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.

Cholesterol gallstone formation risk factors include age, female sex, family history, race, pregnancy, parity, obesity, birth control, diabetes mellitus, cirrhosis, prolonged fasting, rapid weight loss, total parenteral nutrition, ileal disease and impaired gallbladder emptying.

Patients that have gallstones and biliary colic are at increased risk for complications, including cholecystitis. Complications from gallstone disease is 0.3% per year and therefore prophylactic cholecystectomy are rarely indicated unless part of a special population that includes porcelain gallbladder, individuals eligible for organ transplant, diabetics and those with sickle cell anemia.

Rarely, in cases of severe inflammation, gallstones may erode through the gallbladder into adherent bowel potentially causing an obstruction termed gallstone ileus.

Other complications include ascending cholangitis if there is a bacterial infection which can cause purulent inflammation in the biliary tree and liver, and acute pancreatitis as blockage of the bile ducts can prevent active enzymes being secreted into the bowel, instead damaging the pancreas.

Biliary pain is most frequently caused by obstruction of the common bile duct or the cystic duct by a gallstone. However, the presence of gallstones is a frequent incidental finding and does not always necessitate treatment, in the absence of identifiable disease. Furthermore, biliary pain may be associated with functional disorders of the biliary tract, so called acalculous biliary pain (pain without stones), and can even be found in patients post-cholecystectomy (removal of the gallbladder), possibly as a consequence of dysfunction of the biliary tree and the sphincter of Oddi. Acute episodes of biliary pain may be induced or exacerbated by certain foods, most commonly those high in fat.

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.

Cholecystitis occurs when the gallbladder becomes inflamed. Gallstones are the most common cause of gallbladder inflammation but it can also occur due to blockage from a tumor or scarring of the bile duct. The greatest risk factor for cholecystitis is gallstones. Risk factors for gallstones include female sex, increasing age, pregnancy, oral contraceptives, obesity, diabetes mellitus, ethnicity (Native North American), rapid weight loss.

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.

Gallstones blocking the flow of bile account for 90% of cases of cholecystitis (acute calculous cholecystitis). Blockage of bile flow leads to thickening and buildup of bile causing an enlarged, red, and tense gallbladder. The gallbladder is initially sterile but often becomes infected by bacteria, predominantly "E. coli", "Klebsiella", "Streptococcus", and "Clostridium" species. Inflammation can spread to the outer covering of the gallbladder and surrounding structures such as the diaphragm, causing referred right shoulder pain.

Mortality is indirect and caused by complications. After cholangitis occurs, patients typically die within 5–10 years.

There are seven classes of medications associated with acute pancreatitis: statins, ACE inhibitors, oral contraceptives/hormone replacement therapy (HRT), diuretics, antiretroviral therapy, valproic acid, and oral hypoglycemic agents. Mechanisms of these drugs causing panreatitis are not known exactly; but it is possible that statins has direct toxic effect on the pancreas or through the long term accumulation of toxic metabolites. Meanwhile, ACE inhibitors causes angioedema of the pancreas through the accumulation of bradykinin. Oral contraceptives/HRT causes arterial thrombosis of the pancreas through the accumulation of fat (hypertriglyceridemia). Diuretics such as furosemide has direct toxic effect on the pancreas. Meanwhile, thiazide diuretics causes hypertriglyceridemia and hypercalcemia, where the latter is the risk factor for pancreatic stones. HIV infection itself can cause a person to more likely to get pancreatitis. Meanwhile, antiretroviral drugs may cause metabolic disturbances such as hyperglycemia and hypercholesterolemia, which predisposes to pancreatitis. Valproic acid may have direct toxic effect on the pancreas. There are various oral hypoglycemic agents that contributes to pancreatitis including metformin. But, glucagon-like peptide-1 (GLP-1) is more strongly associated with pancreatits by promoting inflammation.

Atypical antipsychotics such as clozapine, risperidone, and olanzapine can also cause pancreatitis.

In adults in the United Kingdom, the estimated average total direct and indirect costs of chronic pancreatitis is roughly £79,000 per person on an annual basis. Acute recurrent pancreatitis and chronic pancreatitis occur infrequently in children, but are associated with high healthcare costs due to substantial disease burden. Globally, the estimated average total cost of treatment for children with these conditions is approximately $40,500 annually.

Caroli disease is typically found in Asia, and diagnosed in persons under the age of 22. Cases have also been found in infants and adults. As medical imaging technology improves, diagnostic age decreases.

In the United States, the annual incidence is 18 cases of acute pancreatitis per 100,000 population, and it accounts for 220,000 hospitalizations in the US. In a European cross-sectional study, incidence of acute pancreatitis increased from 12.4 to 15.9 per 100,000 annually from 1985 to 1995; however, mortality remained stable as a result of better outcomes. Another study showed a lower incidence of 9.8 per 100,000 but a similar worsening trend (increasing from 4.9 in 1963-74) over time.

In Western countries, the most common cause is alcohol, accounting for 65 percent of acute pancreatitis cases in the US, 20 percent of cases in Sweden, and 5 percent of those in the United Kingdom. In Eastern countries, gallstones are the most common cause of acute pancreatitis. The causes of acute pancreatitis also varies across age groups, with trauma and systemic disease (such as infection) being more common in children. Mumps is a more common cause in adolescents and young adults than in other age groups.

Locoregional complications include pancreatic pseudocyst (Most common, occurring in up to 25% of all cases) and phlegmon / abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins (in descending order of frequency), duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, pleural effusion, sterile/infected pancreatic necrosis.

Stones can cause disease by several mechanisms:

- Irritation of nearby tissues, causing pain, swelling, and inflammation

- Obstruction of an opening or duct, interfering with normal flow and disrupting the function of the organ in question

- Predisposition to infection (often due to disruption of normal flow)

A number of important medical conditions are caused by stones:

- Nephrolithiasis (kidney stones)

- Can cause hydronephrosis (swollen kidneys) and renal failure

- Can predispose to pyelonephritis (kidney infections)

- Can progress to urolithiasis

- Urolithiasis (urinary bladder stones)

- Can progress to bladder outlet obstruction

- Cholelithiasis (gallstones)

- Can predispose to cholecystitis (gall bladder infections) and ascending cholangitis (biliary tree infection)

- Can progress to choledocholithiasis (gallstones in the bile duct) and gallstone pancreatitis (inflammation of the pancreas)

- Gastric calculi can cause colic, obstruction, torsion, and necrosis.

In kidney stones, calcium oxalate is the most common mineral type (see Nephrolithiasis). Uric acid is the second most common mineral type, but an "in vitro" study showed uric acid stones and crystals can promote the formation of calcium oxalate stones.

Pancreatic diseases that affect digestion refers to disorders affecting the exocrine pancreas, which is a part of the pancreas involved in digestion.

One of the most common conditions of the exocrine pancreas is acute pancreatitis, which in the majority of cases relates to gallstones that have impacted in the pancreatic part of the biliary tree, or due to acute or chronic alcohol abuse or as a side-effect of ERCP. Other forms of pancreatitis include chronic and hereditary forms. Chronic pancreatitis may predispose to pancreatic cancer and is strongly linked to alcohol use. Other rarer diseases affecting the pancreas may include pancreatic pseudocysts, exocrine pancreatic insufficiency, and pancreatic fistulas.

Pancreatic disease may present with or without symptoms. When symptoms occur, such as in acute pancreatitis, a person may suffer from acute-onset, severe mid-abdominal pain, nausea and vomiting. In severe cases, pancreatitis may lead to rapid blood loss and systemic inflammatory response syndrome. When the pancreas is unable to secrete digestive enzymes, such as with a pancreatic cancer occluding the pancreatic duct, result in jaundice. Pancreatic disease might be investigated using abdominal x-rays, MRCP or ERCP, CT scans, and through blood tests such as measurement of the amylase and lipase enzymes.

SSC is thought to develop as a consequence of known injuries or pathological processes of the biliary tree, such as biliary obstruction, surgical trauma to the bile duct, or ischemic injury to the biliary tree. Secondary causes of SSC include intraductal stone disease, surgical or blunt abdominal trauma, intra-arterial chemotherapy, and recurrent pancreatitis. It has been clearly demonstrated sclerosing cholangitis can develop after an episode of severe bacterial cholangitis. Also it was suggested that it can result from insult to the biliary tree by obstructive cholangitis secondary to choledocholithiasis, surgical damage, trauma, vascular insults, parasites, or congenital fibrocystic disorders. Additional causes of secondary SC are toxic, due to chemical agents or drugs.

The cause of cholangiocarcinoma has not been clearly defined. A number of pathologic conditions, however, resulting in either acute or chronic biliary tract epithelial injury may predispose to malignant change. Primary sclerosing cholangitis, an idiopathic inflammatory condition of the biliary tree, has been clearly associated with the development of cholangiocarcinoma in up to 40% of patients. Congenital biliary cystic disease, such as choledochal cysts or Caroli's disease, has also been associated with malignant transformation in up to 25% of cases. These conditions appear to be related to an anomalous pancreatico-biliary duct junction and, perhaps, are related to the reflux of pancreatic secretions into the bile duct. Chronic biliary tract parasitic infection, seen commonly in Southeast Asia due to "Clonorchis sinensis" and "Opisthorchis viverrini", has also been identified as a risk factor. Although gallstones and cholecystectomy are not thought to be associated with an increased incidence of cholangiocarcinoma, hepatolithiasis and choledocholithiasis may predispose to malignant change. Further, industrial exposure to asbestos and nitrosamines, and the use of the radiologic contrast agent, Thorotrast (thorium dioxide), are considered to be risk factors for the development of cholangiocarcinoma.

Because of their location, these tumors tend to become symptomatic late in their development and therefore are not usually resectable at the time of presentation. This is variable as, due to obstruction, jaundice may present early and compel the patient to seek help. Complete resection of the tumor offers hope of long-term survival, and of late there has been renewed interest in liver transplantation from deceased donors along with add on therapy. Prognosis remains poor.

Hepatic diseases refers to those affecting the liver. Hepatitis refers to inflammation of liver tissue, and may be acute or chronic. Infectious viral hepatitis, such as hepatitis A, B and C, affect in excess of (X) million people worldwide. Liver disease may also be a result of lifestyle factors, such as fatty liver and NASH. Alcoholic liver disease may also develop as a result of chronic alcohol use, which may also cause alcoholic hepatitis. Cirrhosis may develop as a result of chronic hepatic fibrosis in a chronically inflamed liver, such as one affected by alcohol or viral hepatitis.

Liver abscesses are often acute conditions, with common causes being pyogenic and amoebic. Chronic liver disease, such as cirrhosis, may be a cause of liver failure, a state where the liver is unable to compensate for chronic damage, and unable to meet the metabolic demands of the body. In the acute setting, this may be a cause of hepatic encephalopathy and hepatorenal syndrome. Other causes of chronic liver disease are genetic or autoimmune disease, such as hemochromatosis, Wilson's disease, autoimmune hepatitis, and primary biliary cirrhosis.

Acute liver disease rarely results in pain, but may result in jaundice. Infectious liver disease may cause a fever. Chronic liver disease may result in a buildup of fluid in the abdomen, yellowing of the skin or eyes, easy bruising, immunosuppression, and feminsation. Portal hypertension is often present, and this may lead to the development of prominent veins in many parts of the body, such as oesophageal varices, and haemorrhoids.

In order to investigate liver disease, a medical history, including regarding a person's family history, travel to risk-prone areas, alcohol use and food consumption, may be taken. A medical examination may be conducted to investigate for symptoms of liver disease. Blood tests may be used, particularly liver function tests, and other blood tests may be used to investigate the presence of the Hepatitis viruses in the blood, and ultrasound used. If ascites is present, abdominal fluid may be tested for protein levels.

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.

The diagnosis of SSC requires the exclusion of secondary causes of sclerosing cholangitis and recognition of associated conditions that may potentially imitate its classic cholangiographic features. It is morphologically similar to primary sclerosing cholangitis (PSC) but originates from a known pathological process. Its clinical and cholangiographic features may mimic PSC, yet its natural history may be more favorable if recognition is prompt and appropriate therapy is introduced. Sclerosing cholangitis in critically ill patients, however, is associated with rapid disease progression and poor outcome. Serologic testing, radiological imaging and histological analysis can help diagnose SSC.

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.