How can I be sure that the patient has gallstones and/or hepatic cysts?


Gallstones are highly prevalent, and their presence does not necessarily connote disease! Gallstones (80% are cholesterol gallstones; Figure 1) are common (National Health and Nutrition Examination Survey), and their prevalence increases with age and the following factors: female gender, pregnancy, use of female steroid hormones, and body mass index (BMI). Race and ethnicity impact gallstone prevalence. In American nonHispanic Whites, 20% to 30% of women and 10% to 20% of men over age 50 have had gallstones. In Americans, matched for age and BMI, the highest prevalence of gallstones is in Hispanic women (over 40% in Hispanic women over age 50) and the lowest prevalence is in African American men (~10% in African American men over age 50). In a Strong Heart Study, 64% of Amerindian women had gallstones.

Figure 1.

Cross section of almost pure cholesterol gallstone.

Asymptomatic gallstones

Most gallstones are asymptomatic and remain asymptomatic over the course of a person’s life. Asymptomatic gallstones may be discovered during abdominal imaging studies, most commonly, ultrasonography. Another radiologic finding, gallstone sludge, may resolve completely in follow-up or be a harbinger for formation of gallstones. The natural history of asymptomatic gallstones is relatively benign: only 25% of patients develop symptoms over the course of their lifetime. In general, the recommendation for asymptomatic gallstones is “watch and wait” for development of symptoms or disease.

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Biliary colic

Development of symptoms connotes a change in course toward more significant gallbladder disease. Patients with symptomatic gallstones typically experience recurrent symptoms and ultimately may be at risk for complications. However, the reported likelihood of recurrent symptoms varies widely between studies – from a high of 70% within 2 years to a low of 40% over 10 years. When gallstones damage the gallbladder or cause inflammation of the gallbladder, pain is the most common first symptom. The term applied to gallbladder pain is biliary colic. Unlike renal colic, biliary colic is rarely colicky. Nonetheless, the onset of biliary colic heralds consideration of cholecystectomy.

The pain of biliary colic typically builds over 15 to 60 minutes, plateaus for 30 minutes to a few hours, and then dissipates slowly. In some cases, the pain is described as episodic. Between episodes of pain, the patient is pain-free.

Gallbladder pain is typically located in the right upper quadrant (RUQ) of the abdomen but may also localize to the mid-epigastrium or right infrascapular region of the back. Patients may experience nausea and, rarely, vomiting. Pain may be precipitated by fatty meals but is often spontaneous and occurring at night. Biliary colic and symptomatic gallbladder disease signal a need for treatment.

Acute cholecystitis

Acute cholecystitis is defined by persistent RUQ pain, fever, chill, tenderness over the gallbladder when palpated, and leukocytosis on laboratory evaluation (Figure 2). Acute cholecystitis is an indication for cholecystectomy. Underlying diseases such as cirrhosis, cardiac disease, significant systemic disease, immunosuppression, or elderly age may modify the approaches to surgery.

Figure 2.

Clinical features of acute cholecystitis.

Laparoscopic cholecystectomy is the preferred surgical treatment for symptomatic gallbladder disease. Rarely the laparoscopic procedure is converted to an open procedure, rates of complications range from 0 to 5%, and mortality from 0 to 0.9%. Risk factors for mortality after cholecystectomy include severe underlying cardiac or renal disease (Figure 3) or cirrhosis (risk is related to MELD score, Figure 4).

Figure 3.

Factors independently associated with operative mortality after cholecystectomy.

Figure 4.

MELD and 90-day surgical mortality.

Biliary obstruction

Biliary obstruction due to passage of a gallstone is associated with jaundice and elevations in bilirubin and alkaline phosphatase. A stone obstructing the bile duct is best treated by ERCP.

Acute cholangitis

Acute cholangitis may complicate biliary obstruction and is characterized by pain, fever, jaundice, leukocytosis, and risk for sepsis. Charcot’s Triad found in 70% of cases is pain, jaundice, and fever. Raynold’s Pentad found in 10% of cases is pain, jaundice, fever, hypotension, and mental confusion (Figure 5).

Figure 5.

Clinical features of acute cholangitis.

The first step in the management of acute cholangitis is stabilizing the patient – patients with acute cholangitis are sick and may be unstable due to bacteremia or sepsis. Reported morbidity is substantial. The second step is relief of biliary obstruction: ERCP is favored over immediate surgical intervention. Once stabilized and obstruction is relieved or controlled, then cholecystectomy may be performed to reduce the risk of future recurrence of cholangitis or other biliary complications.


Gallstone passage through the common bile duct may also trigger pancreatitis; gallstones are second only to alcohol as a leading cause of acute pancreatitis.

The management of gallstone pancreatitis includes pain management, NPO, and examination of the common bile duct by ERCP for residual stones that may require removal via ERCP. Gallstone pancreatitis tends to recur if the patient’s gallbladder is intact and has residual gallstones. Cholecystectomy is indicated for most patients with gallstone pancreatitis.

Gallbladder carcinoma

Gallbladder carcinoma, although relatively rare, is a complication of chronic cholecystitis and may be an incidental finding at cholecystectomy or on imaging studies of the gallbladder. When symptomatic, gallbladder carcinoma is typically extensive with poor prognosis.

When found incidentally at the time of laparoscopic cholecystectomy, the operation is typically converted to an open procedure to allow more extensive dissection and removal of lymph nodes. Bulk disease should be resected, if possible, to avoid extension of tumor into adjacent structures, such as the colon. Chemotherapy and radiation treatments are used as adjuncts to surgery.

Hepatic cystic diseases

The spectrum of hepatic cystic disease ranges from a simple solitary isolated hepatic cyst to the massive extensive hepatic cysts of polycystic liver. A table summarizing this spectrum, the genetic determinants, and clinical manifestations is provided (Figure 6).

Figure 6.

Characteristics of hepatic cystic diseases.

Solitary hepatic cysts

Hepatic cysts are common, have a female predilection, and prevalence is related to age and ranges from 1% in the young to nearly 8% in the elderly. The vast majority is asymptomatic; they are usually discovered incidentally during work-up of abdominal pain, and appear as smooth-walled water-filled liver masses (Figure 7). If judged to be symptomatic, treatment is percutaneous aspiration and sclerotherapy – surgery is rarely required.

Figure 7.

CT of solitary hepatic cyst.

Multiple hepatic cysts

Polycystic liver.There are two main forms in adults, autosomal dominant polycystic kidney disease (ADPKD) in association with renal cystic disease, and isolated polycystic liver disease (PCLD) (Figure 8). Both are autosomal dominant conditions with multiple genetic forms. The cysts of polycystic liver do not communicate with the biliary tree.

Figure 8.

CT of polycystic liver and kidneys in patient with ADPKD.

The most common symptoms of polycystic liver is abdominal fullness and discomfort. Factors associated with extensive or massive polycystic liver include female gender, use of female steroid hormones, and pregnancy. One study has suggested that oral estrogen may selectively accelerate polycystic liver, compared to kidneys. Perhaps oral estrogen should be avoided in women with extensive hepatic cysts.

Surgical or radiologic intervention is rarely required. In severe cases, interventions may include percutaneous or laparoscopic cyst drainage and sclerotherapy, open laparotomy with cyst fenestration, or hepatic lobectomy. However, with all of these interventions, cysts tend to regrow or new ones emerge and symptoms recur. In highly symptomatic cases where other interventions have failed, liver transplantation may be considered.

Congenital hepatic fibrosis. Multiple hepatic cysts may also be found in other conditions: biliary microhamartoma syndrome, congenital hepatic fibrosis, and other even rarer conditions. Congenital hepatic fibrosis is associated with portal hypertension, development of varices, variceal hemorrhage, splenomegaly, and thrombocytopenia. The unique features of the pattern of fibrosis and von Meyenburg complexes are displayed in Figure 9. Complications are usually managed by endoscopic treatment of varices, portal-systemic shunt, and, rarely, liver transplantation.

Figure 9.

Congenital hepatic fibrosis.

Choledochal cyst

Choledochal cysts are isolated cystic dilations of the common bile duct: the anatomic location of the cysts dictates clinical symptoms and operative approaches (Figure 10). Choledochal cysts may be suspected by imaging (Figure 11) but often requires ERCP for definitive diagnosis. The main treatment of choledochal cysts is surgical resection. The main indications for surgery are recurrent bouts of cholangitis and prevention or treatment of cholangiocarcinoma (CCA). The risk of CCA increases with age, and if cyst drainage instead of resection is performed.

Figure 10.

Classification of choledochal cysts.

Figure 11.

CT of choledochal cyst.

Caroli's disease

Caroli’s disease, a very rare condition, that is characterized by multiple cysts that communicate with the biliary tree (Figure 12). The main complications of Caroli’s disease are biliary stone formation, biliary obstruction, cholangitis, and abscess formation. Endoscopic methods may be used initially, but, commonly, symptoms and complications progress and require surgical approaches: resection, biliary reconstruction, and liver transplantation.

Figure 12.

Cholangiogram in Caroli’s disease.

A tabular or chart listing of features and signs and symptoms

Pain: biliary colic
  • – RUQ or epigastrium

  • – Radiates along right side toward infrascapular region of back

  • – Episodic

  • – Occasionally precipitated by fatty meal

  • – Harbinger of future complications

  • – Acute cholecystitis

  • – Acute cholangitis

  • –Pancreatitis

  • – Chronic cholecystitis

  • – Gallbladder carcinoma

Less common presentations
  • – Gangrenous cholecystitis

  • – Emphysematous cholecystitis (air in wall of gallbladder)

  • – Gallbladder empyema (pus-filled gallbladder)

  • – Gallbladder perforation

  • – Bouveret’s syndrome (obstruction of bowel from stone extrusion from gallbladder into bowel)

  • – Mirrizzi’s syndrome (obstruction of bile duct from inflammatory mass from acute cholecystitis)

Conditions mimicking signs and symptoms of gallbladder disease
  • – Peptic ulcer disease

  • – Dyspepsia

  • – Irritable bowel syndrome

  • – Pancreatitis

  • – Hepatic mass lesion

  • – Renal mass, stone, or infection

  • – Intestinal disease

  • Celiac disease

  • Inflammatory disease (ischemia, inflammatory bower disease [IBD])

  • Polyp or mass

  • – Colonic disease

  • Neoplasm at hepatic flexure or transverse colon

  • Inflammatory disease (diverticulitis, IBD)

  • – Supradiaphragmatic disease

  • Lung mass

  • Pneumonia

Hepatic cysts
Incidental finding on imaging studies
  • – During work-up of abdominal pain of other etiology

  • – During follow-up of patient with known polycystic kidney disease

Abdominal pain
  • – Solitary cyst: if localized over region of cyst

  • – Polycystic liver: generally mild and due to mass of cysts (fullness and discomfort)

  • – Choledochal cysts and Caroli’s disease: generally mild unless complications ensue

Complications arising in hepatic cysts
  • – Cyst hemorrhage: imaging with fluid level

  • – Cyst infection: localized pain, fever, leucocytosis

  • – Cyst carcinoma: mass in cyst wall on imaging

Complications arising in choledochal cysts
  • – Biliary obstruction

  • – Acute cholangitis

  • – Cholangiocarcinoma

Conditions mimicking hepatic cysts
  • – Cystic neoplasms

  • Biliary cystadenoma

  • Biliary cystadenocarcinoma

  • Metastases: carcinoid in particular

  • – Infections

  • Echinococcal disease

  • Pyogenic abscess(es)

Conditions mimicking choledochal cysts
  • – Biliary obstruction

  • – Post-surgical or post-traumatic bile duct injury

Conditions mimicking Caroli's disease
  • – Oriental cholangiohepatitis

How can I confirm the diagnosis?

Initial evaluation to confirm gallstones
  • – Laboratory tests

  • CBC

  • Liver panel

  • Amylase/lipase

  • Urinalysis

  • – Ultrasonography of liver and gallbladder

Diagnosing complications

Acute cholecystitis

  • – If patient has fever, RUQ pain, leucocytosis, and gallstones on ultrasonography: no further work-up is needed, diagnosis is established.

  • – If clinical evaluation is not diagnostic:

  • Ultrasonography shows thickened gallbladder wall: diagnosis is likely.

  • HIDA nonfunction or EF <38%: gallbladder disease is likely.

Acute cholangitis

  • – If patient has fever, leucocytosis, and jaundice and ultrasonography shows gallstones and dilated duct: diagnosis is established.

  • – ERCP is warranted in most cases, mainly for sphincterotomy and stone remove but also for diagnosis in some cases.

Gallstone pancreatitis

  • – Rapid rise and fall in amylase/lipase and gallstones on ultrasonography: diagnosis is established.

  • – ERCP may be warranted for diagnosis in some cases and for treatment in most cases.

Gallbladder carcinoma

  • – Usually an incidental finding at cholecystectomy.

  • – Ultrasonography may demonstrated gallbladder mass.

  • – CT will define mass and vascularity, as well as extension out of gallbladder into surrounding tissues.

  • – ERCP may be needed to exclude bile duct involvement.

Additional diagnostic studies

CCK (cholecystokinin) cholescintigraphy to define function and emptying rate, disease may be indicated by:

  • – Nonvisualization of the gallbladder

  • – Low ejection fraction, <38%

ERCP (or PTC [percutaneous transhepatic cholangiography]) to evaluate for:

  • – Retained stone in bile duct

  • – Stricture

  • – Tumor

  • – Sphincter of Oddi dysfunction

CT or MRI to evaluate for:

  • – Hepatic mass

  • – Abdominal mass

  • – Complex gallbladder disease

EGD (esophagogastroduodenoscopy) to evaluate for:

  • –Peptic disease

  • – UGI mass or inflammation

Scenario 1: Evaluation of abdominal pain in patient with gallstones
  • Step 1: Pain is consistent with gallbladder disease:

    – Single episode: observe, watch, and wait

    – Recurrent episodes: recommend elective cholecystectomy

  • Step 2: Pain is not diagnostic of gallbladder disease:

    – CCK-cholescintigraphy is normal: watch and wait

    – CCK-cholescintigraphy demonstrates nonfunction or <38% EF: recommend cholecystectomy

  • Step 3: Persistent symptoms:

    – EGD to rule out peptic disease or mass

    – Abdominal CT to evaluate for abdominal or hepatic mass

Scenario 2: Suspected acute cholecystitis
  • Step 1: Presentation consistent with acute cholecystitis with positive ultrasonography: urgent cholecystectomy

  • Step 2: Presentation atypical for acute cholecystitis or ultrasonography equivocal:

    – Elevated bilirubin, alkaline phosphatase: MRCP (magnetic resonance cholangiopancreatography)

    – Normal bilirubin and alkaline phosphatase: CCK cholescintigraphy

  • Step 3: Positive findings on MRCP: further evaluation of biliary tree with ERCP (or PTC):

    – Positive CCK-cholescintigraphy: refer for cholecystectomy.

  • Step 4: Negative work-up:

    – Evaluate for other etiologies of signs and symptoms.

    – Watch and wait.

Scenario 3: Evaluation of the jaundiced patient
  • Step 1: Exclude drug reaction.

  • Step 2: Exclude cholestatic parenchymal diseases (primary biliary cirrhosis, hepatitis, cirrhosis).

  • Step 3: Suspect acute biliary obstruction or acute cholangitis: urgent ERCP

    – Sphincterotomy

    – Stone extraction

  • Step 4: Suspect gallstone pancreatitis:

    – CT or MRI to evaluate severity of pancreatic injury

    – Bile duct dilation, elevated bilirubin, elevated alkaline phosphatase: MRCP (or CT cholangiography) or ERCP (if treatment anticipated)

  • Step 5: Suspect obstructive jaundice: MRCP or CT cholangiography

    – Negative study: consider liver biopsy

    – Ducts dilated, obstruction confirmed: ERCP or PTC

    – Obstructing mass noted: EUS at time of ERCP

Hepatic cysts
Initial evaluation to confirm hepatic cysts
  • – Laboratory tests

  • CBC (normal)

  • Liver panel (minimal elevation in GGT or alkaline phosphatase)

  • – Ultrasonography (best to establish cystic nature)

  • – Abdominal CT or MRI (to rule out other causes of cystic lesions)

Initial evaluation to confirm choledochal cysts or Caroli's disease
  • – Laboratory tests

  • CBC (normal)

  • Liver panel (minimal elevation in GGT or alkaline phosphatase)

  • – Ultrasonography (best to establish cystic nature)

  • – Abdominal CT or MRI cholangiography

  • – HIDA may also be useful to document communication with biliary tree

Diagnosing complications
  • Hepatic cysts

    Cyst hemorrhage

    – Sudden onset of pain over cyst

    – CT or MRI demonstrates fluid level in cyst or surrounding hemorrhage

  • Cyst infection

  • – Presents as fever, leucocytosis and localized pain.

  • – Imaging typically not very helpful: tagged WBC scans reportedly positive

  • – Empirical treatment with fluoroquinolone antibiotic (good cyst penetration)

  • Cyst carcinoma

  • – Usually an incidental finding at cholecystectomy

  • – Ultrasonography may demonstrate gallbladder mass

  • – CT will define mass and vascularity, as well as extension out of gallbladder into surrounding tissues.

  • – ERCP may be needed to exclude bile duct involvement.

  • Choledochal cysts and Caroli’s disease

    Acute cholangitis

    – If the patient has fever, leucocytosis, and jaundice and ultrasonography shows dilated duct: treat as cholangitis with fluids, antibiotics, ERCP.

    – ERCP is warranted for both diagnosis and treatment.

  • Biliary obstruction

  • – MRCP or CT cholangiography: evaluate for duct dilation, mass, obstructing stone, single or multiple cysts.

  • – HIDA may be useful to demonstrate communication with biliary tree.

  • Cholangiocarcinoma

  • – MRCP or CT cholangiography: initial evaluation

  • – ERCP/EUS is needed for sampling mass and evaluating for extension outside biliary tree.

What other diseases, conditions, or complications should I look for in patients with gallstones and/or hepatic cysts?

See above sections on features, signs, and symptoms and diagnosis.

What is the right therapy for the patient with gallstones and/or hepatic cysts?

See above sections.

What is the most effective initial therapy?

See above sections.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy

See above sections.

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

See above sections.

Listing of these, including any guidelines for monitoring side effects

See above sections.

How should I monitor the patient with gallstones and/or hepatic cysts?

See above sections.

What is the Evidence?

Everhart, J, Khare, M, Hill, M, Maurer, KR. “Prevalence and ethnic differences in gallbladder disease in the United States”. Gastroenterology. vol. 117. 1999. pp. 632-9.

Soper, NJ, Brunt, LM, Kerbl, K. “Laparoscopic general surgery”. N Engl J Med. vol. 330. 1994. pp. 409-19.

Steiner, CA, Bass, EB, Talamini, MA. “Surgical rates and operative mortality for open and laparoscopic cholecystectomy in Maryland”. N Engl J Med. vol. 330. 1994. pp. 403-8.

Yusoff, IF, Barkun, JS, Barkun, AN. “Diagnosis and management of cholecystitis and cholangitis”. Gastroenterol Clin North Am. vol. 32. 2003. pp. 1145-68.

van Erpecum, KJ. “Pathogenesis of cholesterol and pigment gallstones: an update”. Clin Res Hepatol Gastroenterol. vol. 35. 2011. pp. 281-7.

Sheffield, KM, Ramos, KE, Djukom, CD. “Implementation of a critical pathway for complicated gallstone disease”. J Am Coll Surg. vol. 212. 2011. pp. 835-43.

Gurusamy, K, Sahay, SJ, Burroughs, AK, Davidson, BR. “Systematic review and meta-analysis of intraoperative versus preoperative endoscopic sphincterotomy in patients with gallbladder and suspected common bile duct stones”. Br J Surg. vol. 98. 2011. pp. 908-16.

Everson, GT, Taylor, MR, Doctor, RB. “Polycystic liver disease”. Hepatology. vol. 40. 2004. pp. 774-82.

Everson, GT, Helmke, S, Doctor, RB. “Advances in management of polycystic liver disease”. Expert Rev Gastroenterol Hepatol. vol. 2. 2008. pp. 563-76.

Doctor, RB, Smith, M, Fortune, B, Boyer, TD, Manns, MP, Sanyal, AJ. “Fibrocystic diseases of the liver”. 2011.

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