Chronic Liver Disease
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Chronic liver disease in the clinical context is a disease process of the
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
that involves a process of progressive destruction and regeneration of the liver
parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...
leading to
fibrosis Fibrosis, also known as fibrotic scarring, is the development of fibrous connective tissue in response to an injury. Fibrosis can be a normal connective tissue deposition or excessive tissue deposition caused by a disease. Repeated injuries, ch ...
and
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation (
chronic hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...
), liver
cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...
, and
hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...
. The entire spectrum need not be experienced.


Signs and symptoms

Signs of chronic liver disease detectable on clinical examination can be divided into those that are associated with the diagnosis of chronic liver disease, associated with decompensation, and associated with the cause.


Chronic liver disease

*
Nail clubbing Nail clubbing, also known as digital clubbing or clubbing, is a deformity of the finger or toe Nail (anatomy), nails associated with a number of diseases, anomalies and defects, some congenital, mostly of the heart disease, heart and lung disea ...
* Palmar erythema * Spider nevi (angiomata) * Gynaecomastia * Feminising hair distribution *
Testicular atrophy Testicular atrophy is a medical condition in which one or both testicles (or "testes") diminish in size and may be accompanied by reduced testicular function. Testicular atrophy is not related to the temporary shrinkage of the surrounding scrotum, ...
* Small irregular shrunken liver *
Anaemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availab ...
*
Caput medusae Caput medusae is the appearance of distended and engorged superficial epigastric veins, which are seen radiating from the umbilicus across the abdomen. The name ''caput medusae'' (Latin for "head of Medusa") originates from the apparent simil ...


Decompensation

*
Drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
(encephalopathy) *
Hyperventilation Hyperventilation is irregular breathing that occurs when the rate or tidal volume of breathing eliminates more carbon dioxide than the body can produce. This leads to hypocapnia, a reduced concentration of carbon dioxide dissolved in the blo ...
(encephalopathy) * Metabolic flap/ asterixis (encephalopathy) *
Jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
(excretory dysfunction) *
Ascites Ascites (; , meaning "bag" or "sac") is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdo ...
(portal hypertension and hypoalbuminemia) *
Leukonychia Leukonychia (or leuconychia) is a medical term for white discoloration appearing on nail (anatomy), nails.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. pp. 658–59. . It is derived from the ...
(hypoalbuminaemia) * Peripheral oedema (hypoalbuminaemia) *
Bruising A bruise, also known as a contusion, is a type of hematoma of tissue, the most common cause being capillaries damaged by trauma, causing localized bleeding that extravasates into the surrounding interstitial tissues. Most bruises occur clo ...
(coagulopathy) * Acid-base imbalance, most commonly
respiratory alkalosis Respiratory alkalosis is a medical condition in which Tachypnea, increased respiration elevates the blood pH beyond the normal range (7.35–7.45) with a concurrent reduction in arterial levels of carbon dioxide. This condition is one of the four ...


Signs associated with the cause

* Dupuytren's contracture (alcohol) * Parotid enlargement (alcohol) *
Peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...
(alcohol and some drugs) * Cerebellar signs (alcohol and Wilson's disease) * Liver enlargement (alcohol, NAFLD, haemochromatosis) * Kayser-Fleisher rings (Wilson's disease) * Increased pigmentation of the skin (haemochromatosis) * Signs of right heart failure Note that ''other diseases can involve the liver'' and cause hepatomegaly but would not be considered part of the spectrum of chronic liver disease. Some examples of this would include chronic cancers with liver
metastases Metastasis is a pathogenic agent's spreading from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, ...
, infiltrative haematological disorders such as chronic lymphoproliferative conditions, chronic myeloid leukaemias,
myelofibrosis Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is activation and growth of mutated cells in ...
and metabolic abnormalities such as
Gaucher's disease Gaucher's disease or Gaucher disease () (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low ...
and
glycogen storage disease A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glycolysis, glucose breakdown, typically in m ...
s.


Complications

* Portal hypertension **
Ascites Ascites (; , meaning "bag" or "sac") is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdo ...
**
Hypersplenism Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulatin ...
(with or without splenomegaly) ** Lower
oesophageal varices Esophageal varices are extremely dilated sub-mucosal veins in the lower third of the esophagus. They are most often a consequence of portal hypertension, commonly due to cirrhosis. People with esophageal varices have a strong tendency to develop ...
and rectal varices * Synthetic dysfunction ** Hypoalbuminaemia **
Coagulopathy Coagulopathy (also called a bleeding disorder) is a condition in which the blood's ability to coagulate (form clots) is impaired. This condition can cause a tendency toward prolonged or excessive bleeding ( bleeding diathesis), which may occur s ...
* Hepatopulmonary syndrome *
Hepatorenal syndrome Hepatorenal syndrome (HRS) is a life-threatening medical condition that consists of acute kidney failure, rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transp ...
* Encephalopathy * Hepatocellular carcinoma


Causes

The list of conditions ''associated'' with chronic liver disease is extensive and can be categorised in the following way: Viral causes *
Hepatitis B Hepatitis B is an infectious disease caused by the '' hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. ...
*
Hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include ...
Cytomegalovirus ''Cytomegalovirus'' (CMV) (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order '' Herpesvirales'', in the family '' Herpesviridae'', in the subfamily '' Betaherp ...
(CMV), Epstein Barr virus (EBV), and yellow fever viruses cause acute hepatitis. Toxic and drugs *
Alcoholic liver disease Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosi ...
* Rarely drug induced liver disease from
methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...
,
amiodarone Amiodarone is an antiarrhythmic medication used to treat and prevent a number of types of cardiac dysrhythmias. This includes ventricular tachycardia, ventricular fibrillation, and wide complex tachycardia, atrial fibrillation, and paroxys ...
,
nitrofurantoin Nitrofurantoin, sold under the brand name Macrobid among others, is an antibacterial medication of the nitrofuran class used to treat urinary tract infections (UTIs), although it is not as effective for kidney infections. It is taken by mouth ...
and others
Paracetamol Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...
(acetaminophen) causes acute liver damage. Metabolic *
Non-alcoholic fatty liver disease An alcohol-free or non-alcoholic drink, also known as a temperance drink, is a version of an alcoholic drink made without alcohol, or with the alcohol removed or reduced to almost zero. These may take the form of a non-alcoholic mixed drink or n ...
* Haemochromatosis *
Wilson's disease Wilson's disease (also called hepatolenticular degeneration) is a genetic disorder characterized by the excess build-up of copper in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, wea ...
Autoimmune response causes *
Primary biliary cholangitis Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is an autoimmune disease of the liver. It results from a slow, progressive destruction of the small bile ducts of the liver, causing bile and other toxins to buil ...
(previously known as primary biliary cirrhosis) *
Primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a long-term progressive disease of the liver and gallbladder characterized by inflammation and scarring of the bile ducts, which normally allow bile to drain from the gallbladder. Affected individuals may ...
*
Autoimmune Hepatitis Autoimmune hepatitis, formerly known as lupoid hepatitis, plasma cell hepatitis, or autoimmune chronic active hepatitis, is a chronic, autoimmune disease of the liver that occurs when the body's immune system attacks liver cells, causing the liv ...
Other * Right heart failure


Risk factors

These differ according to the type of chronic liver disease. * Excessive alcohol use * Obesity *
Metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...
including raised blood lipids * Health care professionals who are exposed to
body fluids Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the Body (biology), body of an organism. In lean healthy adult men, the total body water is about 60% (60–67%) of the total Human body weight, body weight; it ...
and infected blood * Sharing infected needle and syringes * Having unprotected sex and multiple sex partners * Working with toxic chemicals without wearing safety clothes * Certain prescription medications


Diagnosis

Chronic liver disease takes several years to develop and the condition may not be recognised unless there is clinical awareness of subtle signs and investigation of abnormal
liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial ...
. Testing for chronic liver disease involves blood tests, imaging including
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
, and a biopsy of the liver. The liver biopsy is a simple procedure done with a fine thin needle under local anaesthesia. The tissue sample is sent to a laboratory where it is examined underneath a microscope.Chronic Liver Disease
Causes, Symptoms And Treatment - 27/01/2007


Treatment

The treatment of chronic liver disease depends on the cause. Specific conditions may be treated with medications including
corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...
,
interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...
,
antivirals Antiviral drugs are a class of medication used for treating viral infections. Most antivirals target specific viruses, while a broad-spectrum antiviral is effective against a wide range of viruses. Antiviral drugs are a class of antimicrobials ...
,
bile acids Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
or other drugs. Supportive therapy for complications of cirrhosis include
diuretics A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics in ...
,
albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...
,
vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...
,
blood products A blood product is any therapeutic substance prepared from blood, usually human blood; in some medicolegal contexts, the term refers specifically to human-blood-derived products. Blood products include whole blood, blood components, and blood pla ...
,
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
and nutritional therapy. Other patients may require surgery or a transplant. Transplant is required when the liver fails and there is no other alternative.


Alternative medicine

Some studies indicate
herbal A herbal is a book containing the names and descriptions of plants, usually with information on their medicinal, Herbal tonic, tonic, culinary, toxic, hallucinatory, aromatic, or Magic (paranormal), magical powers, and the legends associated wi ...
remedies are useful, but there is not conclusive evidence to support their use. Some support may be found in the orthodox medical use of two of these in acute liver failure: ''N''-acetyl cysteine (NAC) is the treatment of choice for acetaminophen overdose; both NAC and milk-thistle ('' Silybum marianum'') or its derivative silibinin are used in liver poisoning from certain mushrooms, notably ''
Amanita phalloides ''Amanita phalloides'' ( ), commonly known as the death cap, is a deadly poisonous basidiomycete fungus and mushroom, one of many in the genus ''Amanita''. Originating in Europe but later introduced to other parts of the world since the late ...
'', although the use of milk-thistle is controversial. Some common herbs are known or suspected to be harmful to the liver, including black cohosh, ma huang,
chaparral Chaparral ( ) is a shrubland plant plant community, community found primarily in California, southern Oregon, and northern Baja California. It is shaped by a Mediterranean climate (mild wet winters and hot dry summers) and infrequent, high-intens ...
,
comfrey ''Symphytum'' is a genus of flowering plants in the borage family, Boraginaceae, known by the common name comfrey (pronounced , from the Latin confervere to 'heal' or literally to 'boil together', referring to uses in ancient traditional medicin ...
, germander,
greater celandine ''Chelidonium majus'', the greater celandine, is a perennial herbaceous flowering plant in the poppy family Papaveraceae. One of two species in the genus ''Chelidonium'', it is native to Europe and western Asia and introduced widely in North Ame ...
,
kava Kava or kava kava (''Piper methysticum'': Latin 'pepper' and Latinized Ancient Greek, Greek 'intoxicating') is a plant in the Piperaceae, pepper family, native to the Pacific Islands. The name ''kava'' is from Tongan language, Tongan and Marqu ...
,
mistletoe Mistletoe is the common name for obligate parasite, obligate parasitic plant, hemiparasitic plants in the Order (biology), order Santalales. They are attached to their host tree or shrub by a structure called the haustorium, through which they ...
, pennyroyal, skull cap and valerian.


See also

*
MELD-Plus MELD-Plus is a risk score to assess severity of chronic liver disease that was resulted from a collaboration between Massachusetts General Hospital and IBM. The score includes nine variables as effective predictors for 90-day mortality after a dis ...
, a rating system used to assess the severity of chronic liver disease


References

{{reflist Diseases of liver