Cholesterol gallstones can sometimes be dissolved with ursodeoxycholic acid taken by mouth, but it may be necessary for the person to take this medication for years. Gallstones may recur, however, once the drug is stopped. Obstruction of the common bile duct with gallstones can sometimes be relieved by endoscopic retrograde sphincterotomy (ERS) following endoscopic retrograde cholangiopancreatography (ERCP). Gallstones can be broken up using a procedure called extracorporeal shock wave lithotripsy (often simply called "lithotripsy"), which is a method of concentrating ultrasonic shock waves onto the stones to break them into tiny pieces. They are then passed safely in the feces. However, this form of treatment is suitable only when there is a small number of gallstones.

Cholecystectomy (gallbladder removal) has a 99% chance of eliminating the recurrence of cholelithiasis. Surgery is only indicated in symptomatic patients. The lack of a gallbladder may have no negative consequences in many people. However, there is a portion of the population—between 10 and 15%—who develop a condition called postcholecystectomy syndrome which may cause gastrointestinal distress and persistent pain in the upper-right abdomen, as well as a 10% risk of developing chronic diarrhea.

There are two surgical options for cholecystectomy:

- Open cholecystectomy is performed via an abdominal incision (laparotomy) below the lower right ribs. Recovery typically requires 3–5 days of hospitalization, with a return to normal diet a week after release and to normal activity several weeks after release.

- Laparoscopic cholecystectomy, introduced in the 1980s, is performed via three to four small puncture holes for a camera and instruments. Post-operative care typically includes a same-day release or a one night hospital stay, followed by a few days of home rest and pain medication. Laparoscopic cholecystectomy patients can, in general, resume normal diet and light activity a week after release, with some decreased energy level and minor residual pain continuing for a month or two. Studies have shown that this procedure is as effective as the more invasive open cholecystectomy, provided the stones are accurately located by cholangiogram prior to the procedure so that they can all be removed.

No pharmacologic treatment has been approved by the U.S. Food and Drug Administration for PSC. Some experts recommend a trial of ursodeoxycholic acid (UDCA), a bile acid occurring naturally in small quantities in humans, as it has been shown to lower elevated liver enzyme numbers in patients with PSC and has proven effective in other cholestatic liver diseases. However, UDCA has yet to be shown to clearly lead to improved liver histology and survival. Guidelines from the American Association for the Study of Liver Diseases and the American College of Gastroenterology do not support the use of UDCA but guidelines from the European Association for the Study of the Liver do endorse the use of moderate doses (13-15 milligrams per kilogram) of UDCA for PSC.

Supportive treatment for PSC symptoms is the cornerstone of management. These therapies are aimed at relieving symptoms such as itching with antipruritics (e.g. bile acid sequestrants such as (cholestyramine)); antibiotics to treat episodes of acute cholangitis; and vitamin supplements, as people with PSC are often deficient in fat-soluble vitamins (vitamin A, vitamin D, vitamin E, and vitamin K).

ERCP and specialized techniques may also be needed to help distinguish between a benign PSC stricture and a bile duct cancer (cholangiocarcinoma).

Liver transplantation is the only proven long-term treatment of PSC, although only a fraction of individuals with PSC will need it. Indications for transplantation include recurrent bacterial cholangitis, decompensated cirrhosis, hepatocellular carcinoma, hilar cholangiocarcinoma, and complications of portal hypertension. Not all patients are candidates for liver transplantation, and some will experience disease recurrence afterward.

Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure.

Treatment involves an operation called a choledocholithotomy, which is the removal of the gallstone from the bile duct using ERCP, although surgeons are now increasingly using laparoscopy with cholangiography. In this procedure, tiny incisions are made in the abdomen and then in the cystic duct that connects the gallbladder to the bile duct, and a thin tube is introduced to perform a cholangiography. If stones are identified, the surgeon inserts a tube with an inflatable balloon to widen the duct and the stones are usually removed using either a balloon or tiny basket.

If laparoscopy is unsuccessful, an open choledocholithotomy is performed. This procedure may be used in the case of large stones, when the duct anatomy is complex, during or after some gallbladder operations when stones are detected, or when ERCP or laparoscopic procedures are not available.

Typically, the gallbladder is then removed, an operation called cholecystectomy, to prevent a future occurrence of common bile duct obstruction or other complications.

Due to the increased risk for gallbladder cancer, the recommended treatment is cholecystectomy which usually includes pre-operative or intra-operative imaging of the biliary tree. Cholecystectomy may be performed via an open incision or via laparoscopic methods, but gallbladder anatomy and consistency may complicate the operation.

For patients without symptoms, no treatment is recommended. If patients become symptomatic and/or develop complications, cholecystectomy is indicated. For those who are poor surgical candidates, endoscopic sphincterotomy may be performed to reduce the risk of developing pancreatitis.

Initial management includes the relief of symptoms and correcting electrolyte and fluid imbalance that may occur with vomiting. Antiemetics, such as dimenhydrinate, are used to treat the nausea. Pain may be treated with anti-inflammatories, NSAIDs such as ketorolac or diclofenac. Opioids, such as morphine, less commonly may be used. NSAIDs are more or less equivalent to opioids. Hyoscine butylbromide, an antispasmodic, is also indicated in biliary colic.

In biliary colic, the risk of infection is minimal and therefore antibiotics are not required. Presence of infection indicates cholecystitis.

It is unclear whether those experiencing a gallstone attack should receive surgical treatment or not. The scientific basis to assess whether surgery outperformed other treatment was insufficient and better studies were needed as of a SBU report in 2017. Treatment of biliary colic is dictated by the underlying cause. The presence of gallstones, usually visualized by ultrasound, generally necessitates a surgical treatment (removal of the gall bladder, typically via laparoscopy). Removal of the gallbladder with surgery, known as a cholecystectomy, is the definitive surgical treatment for biliary colic. A 2013 Cochrane review found tentative evidence to suggest that early gallbladder removal may be better than delayed removal. Early laparoscopic cholescystectomy happens within 72 hours of diagnosis. In a Cochrane review that evaluated receiving early versus delayed surgery, they found that 23% of those who waited on average 4 months ended up in hospital for complications, compared to none with early intervention with surgery. Early intervention has other advantages including reduced number of visits to the emergency department, less conversions to an open surgery, less operating time required, reduced time in hospital post operatively. The Swedish agency SBU estimated in 2017 that increasing acute phase surgeries could

free multiple in-hospital days per patient and would additionally spare pain and suffering in wait of receiving an operation. The report found that those with acute inflammation of the gallbladder can be surgically treated in the acute phase, within a few days of symptom debut, without increasing the risk for complications (compared to when the surgery is done later in an asymptomatic stage).

In cases where a person is too ill to tolerate endoscopy or when a retrograde endoscopic approach fails to access the obstruction, a percutaneous transhepatic cholangiogram (PTC) may be performed to evaluate the biliary system for placement of a percutaneous biliary drain (PBD). This is often necessary in the case of a proximal stricture or a bilioenteric anastomosis (a surgical connection between the bile duct and small bowel, such as the duodenum or jejunum). Once access across the stricture is obtained, balloon dilation can be performed and stones can be swept forward into the duodenum. Due to potential complications of percutaneous biliary drain placement and the necessity of regular drain maintenance, a retrograde approach via ERCP remains first-line therapy.

Simple cholecystectomy is suitable for type I patients. For types II–IV, subtotal cholecystectomy can be performed to avoid damage to the main bile ducts. Cholecystectomy and bilioenteric anastomosis may be required. Roux-en-Y hepaticojejunostomy has shown good outcome in some studies.

Laparoscopic cholecystectomy has been used to treat the condition when due to dyskinesia of the gallbladder.

Symptoms may persist after cholecystectomy, and have been linked to the use of proton pump inhibitors.

Osteopathic treatment, oral magnesium supplementation with 325 mg and the use of digestive enzymes caused improvement in one case.

Supportive measures may be instituted prior to surgery. These measures include fluid resuscitation. Intravenous opioids can be used for pain control.

Antibiotics are often not needed. If used they should target enteric organisms (e.g. Enterobacteriaceae), such as "E. coli" and "Bacteroides". This may consist of a broad spectrum antibiotic; such as piperacillin-tazobactam, ampicillin-sulbactam, ticarcillin-clavulanate (Timentin), a third generation cephalosporin (e.g.ceftriaxone) or a quinolone antibiotic (such as ciprofloxacin) and anaerobic bacteria coverage, such as metronidazole. For penicillin allergic people, aztreonam or a quinolone with metronidazole may be used.

In cases of severe inflammation, shock, or if the person has higher risk for general anesthesia (required for cholecystectomy), an interventional radiologist may insert a percutaneous drainage catheter into the gallbladder ('percutaneous cholecystostomy tube') and treat the person with antibiotics until the acute inflammation resolves. A cholecystectomy may then be warranted if the person's condition improves.

Homeopathic approaches to treating cholecystitis have not been validated by evidence and should not be used in place of surgery.

For most people with acute cholecystitis, the treatment of choice is surgical removal of the gallbladder, laparoscopic cholecystectomy. Laparoscopic cholecystectomy is performed using several small incisions located at various points across the abdomen. Several studies have demonstrated the superiority of laparoscopic cholecystectomy when compared to open cholecystectomy (using a large incision in the right upper abdomen under the rib cage). People undergoing laparoscopic surgery report less incisional pain postoperatively as well as having fewer long term complications and less disability following the surgery. Additionally, laparoscopic surgery is associated with a lower rate of surgical site infection.

During the days prior to laparoscopic surgery, studies showed that outcomes were better following early removal of the gallbladder, preferably within the first week. Early laparoscopic cholecystectomy (within 7 days of visiting a doctor with symptoms) as compared to delayed treatment (more than 6 weeks) may result in shorter hospital stays and a decreased risk of requiring an emergency procedure. There is no difference in terms of negative outcomes including bile duct injury or conversion to open cholecystectomy. For early cholecystectomy, the most common reason for conversion to open surgery is inflammation that hides Calot's triangle. For delayed surgery, the most common reason was fibrotic adhesions.

In simple cases of obstruction, where there are no complications, a variety of non-surgical and surgical techniques are used to remove the enterolith. These include crushing the enterolith and milking it back to the stomach or forward to the colon, surgical removal via an uninvolved segment of the gastrointestinal tract, and resection of the involved segment.

Severe pancreatitis can cause organ failure, necrosis, infected necrosis, pseudocyst, and abscess. If diagnosed with severe acute pancreatitis, people will need to be admitted to a high dependency unit or intensive care unit. It is likely that the levels of fluids inside the body will have dropped significantly as it diverts bodily fluids and nutrients in an attempt to repair the pancreas. The drop in fluid levels can lead to a reduction in the volume of blood within the body, which is known as hypovolemic shock. Hypovolemic shock can be life-threatening as it can very quickly starve the body of the oxygen-rich blood that it needs to survive. To avoid going into hypovolemic shock, fluids will be pumped intravenously. Oxygen will be supplied through tubes attached to the nose and ventilation equipment may be used to assist with breathing. Feeding tubes may be used to provide nutrients, combined with appropriate analgesia.

As with mild acute pancreatitis, it will be necessary to treat the underlying cause—gallstones, discontinuing medications, cessation of alcohol, etc. If the cause is gallstones, it is likely that an ERCP procedure or removal of the gallbladder will be recommended. The gallbladder should be removed during the same hospital admission or within two weeks of pancreatitis onset so as to limit the risk of recurrent pancreatitis. If the cause of pancreatitis is alcohol, cessation of alcohol consumption and treatment for alcohol dependency may improve pancreatitis. Even if the underlying cause is not related to alcohol consumption, doctors recommend avoiding it for at least six months as this can cause further damage to the pancreas during the recovery process. Oral intake, especially fats, is generally restricted initially but early enteral feeding within 48 hours has been shown to improve clinical outcomes. Fluids and electrolytes are replaced intravenously. Nutritional support is initiated via tube feeding to surpass the portion of the digestive tract most affected by secreted pancreatic enzymes if there is no improvement in the first 72–96 hours of treatment.

The treatment of pancreatitis is supportive and depends on severity. Morphine generally is suitable for pain control. There are no clinical studies to suggest that morphine can aggravate or cause pancreatitis or cholecystitis.

The treatment that is received for acute pancreatitis will depend on whether the diagnosis is for the mild form of the condition, which causes no complications, or the severe form, which can cause serious complications.

Although there is no curative treatment, several clinical trials are underway that aim to slow progression of this liver disease. Obeticholic acid is being investigated as a possible treatment for PSC due to its antifibrotic effects. Simtuzumab is a monoclonal antibody against the pro-fibrotic enzyme LOXL2 that is being developed as a possible therapy for PSC.

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.

Women are almost twice as likely as men to form gallstones especially during the fertile years; the gap narrows after the menopause. The underlying mechanism is female sex hormones; parity, oral contraceptive use and estrogen replacement therapy are established risk factors for cholesterol gallstone formation. Female sex hormones adversely influence hepatic bile secretion and gallbladder function. Estrogens increase cholesterol secretion and diminish bile salt secretion, while progestins act by reducing bile salt secretion and impairing gallbladder emptying leading to stasis. A new 4th generation progestin, drospirenone, used in some oral contraceptives may further heighten the risk of gallstone disease and cholecystectomy; however, the increased risk is quite modest and not likely to be clinically meaningful.

A retrospective (historical) cohort study was performed on a very large data base including 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared with 341,478 nonusers. Oral contraceptives were shown as risk factors for gallbladder disease, although the risk is of sufficient magnitude to be of potential clinical importance only in young women.

The 1984 Royal College of General Practitioners' Oral Contraception Study suggests that, in the long-term, oral contraceptives are not associated with any increased risk of gallbladder disease, although there is an acceleration of the disease in those women susceptible to it.

Newer research suggests otherwise. A 1993 meta-analysis concludes that oral contraceptive use is associated with a slightly and transiently increased rate of gallbladder disease, but laters confirms that modern low-dose oral contraceptives are safer than older formulas, though an effect cannot be excluded.

A 2001 comparative study of the IMS LifeLink Health Plan Claims Database interpreted that in a large cohort of women using oral contraceptives, there was found a small, statistically significant increase in the risk of gallbladder disease associated with desogestrel, drospirenone and norethisterone compared with levonorgestrel. No statistically significant increase in risk was associated with the other formulations of oral contraceptive (etynodiol diacetate, norgestrel and norgestimate).

Treatment of accessory pancreas depends on the location and extent of the injured tissue. Surgery may be an option, or some physicians order prophylactic antibiotics.

Choledocholithiasis (stones in common bile duct) is one of the complications of cholelithiasis (gallstones), so the initial step is to confirm the diagnosis of cholelithiasis. Patients with cholelithiasis typically present with pain in the right-upper quadrant of the abdomen with the associated symptoms of nausea and vomiting, especially after a fatty meal. The physician can confirm the diagnosis of cholelithiasis with an abdominal ultrasound that shows the ultrasonic shadows of the stones in the gallbladder.

The diagnosis of choledocholithiasis is suggested when the liver function blood test shows an elevation in bilirubin and serum transaminases. Other indicators include raised indicators of ampulla of vater (pancreatic duct obstruction) such as lipases and amylases. In prolonged cases the INR may change due to a decrease in vitamin K absorption. (It is the decreased bile flow which reduces fat breakdown and therefore absorption of fat soluble vitamins).

The diagnosis is confirmed with either an MRCP (magnetic resonance cholangiopancreatography), an ERCP, or an intraoperative cholangiogram. If the patient must have the gallbladder removed for gallstones, the surgeon may choose to proceed with the surgery, and obtain a cholangiogram during the surgery. If the cholangiogram shows a stone in the bile duct, the surgeon may attempt to treat the problem by flushing the stone into the intestine or retrieve the stone back through the cystic duct.

On a different pathway, the physician may choose to proceed with ERCP before surgery. The benefit of ERCP is that it can be utilized not just to diagnose, but also to treat the problem. During ERCP the endoscopist may surgically widen the opening into the bile duct and remove the stone through that opening. ERCP, however, is an invasive procedure and has its own potential complications. Thus, if the suspicion is low, the physician may choose to confirm the diagnosis with MRCP, a non-invasive imaging technique, before proceeding with ERCP or surgery.

Some individuals may benefit from diet modification, such as a reduced fat diet, following cholecystectomy. The liver produces bile and the gallbladder acts as reservoir. From the gallbladder, bile enters the intestine in individual portions. In the absence of gallbladder, bile enters the intestine constantly, but in small quantities. Thus, it may be insufficient for digestion of fatty foods. Postcholecystectomy syndrome treatment depends on the identified violations that led to it. Typically, the patient is recommended dietary restriction table with fatty foods, enzyme preparations, antispasmodics, sometimes cholagogue.

If the pain is caused by biliary microlithiasis, oral ursodeoxycholic acid can alleviate the condition.

A trial of bile acid sequestrant therapy is recommended for bile acid diarrhoea.

Most polyps are benign and do not need to be removed. Polyps larger than 1 cm with co-occurring gallstones occurring in people over the age of 50 may have the gallbladder removed (cholecystectomy), especially if the polyps are several or appear malignant. Laparoscopic surgery is an option for small or solitary polyps.

Antacids are a common treatment for mild to medium gastritis. When antacids do not provide enough relief, medications such as H blockers and proton-pump inhibitors that help reduce the amount of acid are often prescribed.

Cytoprotective agents are designed to help protect the tissues that line the stomach and small intestine. They include the medications sucralfate and misoprostol. If NSAIDs are being taken regularly, one of these medications to protect the stomach may also be taken. Another cytoprotective agent is bismuth subsalicylate.

Several regimens are used to treat "H. pylori" infection. Most use a combination of two antibiotics and a proton pump inhibitor. Sometimes bismuth is added to the regimen.