Hepatic Dysfunction Symptoms and Causes

The liver is the largest organ in the human body and is responsible for well over 200 functions. It is also the most resilient organ, able to withstand some of the harshest assaults by today’s mix of air pollution, environmental contaminants, pharmaceuticals, bacteria, fungi, mold, and viruses.

Functions of the Liver

Detoxification – The liver filters 1 liter of blood each minute and eliminates the multitude of toxins that the body encounters on a daily basis. The liver must dispose of ammonia, an extremely toxic by-product of protein metabolism. It converts ammonia to urea, which is excreted through urine.

The liver also breaks down toxic chemicals, heavy metals, as well as synthetic pharmaceuticals.

Storage, energy production, and nutrient conversion –The liver is the critical organ for metabolism on all levels. Among its vast array of metabolic tasks, the liver:

Stores essential vitamins (like vitamins A, B, D, and K), minerals (like iron and copper), and glucose (in the form of glycogen).

Produces quick bursts of energy when the body needs it most (as part of the body’s “fight or flight” reaction to stress).

Plays a key role in carbohydrate metabolism, by converting glucose to glycogen. Glycogen is stored as fat in the body.
Converts vitamins, minerals, and amino acids into their biologically active forms.

All nutrients must be “biotransformed” in order to be used by the body. For example, the liver activates B vitamins; converts beta carotene to bio-available vitamin A; converts iron into ferritin; and converts lysine into active carnitine.

If the liver is not functioning optimally, nutrients cannot be converted and won’t be absorbed by the body, leading to malabsorption. If you have one or more chronic conditions, make sure that you choose supplements that contain active forms. (Many supplements on the market contain non-active forms of vitamins that inevitably pass through the body instead of being absorbed.)

Taking activated supplements eases the burden on the liver.

Helps to regulate blood sugar levels. When blood sugar is low, the liver uses its store of glycogen, and converts it to glucose (blood sugar). When blood sugar is high, a healthy liver will eliminate excess glucose by converting it to glycogen (stored as fat).

Regulates protein metabolism. The liver converts essential amino acids so that the body can utilize them.

Immunity – The liver produces some immune factors (such as fibrinogen) that help the body fight off infection.

Hormonal balance – The liver helps maintain the proper level of hormones, and is a key organ in regulating the hormone insulin (produced by the pancreas) for efficient food metabolism (as mentioned above).

The liver converts the thyroid hormone thyroxin (T4) into its more active form (T3).

Digestion and fat regulation – The liver is responsible for the production of bile that aids in the digestion of fats and fat-soluble vitamins. Bile is used to emulsify fats and fat-soluble vitamins (A, D, E, and K) for proper digestive absorption.

The liver also removes some fat-soluble toxins from the body by first dissolving them in bile salts, and then excreting them in feces. The liver also controls the production of cholesterol and triglycerides (blood fats).

Additional Information about Liver Dysfunction

Hepatic failure occurs when the liver loses the ability to regenerate or repair, so that decompensation occurs. It is marked by:

  • Hepatic encephalopathy
  • Abnormal bleeding
  • Ascites
  • Jaundice

Classification

Fulminant hepatic failure (FHF) occurs when the failure takes place within eight weeks of the onset of the underlying illness.

Late-onset hepatic failure (also called subacute FHF) occurs when there has been a gap of 8 to 26 weeks. The difference may not immediately be obvious, as the underlying disease may have been present for a long time but undiagnosed.

Chronic decompensated hepatic failure occurs when the latent period is over six months.

Epidemiology

In the UK, 775 liver transplants a year were performed in the year April 2012 to April 2013. The number of transplants has been increasing in recent years.

The annual incidence of acute liver failure in the Scottish population was 0.62 per 100,000 between 1992 and 2009. Paracetamol overdose was the largest causative factor.

Aetiology

There are many causes of hepatic failure and the following represent just a few.

  • Toxins
  • Chronic alcohol abuse.
  • Paracetamol poisoning. This can occur at a lower level than expected in chronic alcohol users.
  • Drug toxicity associated with co-amoxiclav, ciprofloxacin, doxycycline, erythromycin, isoniazid, nitrofurantoin, halothane, statins, cyclophosphamide, methotrexate, disulfiram, flutamide, gold and propylthiouracil.[3] NB: the list is NOT comprehensive.
  • Poisoning by various substances, including mushrooms or chemicals containing carbon tetrachloride and other organic solvents and phosphorus.
  • Herbal preparations, plants and plant products.[4]
  • Illicit drugs including ecstasy and cocaine.
  • Reye’s syndrome.
  • Infections
  • Viral hepatitis.
  • Adenovirus, Epstein-Barr virus, cytomegalovirus and viral haemorrhagic fevers
  • Neoplastic
  • Hepatocellular carcinoma or metastatic carcinoma.
  • Metabolic
  • Wilson’s disease.
  • Others – eg, alpha-1-antitrypsin deficiency, fructose intolerance, galactosaemia and tyrosinaemia.
  • Pregnancy-related
  • Acute fatty liver of pregnancy – see the separate article on Jaudice in Pregnancy.
  • Vascular
  • Ischaemia or veno-occlusive disease.
  • Budd-Chiari syndrome.

Others

  • Autoimmune liver disease.
  • Unknown cause – 15%.
  • History
  • Mental faculties may be so impaired that history from someone close may be required. There may be hallucinations. Haematemesis or melaena may indicate gastrointestinal bleeding.

Ask about:

  • Date of onset of jaundice and encephalopathy.
  • Alcohol use.
  • Medication, including prescription medicines, illicit drugs and alternative medicines.
  • Family history of liver disease (Wilson’s disease or haemochromatosis).
  • Exposure risk factors for viral hepatitis (travel, transfusions, sexual contacts, occupation, body piercing).
  • Toxin ingestion (mushrooms, organic solvents, phosphorus contained in fireworks).
  • Past medical history.

Examination

  • Mental state shows drowsiness and possibly confusion.
  • Jaundice.
  • Hyperdynamic circulation with multiple organ failure may mimic septic shock.
  • Abdominal distension and abdominal masses, including:
  • Possible massive ascites and anasarca due to fluid redistribution and hypoalbuminaemia.
  • A dehydrated patient may not show much ascites.
  • Hepatomegaly and splenomegaly but not invariably.
  • Cerebral oedema with increased intracranial pressure (ICP), may produce papilloedema, hypertension, and bradycardia.
  • Liver palms are red and an hepatic flap, also called asterixis, may be present.
  • Hyperextend the fingers and wrist, gently pushing back and a slow clonic movement is the liver flap.

Differential diagnosis

  • Structural lesions or space-occupying lesions in the brain.
  • Cerebral infection – bacterial or viral.
  • Drug or alcohol intoxication.
  • Delirium tremens or Wernicke’s encephalopathy.
  • Metabolic upset such as hypoglycaemia, ketoacidosis, electrolyte imbalance, hypoxia, hypercapnia.

Investigations

  • Blood
  • FBC may show thrombocytopenia.
  • INR will be raised. Although these are sensitive tests they may indicate other causes, such as vitamin K deficiency or disseminated intravascular coagulation.
  • Transaminases are very markedly raised but alkaline phosphatase may be slightly high or normal.
  • Bilirubin is raised.
  • Pseudocholinesterase is low.
  • Ammonia levels are high. This should preferably be estimated on arterial blood.
  • Glucose can be dangerously low and must be monitored.
  • There may be elevated lactate, hypoxia and raised creatinine, especially if there is hepatorenal syndrome or acute kidney injury.
  • Blood cultures. They are very susceptible to infection.
  • Viral serology may indicate the infection that precipitated the hepatic failure.
  • Tests for specific conditions include free copper for Wilson’s disease and paracetamol levels in case of poisoning.
  • Imaging
  • Doppler ultrasound may establish whether or not the hepatic vein is patent (Budd-Chiari syndrome) as well as looking for primary or secondary carcinoma and checking for ascites.
  • CT or MRI scanning may demonstrate the hepatic anatomy and can exclude other pathology, particularly if there are massive ascites, obesity, or transplantation is considered. Avoid contrast in case it damages the kidneys.
  • Imaging of the head may demonstrate cerebral oedema.
  • EEG may help define level of encephalopathy.
  • Liver biopsy should be avoided with compromised coagulation, although a transjugular approach is sometimes used.

Management

Early recognition of the diagnosis and transfer to a specialist unit is required. The possibility of liver transplantation should be considered at an early stage.

  • Poisoning with drugs such as paracetamol or mushrooms may require specific interventions.
  • Lactulose, often with neomycin, is given to reduce ammonia production.
  • Protein restriction may not be as important as is traditionally taught.
  • Mannitol may reduce raised intracranial pressure. Try to avoid sedatives, as they make assessment difficult.
  • Intracranial pressure monitoring is sometimes required.
  • Cerebral oedema often leads to brain herniation and death. A possible treatment that is being assessed is hypothermia.
  • Acute kidney injury may require haemodialysis or continuous arteriovenous haemofiltration, as the former can drop blood pressure to a dangerous level.
  • Fresh-frozen plasma, platelet concentrates, antifibrinolytic drugs, prothrombin complex concentrates and recombinant activated factor VII are often used to treat or prevent abnormal bleeding.
  • Monitor glucose and other biochemical parameters. Large amounts of IV glucose may be required.

Liver transplantation

The most important variables for predicting the need of transplantation in fulminant hepatic failure are the degree of encephalopathy, the patient’s age and the underlying cause of liver failure.

May be life-saving if a graft becomes available. Various artificial liver devices have been developed and they may bridge the gap until transplant or spontaneous recovery. These include a bio-artificial liver.

Complications

Infection is a great problem. Spontaneous peritonitis is common, as is infection of one of the access lines. Opportunistic infection and pneumonia may occur.

Cerebral oedema may be associated with intracranial hypertension and death.

Haemorrhage can be a considerable problem. Oesophageal varices may require attention. If large transfusion requirements exceed apparent blood loss consider retroperitoneal haemorrhage.

The major complications that cause death, even after transplantation, are bleeding, sepsis, cerebral oedema, acute kidney injury, and respiratory failure.

Prognosis

Prognosis depends on the cause of the hepatic failure:

  • Acute liver failure remains unpredictable with high morbidity and mortality. Early and accurate diagnosis, management and prognostic assessment of patients with acute liver failure are essential.
  • Two key factors involved in determining outcome are aetiology and coma grade on admission.
  • Paracetamol overdose, hepatitis A, ischaemia and pregnancy are all associated with at least 60% short-term survival without transplantation
  • Idiosyncratic drug-induced liver injury, hepatitis B, autoimmune hepatitis and indeterminate causes are associated with about 30% spontaneous survival. Presenting with early coma grade allows for a much more favourable outcome prediction across all aetiologies.

Source & More Info: patient.co.uk and neuropathconnect

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