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.
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.
Steatosis, also called fatty change, is abnormal retention of fat (lipids) within a cell or organ. Steatosis most often affects the liver – the primary organ of lipid metabolism – where the condition is commonly referred to as fatty liver disease. Steatosis can also occur in other organs, including the kidneys, heart, and muscle. When the term is not further specified, it is assumed to refer to the liver.
Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of at least 10 years 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.
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), 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.
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.
Metabolic dysfunction–associated steatotic liver disease (MASLD) is the name adopted in 2023 for the condition previously known as non-alcoholic fatty liver disease (NAFLD). This condition is diagnosed when there is excessive fat build-up in the liver, and at least one metabolic risk factor. When there is also moderate alcohol use, the term MetALD is used, and these are differentiated from alcoholic liver disease (ALD) when this is the sole cause of steatotic liver disease. The terms non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis have been used to describe different severities, the latter indicating the presence of further liver inflammation. NAFL is less dangerous than NASH and usually does not progress to it, but this progression may eventually lead to complications, such as cirrhosis, liver cancer, liver failure, and cardiovascular disease.
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.
Succinate receptor 1 (SUCNR1), previously named G protein-coupled receptor 91 (GPR91), is a receptor that is activated by succinate, i.e., the anionic form of the dicarboxylic acid, succinic acid. Succinate and succinic acid readily convert into each other by gaining (succinate) or losing (succinic acid) protons, i.e., H+ (see Ions). Succinate is by far the predominant form of this interconversion in living organisms. Succinate is one of the intermediate metabolites in the citric acid cycle (also termed the TCA cycle or tricarboxylic acid cycle). This cycle is a metabolic pathway that operates in the mitochondria of virtually all eucaryotic cells. It consists of a series of biochemical reactions that serve the vital function of releasing the energy stored in nutrient carbohydrates, fats, and proteins. Recent studies have found that some of the metabolites in this cycle are able to regulate various physiological and pathological functions in a wide range of cell types. The succinyl CoA in this cycle may release its bound succinate; succinate is one of these mitochondrial-formed bioactive metabolites.
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 to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue 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 develop into spontaneous infections. More serious complications include hepatic encephalopathy, bleeding from dilated veins in the esophagus, stomach, or intestines, and liver cancer.
Obeticholic acid (OCA), sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Intercept Pharmaceuticals Inc. hold the worldwide rights to develop OCA outside Japan and China, where it is licensed to Dainippon Sumitomo Pharma.
Detlef Schuppan is a German biochemist and physician. He focuses on the diagnosis and treatment of coeliac disease and wheat sensitivity, fibrotic liver diseases and the immunology of chronic diseases and cancer. He is the director of the Institute of Translational Immunology and a professor of internal medicine, gastroenterology, and hepatology at the Medical Center of the Johannes Gutenberg University of Mainz in Germany. He directs the outpatient clinic for coeliac disease and small intestinal diseases. He is also a professor of medicine and a senior visiting scientist at Harvard Medical School.
Aramchol is an investigational drug being developed by Galmed Pharmaceuticals as a first-in-class, potentially disease modifying treatment for nonalcoholic steatohepatitis, or NASH, a more advanced condition of non-alcoholic fatty liver disease.
Melissa Palmer is an American hepatologist. She is recognized for her research and treatment of hepatitis and liver disease. Palmer is the Chief Medical Officer of Gannex Pharma, a wholly owned company of Ascletis Pharma.
Claudio Tiribelli is an Italian hepatologist best known for his studies on bilirubin and Kernicterus, a bilirubin-induced neurological condition.
Cilofexor is a nonsteroidal farnesoid X receptor (FXR) agonist in clinical trials for the treatment of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). It is being investigated for use alone or in combination with firsocostat, selonsertib, or semaglutide. In rat models and human clinical trials of NASH it has been shown to reduce fibrosis and steatosis, and in human clinical trials of PSC it improved cholestasis and reduced markers of liver injury.
Hyperbilirubinemia is a clinical condition describing an elevation of blood bilirubin level due to the inability to properly metabolise or excrete bilirubin, a product of erythrocytes breakdown. In severe cases, it is manifested as jaundice, the yellowing of tissues like skin and the sclera when excess bilirubin deposits in them. The US records 52,500 jaundice patients annually. By definition, bilirubin concentration of greater than 3 mg/ml is considered hyperbilirubinemia, following which jaundice progressively develops and becomes apparent when plasma levels reach 20 mg/ml. Rather than a disease itself, hyperbilirubinemia is indicative of multifactorial underlying disorders that trace back to deviations from regular bilirubin metabolism. Diagnosis of hyperbilirubinemia depends on physical examination, urinalysis, serum tests, medical history and imaging to identify the cause. Genetic diseases, alcohol, pregnancy and hepatitis viruses affect the likelihood of hyperbilirubinemia. Causes of hyperbilirubinemia mainly arise from the liver. These include haemolytic anaemias, enzymatic disorders, liver damage and gallstones. Hyperbilirubinemia itself is often benign. Only in extreme cases does kernicterus, a type of brain injury, occur. Therapy for adult hyperbilirubinemia targets the underlying diseases but patients with jaundice often have poor outcomes.
Hepatokines are proteins produced by liver cells (hepatocytes) that are secreted into the circulation and function as hormones across the organism. Research is mostly focused on hepatokines that play a role in the regulation of metabolic diseases such as diabetes and fatty liver and include: Adropin, ANGPTL4, Fetuin-A, Fetuin-B, FGF-21, Hepassocin, LECT2, RBP4,Selenoprotein P, Sex hormone-binding globulin.
