Gallstone

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Gallstone
Other namesGallstone disease, cholelith, cholecystolithiasis (gallstone in the gallbladder), choledocholithiasis (gallstone in a bile duct) [1]
Gallstones.png
Gallstones typically form in the gallbladder and may result in symptoms if they block the biliary system.
Pronunciation
Specialty Gastroenterology
General surgery
Symptoms None, crampy pain in the right upper abdomen [2] [3] [4]
Complications Inflammation of the gallbladder, inflammation of the pancreas, liver inflammation [2] [4]
Usual onsetAfter 40 years old [2]
Risk factors Birth control pills, pregnancy, family history, obesity, diabetes, liver disease, rapid weight loss [2]
Diagnostic method Based on symptoms, confirmed by ultrasound [2] [4]
PreventionHealthy weight, diet high in fiber, diet low in simple carbohydrates [2]
TreatmentAsymptomatic: none, [2] ursodeoxycholic acid (UDCA) and Chenodeoxycholic acid
Pain: surgery ERCP, Cholecystectomy [2]
Prognosis Good after surgery [2]
Frequency10–15% of adults (developed world) [4]

A gallstone is a stone formed within the gallbladder from precipitated bile components. [2] The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, [5] and choledocholithiasis refers to the presence of migrated gallstones within bile ducts.

Contents

Most people with gallstones (about 80%) are asymptomatic. [2] [3] However, when a gallstone obstructs the bile duct and causes acute cholestasis, a reflexive smooth muscle spasm often occurs, resulting in an intense cramp-like visceral pain in the right upper part of the abdomen known as a biliary colic (or "gallbladder attack"). [4] This happens in 1–4% of those with gallstones each year. [4] Complications from gallstones may include inflammation of the gallbladder (cholecystitis), inflammation of the pancreas (pancreatitis), obstructive jaundice, and infection in bile ducts (cholangitis). [4] [6] Symptoms of these complications may include pain that lasts longer than five hours, fever, yellowish skin, vomiting, dark urine, and pale stools. [2]

Risk factors for gallstones include birth control pills, pregnancy, a family history of gallstones, obesity, diabetes, liver disease, or rapid weight loss. [2] The bile components that form gallstones include cholesterol, bile salts, and bilirubin. [2] Gallstones formed mainly from cholesterol are termed cholesterol stones, and those formed mainly from bilirubin are termed pigment stones. [2] [3] Gallstones may be suspected based on symptoms. [4] Diagnosis is then typically confirmed by ultrasound. [2] Complications may be detected using blood tests. [2]

The risk of gallstones may be decreased by maintaining a healthy weight with exercise and a healthy diet. [2] If there are no symptoms, treatment is usually not needed. [2] In those who are having gallbladder attacks, surgery to remove the gallbladder is typically recommended. [2] This can be carried out either through several small incisions or through a single larger incision, usually under general anesthesia. [2] In rare cases when surgery is not possible, medication can be used to dissolve the stones or lithotripsy can be used to break them down. [7]

In developed countries, 10–15% of adults experience gallstones. [4] Gallbladder and biliary-related diseases occurred in about 104 million people (1.6% of people) in 2013 and resulted in 106,000 deaths. [8] [9] Gallstones are more common among women than men and occur more commonly after the age of 40. [2] Gallstones occur more frequently among certain ethnic groups than others. [2] For example, 48% of Native Americans experience gallstones, whereas gallstone rates in many parts of Africa are as low as 3%. [10] [2] Once the gallbladder is removed, outcomes are generally positive. [2]

Definition

Gallstone disease refers to the condition where gallstones are either in the gallbladder or common bile duct. [5] The presence of stones in the gallbladder is referred to as cholelithiasis, from the Greek chole- (χολή, 'bile') + lith- (λίθος, 'stone') + -iasis (ἴασις, 'process'). [1] The presence of gallstones in the common bile duct is called choledocholithiasis , from the Greek choledocho- (χοληδόχος, 'bile-containing', from chol- + docho-, 'duct') + lith- + -iasis. [1] Choledocholithiasis is frequently associated with obstruction of the bile ducts, which can lead to cholangitis , from the Greek: chol- + ang- (ἄγγος, 'vessel') + -itis ( -ῖτις , 'inflammation'), a serious infection of the bile ducts. Gallstones within the ampulla of Vater can obstruct the exocrine system of the pancreas and can result in pancreatitis.[ citation needed ]

Signs and symptoms

The proportion of people with gallstones who experience symptoms as a result of them. Prevalence2.png
The proportion of people with gallstones who experience symptoms as a result of them.

Gallstones, regardless of size or number, are often asymptomatic. [12] These "silent stones" do not require treatment and can remain asymptomatic even years after they form. [13] [14] Sometimes, the pain may be referred to tip of the scapula in cholelithiasis; this is called "Collin's sign". [15]

A characteristic symptom of a gallstone attack is the presence of colic-like pain in the upper-right side of the abdomen, often accompanied by nausea and vomiting. Pain from symptomatic gallstones may range from mild to severe and can steadily increase over a period lasting from 30 minutes to several hours. Other symptoms may include fever, as well as referred pain between the shoulder blades or below the right shoulder. If one or more gallstones block the bile ducts and cause bilirubin to leak into the bloodstream and surrounding tissue, jaundice and itching may also occur. In this case, liver enzyme levels are likely to be raised. [16]

Often, gallbladder attacks occur after eating a heavy meal. Attacks are most common in the evening or at night. [17]

Other complications

In rare cases, gallstones that cause severe inflammation can erode through the gallbladder into adherent bowel, potentially causing an obstruction termed gallstone ileus. [18]

Other complications can include ascending cholangitis, which occurs when a bacterial infection causes purulent inflammation in the biliary tree and liver, and acute pancreatitis caused by blockage of the bile ducts that prevents active enzymes from being secreted into the bowel, instead damaging the pancreas. [16] Rarely, gallbladder cancer may occur as a complication. [6]

Risk factors

Gallstone risk increases for females (especially before menopause) and for people near or above 40 years; [19] the condition is more prevalent among people of European or American Indigenous descent than among other ethnicities. [20] A lack of melatonin could significantly contribute to gallbladder stones, as melatonin inhibits cholesterol secretion from the gallbladder, enhances the conversion of cholesterol to bile, and is an antioxidant, which is able to reduce oxidative stress to the gallbladder. [21] Gilbert syndrome has been linked to an increased risk of gallstones. [22] Researchers believe that gallstones may be caused by a combination of factors, including inherited body chemistry, body weight, gallbladder motility (movement), and low-calorie diet. [20] The absence of such risk factors does not, however, preclude the formation of gallstones.

Nutritional factors that may increase risk of gallstones include constipation; eating fewer meals per day; low intake of the nutrients folate, magnesium, calcium, and vitamin C; [23] low fluid consumption; [24] and, at least for men, a high intake of carbohydrate, a high glycemic load, and high glycemic index diet. [25] Wine and whole-grained bread may decrease the risk of gallstones. [26]

Rapid weight loss increases risk of gallstones. [27] The weight loss drug orlistat is known to increase the risk of gallstones. [28]

Cholecystokinin deficiency caused by celiac disease increases risk of gallstone formation, especially when diagnosis of celiac disease is delayed. [29]

Pigment gallstones are most commonly seen in the developing world. Risk factors for pigment stones include hemolytic anemias (such as from sickle-cell disease and hereditary spherocytosis), cirrhosis, and biliary tract infections. [30] People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones. [31] [32] Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation. [33]

Cholesterol modifying medications can affect gallstone formation. Statins inhibit cholesterol synthesis and there is evidence that their use may decrease the risk of getting gallstones. [34] [35] Fibrates increase cholesterol concentration in bile and their use has been associated with an increased risk of gallstones. [35] Bile acid malabsorption may also be a risk.

Pathophysiology

Cholesterol gallstones develop when bile contains too much cholesterol and not enough bile salts. Besides a high concentration of cholesterol, two other factors are important in causing gallstones. The first is how often and how well the gallbladder contracts; incomplete and infrequent emptying of the gallbladder may cause the bile to become overconcentrated and contribute to gallstone formation. This can be caused by high resistance to the flow of bile out of the gallbladder due to the complicated internal geometry of the cystic duct. [36] The second factor is the presence of proteins in the liver and bile that either promote or inhibit cholesterol crystallization into gallstones. In addition, increased levels of the hormone estrogen, as a result of pregnancy or hormone therapy, or the use of combined (estrogen-containing) forms of hormonal contraception, may increase cholesterol levels in bile and also decrease gallbladder motility, resulting in gallstone formation.[ citation needed ]

Composition

From left to right: cholesterol stone, mixed stone, pigment stone. Types of Gallstones.jpg
From left to right: cholesterol stone, mixed stone, pigment stone.

The composition of gallstones is affected by age, diet and ethnicity. [37] On the basis of their composition, gallstones can be divided into the following types: cholesterol stones, pigment stones, and mixed stones. [3] An ideal classification system is yet to be defined. [38]

Cholesterol stones

Cholesterol stones vary from light yellow to dark green or brown or chalk white and are oval, usually solitary, between 2 and 3 cm long, each often having a tiny, dark, central spot. To be classified as such, they must be at least 80% cholesterol by weight (or 70%, according to the Japanese classification system). [38] Between 35% and 90% of stones are cholesterol stones. [3]

Pigment stones

Bilirubin ("pigment", "black pigment") stones are small, dark (often appearing black), and usually numerous. They are composed primarily of bilirubin (insoluble bilirubin pigment polymer) and calcium (calcium phosphate) salts that are found in bile. They contain less than 20% of cholesterol (or 30%, according to the Japanese classification system). [38] Between 2% and 30% of stones are bilirubin stones. [3]

Mixed stones

Mixed (brown pigment stones) typically contain 20–80% cholesterol (or 30–70%, according to the Japanese classification system). [38] Other common constituents are calcium carbonate, palmitate phosphate, bilirubin and other bile pigments (calcium bilirubinate, calcium palmitate and calcium stearate). Because of their calcium content, they are often radiographically visible. They typically arise secondary to infection of the biliary tract which results in the release of β-glucuronidase (by injured hepatocytes and bacteria) which hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin in bile. Between 4% and 20% of stones are mixed. [3]

Gallstones can vary in size and shape from as small as a grain of sand to as large as a golf ball. [39] The gallbladder may contain a single large stone or many smaller ones. Pseudoliths, sometimes referred to as sludge, are thick secretions that may be present within the gallbladder, either alone or in conjunction with fully formed gallstones.

Diagnosis

Diagnosis is typically confirmed by abdominal ultrasound. Other imaging techniques used are ERCP and MRCP. Gallstone complications may be detected on blood tests. [2]

On abdominal ultrasound, sinking gallstones usually have posterior acoustic shadowing. In floating gallstones, reverberation echoes (or comet-tail artifact) is seen instead in a clinical condition called adenomyomatosis. Another sign is wall-echo-shadow (WES) triad (or double-arc shadow) which is also characteristic of gallstones. [40]

A positive Murphy's sign is a common finding on physical examination during a gallbladder attack.

Prevention

Maintaining a healthy weight by getting sufficient exercise and eating a healthy diet that is high in fiber may help prevent gallstone formation. [2]

Ursodeoxycholic acid (UDCA) appears to prevent formation of gallstones during weight loss. A high fat diet during weight loss also appears to prevent gallstones. [41]

Treatment

Lithotripsy

Extracorporeal shock wave lithotripsy is a non-invasive method to manage gallstones that uses high-energy sound waves to disintegrate them first applied in January 1985. [42] [43] Side effects of extracorporeal shock wave lithotripsy include biliary pancreatitis and liver haematoma. [44] The term is derived from the Greek words meaning 'breaking (or pulverizing) stones': litho- + τρίψω , tripso).

Surgical

Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. The lack of a gallbladder has no negative consequences in most people, however 10 to 15% of people develop postcholecystectomy syndrome, [45] which may cause nausea, indigestion, diarrhea, and episodes of abdominal pain. [46]

The outcomes of choosing to 'do nothing' (watchful waiting) and having cholecystectomy in the case of symptomatic gallstones, as shown in the NHS decision aid for gallstones. Data from . Benefits.png
The outcomes of choosing to 'do nothing' (watchful waiting) and having cholecystectomy in the case of symptomatic gallstones, as shown in the NHS decision aid for gallstones. Data from .

There are two surgical options for cholecystectomy:

Risks of cholecystectomy. Risks.png
Risks of cholecystectomy.

Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP). [54]

Risks of ERCP. ERCP Risks.png
Risks of ERCP.

Surgery carries risks and some people continue to experience symptoms (including pain) afterwards, for reasons that remain unclear. An alternative option is to adopt a ‘watch and wait’ strategy before operating to see if symptoms resolve. A study compared the 2 approaches for uncomplicated gallstones and after 18 months, both approaches were associated with similar levels of pain. The watch and wait approach was also less costly (more than £1000 less per patient). [56] [57]

Medical

The medications ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) have been used in treatment to dissolve gallstones. [58] [59] A 2013 meta-analysis concluded that UDCA or higher dietary fat content appeared to prevent formation of gallstones during weight loss. [41] Medical therapy with oral bile acids has been used to treat small cholesterol stones, and for larger cholesterol gallstones when surgery is either not possible or unwanted. CDCA treatment can cause diarrhea, mild reversible hepatic injury, and a small increase in the plasma cholesterol level. [59] UDCA may need to be taken for years. [54]

Use in alternative medicine

Gallstones can be a valued by-product of animals butchered for meat because of their use as an antipyretic and antidote in the traditional medicine of some cultures, particularly traditional Chinese medicine. The most highly prized gallstones tend to be sourced from old dairy cows, termed calculus bovis or niu-huang (yellow thing of cattle) in Chinese. Some slaughterhouses carefully scrutinize workers for gallstone theft. [60]

See also

Related Research Articles

<span class="mw-page-title-main">Gallbladder</span> Organ in humans and other vertebrates

In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although the structure and position of the gallbladder can vary significantly among animal species. It receives bile, produced by the liver, via the common hepatic duct, and stores it. The bile is then released via the common bile duct into the duodenum, where the bile helps in the digestion of fats.

<span class="mw-page-title-main">Bile duct</span> Type of organ

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).

<span class="mw-page-title-main">Cholecystitis</span> Inflammation of the gallbladder

Cholecystitis is inflammation of the gallbladder. Symptoms include right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. Often gallbladder attacks precede acute cholecystitis. The pain lasts longer in cholecystitis than in a typical gallbladder attack. Without appropriate treatment, recurrent episodes of cholecystitis are common. Complications of acute cholecystitis include gallstone pancreatitis, common bile duct stones, or inflammation of the common bile duct.

<span class="mw-page-title-main">Cholecystectomy</span> Surgical removal of the gallbladder

Cholecystectomy is the surgical removal of the gallbladder. Cholecystectomy is a common treatment of symptomatic gallstones and other gallbladder conditions. In 2011, cholecystectomy was the eighth most common operating room procedure performed in hospitals in the United States. Cholecystectomy can be performed either laparoscopically, or via an open surgical technique.

<span class="mw-page-title-main">Common bile duct stone</span> Medical condition

Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (CBD). This condition can cause jaundice and liver cell damage. Treatments include choledocholithotomy and endoscopic retrograde cholangiopancreatography (ERCP).

<span class="mw-page-title-main">Gallbladder cancer</span> Medical condition

Gallbladder cancer is a relatively uncommon cancer, with an incidence of fewer than 2 cases per 100,000 people per year in the United States. It is particularly common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics. If it is diagnosed early enough, it can be cured by removing the gallbladder, part of the liver and associated lymph nodes. Most often it is found after symptoms such as abdominal pain, jaundice and vomiting occur, and it has spread to other organs such as the liver.

Adenomyoma is a tumor (-oma) including components derived from glands (adeno-) and muscle (-my-). It is a type of complex and mixed tumor, and several variants have been described in the medical literature. Uterine adenomyoma, the localized form of uterine adenomyosis, is a tumor composed of endometrial gland tissue and smooth muscle in the myometrium. Adenomyomas containing endometrial glands are also found outside of the uterus, most commonly on the uterine adnexa but can also develop at distant sites outside of the pelvis. Gallbladder adenomyoma, the localized form of adenomyomatosis, is a polypoid tumor in the gallbladder composed of hyperplastic mucosal epithelium and muscularis propria.

<span class="mw-page-title-main">Ascending cholangitis</span> Medical condition

Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum. It tends to occur if the bile duct is already partially obstructed by gallstones.

Postcholecystectomy syndrome (PCS) describes the presence of abdominal symptoms after a cholecystectomy.

<span class="mw-page-title-main">Biliary colic</span> Medical condition in which gallstones cause acute pain

Biliary colic, also known as symptomatic cholelithiasis, a gallbladder attack or gallstone attack, is when a colic occurs due to a gallstone temporarily blocking the cystic duct. Typically, the pain is in the right upper part of the abdomen, and can be severe. Pain usually lasts from 15 minutes to a few hours. Often, it occurs after eating a heavy meal, or during the night. Repeated attacks are common. Cholecystokinin - a gastrointestinal hormone - plays a role in the colic, as following the consumption of fatty meals, the hormone triggers the gallbladder to contract, which may expel stones into the duct and temporarily block it until being successfully passed.

<span class="mw-page-title-main">Biliary tract</span> Organ system which creates, stores, and transports bile

The biliary tract refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and conjugated bilirubin. Some components are synthesized by hepatocytes ; the rest are extracted from the blood by the liver.

<span class="mw-page-title-main">Gallbladder disease</span> Medical condition

Gallbladder diseases are diseases involving the gallbladder and is closely linked to biliary disease, with the most common cause being gallstones (cholelithiasis).

<span class="mw-page-title-main">Recurrent pyogenic cholangitis</span> Medical condition

Recurrent pyogenic cholangitis (RPC), also known as Hong Kong disease, Oriental cholangitis, and Oriental infestational cholangitis, is a chronic infection characterized by recurrent bouts of bacterial cholangitis with primary hepatolithiasis. It is exclusive to people who live or have lived in southeast Asia.

Biliary dyskinesia is a disorder of some component of biliary part of the digestive system in which bile cannot physically move in the proper direction through the tubular biliary tract. It most commonly involves abnormal biliary tract peristalsis muscular coordination within the gallbladder in response to dietary stimulation of that organ to squirt the liquid bile through the common bile duct into the duodenum. Ineffective peristaltic contraction of that structure produces postprandial right upper abdominal pain (cholecystodynia) and almost no other problem. When the dyskinesia is localized at the biliary outlet into the duodenum just as increased tonus of that outlet sphincter of Oddi, the backed-up bile can cause pancreatic injury with abdominal pain more toward the upper left side. In general, biliary dyskinesia is the disturbance in the coordination of peristaltic contraction of the biliary ducts, and/or reduction in the speed of emptying of the biliary tree into the duodenum.

Biliary injury is the traumatic damage of the bile ducts. It is most commonly an iatrogenic complication of cholecystectomy, but can also be caused by other operations or by major trauma. The risk of biliary injury is higher during laparoscopic cholecystectomy than during open cholecystectomy. Biliary injury may lead to several complications and may even cause death if not diagnosed in time and managed properly. Ideally biliary injury should be managed at a center with facilities and expertise in endoscopy, radiology and surgery.

<span class="mw-page-title-main">Sphincter of Oddi dysfunction</span> Medical condition

Sphincter of Oddi dysfunction refers to a group of functional disorders leading to abdominal pain due to dysfunction of the Sphincter of Oddi: functional biliary sphincter of Oddi and functional pancreatic sphincter of Oddi disorder. The sphincter of Oddi is a sphincter muscle, a circular band of muscle at the bottom of the biliary tree which controls the flow of pancreatic juices and bile into the second part of the duodenum. The pathogenesis of this condition is recognized to encompass stenosis or dyskinesia of the sphincter of Oddi ; consequently the terms biliary dyskinesia, papillary stenosis, and postcholecystectomy syndrome have all been used to describe this condition. Both stenosis and dyskinesia can obstruct flow through the sphincter of Oddi and can therefore cause retention of bile in the biliary tree and pancreatic juice in the pancreatic duct.

<span class="mw-page-title-main">Biliary sludge</span> Medical condition

Biliary sludge refers to a viscous mixture of small particles derived from bile. These sediments consist of cholesterol crystals, calcium salts, calcium bilirubinate, mucin, and other materials.

<span class="mw-page-title-main">Biloma</span> Circumscribed abdominal collection of bile outside the biliary tree

A biloma is a circumscribed abdominal collection of bile outside the biliary tree. It occurs when there is excess bile in the abdominal cavity. It can occur during or after a bile leak. There is an increased chance of a person developing biloma after having a gallbladder removal surgery, known as laparoscopic cholecystectomy. This procedure can be complicated by biloma with incidence of 0.3–2%. Other causes are liver biopsy, abdominal trauma, and, rarely, spontaneous perforation. The formation of biloma does not occur frequently. Biliary fistulas are also caused by injury to the bile duct and can result in the formation of bile leaks. Biliary fistulas are abnormal communications between organs and the biliary tract. Once diagnosed, they usually require drainage. The term "biloma" was first coined in 1979 by Gould and Patel. They discovered it in a case with extrahepatic bile leakage. The cause of this was trauma to the upper right quadrant of the abdomen. Originally, biloma was described as an "encapsulated collection" of extrahepatic bile. Biloma is now described as extrabiliary collections of bile that can be either intrahepatic or extrahepatic. The most common cause of biloma is trauma to the liver. There are other causes such as abdominal surgery, endoscopic surgery and percutaneous catheter drainage. Injury and abdominal trauma can cause damage to the biliary tree. The biliary tree is a system of vessels that direct secreations from the liver, gallbladder, and pancreas through a series of ducts into the duodenum. This can result in a bile leak which is a common cause of the formation of biloma. It is possible for biloma to be associated with mortality, though it is not common. Bile leaks occur in about one percent of causes.

<span class="mw-page-title-main">Choledochoduodenostomy</span>

Choledochoduodenostomy (CDD) is a surgical procedure to create an anastomosis, a surgical connection, between the common bile duct (CBD) and an alternative portion of the duodenum. In healthy individuals, the CBD meets the pancreatic duct at the ampulla of Vater, which drains via the major duodenal papilla to the second part of duodenum. In cases of benign conditions such as narrowing of the distal CBD or recurrent CBD stones, performing a CDD provides the diseased patient with CBD drainage and decompression. A side-to-side anastomosis is usually performed.

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/dL is considered hyperbilirubinemia, following which jaundice progressively develops and becomes apparent when plasma levels reach 20 mg/dL. 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.

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