Diseases of the hepatobiliary system affect the biliary tract (also known as the "biliary tree"), which secretes bile in order to aid digestion of fats. Diseases of the gallbladder and bile ducts are commonly diet-related, and may include the formation of gallstones that impact in the gallbladder (cholecystolithiasis) or in the common bile duct (choledocholithiasis).

Gallstones are a common cause of inflammation of the gallbladder, called cholecystitis. Inflammation of the biliary duct is called cholangitis, which may be associated with autoimmune disease, such as primary sclerosing cholangitis, or a result of bacterial infection, such as ascending cholangitis.

Disease of the biliary tree may cause pain in the upper right abdomen, particularly when pressed. Disease might be investigated using ultrasound or ERCP, and might be treated with drugs such as antibiotics or UDCA, or by the surgical removal of the gallbladder.

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.

Most affected individuals with pyruvate kinase deficiency do not require treatment. Those individuals who are more severely affected may die in utero of anemia or may require intensive treatment. With these severe cases of pyruvate kinase deficiency in red blood cells, treatment is the only option, there is no cure. However, treatment is usually effective in reducing the severity of the symptoms.

The most common treatment is blood transfusions, especially in infants and young children. This is done if the red blood cell count has fallen to a critical level. The transplantation of bone marrow has also been conducted as a treatment option.

There is a natural way the body tries to treat this disease. It increases the erythrocyte production (reticulocytosis) because reticulocytes are immature red blood cells that still contain mitochondria and so can produce ATP via oxidative phosphorylation. Therefore, a treatment option in extremely severe cases is to perform a splenectomy. This does not stop the destruction of erythrocytes but it does help increase the amount of reticulocytes in the body since most of the hemolysis occurs when the reticulocytes are trapped in the hypoxic environment of the spleen. This reduces severe anemia and the need for blood transfusions.

Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.