Liver disease, or hepatic disease, is any of many

disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...

s 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 ...

. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.

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 is an image, captured photographically or digitally, taken through a microscope or similar device to show a magnify, magnified image of an object. This is opposed to a macrograph or photomacrograph, an image which is also taken ...

of non-alcoholic fatty liver disease There are more than a hundred different liver diseases. Some of the most common are: * Fascioliasis, 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, ...

of the genus '' FascioIa'', mostly '' FascioIa hepatica''. *

Hepatitis Hepatitis is inflammation of the liver parenchyma, 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), Anorexia (symptom), poor appetite ...

, inflammation of the liver, is caused by various viruses ( viral hepatitis) also by some liver toxins (e.g. alcoholic hepatitis), autoimmunity ( autoimmune hepatitis) or hereditary conditions. * Alcoholic liver disease is a hepatic manifestation of alcohol overconsumption, including fatty liver disease, alcoholic hepatitis, 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 ...

. 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 (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...

fat accumulate in liver cells. Non-alcoholic fatty liver disease 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 syndro ...

. * Hereditary diseases that cause damage to the liver include hemochromatosis, involving accumulation of

iron Iron is a chemical element; it has symbol Fe () 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, forming much of Earth's o ...

in the body, and Wilson's disease. Liver damage is also a clinical feature of alpha 1-antitrypsin deficiency and glycogen storage disease type II. * 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 Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority resulting in higher levels in the blood. Many people never have symptoms. Occasionally jaundice (a yellowing of the ...

, a genetic disorder of

bilirubin Bilirubin (BR) (adopted from German, originally bili—bile—plus ruber—red—from Latin) is a red-orange compound that occurs in the normcomponent of the straw-yellow color in urine. Another breakdown product, stercobilin, causes the brown ...

metabolism found in a small percent of the population, can cause mild

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 ...

. *

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 ...

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 most commonly manifests as hepatocellular carcinoma or cholangiocarcinoma; 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 buil ...

is a serious

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease" ...

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 ...

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. The bile duct is separated into three main parts: the fundus (superior), the body (middle), and the neck (inferior). Bile is requ ...

, which is believed to be autoimmune in origin. *

Budd–Chiari syndrome Budd–Chiari syndrome is a condition when an occlusion or obstruction in the hepatic veins prevent normal outflow of blood from the liver. The symptoms are non-specific and vary widely, but it may present with the classical triad of abdomin ...

is the clinical picture caused by occlusion of the hepatic vein.

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, 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 ...

* 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 stag ...

. * Thrombocytopenia 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 s ...

. * Risk of bleeding symptoms, particularly taking place in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

Mechanisms

Liver diseases can develop through several mechanisms:

DNA damage

One general mechanism, increased DNA damage, is shared by some of the major liver diseases, including infection by ''

hepatitis B virus Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus '' Orthohepadnavirus'' and a member of the '' Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Classification Hepatitis B ...

'' or '' hepatitis C virus'', heavy alcohol consumption, and

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

. Viral infection by hepatitis B virus, or hepatitis C virus causes an increase of

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

. The increase in

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

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

mutagen In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...

ic and also causes epigenetic alterations at the sites of DNA repair. Epigenetic 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 ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

, 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 cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...

than mutations. Only one gene,

TP53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

, 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 (IUPAC systematic name ethanal) is an organic compound, organic chemical compound with the chemical formula, formula , sometimes abbreviated as . It is a colorless liquid or gas, boiling near room temperature. It is one of the most ...

. Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage and

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

. 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 Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

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 Hepatitis B virus (HBV) is a partially double-stranded DNA virus, a species of the genus '' Orthohepadnavirus'' and a member of the '' Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B. Classification Hepatitis B ...

and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. According to a 2012

NICE Nice ( ; ) is a city in and the prefecture of the Alpes-Maritimes department in France. The Nice agglomeration extends far beyond the administrative city limits, with a population of nearly one million DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

, 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 existing hepatitis B infection. Structure and function The viral envelope of an enveloped virus has different su ...

is negative. High consumption of

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease,

, and liver cancer. 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 specif ...

builds up in the liver's cells due to increased creation of

s and

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

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 A scar (or scar tissue) is an area of fibrous tissue that replaces normal skin after an injury. Scars result from the biological process of wound repair in the skin, as well as in other organs, and tissues of the body. Thus, scarring is a nat ...

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. 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 and kinome profiling

Air pollutants

Particulate matter Particulate matter (PM) or particulates are microscopic particles of solid or liquid matter suspended in the air. An ''aerosol'' is a mixture of particulates and air, as opposed to the particulate matter alone, though it is sometimes defin ...

or carbon black are common pollutants. They have a direct toxic effect on the liver; cause

inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...

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.

Epidemiology

Liver diseases, including conditions such as non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ALD), and viral hepatitis, are significant public health concerns worldwide. In the United States, NAFLD is the most common chronic liver condition, affecting approximately 24% of the population, with the prevalence rising due to increasing rates of obesity and metabolic syndrome. Alcohol-related liver disease accounts for about 4.5% of liver-related deaths globally, underscoring the substantial burden of alcohol misuse. Viral hepatitis, primarily

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. ...

and

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 ...

, remains a leading cause of liver cirrhosis and liver cancer worldwide, despite advances in antiviral therapies and vaccination efforts. Additionally, recent studies have highlighted lean steatotic liver disease (SLD), a subset of NAFLD, affecting over 12% of U.S. adults even in the absence of obesity. These data emphasize the importance of early detection and targeted interventions to manage liver disease and its associated complications effectively. New research reports the prevalence of lean steatotic liver disease (SLD) in the United States using data from the National Health and Nutrition Examination Survey (2017-2023), researchers estimated the age-adjusted prevalence of lean SLD at 12.8%. This includes 9.3% for lean metabolic dysfunction-associated steatotic liver disease, 1.3% for metabolic dysfunction and alcohol-related steatotic liver disease, and 1.0% for alcohol-related liver disease.

Diagnosis

A number of liver function tests are available to test the proper function of the liver. These test for the presence of

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

s in blood that are normally most abundant in liver tissue, metabolites or products. serum proteins,

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 chem ...

, serum globulin, alanine transaminase, aspartate transaminase, prothrombin time, partial thromboplastin time. Imaging tests such as transient elastography,

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

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

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 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 factors 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. 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 Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Primary fibrinolysis is a normal body process, while secondary fibrinolysis is the breakdown of clots due to a medicine, a medical disorder, or some other c ...

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 (also referred to as 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 deat ...

. Following are gross pathology images: File:Gross pathology of alcoholic liver cirrhosis.jpg, Diffuse

File:Wątroba marska (Ultima Thule).jpg, Macronodular cirrhosis File:Nutmeg liver (crop).jpg, Nutmeg texture of congestive hepatopathy

Treatment

Anti-viral medications are available to treat infections such as

. 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. * Wilson's disease, 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.

References

External links

{{Authority control * Health effects of alcohol