Liver disease

Last updated
Liver disease
Other namesHepatic disease
Human liver with metastatic lesions from primary pancreas carcinoma (2).jpg
A gross pathology specimen of liver metastases caused by pancreatic cancer
Specialty Hepatology, gastroenterology
Types Fatty liver disease, Hepatitis (and several more) [1]
Diagnostic method Liver function tests [2]
TreatmentDepends on type(See types)

Liver disease (also called hepatic disease) is a type of damage to or disease of the liver. [1] Whenever the course of the problem lasts long, chronic liver disease ensues. [3]

Contents

Signs and symptoms

Some of the signs and symptoms of liver disease are the following:

Cause

There are more than a hundred different kinds of liver disease. These are some of the most common: [8]

Mechanism

Liver disease can occur through several mechanisms:

DNA damage

One general mechanism, increased DNA damage, is shared by some of the major causes of liver disease. These major causes include infection by hepatitis B virus or hepatitis C virus , heavy alcohol consumption, and obesity. [24]

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. [25] This increase in reactive oxygen species causes inflammation [25] and more than 20 types of DNA damage. [26] Oxidative DNA damage is mutagenic [27] and also causes epigenetic alterations at the sites of DNA repair. [28] 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, and thus contribute to liver disease. [29] By the time accumulating epigenetic and mutational changes eventually cause hepatocellular carcinoma, epigenetic alterations appear to have an even larger role in carcinogenesis 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. [30]

Alcohol consumption in excess causes a build-up of acetaldehyde. Acetaldehyde and free radicals generated by metabolizing alcohol induce DNA damage and oxidative stress. [31] [32] [33] 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). [34] The level of oxidative stress and acetaldehyde-induced DNA adducts due to alcohol consumption does not appear sufficient to cause increased mutagenesis. [34] However, as reviewed by Nishida et al., [28] 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. [35]

Obesity is associated with a higher risk of primary liver cancer. [36] 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. [37]

Other relevant aspects

A common form of liver disease is viral infection. Viral hepatitides such as Hepatitis B virus and Hepatitis C virus can be vertically transmitted during birth via contact with infected blood. [38] [39] According to a 2012 NICE publication, "about 85% of hepatitis B infections in newborns become chronic". [40] In occult cases, Hepatitis B virus is present by hepatitis B virus DNA, but testing for HBsAg is negative. [41] High consumption of alcohol can lead to several forms of liver disease including alcoholic hepatitis, alcoholic fatty liver disease, cirrhosis, and liver cancer. [42] In the earlier stages of alcoholic liver disease, fat builds up in the liver's cells due to increased creation of triglycerides and fatty acids and a decreased ability to break down fatty acids. [43] 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. [43] Approximately 3–10% of individuals with cirrhosis develop a form of liver cancer known as hepatocellular carcinoma. [43] 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. [44] 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 [45]

Air pollutants

Particulate matter or carbon black are common pollutants. They have an 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. [46]

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. [46]

Diagnosis

A number of liver function tests are available to test the proper function of the liver. These test for the presence of enzymes in 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. [2]

Imaging tests such as transient elastography, ultrasound and magnetic resonance imaging can be used to examine 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. [47]

In liver disease, prothrombin time is longer than usual. [6] In addition, the amounts of both coagulation factors and anticoagulation factors are reduced because the liver cannot productively synthesize them as it did when healthy. [48] Nonetheless, there are two exceptions in this falling tendency, that are, coagulation factor VIII and von Willebrand factor, a platelet adhesive protein. [48] 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. [48] Fibrinolysis generally proceeds faster in the scenarios of acute liver failure as well as advanced stage of liver disease in contrast to chronic liver disease in which concentration of fibrinogen remains unchanged. [48]

A previously undiagnosed liver disease may become evident first after autopsy.[ citation needed ] Following are gross pathology images:

Treatment

Ursodeoxycholic acid Ursodeoxycholic acid ball-and-stick.png
Ursodeoxycholic acid

Anti-viral medications are available to treat infections such as hepatitis B. [49] Other conditions may be managed by slowing down disease progression, for example:

See also

Related Research Articles

Hepatitis Inflammation of the liver

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 pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.

Hepatitis C Human viral infection

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 people often have mild or no symptoms. Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs. The virus persists in the liver in about 75% to 85% of those initially infected. Early on chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach.

Liver function tests, 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 Time (aPTT), albumin, bilirubin, and others. The liver transaminases aspartate transaminase and alanine transaminase are useful biomarkers of liver injury in a patient with some degree of intact liver function. Most liver diseases cause only mild symptoms initially, but these diseases must be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This testing is performed on a patient's blood sample. Some tests are associated with functionality, some with cellular integrity, and some with conditions linked to the biliary tract. Because some of these tests do not measure function, it is more accurate to call these liver chemistries or liver tests rather than liver function tests. Several biochemical tests are useful in the evaluation and management of patients with hepatic dysfunction. These tests can be used to detect the presence of liver disease, distinguish among different types of liver disorders, gauge the extent of known liver damage, and monitor the response to treatment. Some or all of these measurements are also carried out on those individuals taking certain medications, such as anticonvulsants, to ensure that the medications are not adversely impacting the person's liver.

Hepatocellular carcinoma Medical condition

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.

Alcoholic liver disease Medical condition

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 or cirrhosis.

Viral hepatitis Hepatitis that involves viral infection causing inflammation of the liver

Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form.

Alcoholic hepatitis Medical condition

Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of decades of heavy alcohol intake, typically 8-10 drinks per day. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice, ascites, fatigue and hepatic encephalopathy. Mild cases are self-limiting, but severe cases have a high risk of death. Severe cases may be treated with glucocorticoids. The condition often comes on suddenly and may progress in severity very rapidly.

Fatty liver disease Medical condition related to obesity

Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.

Gastrointestinal disease Medical condition

Gastrointestinal diseases refer to diseases involving the gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory organs of digestion, the liver, gallbladder, and pancreas.

Liver biopsy

Liver biopsy is the biopsy from the liver. It is a medical test that is done to aid diagnosis of liver disease, to assess the severity of known liver disease, and to monitor the progress of treatment.

Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "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, liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.

Steatohepatitis Medical condition

Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes.

Non-alcoholic fatty liver disease Excessive fat build-up in the liver not caused by alcohol use

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 fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), with the latter also including liver inflammation. Non-alcoholic fatty liver disease is less dangerous than NASH and usually does not progress to NASH or liver cirrhosis. When NAFLD does progress to NASH, it may eventually lead to complications such as cirrhosis, liver cancer, liver failure, or cardiovascular disease.

Liver failure Inability of the liver to perform its normal functions

Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis). Recently, a third form of liver failure known as acute-on-chronic liver failure (ACLF) is increasingly being recognized.

Liver cancer Medical condition

Liver cancer is cancer that starts in the liver. Liver cancer can be primary or secondary. Liver metastasis is more common than that which starts in the liver. Liver cancer is increasing globally.

Hepatitis B Human viral infection

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.

Cirrhosis Chronic disease of the liver, characterized by fibrosis

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 repair and subsequent formation of scar tissue, which over time can replace normal functioning tissue, leading to the impaired liver function of cirrhosis. The disease typically develops slowly over months or years. Early symptoms may include tiredness, weakness, loss of appetite, unexplained weight loss, nausea and vomiting, and discomfort in the right upper quadrant of the abdomen. As the disease worsens, symptoms may include itchiness, swelling in the lower legs, fluid build-up in the abdomen, jaundice, bruising easily, and the development of spider-like blood vessels in the skin. The fluid build-up in the abdomen may become spontaneously infected. More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer.

<i>Hepatitis B virus</i> Species of the genus Orthohepadnavirus

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.

Infectious causes of cancer

Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. This proportion varies in different regions of the world from a high of 32.7% in Sub-Saharan Africa to 3.3% in Australia and New Zealand. Helicobacter pylori is associated with stomach cancer, and Mycobacterium, some other bacteria and parasites also have an effect.

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Further reading