Liver disease

Liver disease, orhepatic disease, is any of manydiseasesof theliver.If long-lasting it is termedchronic liver disease.Although the diseases differ in detail, liver diseases often have features in common.
There are more than a hundred different liver diseases. Some of the most common are:
Some of the signs and symptoms of a liver disease are the following:
Liver diseases can develop through several mechanisms:
One general mechanism, increasedDNA damage, is shared by some of the major liver diseases, including infection byhepatitis B virusorhepatitis C virus,heavy alcohol consumption, andobesity.
Viral infection by hepatitis B virus, or hepatitis C virus causes an increase ofreactive oxygen species.  The increase inintracellularreactive 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 inflammationand more than 20 types of DNA damage.Oxidative DNA damage ismutagenicand also causes epigenetic alterations at the sites of DNA repair.Epigeneticalterations and mutations affect the cellular machinery that may cause the cell to replicate at a higher rate or result in the cell avoidingapoptosis, 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 incarcinogenesisthan 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 ofacetaldehyde. Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage andoxidative 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-inducedepigeneticalterations of gene expression appear to lead to liver injury and ultimatelycarcinoma.
Obesityis 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 ofbile acidalteration by certain gut microbes, and these microbes are increased with obesity.  The excessdeoxycholic acidcauses DNA damage and inflammation in the liver, which, in turn, can lead to liver cancer.
Several liver diseases are due to viral infection.Viral hepatitidessuch asHepatitis B virusandHepatitis C viruscan be vertically transmitted during birth via contact with infected blood.According to a 2012NICEpublication, "about 85% of hepatitis B infections in newborns become chronic".In occult cases, Hepatitis B virus is present by hepatitis B virusDNA, but testing forHBsAgis negative.High consumption ofalcoholcan lead to several forms of liver disease includingalcoholic hepatitis,alcoholic fatty liver disease,cirrhosis, andliver cancer.In the earlier stages of alcoholic liver disease,fatbuilds up in the liver's cells due to increasedcreation oftriglyceridesandfatty acidsand a decreased ability tobreak down fatty acids.Progression of the disease can lead toliver inflammation from the excess fat in the liver.Scarringin 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 ashepatocellular 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 likeSingle cell sequencingand kinome profiling
Particulate matteror carbon black are common pollutants. They have a direct toxic effect on the liver; causeinflammationof 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 cytokinesare released and cause disease progression.
Liver diseases, including conditions such asnon-alcoholic fatty liver disease(NAFLD),alcohol-related liver disease(ALD), andviral 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, primarilyhepatitis Bandhepatitis C, 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.
A number  ofliver function testsare available to test the proper function of the liver. These test for the presence ofenzymesin blood that are normally most abundant in liver tissue, metabolites or products.serum proteins,serum albumin,serum globulin,alanine transaminase,aspartate transaminase,prothrombin time,partial thromboplastin time.
Imaging tests such astransient elastography,ultrasoundandmagnetic resonance imagingcan be used to show the liver tissue and the bile ducts.Liver biopsycan be performed to examine liver tissue to distinguish between various conditions; tests such aselastographymay reduce the need for biopsy in some situations.
In liver disease,prothrombin timeis longer than usual.In addition, the amounts of bothcoagulation factorsandanticoagulation factorsare 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 VIIIandvon Willebrand factor, aplatelet adhesive protein.Both inversely rise in the setting of hepatic insufficiency, thanks to the drop ofhepatic clearanceand compensatory productions from other sites of the body.Fibrinolysisgenerally proceeds faster with acute liver failure and advanced stage liver disease, unlikechronic liver diseasein which concentration offibrinogenremains unchanged.
A previously undiagnosed liver disease may become evident first afterautopsy.Following aregross pathologyimages:
Anti-viral medications are available to treat infections such ashepatitis B.Other conditions may be managed by slowing down disease progression, for example: