Generality
Liver failure is a serious discomfort that affects the liver.
"Insufficiency" is synonymous with "incapacity" and refers to the malfunctioning of the organ.
Specifically, we talk about liver failure when the liver is NO longer able to turn the metabolic functions it is intended for.
Liver failure is divided into two types: acute and chronic.
Acute liver failure is characterized by a very rapid development and in some cases it can be reversible. The chronic one, on the other hand, is progressive and is associated, in the most advanced form, with cirrhosis and carcinoma; rarely these two complications of the chronic form can be reversed.
The possible causes of liver failure are many: pathogenic, pharmacological or toxic, hereditary, autoimmune, etc.
Symptoms, clinical signs and complications of liver failure can be of various kinds; certain factors are present in both acute and chronic forms, while others are more specific.
The treatment is bound to the causative agent and can vary significantly based on the related complications, such as: portal hypertension, ascites, encephalopathy, haemorrhages etc.
Acute Liver Failure
Acute liver failure is characterized by a very rapid development. In this case, the dysfunction affects up to 80-90% of the cells present in the liver.
It typically occurs without any pre-existing disease.
The evolutionary rhythm of acute liver failure influences the prognosis; the faster it is, the greater the chance of a fatal outcome.
Partition
Accurately defining the rate of onset in acute liver failure is not simple.
There are many subdivisions that are based on the onset of the first hepato-specific symptoms and / or encephalopathy.
A classification defines acute liver failure as "the development of encephalopathy within 26 weeks of the onset of liver symptoms". It then operates a further subdivision into:
- Fulminant insufficiency: which foresees the onset of encephalopathy within 8 weeks;
- Sub-fulminant: which foresees the onset of encephalopathy after 8 weeks MA no later than 25.
Another subdivision defines:
- Hyperacute hepatic insufficiency: which foresees the onset within 7 days;
- Acute liver failure: which includes onset between 7 and 28 days;
- Sub-acute hepatic insufficiency: which foresees the onset between 28 days and 24 weeks.
Causes
The most common causes of acute liver failure are:
- Overdose of paracetamol : it is a painkiller and against fever (for example, tachypirina).
- Idiosyncratic reaction to drugs: this is an adverse response to normally tolerated products (eg tetracyclines and troglitazone).
- Alcohol abuse: beyond the acceptable dose of 1-3 units per day (12-36g / day), but no true pathogenetic threshold is known.
- Viral infection: caused by HAV (hepatitis A) and HBV (hepatitis B); very rarely from HCV (hepatitis C), more often responsible for chronic liver failure.
- Acute gravid steatosis: it occurs in the terminal phase of pregnancy; it is rare and little known.
- Idiopathic: that is of unknown cause.
- Reye syndrome: it occurs in the child. It is caused by infections that generally do not compromise the liver (for example Herpes zoster of chickenpox). The use of aspirin may have a significant role in liver damage.
- Wilson syndrome: it is a hereditary disease that causes the accumulation of copper and can damage the liver.
Clinical Signs, Symptoms and Complications
Acute liver failure can be identified thanks to early and late clinical symptoms and signs.
The most important are:
- Jaundice: yellowish pigmentation of the skin, eyes and mucous membranes. It is caused by the accumulation of bilirubin in the blood. It is the earliest clinical sign and determines an itchy symptomatology.
- Cerebral edema: it is due to an excessive concentration of liquids in the intra- and extra-cellular spaces of the brain. It is caused by the modification of the oncotic blood pressure and by the excess of toxic substances commonly metabolized by the liver. The residual nitrogen compounds from the protein metabolism (for example ammonia) seem to be involved. The reduction in oncotic pressure is caused by insufficient protein in the blood (due to impaired synthesis by the liver).
- Encephalopathy: it is a cerebral suffering that, if not treated, from a very mild initial phase can worsen up to coma and death. It is caused by edema and intoxication of the brain.
- Coagulopathy: is the alteration of the coagulant function of the blood. It is measured with some laboratory tests that reveal: levels of serum proteins, prothrombin time and any platelet deficiency. The latter, called thrombocytopenia, is the most common coagulation defect.
- Hemorrhages: are spills, hematomas and petechiae caused by coagulopathies. They can be trivial bruises or severe effusions (for example in the stomach).
- Renal insufficiency: it is mainly caused by the pharmacological damage (for example paracetamol) or by the circulatory defect. Induces the so-called hepatorenal syndrome or functional renal failure. In acute liver failure it occurs in 50% of cases. Diagnosis can be confused with normal blood urea levels (should be high).
- Inflammation and infection: systemic inflammation is present in 60% of cases. This progressively induces multiple organ failure and increases the risk of septicemia. Sepsis, or systemic infection, occurs in 30-60% of patients.
- Metabolic disorders: hyponatremia (reduced sodium in the blood), hypoglycemia (of glucose), hypokalemia (of potassium), hypophosphatemia (of phosphorus) and metabolic alkalosis. They are independent of renal function. Sometimes, lactic acidosis (excess lactic acid) occurs due to peripheral hypoxia (lack of oxygen to the tissues).
- Hemodynamic and cardiorespiratory impairment: determine the lowering of blood pressure (hypotension) and tissue hypoxia (lack of oxygen in the periphery). In 60% of cases, adrenal insufficiency occurs and in 50% pulmonary complications arise.
The clinical picture of acute steatosis determines: hemodynamic impairment, decreased appetite, dark urine, jaundice, nausea, vomiting and abdominal distention.
Pathophysiology
Acute liver failure generally develops with central cellular necrosis, which expands to the portal sections.
The degree of inflammation is variable and proportional to the duration of the disease.
Evaluation and Diagnosis
All patients with clinical evidence suggestive of a moderate-severe level of acute liver failure should be evaluated for prothrombin time and mental status.
The objectives of the investigations are those of:
- Monitor mental suffering
- Estimate the efficiency of coagulation
- Assess the speed of global onset
- To ascertain the absence of pre-existing diseases.
Overall, the diagnosis of acute liver failure is based on:
- Physical examination
- Laboratory tests
- Patient history
- Past medical history.
It is always necessary to investigate possible exposures to viruses, drugs or other toxins that can trigger the disease.
In addition, the patient's history and clinical examinations must exclude the presence of chronic diseases, which may require different treatment than acute liver failure.
Treatment
Patients with acute liver failure should be managed in intensive care as quickly as possible.
The disease involves the sudden deterioration of the mental state and the multiple insufficiency of various organs.
Death from acute liver failure is possible and probable. Sometimes, to avoid death, it is necessary to resort to liver transplantation. The introduction of this practice has increased survival up to 60% (against the 15% that already existed).
The early administration of antidotes, specific treatments and therapies contributes to the prevention of these ominous possibilities.
Treatment of acute liver failure should take into consideration morbid conditions and various comorbidities. In particular:
- Neurological complications: it is necessary to avoid hyperhydration and the consequent increase in pressure in the skull and neuropathy; in addition, it is necessary to avoid intoxication with ammonium ions. Sometimes, excretion of excess nitrogenous groups and liquids is favored with lactulose (a laxative that causes watery diarrhea); sometimes even diuretics are used. The uncontrollable state of agitation of neuropathy is fought with sedatives.
- Pulmonary complications: edema and pulmonary infections are common and may require the application of mechanical ventilation. NB . Sometimes the use of the machine worsens the cerebral edema.
- Coagulopathies and gastrointestinal bleeding: often require supplementation with vitamin K and the administration of coagulation factors or replacement therapies. To avoid gastric bleeding, proton-inhibitor or similar drugs are needed.
- Nutrition: sometimes it is necessary to establish the enteral feeding system early (with a nasogastric tube). It should be avoided the parenteral one, which exposes the patient more to the risk of systemic infection. Excessive protein restriction is NOT as beneficial as was assumed in the past. Today, a protein intake of about 60g / day is recommended. Colloidal solutions (based on albumin), with glucose (to maintain blood sugar) and mineral salts against electrolyte disorders should be preferred.
- Infections: they occur in 80% of cases and are due to the malfunction of the immune system. Diffuse fungal disease (mycosis in the blood) is a very serious indicator. Prophylactic drug therapies are not particularly effective.
Prognosis
Mortality from acute liver failure is high. Before the technological discovery of liver transplantation, it exceeded 80% of cases. At present, the short-term overall survival with transplantation is over 65%.
Chronic hepatic insufficiency
Chronic liver failure occurs due to long-term liver damage. It often evolves in cirrhosis of the liver and finally in hepatic carcinoma.
Causes
The causes of chronic liver failure can be of various kinds, sometimes co-present.
For example:
- Alcohol abuse and alcoholic hepatic steatosis (in some cases, it is associated with non-alcoholic steatohepatitis): chronic hepatic failure occurs in 10-20% of subjects who make chronic alcohol abuse. The damage is caused by the alteration of cellular metabolism, due to the excessive production of acetaldehyde and accumulation of other substances. Excess can contribute: carbohydrates, especially refined, and fats, especially saturated or hydrogenated; in principle, all junk foods.
- Hepatitis B or C: is caused by a viral infection. In the case of hepatitis C, 20-30% of the subjects are destined to develop chronic liver failure. Hepatitis B is less severe but can lead to the same fate, especially in the presence of HDV (closely related hepatitis D).
- Primary biliary cirrhosis: it is triggered by a problem of the bile duct, which secondarily damages the liver.
- Primary sclerosing cholangitis: it is a cholestatic disease (of the gallbladder) related to inflammatory intestinal pathologies (especially rectum ulcerative colitis).
- Autoimmune hepatitis: is caused by an immune reaction against liver cells.
- Hereditary hemochromatosis: it is caused by the accumulation of iron. It is accompanied by a family history of chronic liver failure.
- Wilson's disease: as mentioned for acute liver failure, it is a hereditary disease that causes copper to build up and can damage the liver.
- NON alcoholic steatohepatitis: it is caused by some metabolism impairment. It causes inflammation and hepatic accumulation of fat, which is later replaced by scar tissue. It is associated with obesity, diabetes, protein malnutrition, coronary heart disease and treatment with corticosteroid drugs. It is similar to alcoholic hepatic steatosis, with which it is sometimes accompanied.
Other less frequent forms are: Indian childhood cirrhosis (neonatal cholestasis with accumulation of copper in the liver), alpha 1-antitrypsin deficiency, cardiac cirrhosis, galactosemia, type IV glycogen storage disease, cystic fibrosis and the use of hepatotoxic drugs or other toxins.
Globally, 57% of cases are attributable to viral hepatitis (type B in 30% of cases and type C in 27%). Alcohol abuse accounts for 20% of cases. Chronic liver failure is NOT caused by HAV infection, which is responsible - albeit rarely - for the acute form.
Signs and Symptoms
The signs and symptoms of chronic liver failure are often related to necrosis (death) of liver cells. Secondly, they bind to portal hypertension (increase in blood pressure in the portal vein).
The only symptoms and early clinical signs are: weakness and weight loss.
Late ones are the most serious and are related to liver dysfunction or advanced disease. It is:
- Jaundice: is the yellowish coloration of the skin, eyes and mucous membranes, caused by the increase in bilirubin. Sometimes it is associated with browning of urine.
- Spider angioma: these are vascular lesions caused by the increase in estradiol (a typically female hormone).
- Palmular erythema: shows how the redness of the palms caused by the increase in estrogens.
- Gynecomastia: it is the enlargement of the mammary gland in men. It too is caused by the increase in estrogen (sometimes from obesity).
- Hypogonadism: is a decrease in sex hormones; may result from primary gonadal lesions or suppression of hypothalamic (part of the brain) or pituitary (of the pituitary gland) function.
- Alteration of liver size: varies depending on the case. In cirrhosis, the organ is shrunken.
- Hepatic fetor: the breath smells of mold due to the haematic increase of dimethylsulfide.
- Bruising and bleeding: caused by reduced hepatic synthesis of coagulation factors.
- Portal hypertension: it is prevented with the use of the propranolol drug. It can cause the onset of:
- Bleeding oesophageal varices; in the most serious cases they must be operated.
- Ascites: accumulation of fluid in the peritoneal cavity. It is detectable with the increase in abdominal circumference.
- Hypersplenism: increased spleen size and reduced blood platelets.
- Pharmacological hypersensitivity: it is caused by the reduction of the hepatic capacity to metabolize drugs.
- Portal hypertensive gastropathy: refers to changes in the mucous membrane of the stomach. It occurs in people with portal hypertension. It is associated with aggravation of cirrhosis.
- Hepatic encephalopathy, renal damage and tendency to infections: these are the same as described in the chapter: "Clinical Signs, Symptoms and Complications" of acute liver failure.
- Hepatocellular carcinoma: it is the most common primary liver cancer in people with liver cirrhosis.
Pathophysiology
Chronic liver failure is often preceded by hepatitis or hepatic steatosis.
If the causes are eliminated in a timely manner, the condition is reversible. Otherwise, the damage becomes permanent and can only get worse.
Chronic liver failure is typical of cirrhosis; this is characterized by the development of scar tissue (fibrosis) that replaces the normal one.
In this way an alteration of the blood flow occurs; moreover, a hyper-activation of the stellate cells and of the fibroblasts takes place which worsens the fibrosis. In parallel, the secretion of various chemical mediators that promote the synthesis of fibrous tissue and prevent its demolition increases.
The spleen remains congested and causes hypersplenism, with greater sequestration of platelets circulating in the blood.
Portal hypertension also appears, which is the primary complication responsible for very severe morbid conditions.
Evaluation and Diagnosis
The methods for the diagnosis of chronic liver failure are the same as those of acute. For cirrhosis, however, liver biopsy is required.
The most predictive factors of cirrhosis are: ascites, very low platelet values, spider angioma and a score greater than 7 on the Bonacini test (diagnostic tool).
Prevention
Prevention for large-scale chronic liver failure involves:
- Reduction in the consumption of ethyl alcohol.
- Reduction of transmission of viral hepatitis.
- Screening of relatives of people with inherited liver disease.
There is little information on the modulators of risk and progression of cirrhosis.
Management and Treatment
Hepatic failure and advanced cirrhosis are NOT reversible.
Treatment could halt or delay pathological progression and reduce complications or the possibility of cancer. Each complication may require specific treatment.
It is necessary to undertake a healthy and balanced diet, with the right contribution: of calories (cirrhosis may require more energy), of nutrients (especially essential) and of antioxidants.
To learn more: Diet for liver failure »
From a pharmacological point of view, various medications can be used to reduce itching and some antibiotics for bacterial infections.
Laxatives reduce the risk of constipation; lactulose is used to prevent the accumulation of ammonium ions and hyperhydration.
It is always necessary to eliminate ethyl alcohol.
In the case of viral hepatitis, the administration of interferon may be useful. In the autoimmune one, they help corticosteroids. To learn more: Medications to treat hepatitis
Liver failure caused by Wilson's disease is treated with chelation therapy to remove copper. To learn more: Drugs for Curing Wilson's Disease
Complications and Treatment
There are typical complications of chronic liver failure that require special precautions.
These are:
- Ascites: food salt restriction is required. The administration of diuretics, aldosterone antagonists and osmotic laxatives (little used) may be decisive. In case of urgency, paracentesis (drainage) is applied.
- Esophageal bleeding varices: due to portal hypertension, they are prevented with the use of propranolol. In the most serious cases, surgery is performed.
- Hepatic encephalopathy: caused by an excess of azotemia and edema, it can be prevented by partially reducing the total proteins or by using branched amino acids to replace the aromatic ones. The reduction in protein intake cannot be excessive or there is the risk of further complicating the ability of protein synthesis in the liver.
- Portal hypertensive gastropathy: refers to changes in the mucous membrane of the stomach in people with portal hypertension; is associated with aggravation of cirrhosis.
- Hepatocellular carcinoma: it is the primary tumor of the liver, which is the most common in people with liver cirrhosis. To learn more: Drugs for the Treatment of Liver Cancer
