In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II (Acute Physiology and Chronic Health Evaluation) indices. Most, but not all studies report that the Apache score may be more accurate. In the negative study of the APACHE-II, the APACHE-II 24-hour score was used rather than the 48-hour score. In addition, all patients in the study received an ultrasound twice which may have influenced allocation of co-interventions. Regardless, only the APACHE-II can be fully calculated upon admission. As the APACHE-II is more cumbersome to calculate, presumably patients whose only laboratory abnormality is an elevated lipase or amylase do not need assessment with the APACHE-II; however, this approach is not studied. The APACHE-II score can be calculated at www.sfar.org.

Practice guidelines state:

The Ranson criteria are a clinical prediction rule for predicting the severity of acute pancreatitis. They were introduced in 1974.

Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound, as this is the most easily available. Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones farther down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis (inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound. A better test is magnetic resonance cholangiopancreatography (MRCP), which uses magnetic resonance imaging (MRI); this has a comparable sensitivity to ERCP. Smaller stones, however, can still be missed on MRCP depending on the quality of the hospital's facilities.

The gold standard test for biliary obstruction is still endoscopic retrograde cholangiopancreatography (ERCP). This involves the use of endoscopy (passing a tube through the mouth into the esophagus, stomach and thence to the duodenum) to pass a small cannula into the bile duct. At that point, radiocontrast is injected to opacify the duct, and X-rays are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.

If other causes rather than gallstones are suspected (such as a tumor), computed tomography and endoscopic ultrasound (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy (tissue sample) of suspicious masses. EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.

In someone suspected of having cholecystitis, blood tests are performed for markers of inflammation (e.g. complete blood count, C-reactive protein), as well as bilirubin levels in order to assess for bile duct blockage. Complete blood count typically shows an increased white blood count (12,000–15,000/mcL). C-reactive protein is usually elevated although not commonly measured in the United States. Bilirubin levels are often mildly elevated (1–4 mg/dL). If bilirubin levels are more significantly elevated, alternate or additional diagnoses should be considered such as gallstone blocking the common bile duct (common bile duct stone). Less commonly, blood aminotransferases are elevated. The degree of elevation of these laboratory values may depend on the degree of inflammation of the gallbladder.

Right upper quadrant abdominal ultrasound is most commonly used to diagnose cholecystitis. Ultrasound findings suggestive of acute cholecystitis include gallstones, fluid surrounding the gallbladder, gallbladder wall thickening (wall thickness over 3 mm), dilation of the bile duct, and sonographic Murphy's sign. Given its higher sensitivity, hepatic iminodiacetic acid (HIDA) scan can be used if ultrasound is not diagnostic. CT scan may also be used if complications such as perforation or gangrene are suspected.

Routine blood tests show features of acute inflammation (raised white blood cell count and elevated C-reactive protein level), and usually abnormal liver function tests (LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis, with elevations in alanine transaminase and aspartate transaminase.

Blood cultures are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases, usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli: "Escherichia coli" (25–50%), Klebsiella (15–20%) and Enterobacter (5–10%). Of the gram-positive cocci, Enterococcus causes 10–20%.

Diagnosis is guided by the person's presenting symptoms and laboratory findings. The gold standard imaging modality for the presence of gallstones is ultrasound of the right upper quadrant. There are many reasons for this choice, including no exposure to radiation, low cost, and availability in city, urban, and rural hospitals. Gallstones are detected with a specificity and sensitivity of greater than 95% with ultrasound. Further signs on ultrasound may suggest cholecystitis or choledocholithiasis. Computed Topography (CT) is not indicated when investigating for gallbladder disease as 60% of stones are "not" radiopaque. CT should only be utilized if other intraabdominal pathology exists or the diagnosis is uncertain. Endoscopic retrograde cholangiopancreatography (ERCP) should be used only if lab tests suggest the existence of a gallstone in the bile duct. ERCP is then both diagnostic and therapeutic.

PSC is generally diagnosed on the basis of having at least two of three clinical criteria after secondary causes of sclerosing cholangitis have been ruled out:

- serum alkaline phosphatase (ALP) > 1.5x the upper limit of normal for longer than 6 months;

- cholangiography demonstrating biliary strictures or irregularity consistent with PSC; and,

- liver biopsy consistent with PSC (if available).

Historically, a cholangiogram would be obtained via endoscopic retrograde cholangiopancreatography (ERCP), which typically reveals "beading" (alternating strictures and dilation) of the bile ducts inside and/or outside the liver. Currently, the preferred option for diagnostic cholangiography, given its non-invasive yet highly accurate nature, is magnetic resonance cholangiopancreatography (MRCP), a magnetic resonance imaging technique. MRCP has unique strengths, including high spatial resolution, and can even be used to visualize the biliary tract of small animal models of PSC.

Most people with PSC have evidence of autoantibodies and abnormal immunoglobulin levels. For example, approximately 80% of people with PSC have perinuclear anti-neutrophil cytoplasmic antibodies; however, this and other immunoglobulin findings are not specific to those with PSC and are of unclear clinical significance/consequence. Antinuclear antibodies and anti-smooth muscle antibody are found in 20%-50% of PSC patients and, likewise, are not specific for the disease but may identify a subgroup of PSC patients who also have autoimmune hepatitis (i.e. PSC-AIH overlap syndrome).

Other markers which may be measured and monitored are a complete blood count, serum liver enzymes, bilirubin levels (usually grossly elevated), kidney function, and electrolytes. Fecal fat measurement is occasionally ordered when symptoms of malabsorption (e.g., gross steatorrhea) are prominent.

The differential diagnosis can include primary biliary cholangitis (formerly referred to as primary biliary cirrhosis), drug-induced cholestasis, cholangiocarcinoma, IgG4-related disease, post-liver transplantation non-anastomotic biliary strictures, and HIV-associated cholangiopathy. Primary sclerosing cholangitis and primary biliary cholangitis are distinct entities and exhibit important differences, including the site of tissue damage within the liver, associations with inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, response to treatment, and risks of disease progression.

Biliary sludge is typically diagnosed by CT scan or transabdominal ultrasonography. Endoscopic ultrasonography is another more sensitive option. However, the gold standard is considered to be direct microscopy of aspirated gallbladder bile. This method is much more sensitive, although it is less practical.

Diagnosis is typically confirmed by ultrasound. Complications may be detected on blood tests.

A positive Murphy's sign is a common finding on physical examination during a gallbladder attack.

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.

Stable patients presenting to A&E (accident and emergency department) or ER (emergency room) with severe abdominal pain will almost always have an abdominal x-ray and/or a CT scan. These tests can provide a differential diagnosis between simple and complex pathologies. However, in the unstable patient, fluid resuscitation and a FAST-ultrasound are done first, and if the latter is positive for free fluid, straight to surgery. They may also provide evidence to the doctor whether surgical intervention is necessary.

Patients will also most likely receive a complete blood count (or full blood count in the U.K.), looking for characteristic findings such as neutrophilia in appendicitis.

Traditionally, the use of opiates or other painkillers in patients with an acute abdomen has been discouraged before the clinical examination, because these would alter the examination. However, the scientific literature does not reveal any negative results from these alterations.

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.

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.

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.

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.

Computed tomography (CT) findings in AIP include a "diffusely enlarged hypodense" pancreas or a focal mass that may be mistaken for a pancreatic malignancy. A low-density, "capsule-like rim on CT" (possibly corresponding to an inflammatory process involving peripancreatic tissues) is thought to be an additional characteristic feature (thus the mnemonic: "sausage-shaped"). Magnetic resonance imaging (MRI) reveals a diffusely decreased signal intensity and delayed enhancement on dynamic scanning. The characteristic ERCP finding is segmental or diffuse irregular narrowing of the main pancreatic duct, usually accompanied by an extrinsic-appearing stricture of the distal bile duct. Changes in the extrapancreatic bile duct similar to those of primary sclerosing cholangitis (PSC) have been reported.

The role of endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of AIP is not well described, and EUS findings have been described in only a small number of patients. In one study, EUS revealed a diffusely swollen and hypoechoic pancreas in 8 of the 14 (57%) patients, and a solitary, focal, irregular mass was observed in 6 (46%) patients. Whereas EUS-FNA is sensitive and specific for the diagnosis of pancreatic malignancy, its role in the diagnosis of AIP remains unclear.

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.

Cholestasis can be suspected when there is an elevation of both 5'-nucleotidase and ALP enzymes. With a few exceptions, the optimal test for cholestasis would be elevations of serum bile acid levels. However, this is not normally available in most clinical settings. The gamma-glutamyl transferase (GGT) enzyme was previously thought to be helpful in confirming a hepatic source of ALP; however, GGT elevations lack the necessary specificity to be a useful confirmatory test for ALP. Normally GGT and ALP are anchored to membranes of hepatocytes and are released in small amounts in hepatocellular damage. In cholestasis, synthesis of these enzymes is induced and they are made soluble. GGT is elevated because it leaks out from the bile duct cells due to pressure from inside bile ducts.

In a later stage of cholestasis AST, ALT and bilirubin may be elevated due to liver damage as a secondary effect of cholestasis.

Most recently the fourteenth Congress of the International Association of Pancreatology developed the International Consensus Diagnostic Criteria (ICDC) for AIP. The ICDC emphasizes five cardinal features of AIP which includes the imaging appearance of pancreatic parenchyma and the pancreatic duct, serum IgG4 level, other organ involvement with IgG4-related disease, pancreatic histology and response to steroid therapy.

In 2002, the Japanese Pancreas Society proposed the following diagnostic criteria for autoimmune pancreatitis:

For diagnosis, criterion I (pancreatic imaging) must be present with criterion II (laboratory data) and/or III (histopathologic findings).

Mayo Clinic has come up with five diagnostic criteria called HISORt criteria which stands for histology, imaging, serology, other organ involvement, and response to steroid therapy.

Recurrent pyogenic cholangitis is characterised by recurrent bouts of bacterial cholangitis with primary hepatolithiasis. It is prevalent in Hong Kong and East Asian including China, Taiwan, Korea, Japan, Indonesia and the Philippines. Apart from affecting humans it is also a common disease in cats.

The initial diagnostic workup for ulcerative colitis includes the following:

- A complete blood count is done to check for anemia; thrombocytosis, a high platelet count, is occasionally seen

- Electrolyte studies and renal function tests are done, as chronic diarrhea may be associated with hypokalemia, hypomagnesemia and pre-renal failure.

- Liver function tests are performed to screen for bile duct involvement: primary sclerosing cholangitis.

- X-ray

- Urinalysis

- Stool culture, to rule out parasites and infectious causes.

- Erythrocyte sedimentation rate can be measured, with an elevated sedimentation rate indicating that an inflammatory process is present.

- C-reactive protein can be measured, with an elevated level being another indication of inflammation.

- Sigmoidoscopy a type of endoscopy which can detect the presence of ulcers in the large intestine after a trial of an enema.

Although ulcerative colitis is a disease of unknown causation, inquiry should be made as to unusual factors believed to trigger the disease.

The simple clinical colitis activity index was created in 1998 and is used to assess the severity of symptoms.

Modern imaging techniques allow the diagnosis to be made more easily and without invasive imaging of the biliary tree. Commonly, the disease is limited to the left lobe of the liver. Images taken by CT scan, X-ray, or MRI show enlarged intrahepatic (in the liver) bile ducts due to ectasia. Using an ultrasound, tubular dilation of the bile ducts can be seen. On a CT scan, Caroli disease can be observed by noting the many fluid-filled, tubular structures extending to the liver. A high-contrast CT must be used to distinguish the difference between stones and widened ducts. Bowel gas and digestive habits make it difficult to obtain a clear sonogram, so a CT scan is a good substitution. When the intrahepatic bile duct wall has protrusions, it is clearly seen as central dots or a linear streak. Caroli disease is commonly diagnosed after this “central dot sign” is detected on a CT scan or ultrasound. However, cholangiography is the best, and final, approach to show the enlarged bile ducts as a result of Caroli disease.

Extrahepatic cholestasis can usually be treated by surgery.

Pruritis in cholestatic jaundice is treated by Antihistamines, Ursodeoxycholic Acid, Phenobarbital

Suppurative cholangitis, liver abscess, empyema of the gallbladder, acute pancreatitis, thrombophlebitis of hepatic or portal veins, and septicemia are acute complications of the disease, to which patients may succumb during the acute attacks.

Chronically, complications include cholangiocarcinoma and intraductal papillary neoplasm.