alcohol, * Toxins or * Ischemic hepatitis.

Question 20

Acute liver failure

Answer 20

The development of severe acute liver injury with hepatic
encephalopathy (altered mental status) and impaired synthetic
function (INR of ≥1.5) in a patient without cirrhosis or pre-existing liver
disease.

Question 21

Hepatic encephalopathy

Answer 21

Hyperammonaemia plays an
important role in the
pathogenesis of hepatic
encephalopathy

Question 22

Acute liver failure:General measures

Answer 22

Patient education. * Avoid hepatotoxic drugs and alcohol.
* Rest and reduce physical activity.
* Monitor blood glucose regularly because hypoglycemia is common.
* Correct electrolyte disturbances.
* Exclude GI bleed as precipitant. . s.
* Exclude infection as precipitant.
* If the patient is bleeding, check INR and correct coagulopathy with FFP or lyophilised plasma. Routine administration of parenteral vitamin K1 is of unproven value.

Question 23

Medicine treatment

Answer 23

Lactulose, oral, 10–30 mL 8 hourly, titrated to attain 2–3 soft stools
per day.
Do not give antibiotics unless there is evidence of bacterial sepsis.

Question 24

Lactulose

Answer 24

1,4 beta galactoside-fructose, is a non-absorbable synthetic
disaccharide made up of galactose and fructose.
The human small intestinal mucosa does not have the enzymes to split
lactulose, and hence lactulose reaches the large bowel unchanged. Lactulose is metabolized in the colon by colonic bacteria to
monosaccharides, and then to volatile fatty acids, hydrogen, and
methane – lowering the intestinal pH

Question 25

Lactulose reduces intestinal ammonia production and absorption in three
ways.

Answer 25

The colonic metabolism of sugars causes a laxative effect via an increase in
intraluminal gas formation and osmolality which leads to a reduction in
transit time and intraluminal pH. * Promote increased uptake of ammonia by colonic bacteria which utilize
the trapped colonic ammonia as a nitrogen source for protein synthesis. The reduction of intestinal pH facilitates this process, which favours the conversion of ammonia (NH3) produced by the gut bacteria, to ammonium (NH4+),an ionized form of the molecule, unable to cross biological membranes. * Reduction in intestinal production of ammonia. The acidic pH destroys urease-producing bacteria involved in the production of ammonia. The unabsorbed disaccharide also inhibits intestinal glutaminase activity, which blocks the intestinal uptake of glutamine, and its metabolism to ammonia.

Question 26

Liver cirrhosis, chronic

Answer 26

Cirrhosis is a severe, chronic,
potentially irreversible disease
associated with significant
morbidity and mortality. * Major clinical consequences of
portal hypertension in the
setting of cirrhosis.

Question 27

Treatment of ascites

Answer 27

• Single morning dose of oral spironolactone, oral 100 mg and
  furosemide, oral, 40 mg
  Spironolactone may cause hyperkalaemia

Measure response to diuretics by weighing patient daily. Aim for
maximal weight loss of: * 500 g/day patients without oedema
* 1 000 g/day patients with oedema