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.

Biliary pruritus is caused by chronic liver disease with obstructive jaundice, characterized by a severe generalized itchy sensation.

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.

Possible causes:

- pregnancy

- androgens

- birth control pills

- antibiotics (such as TMP/SMX)

- abdominal mass (e.g. cancer)

- biliary atresia and other pediatric liver diseases

- biliary trauma

- congenital anomalies of the biliary tract

- gallstones

- acute hepatitis

- cystic fibrosis

- intrahepatic cholestasis of pregnancy (obstetric cholestasis)

- primary biliary cirrhosis, an autoimmune disorder

- primary sclerosing cholangitis, associated with inflammatory bowel disease

- some drugs (e.g. flucloxacillin and erythromycin)

Drugs such as gold salts, nitrofurantoin, anabolic steroids, chlorpromazine, prochlorperazine, sulindac, cimetidine, erythromycin, estrogen, and statins can cause cholestasis and may result in damage to the liver.

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.

The exact mechanism of the condition is unknown, though some studies have suggested the itching occurs in response to increased fibrinolytic activity in the skin. Later studies indicated inappropriate activation of the sympathetic nervous system may play a part.

Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and whites of the eyes due to high bilirubin levels. It is commonly associated with itchiness. The feces may be pale and the urine dark. Jaundice in babies occurs in over half in the first week following birth and in most is not a problem. If bilirubin levels in babies are very high for too long, a type of brain damage, known as kernicterus, may occur.

Causes of jaundice vary from non-serious to potentially fatal. Levels of bilirubin in blood are normally below 1.0 mg/dL (17 µmol/L) and levels over 2–3 mg/dL (34-51 µmol/L) typically results in jaundice. High bilirubin is divided into two types: unconjugated (indirect) and conjugated (direct). Conjugated bilirubin can be confirmed by finding bilirubin in the urine. Other conditions that can cause yellowish skin but are not jaundice include carotenemia from eating large amounts of certain foods and medications like rifampin.

High unconjugated bilirubin may be due to excess red blood cell breakdown, large bruises, genetic conditions such as Gilbert's syndrome, not eating for a prolonged period of time, newborn jaundice, or thyroid problems. High conjugated bilirubin may be due to liver diseases such as cirrhosis or hepatitis, infections, medications, or blockage of the bile duct. In the developed world, the cause is more often blockage of the bile duct or medications while in the developing world, it is more often infections such as viral hepatitis, leptospirosis, schistosomiasis, or malaria. Blockage of the bile duct may occur due to gallstones, cancer, or pancreatitis. Medical imaging such as ultrasound is useful for detecting bile duct blockage.

Treatment of jaundice is typically determined by the underlying cause. If a bile duct blockage is present, surgery is typically required; otherwise, management is medical. Medical management may involve treating infectious causes and stopping medication that could be contributing. Among newborns, depending on age and prematurity, a bilirubin greater than 4–21 mg/dL (68-360 µmol/L) may be treated with phototherapy or exchanged transfusion. The itchiness may be helped by draining the gallbladder or ursodeoxycholic acid. The word "jaundice" is from the French "", meaning "yellow disease".

The name is derived from Latin: aquagenic, meaning water-induced, and pruritus, meaning itch.

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.

The serum bilirubin level is an indicator of the prognosis of PBC, with levels of 2–6 mg/dL having a mean survival time of 4.1 years, 6–10 mg/dL having 2.1 years and those above 10 mg/dL having a mean survival time of 1.4 years.

After liver transplant, the recurrence rate may be as high as 18% at 5 years, and up to 30% at 10 years. There is no consensus on risk factors for recurrence of the disease.

Complications of PBC can be related to chronic cholestasis or cirrhosis of the liver. Chronic cholestasis leads to osteopenic bone disease and osteoporosis, alongside hyperlipidaemia and vitamin deficiencies.

Patients with PBC have an increased risk of hepatocellular carcinoma compared to the general population, as is found in other cirrhotic patients. In patients with advanced disease, one series found an incidence of 20% in men and 4% in women.

Gallstone risk increases for females (especially before menopause) and for people near or above 40 years; the condition is more prevalent among both North and South Americans and among those of European descent than among other ethnicities. 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. 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. 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; low fluid consumption; and, at least for men, a high intake of carbohydrate, a high glycemic load, and high glycemic index diet. Wine and whole-grained bread may decrease the risk of gallstones.

Rapid weight loss increases risk of gallstones. Patients taking orlistat, a weight loss drug, may already be at increased risk for the formation of gallstones. Weight loss with orlistat can increase the risk of gallstones. On the contrary, ursodeoxycholic acid (UDCA), a bile acid, also a drug marketed as Ursodiol, appears to prevent formation of gallstones during weight loss. A high fat diet during weight loss also appears to prevent gallstones.

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

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. People with erythropoietic protoporphyria (EPP) are at increased risk to develop gallstones. Additionally, prolonged use of proton pump inhibitors has been shown to decrease gallbladder function, potentially leading to gallstone formation.

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. Fibrates increase cholesterol concentration in bile and their use has been associated with an increased risk of gallstones.

Cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications.

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.

A prospective study in 1994 noted that body mass index remains the strongest predictor of symptomatic gallstones among young women. Other risk factors are having over four pregnancies, weight gain, and cigarette smoking. Alcohol was shown to have an inverse relationship between use and gallbladder disease.

Drug-induced pruritus is itchiness of the skin caused by medication, a pruritic reaction that is generalized.

Biliary atresia seems to affect females slightly more often than males, and Asians and African Americans more often than Caucasians. It is common for only one child in a pair of twins or within the same family to have the condition. There seems to be no link to medications or immunizations given immediately before or during pregnancy. Diabetes during pregnancy particularly during the first trimester seems to predispose to a number of distinct congenital abnormalities in the infant such as sacral agenesis and the syndromic form of biliary atresia.

Key prevention strategies for cirrhosis are population-wide interventions to reduce alcohol intake (through pricing strategies, public health campaigns, and personal counseling), programs to reduce the transmission of viral hepatitis, and screening of relatives of people with hereditary liver diseases.

Little is known about factors affecting cirrhosis risk and progression. Research has suggested that coffee consumption appears to help protect against cirrhosis.

If a specific cause for pruritus ani is found it is classified as "secondary pruritus ani". If a specific cause is NOT found it is classified as "idiopathic pruritus ani". The irritation can be caused by intestinal parasites, anal perspiration, frequent liquid stools, diarrhea, residual stool deposits, or the escape of small amounts of stool as a result of incontinence or flatulence. Another cause is yeast infection or candidiasis. Some diseases increase the possibility of yeast infections, such as diabetes mellitus or HIV infection. Treatment with antibiotics can bring about a disturbance of the natural balance of intestinal flora, and lead to perianal thrush, a yeast infection affecting the anus. Psoriasis also can be present in the anal area and cause irritation. Abnormal passageways (fistulas) from the small intestine or colon to the skin surrounding the anus can form as a result of disease (such as Crohn's disease), acting as channels which may allow leakage of irritating fluids to the anal area. Other problems that can contribute to anal itching include pinworms, hemorrhoids, tears of the anal skin near the mucocutaneous junction (fissures), and skin tags (abnormal local growth of anal skin). Aside from diseases relative to the condition, a common view suggests that the initial cause of the itch may have passed, and that the illness is in fact prolonged by what is known as an itch-scratch-itch cycle. It states that scratching the itch encourages the release of inflammatory chemicals, which worsen redness, intensifies itchiness and increases the area covered by dry skin, thereby causing a snowball effect.

Some authorities describe “psychogenic pruritus” or "functional itch disorder", where psychological factors may contribute to awareness of itching.

Ingestion of helminth (worm) "Enterobius vermicularis" (pinworm, or threadworm) eggs leads to enterobiasis, indicative of severe itching around the anus from migration of gravid females from the bowel. Severe cases of enterobiasis result in hemorrhage and eczema.

The clinical course of biliary sludge can do one of three things: (1) it can resolve completely, (2) wax and wane, or (3) progress to gallstones. If the biliary sludge has a cause (e.g. pregnancy), it oftentimes is resolved when the underlying cause is removed.

Uremic pruritus (also known as uraemic pruritus or renal pruritus) is caused by chronic kidney failure and is the most common internal systemic cause of itching.

Nalfurafine, an orally-administered, centrally-acting κ-opioid receptor agonist, is approved to treat the condition in Japan.

The prevalence of biliary sludge is low in the general population. It has been reported that the prevalence ranges from 0-0.20% in men and 0.18-0.27% in women. However, in patients with certain conditions, the prevalence may be higher.

Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system). Parasites which may infect the liver and bile ducts may cause cholangitis; these include the roundworm "Ascaris lumbricoides" and the liver flukes "Clonorchis sinensis", "Opisthorchis viverrini" and "Opisthorchis felineus". In people with AIDS, a large number of opportunistic organisms has been known to cause "AIDS cholangiopathy", but the risk has rapidly diminished since the introduction of effective AIDS treatment. Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.

The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.

Case reports suggest that EPP is prevalent globally. The prevalence has been estimated somewhere between 1 in 75,000 and 1 in 200,000 however it has been noted that the prevalence of EPP may be increasing due to a better understanding of the disease and improved diagnosis. An estimated 5,000-10,000 individuals worldwide have EPP. EPP is considered the most common form of porphyria in children. The prevalence in Sweden has been published as 1:180,000.

People with ascites due to cirrhosis are at risk of spontaneous bacterial peritonitis.

Acute cholangitis carries a significant risk of death, the leading cause being irreversible shock with multiple organ failure (a possible complication of severe infections). Improvements in diagnosis and treatment have led to a reduction in mortality: before 1980, the mortality rate was greater than 50%, but after 1980 it was 10–30%. Patients with signs of multiple organ failure are likely to die unless they undergo early biliary drainage and treatment with systemic antibiotics. Other causes of death following severe cholangitis include heart failure and pneumonia.

Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis, biliary narrowing due to cancer, acute renal failure and the presence of liver abscesses. Complications following severe cholangitis include renal failure, respiratory failure (inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), cardiac arrhythmia, wound infection, pneumonia, gastrointestinal bleeding and myocardial ischemia (lack of blood flow to the heart, leading to heart attacks).