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.
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 metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine.
Bilirubin (BR) 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 destruction of aged or abnormal red blood cells. In the first step of bilirubin synthesis, the heme molecule is stripped from the hemoglobin molecule. Heme then passes through various processes of porphyrin catabolism, which varies according to the region of the body in which the breakdown occurs. For example, the molecules excreted in the urine differ from those in the feces. The production of biliverdin from heme is the first major step in the catabolic pathway, after which the enzyme biliverdin reductase performs the second step, producing bilirubin from biliverdin.
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.
Kernicterus is a bilirubin-induced brain dysfunction. The term was coined in 1904 by Christian Georg Schmorl. Bilirubin is a naturally occurring substance in the body of humans and many other animals, but it is neurotoxic when its concentration in the blood is too high, a condition known as hyperbilirubinemia. Hyperbilirubinemia may cause bilirubin to accumulate in the grey matter of the central nervous system, potentially causing irreversible neurological damage. Depending on the level of exposure, the effects range from clinically unnoticeable to severe brain damage and even death.
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.
Gilbert syndrome (GS) is a syndrome in which the liver of affected individuals processes bilirubin more slowly than the majority. Many people never have symptoms. Occasionally jaundice may occur.
Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.
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. Severity in alcoholic hepatitis is determined several clinical prediction models such as the Maddrey's Discriminant Function and the MELD score.
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.
Crigler–Najjar syndrome is a rare inherited disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red blood cells. The disorder results in a form of nonhemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants. The disorder is inherited in an autosomal recessive manner. The annual incidence is estimated at 1 in 1,000,000.
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.
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.
Acute fatty liver of pregnancy is a rare life-threatening complication of pregnancy that occurs in the third trimester or the immediate period after delivery. It is thought to be caused by a disordered metabolism of fatty acids by mitochondria in the fetus, caused by long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. This leads to decreased metabolism of long chain fatty acids by the feto-placental unit, causing subsequent rise in hepatotoxic fatty acids in maternal plasma. The condition was previously thought to be universally fatal, but aggressive treatment by stabilizing the mother with intravenous fluids and blood products in anticipation of early delivery has improved prognosis.
FibroTest, known as FibroSure in the US, is a biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy. FibroSure uses quantitative results of five serum biochemical markers, α2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, gamma glutamyl transpeptidase (GGT), with a patient’s age and gender to generate a measure of fibrosis and necroinflammatory activity in the liver.
Bilirubin glucuronide is a water-soluble reaction intermediate over the process of conjugation of indirect bilirubin. Bilirubin glucuronide itself belongs to the category of conjugated bilirubin along with bilirubin di-glucuronide. However, only the latter one is primarily excreted into the bile in the normal setting.
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.
Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.
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.
