Liver disease, or hepatic disease, is any of many
disease
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
s of the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
.
If long-lasting it is termed
chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the signs and symptoms of a liver disease are the following:
*
Jaundice
Jaundice, also known as icterus, is a yellowish or 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 abnormal heme meta ...
* Confusion and altered consciousness caused by
hepatic encephalopathy
Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stages ...
.
*
Thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...
and
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 spo ...
.
* Risk of
bleeding symptoms particularly taking place in
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...
Liver diseases
File:Ground glass hepatocytes high mag cropped 2.jpg, Ground glass hepatocytes
File:Primary biliary cirrhosis intermed mag much cropping.jpg, Primary biliary cirrhosis
File:Buddchiari2.PNG, Budd-chiari syndrome
File:Non-alcoholic_fatty_liver_disease1.jpg, Micrograph
A micrograph or photomicrograph is a photograph or digital image taken through a microscope or similar device to show a magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken on a mic ...
of non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...
There are more than a hundred different liver diseases. Some of the most common are:
*
Fascioliasis
Fasciolosis is a helminth, parasitic worm infection caused by the common liver fluke ''Fasciola hepatica'' as well as by ''Fasciola gigantica''. The disease is a plant-borne Trematoda, trematode zoonosis, and is classified as a Neglected tropic ...
, a parasitic infection of liver caused by a
liver fluke
Liver fluke is a collective name of a polyphyletic group of parasitic trematodes under the phylum Platyhelminthes.
They are principally parasites of the liver of various mammals, including humans. Capable of moving along the blood circulation, t ...
of the genus ''
Fasciola
''Fasciola'', commonly known as the liver fluke, is a genus of parasitic trematodes. There are two species within the genus ''Fasciola'': ''Fasciola'' ''hepatica'' and ''Fasciola'' ''gigantica'', as well as hybrids between the two species. Bot ...
'', mostly ''
Fasciola hepatica
''Fasciola hepatica'', also known as the common liver fluke or sheep liver fluke, is a parasitic trematode (fluke or flatworm, a type of helminth) of the class Trematoda, phylum Platyhelminthes. It infects the livers of various mammals, inc ...
''.
*
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 ...
, inflammation of the liver, is caused by various viruses (
viral hepatitis) also by some
liver toxins (e.g.
alcoholic hepatitis), autoimmunity (
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 ...
) or hereditary conditions.
*
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 fibrosis ...
is a hepatic manifestation of
alcohol overconsumption, including
fatty liver disease, alcoholic hepatitis, and
cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
. Analogous terms such as "drug-induced" or "toxic" liver disease are also used to refer to disorders caused by various drugs.
*
Fatty liver disease (hepatic
steatosis) is a reversible condition where large vacuoles of
triglyceride
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride'').
Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...
fat accumulate in liver cells.
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic ...
is a spectrum of disease associated with obesity and
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 syndrome ...
.
*
Hereditary diseases that cause damage to the liver include
hemochromatosis
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...
, involving accumulation of
iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
in the body, and
Wilson's disease. Liver damage is also a clinical feature of
alpha 1-antitrypsin deficiency
Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease. Onset of lung problems is typically between 20 and 50 years of age. This may result in shortness of breath, wheezing, or an inc ...
and
glycogen storage disease type II
Glycogen storage disease type II, also called Pompe disease, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of th ...
.
* In
transthyretin-related hereditary amyloidosis, the liver produces a mutated transthyretin protein which has severe neurodegenerative or cardiopathic effects. Liver transplantation can be curative.
*
Gilbert's syndrome, a genetic disorder of
bilirubin
Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...
metabolism found in a small percent of the population, can cause mild
jaundice
Jaundice, also known as icterus, is a yellowish or 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 abnormal heme meta ...
.
*
Cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
is the formation of fibrous tissue (
fibrosis) in the place of liver cells that have died due to a variety of causes, including viral hepatitis, alcohol overconsumption, and other forms of liver toxicity. Cirrhosis causes chronic
liver failure.
* Primary
liver cancer
Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...
most commonly manifests as
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.
It occurs in t ...
or
cholangiocarcinoma
Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stool ...
; rarer forms include
angiosarcoma and
hemangiosarcoma of the liver. (Many liver malignancies are secondary lesions that have metastasized from primary cancers in the gastrointestinal tract and other organs, such as the kidneys, lungs.)
*
Primary biliary cirrhosis
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 build ...
is a serious
autoimmune disease of the
bile capillaries.
*
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 ha ...
is a serious chronic
inflammatory disease of the
bile duct
A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates.
Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...
, which is believed to be autoimmune in origin.
*
Budd–Chiari syndrome
Budd–Chiari syndrome is a very rare condition, affecting one in a million adults. The condition is caused by occlusion of the hepatic veins that drain the liver. It presents with the classical triad of abdominal pain, ascites, and liver enlarge ...
is the clinical picture caused by
occlusion of the
hepatic vein
In human anatomy, the hepatic veins are the veins that drain venous blood from the liver into the inferior vena cava (as opposed to the hepatic portal vein which conveys blood from the gastrointestinal organs to the liver). There are usually thr ...
.
Mechanisms
Liver diseases can develop through several mechanisms:
DNA damage
One general mechanism, increased
DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
, is shared by some of the major liver diseases, including infection by ''
hepatitis B virus'' or ''
hepatitis C virus'',
heavy alcohol consumption, and
obesity
Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
.
Viral infection by hepatitis B virus, or hepatitis C virus causes an increase of
reactive oxygen species. The increase in
intracellular reactive oxygen species is about 10,000-fold with chronic hepatitis B virus infection and 100,000-fold following hepatitis C virus infection.
This increase in reactive oxygen species causes inflammation
[ and more than 20 types of DNA damage.] Oxidative DNA damage is mutagenic and also causes epigenetic alterations at the sites of DNA repair. Epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
alterations and mutations affect the cellular machinery that may cause the cell to replicate at a higher rate or result in the cell avoiding apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, and thus contribute to liver disease. By the time accumulating epigenetic and mutational changes eventually cause hepatocellular carcinoma, epigenetic alterations appear to have an even larger role in carcinogenesis
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnor ...
than mutations. Only one gene, TP53, is mutated in more than 20% of liver cancers while 41 genes each have hypermethylated promoters (repressing gene expression) in more than 20% of liver cancers.
Alcohol consumption in excess causes a build-up of acetaldehyde. Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage and oxidative stress. In addition, activation of neutrophils in alcoholic liver disease contributes to the pathogenesis of hepatocellular damage by releasing reactive oxygen species (which can damage DNA). The level of oxidative stress and acetaldehyde-induced DNA adducts due to alcohol consumption does not appear sufficient to cause increased mutagenesis. However, as reviewed by Nishida et al., alcohol exposure, causing oxidative DNA damage (which is repairable), can result in epigenetic alterations at the sites of DNA repair. Alcohol-induced epigenetic alterations of gene expression appear to lead to liver injury and ultimately carcinoma.
Obesity is associated with a higher risk of primary liver cancer. As shown with mice, obese mice are prone to liver cancer, likely due to two factors. Obese mice have increased pro-inflammatory cytokines. Obese mice also have higher levels of deoxycholic acid, a product of bile acid alteration by certain gut microbes, and these microbes are increased with obesity. The excess deoxycholic acid causes DNA damage and inflammation in the liver, which, in turn, can lead to liver cancer.
Other relevant aspects
Several liver diseases are due to viral infection. Viral hepatitides such as Hepatitis B virus and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. According to a 2012 NICE
Nice ( , ; Niçard: , classical norm, or , nonstandard, ; it, Nizza ; lij, Nissa; grc, Νίκαια; la, Nicaea) is the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative c ...
publication, "about 85% of hepatitis B infections in newborns become chronic". In occult cases, Hepatitis B virus is present by hepatitis B virus DNA, but testing for HBsAg
HBsAg (also known as the Australia antigen) is the surface antigen of the hepatitis B virus (HBV). Its presence in blood indicates current hepatitis B infection.
Structure and function
The viral envelope of an enveloped virus has different sur ...
is negative. High consumption of alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty 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 fibrosis ...
, cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
, and liver cancer
Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...
. In the earlier stages of alcoholic liver disease, fat
In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food.
The term often refers spec ...
builds up in the liver's cells due to increased creation of triglyceride
A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride'').
Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...
s and fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s and a decreased ability to break down fatty acids. Progression of the disease can lead to liver inflammation from the excess fat in the liver. Scarring in the liver often occurs as the body attempts to heal and extensive scarring can lead to the development of cirrhosis in more advanced stages of the disease.[ Approximately 3–10% of individuals with cirrhosis develop a form of liver cancer known as ]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.
It occurs in t ...
.[ According to Tilg, et al., gut microbiome could very well have an effect, be involved in the pathophysiology, on the various types of liver disease which an individual may encounter. Insight into the exact causes and mechanisms mediating pathophysiology of the liver is quickly progressing due to the introduction new technological approaches like ]Single cell sequencing
Single-cell sequencing examines the sequence information from individual cells with optimized next-generation sequencing technologies, providing a higher resolution of cellular differences and a better understanding of the function of an individual ...
and kinome profiling
Air pollutants
Particulate matter
Particulates – also known as atmospheric aerosol particles, atmospheric particulate matter, particulate matter (PM) or suspended particulate matter (SPM) – are microscopic particles of solid or liquid matter suspended in the air. The ter ...
or carbon black are common pollutants. They have a direct toxic effect on the liver; cause inflammation of liver caused by and thereby impact lipid metabolism and fatty liver disease; and can translocate from the lungs to the liver.
Because particulate matter and carbon black are very diverse and each has different toxicodynamics, detailed mechanisms of translocation are not clear. Water-soluble fractions of particulate matter are the most important part of translocation to the liver, through extrapulmonary circulation. When particulate matter gets into the bloodstream, it combines with immune cells and stimulates innate immune responses. Pro-inflammatory cytokines are released and cause disease progression.[
]
Diagnosis
A number of liver function tests
Liver function tests (LFTs or LFs), also referred to as a hepatic 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 thromboplastin ti ...
are available to test the proper function of the liver. These test for the presence of enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s in blood that are normally most abundant in liver tissue, metabolites or products. serum proteins
Serum protein electrophoresis (SPEP or SPE) is a laboratory test that examines specific Blood proteins, proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multip ...
, serum albumin
Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chemical ...
, serum globulin, alanine transaminase, aspartate transaminase, prothrombin time, partial thromboplastin time.
Imaging tests such as transient elastography
Elastography is any of a class of medical imaging modalities that map the elastic properties and stiffness of soft tissue.Sarvazyan A, Hall TJ, Urban MW, Fatemi M, Aglyamov SR, Garra BSOverview of elastography–an emerging branch of medical im ...
, ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
and magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
can be used to show the liver tissue and the bile ducts. Liver biopsy can be performed to examine liver tissue to distinguish between various conditions; tests such as elastography
Elastography is any of a class of medical imaging modalities that map the elastic properties and stiffness of soft tissue.Sarvazyan A, Hall TJ, Urban MW, Fatemi M, Aglyamov SR, Garra BSOverview of elastography–an emerging branch of medical im ...
may reduce the need for biopsy in some situations.
In liver disease, prothrombin time is longer than usual. In addition, the amounts of both coagulation factors and anticoagulation factor
Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where they ...
s are reduced as a diseased liver cannot productively synthesize them as it did when healthy. Nonetheless, there are two exceptions in this falling tendency: coagulation factor VIII and von Willebrand factor, a platelet adhesive protein
Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ...
. Both inversely rise in the setting of hepatic insufficiency, thanks to the drop of hepatic clearance and compensatory productions from other sites of the body. Fibrinolysis generally proceeds faster with acute liver failure and advanced stage liver disease, unlike chronic liver disease in which concentration of fibrinogen remains unchanged.
A previously undiagnosed liver disease may become evident first after autopsy
An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any di ...
. Following are gross pathology
Gross pathology refers to macroscopic manifestations of disease in organs, tissues, and body cavities. The term is commonly used by anatomical pathologists to refer to diagnostically useful findings made during the gross examination portion of ...
images:
File:Gross pathology of alcoholic liver cirrhosis.jpg, Diffuse cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
File:Wątroba marska (Ultima Thule).jpg, Macronodular cirrhosis
File:Nutmeg liver (crop).jpg, Nutmeg texture of congestive hepatopathy
Congestive hepatopathy, is liver dysfunction due to venous congestion, usually due to congestive heart failure. The gross pathological appearance of a liver affected by chronic passive congestion is "speckled" like a grated nutmeg kernel; the dar ...
Treatment
Anti-viral medications are available to treat infections such as hepatitis B. Other conditions may be managed by slowing down disease progression, for example:
* By using steroid-based drugs in autoimmune hepatitis.
* Regularly removing a quantity of blood from a vein (venesection) in the iron overload condition, hemochromatosis
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...
.
* Wilson’s disease
Wilson's disease is a genetic disorder in which excess copper builds up in the body. Symptoms are typically related to the brain and liver. Liver-related symptoms include vomiting, weakness, fluid build up in the abdomen, swelling of the legs, ...
, a condition where copper builds up in the body, can be managed with drugs that bind copper, allowing it to be passed from the body in urine.
* In cholestatic liver disease, (where the flow of bile is affected due to cystic fibrosis) a medication called ursodeoxycholic acid may be given.
See also
* Model for end-stage liver disease (MELD)
References
Further reading
*
External links
{{Authority control
*
Alcohol and health