"Breastfeeding jaundice" or "lack of breastfeeding jaundice," is caused by insufficient breast milk intake, resulting in inadequate quantities of bowel movements to remove bilirubin from the body. This leads to increased enterohepatic circulation, resulting in increased reabsorption of bilirubin from the intestines. Usually occurring in the first week of life, most cases can be ameliorated by frequent breastfeeding sessions of sufficient duration to stimulate adequate milk production.

Whereas breastfeeding jaundice is a mechanical problem, breast milk jaundice is a biochemical occurrence and the higher bilirubin possibly acts as an antioxidant. Breast milk jaundice occurs later in the newborn period, with the bilirubin level usually peaking in the sixth to 14th days of life. This late-onset jaundice may develop in up to one third of healthy breastfed infants.

- First, at birth, the gut is sterile, and normal gut flora takes time to establish. The bacteria in the adult gut convert conjugated bilirubin to stercobilinogen which is then oxidized to stercobilin and excreted in the stool. In the absence of sufficient bacteria, the bilirubin is de-conjugated by brush border β-glucuronidase and reabsorbed. This process of re-absorption is called enterohepatic circulation. It has been suggested that bilirubin uptake in the gut (enterohepatic circulation) is increased in breast fed babies, possibly as the result of increased levels of epidermal growth factor (EGF) in breast milk. Breast milk also contains glucoronidase which will increase deconjugation and enterohepatic recirculation of bilirubin.

- Second, the breast-milk of some women contains a metabolite of progesterone called 3-alpha-20-beta pregnanediol. This substance inhibits the action of the enzyme uridine diphosphoglucuronic acid (UDPGA) glucuronyl transferase responsible for conjugation and subsequent excretion of bilirubin. In the newborn liver, activity of glucuronyl transferase is only at 0.1-1% of adult levels, so conjugation of bilirubin is already reduced. Further inhibition of bilirubin conjugation leads to increased levels of bilirubin in the blood. However, these results have not been supported by subsequent studies.

- Third, an enzyme in breast milk called lipoprotein lipase produces increased concentration of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase, which again leads to decreased conjugation and subsequent excretion of bilirubin.

Yellow discoloration of the skin, especially on the palms and the soles, but not of the sclera or inside the mouth is due to carotenemia—a harmless condition.

"Neonatal jaundice" is usually harmless: this condition is often seen in infants around the second day after birth, lasting until day 8 in normal births, or to around day 14 in premature births. Typical causes for neonatal jaundice include normal physiologic jaundice, jaundice due to formula supplementation, and hemolytic disorders that include hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, ABO/Rh blood type autoantibodies, or infantile pyknocytosis. Serum bilirubin normally drops to a low level without any intervention required. In cases where bilirubin rises higher, a brain-damaging condition known as kernicterus can occur, leading to significant disability. This condition has been rising in recent years due to less time spent outdoors. A Bili light is often the tool used for early treatment, which often consists of exposing the baby to intensive phototherapy. Sunbathing is effective treatment, and has the advantage of ultra-violet-B, which promotes Vitamin D production. Bilirubin count is lowered through bowel movements and urination, so frequent and effective feedings are especially important.

Cholestatic pruritus is the sensation of itch due to nearly any liver disease, but the most commonly associated entities are primary biliary cirrhosis, primary sclerosing cholangitis, obstructive choledocholithiasis, carcinoma of the bile duct, cholestasis (also see drug-induced pruritus), and chronic hepatitis C viral infection and other forms of viral hepatitis.

Cholestasis means "the slowing or stopping of bile flow" which can be caused by any number of diseases of the liver (which produces the bile), the gallbladder (which stores the bile), or biliary tract (also known as the biliary tree, the conduit that allows the bile to leave the liver and gallbladder and enter the small intestine). When this occurs, conjugated bilirubin and the waste products that usually would be cleared in bile reflux back into the bloodstream. This causes a primarily conjugated hyperbilirubinemia and jaundice; the liver conjugates the bile to make it water-soluble and because the bile has already been processed by the liver, when it gets backed up because of a blockage and is refluxed into the blood, the blood will have high levels of conjugated bilirubin. This is in contrast to primarily unconjugated hyperbilirubinemia which is the water-insoluble form that is bound to serum albumin; the liver has not had a chance to conjugate the bilirubin yet and can be caused either because too much unconjugated bilirubin is made (such as in massive hemolysis or ineffective erythropoiesis) or because too little is conjugated (Gilbert's disease or Crigler-Najjar syndrome). Unconjugated hyperbilirubinemia does not typically cause pruritus.

It is thought that bile salts that deposit into the skin are responsible for the pruritus (itching) but the levels of bilirubin in the bloodstream and the severity of the pruritus does not appear to be highly correlated. Patients that have been administered bile salt chelating agents do report some relief, however, and patients that have complete liver cell failure (and therefore cannot make these products to begin with) do not have pruritus. This suggests that products made by the liver must have some role in pruritus although it is not known exactly which product is responsible.

Neonatal cholestasis defines persisting conjugated hyperbilirubinemia in the newborn with conjugated bilirubin levels exceeding 15% (5.0 mg/dL) of total bilirubin level. The disease is either due to defects in bile excretion from hepatocytes or impaired bile flow.

General presentations in neonates include abdominal pain and general GI upset. Physical examination may show palpable liver and enlarged spleen. Differential diagnosis typically presents with a host of possibilities, many of them not treatable. Histopathology shows dilated bile duct system at all levels and bile duct proliferation in response to back pressure. The incidence has been found to be about 1:2,500 live births.

There are three main types of extra-hepatic biliary atresia:

- Type I: Atresia is restricted to the common bile duct.

- Type II: Atresia of the common hepatic duct.

- Type III: Atresia involves the most proximal part of the bile ducts (>95% of all cases).

In approximately 10% of cases, anomalies associated with biliary atresia include heart lesions, polysplenia, situs inversus, absent venae cavae, and a preduodenal portal vein. Progressive cirrhosis, is associated with signs and symptoms of portal hypertension, such as esophagogastric varix bleeding, hypersplenism, hepatorenal syndrome, and hepatopulmonary syndrome.

The cause of biliary atresia in most infants is not known and it is likely that a number of factors may play a role. Some may be due to a defect in early bile duct development (particularly those with other abnormalities) and some may arise in the perinatal period due to an external cause such as an hepatotropic virus reovirus 3 infection, congenital cytomegalovirus infection, and autoimmunity. However, experimental evidence is insufficient to confirm any of these theories.

In an Egyptian study, abnormally high levels of aflatoxin B1 and to a lesser extent aflatoxin B2 was found in liver tissue and blood of all neonates suffering from biliary atresia. Aflatoxins may cause extensive damage to the hepatocytes leading to hepatitis and damage to bile ducts causing inflammation, adhesions and final obstruction of bile ducts. The affected neonates have a genetic detoxification defect that does not allow them to detoxify these aflatoxins timely or effectively. The babies have homozygous deficiency of glutathione S transferase (GST) M1. The aflatoxin damaged liver cells and bile duct cells are removed by neutrophil elastase and by involvement of immune system mediators such as CCL-2 or MCP-1, tumor necrosis factor (TNF), interleukin-6 (IL-6), TGF-beta, endothelin (ET), and nitric oxide (NO). Among these, TGF-beta is the most important pro-fibrogenic cytokine that can be seen in progressive cirrhosis.

The cascade of immune involvement to remove damaged hepatocytes and cholangiocytes ushers regeneration. Yet in infants with biliary atresia regeneration is defective, and results in cirrhosis, as these infants have disrupted p53 and disrupted GSTPi. p53 and GSTPi are responsible for DNA fidelity at regeneration. Hence, these infants get accelerated cirrhosis and march to portal hypertension.

Biliary atresia, also known as extrahepatic ductopenia and progressive obliterative cholangiopathy, is a childhood disease of the liver in which one or more bile ducts are abnormally narrow, blocked, or absent. It can be congenital or acquired. As a birth defect in newborn infants, it has an incidence of one in 10,000–15,000 live births in the United States, and a prevalence of one in 16,700 in the British Isles. Biliary atresia is most common in East Asia, with a frequency of one in 5,000.

The causes of biliary atresia are not well understood. Congenital biliary atresia has been associated with certain genes, while acquired biliary atresia is thought to be a result of an autoimmune inflammatory response, possibly due to a viral infection of the liver soon after birth. The only effective treatments are surgeries such as the Kasai procedure and liver transplantation.

Gilbert's syndrome (GS) is a mild liver disorder in which the liver does not properly process bilirubin. Many people never have symptoms. Occasionally a slight yellowish color of the skin or whites of the eyes may occur. Other possible symptoms include feeling tired, weakness, and abdominal pain.

Gilbert's syndrome is due to a mutation in the UGT1A1 gene which results in decreased activity of the bilirubin uridine diphosphate glucuronosyltransferase enzyme. It is typically inherited in an autosomal recessive pattern and occasionally in an autosomal dominant pattern depending on the type of mutation. Episodes of jaundice may be triggered by stress such as exercise, menstruation, or not eating. Diagnosis is based on higher levels of unconjugated bilirubin in the blood without either signs of other liver problems or red blood cell breakdown.

Typically no treatment is needed. If jaundice is significant phenobarbital may be used. Gilbert's syndrome affects about 5% of people in the United States. Males are more often diagnosed than females. It is often not noticed until late childhood to early adulthood. The condition was first described in 1901 by Augustin Nicolas Gilbert.

In those with cirrhosis, the risk of developing hepatic encephalopathy is 20% per year, and at any time about 30–45% of people with cirrhosis exhibit evidence of overt encephalopathy. The prevalence of minimal hepatic encephalopathy detectable on formal neuropsychological testing is 60–80%; this increases the likelihood of developing overt encephalopathy in the future. Once hepatic encephalopathy has developed, the prognosis is determined largely by other markers of liver failure, such as the levels of albumin (a protein produced by the liver), the prothrombin time (a test of coagulation, which relies on proteins produced in the liver), the presence of ascites and the level of bilirubin (a breakdown product of hemoglobin which is conjugated and excreted by the liver). Together with the severity of encephalopathy, these markers have been incorporated into the Child-Pugh score; this score determines the one- and two-year survival and may assist in a decision to offer liver transplantation.

In acute liver failure, the development of severe encephalopathy strongly predicts short-term mortality, and is almost as important as the nature of the underlying cause of the liver failure in determining the prognosis. Historically, widely used criteria for offering liver transplantation, such as King's College Criteria, are of limited use and recent guidelines discourage excessive reliance on these criteria. The occurrence of hepatic encephalopathy in people with Wilson's disease (hereditary copper accumulation) and mushroom poisoning indicates an urgent need for a liver transplant.

The enzymes that are defective in GS - UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) - are also responsible for some of the liver's ability to detoxify certain drugs. For example, Gilbert's syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.

While paracetamol (acetaminophen) is not metabolized by UGT1A1, it is metabolized by one of the other enzymes also deficient in some people with GS. A subset of people with GS may have an increased risk of paracetamol toxicity.

In a small proportion of cases, the encephalopathy is caused directly by liver failure; this is more likely in acute liver failure. More commonly, especially in chronic liver disease, hepatic encephalopathy is triggered by an additional cause, and identifying these triggers can be important to treat the episode effectively.

Hepatic encephalopathy may also occur after the creation of a transjugular intrahepatic portosystemic shunt (TIPS). This is used in the treatment of refractory ascites, bleeding from oesophageal varices and hepatorenal syndrome. TIPS-related encephalopathy occurs in about 30% of cases, with the risk being higher in those with previous episodes of encephalopathy, higher age, female sex and liver disease due to causes other than alcohol.

There is a 2-3:1 male-to-female predilection in primary sclerosing cholangitis. PSC can affect men and women at any age, although it is commonly diagnosed in the fourth decade of life, most often in the presence of inflammatory bowel disease (IBD). PSC progresses slowly and is often asymptomatic, so it can be present for years before it is diagnosed and before it causes clinically significant consequences. There is relatively little data on the prevalence and incidence of primary sclerosing cholangitis, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, it is likely that the risk is higher in populations where UC is more common. In the United States, an estimated 29,000 individuals have PSC.

Dubin–Johnson syndrome (DJS) is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests. No treatment is usually needed.

While inherited deficiencies in uroporphyrinogen decarboxylase often lead to the development of PCT, there are a number of risk factors that can both cause and exacerbate the symptoms of this disease. One of the most common risk factors observed is infection with the Hepatitis C virus. One review of a collection of PCT studies noted Hepatitis C infection in 50% of documented cases of PCT. Additional risk factors include alcohol abuse, excess iron (from iron supplements as well as cooking on cast iron skillets), and exposure to chlorinated cyclic hydrocarbons and Agent Orange.

It can be a paraneoplastic phenomenon.

The development of any of the cancers associated with PSC predicts a poor prognosis. Complications from PSC-associated cancers account for 40% of deaths from PSC. Primary sclerosing cholangitis is one of the major known risk factors for cholangiocarcinoma, a cancer of the biliary tree, for which the lifetime risk among patients with PSC is 10-15%. This represents a 400-fold greater risk of developing cholangiocarcinoma compared to the general population. Surveillance for cholangiocarcinoma in patients with PSC is encouraged, with some experts recommending annual surveillance with a specialized imaging study and serum markers, although consensus regarding the modality and interval has yet to be established. Similarly, a screening colonoscopy is recommended in people who receive a new diagnosis of primary sclerosing cholangitis since their risk of colorectal cancer is 10 times higher than that of the general population.

PSC is strongly associated with inflammatory bowel disease (IBD), in particular ulcerative colitis (UC) and to a lesser extent Crohn's disease. As many as 5% of patients with IBD are co-diagnosed with PSC and approximately 70% of people with PSC have IBD. Of note, the presence of colitis appears to be associated with a greater risk of liver disease progression and bile duct cancer (cholangiocarcinoma) development, although this relationship remains poorly understood. Close monitoring of PSC patients is vital.

Various forms of gallbladder disease such as gallstones and gallbladder polyps are also common in those with PSC. Approximately 25% of people with PSC have gallstones. Ultrasound surveillance of the gallbladder every year is recommended for people with PSC. Any person with PSC who is found to have a mass in the gallbladder should undergo surgical removal of the gallbladder due to the high risk of cholangiocarcinoma. Osteoporosis (hepatic osteodystrophy) and hypothyroidism are also associated with PSC.

Porphyria cutanea tarda has a prevalence estimated at approximately 1 in 10,000. An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives.

The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile. Impaired biliary excretion of bilirubin glucuronides is due to a mutation in the canalicular multiple drug-resistance protein 2 (MRP2). A darkly pigmented liver is due to polymerized epinephrine metabolites, not bilirubin.

DJS is due to a defect in the multiple drug-resistance protein 2 gene (ABCC2), located on chromosome 10. It is an autosomal recessive disease and is likely due to a loss of function mutation, since the mutation affects the cytoplasmic/binding domain.

To minimise the risks associated with splenectomy, antibiotic and vaccination protocols have been established, but are often poorly adhered to by physicians and patients due to the complications resulting from antibiotic prophylaxis such as development of an overpopulation of Clostridium difficile in the intestinal tract.

Type 1 tyrosinemia, also known as hepatorenal tyrosinemia or tyrosinosis, is the most severe form of tyrosinemia, a buildup of too much of the amino acid tyrosine in the blood and tissues due to an inability to metabolize it. It is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase.

This obstruction may lead to jaundice, elevation in alkaline phosphatase, increase in conjugated bilirubin in the blood and increase in cholesterol in the blood. It can also cause acute pancreatitis and ascending cholangitis.

In addition to the normal immunizations advised for the countries to be visited, Group A meningococcus should be included if visiting countries of particular risk (e.g. sub-saharan Africa). The non-conjugated Meningitis A and C vaccines usually used for this purpose give only 3 years coverage and provide less-effective long-term cover for Meningitis C than the conjugated form already mentioned.

Those lacking a functional spleen are at higher risk of contracting malaria, and succumbing to its effects. Travel to malarial areas will carry greater risks and is best avoided. Travellers should take the most appropriate anti-malarial prophylaxis medication and be extra vigilant over measures to prevent mosquito bites.

The pneumococcal vaccinations may not cover some of the other strains of pneumococcal bacteria present in other countries. Likewise their antibiotic resistance may also vary, requiring a different choice of stand-by antibiotic.

While stones can frequently pass through the common bile duct (CBD) into the duodenum, some stones may be too large to pass through the CBD and may cause an obstruction. One risk factor for this is duodenal diverticulum.

Rotor syndrome, also called Rotor type hyperbilirubinemia, is a rare, relatively benign autosomal recessive bilirubin disorder. It is a distinct, yet similar disorder to Dubin–Johnson syndrome — both diseases cause an increase in conjugated bilirubin.