Ascending cholangitis overview

# Overview
Ascending Cholangitis, also known as acute cholangitis is a systemic disease caused by the inflammation and infection of the biliary tree most commonly following an obstruction in the biliary tract. It is characterized by a triad (Charcot's Triad) of fever, jaundice and right upper quadrant pain. A pentad (also known as Reynold's pentad) can also be seen in which altered mental status and sepsis are present in addition to usual findings. The severity of disease range anywhere from mild infection to life-threatening sepsis by the translocation of bacteria into the bloodstream.

# Historical Perspective
Dr. Jean-Martin Charcot, a French physician, is credited with discovering cholangitis in the late 19th century. He referred to the condition as "hepatic fever." Charcot's triad of fever, jaundice, and right upper quadrant abdominal pain is the classical presentation of cholangitis. By adding septic shock and mental status changes to the list of symptoms, Dr. B. M. Reynolds and Dr. Everett L. Dargan changed Charcot's triad to Reynold's pentad. Until 1968, the mainstay of treatment of cholangitis was surgery, with the exploration of the bile duct and excision of gallstones, until the advent of endoscopic retrograde cholangiopancreatography (ERCP).

# Classification
Acute cholangitis may be classified into grade I, II, or III, depending on the severity of the condition. The severity assessment criteria for acute cholangitis according to Tokyo guidelines is as follows:Grade I - Grade I, or mild acute cholangitis, does not meet the criteria of either grade II (moderate) or grade III (severe) acute cholangitis. The patient responds to initial medical treatment, grade II - Grade II, or moderate acute cholangitis, is characterized by the presence of any two of the following: abnormal white blood cell (WBC) count: >12,000/mm3, 5 g/kg/min) or norepinephrine, neurological system: abnormal consciousness, Respiratory system: PaO2/FiO2 ratio 2.0 mg/dl, decreased urine output, hepatic system: PT-INR >1.5, hematological system: platelet count < 100,000/ml.

# Pathophysiology
Main factors that are involved in the pathogenesis of ascending cholangitis include obstruction of the biliary tract, increased intraluminal pressure and the infection of bile. Bacterial contamination alone in absence of obstruction does not usually result in cholangitis. However increased pressure within the biliary system (above 20 cmH2O) resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the bloodstream while affecting the function of infection prevention macrophages (Kupffer cells) at the same time.  In addition, high biliary pressure also spreads the infection into biliary canaliculi, hepatic veins and perihepatic lymph vessels resulting in bacteremia (bacteria in the bloodstream).

# Causes
Any condition that leads to stasis or obstruction of bile in the common bile duct can lead to bacterial infection and cholangitis. Most common causes include bile duct stones and benign or malignant strictures. Less common causes include parasitic infection, malignancy, or extrinsic compression by the pancreas. Partial obstruction has a higher rate of infection as compared to complete obstruction.

# Differentiating ascending cholangitis from other diseases
Ascending cholangitis must be differentiated from other diseases that cause abdominal pain and fever, such as acute cholecystitis, acute hepatitis, acute pancreatitis, diverticulitis, biliary leakage or stricture, hepatic abscess, duodenal and gastric ulcer, cholestatic liver disease and pancreatic cancer.

# Epidemiology and Demographics
Ascending cholangitis is a relatively uncommon disease. It usually occurs following other diseases that lead to biliary infection and stasis. In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten years, 1526% will suffer one or more episodes of biliary colic (abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 23% will develop complications of obstruction: acute pancreatitis, cholecystitisor acute cholangitis. 0.5-2.4 percent people can develop acute cholangitis following ERCP. Mortality rate of acute cholangitis after the year 2000 was found to be 2700-10,000 per 100,000 people. More commonly seen in Latin-Americans and Native American, However anyone can be affected by the disease. Risk is higher in old age particularly more than 70 years of age. Ascending cholangitis affects men and women equally although the gallstones are more frequently seen in women. Parasitic infections, specifically including the species Ascaris, Opisthorchis, Clonorchis, Fasciola and Echinococcus, are commonly associated with cholangitis outside of the United States.

# Risk Factors
Common risk factors in the development of ascending cholangitis include bile duct stones, history of gall stones, biliary strictures, and biliary tract surgery. Less common factors include immunodeffeciency, comorbidities and sclerosing cholangitis. There is a higher risk of acute cholangitis in patients with advanced age (>70) and smoking.

# Screening
The cancer predominantly associated with cholangitis is cholangiocarcinoma. There are no accepted screening programs for either disease. However, methods for detecting early onsets of cholangitis and cholangiocarcinoma include using biochemical markers, scanning using positron emission tomography (PET) scan or magnetic resonance imaging (MRI), and endoscopic procedures such as endosonography and endoscopic retrograde cholangiopancreatography.

# Natural History, Complications, and Prognosis
The severity of ascending cholangitis can range anywhere from mild to life-threatening and can be fatal if left untreated. Complications of acute cholangitis may include sepsis, hepatic abscesses, liver failure, renal failure, pancreatitis as well as postoperative complications like pneumonia, respiratory failure, heart failure, cardiac arrhythmias, cardiac ischemia, gastrointestinal bleeding, bile leaking into peritoneum or abdomen, renal abscess, fistulae, wound infection, wound dehiscence and disseminated intravascular coagulation (DIC). Acute cholangitis bears a significant risk of death, with the leading cause being irreversible shock with multiple organ failure (which could have multiple possible complications of severe infections). Modern improvements in diagnosis and treatment have led to a reduction in mortality. Prognosis is good for patients who have quick and adequate drainage where there is an improvement in hemodynamic and inflammatory parameters. Prognosis of the disease depends on the severity of the illness. Poor outcomes are seen if urgent surgery is required for drainage.

# Diagnosis

## Diagnostic Study of Choice
MRCP is the diagnostic study of choice for identifying lesions of the biliary tree with sensitivity comparable to that of endoscopic retrograde cholangiopancreaticography (ERCP). However, ERCP is the gold standard test in the diagnosis of ascending cholangitis and is the test of choice for patients who may need therapeutic drainage.

## History and Symptoms
Symptoms
Ascending Cholangitis, also known as acute cholangitis is a systemic disease caused by the inflammation and infection of the biliary tree most commonly following an obstruction in the biliary tract. It is characterized by a triad (Charcot's Triad) of fever, jaundice and right upper quadrant pain. A pentad (also known as Reynold's pentad) can also be seen in which altered mental status and sepsis are present in addition to usual findings. The typical clinical picture with a triad is present in only 50 to 70 percent of cases.
History
Patients with ascending cholangitis may have a positive history of gallstones, common bile duct stones, recent cholecystectomy, endoscopic procedures like cholangiogram or ERCP, previous history of cholangitis, and HIV.

## Physical Examination
Patients with ascending cholangitis usually appear sick and fatigued. Physical examination of patients is usually remarkable for fever, abdominal tenderness and jaundice. Other findings that may be seen include hypotension, tachycardia and altered mental status in patients with septic shock or elderly.

## Laboratory Findings
Certain laboratory tests may be helpful in the diagnosis of cholangitis. Some commonly conducted tests include complete blood count, basic metabolic panel, liver function tests, blood culture, and other body fluid cultures. Findings include leucocytosis, elevated liver enzymes, elevated CRP and ESR, abnormal serum electrolytes. Positive bile and blood cultures may also be seen.

## Electrocardiogram
There are no specific electrocardiographic findings regarding ascending cholangitis.

## X-ray
There are no particular x-ray findings associated with ascending cholangitis. However, gallstones may be visible on radiographs in 15-20 percent of the cases depending on the degree of calcification. An ileus can also be seen sometimes.

## Ultrasound
A trans-abdominal ultrasound is the initial test of choice in patients with suspicion of ascending cholangitis to detect common bile duct stones or dilatation. USG is both sensitive and specific in detecting bile duct dilatation yet has a lower sensitivity for detecting bile duct stones. However, bile duct dilatation is not always seen in initial stages of bile duct obstruction making it less reliable. The main finding of ascending cholangitis on an ultrasound is the thickening of the bile duct walls.

## CT scan
Ct scan can be used to detect the bile duct dilatation with diagnosis of possible causes of cholangitis. Unenhanced and contrast enhanced MDCT scan has moderate sensitivity and specificity for detection of bile duct stones.

## MRI
Magnetic resonance cholangiopancreaticography (MRCP) is highly sensitive and accurate in the diagnosis of choledocholithiasis and biliary abnormalities in the patients of cholangitis. It is performed in patients with negative ultrasound and CT scan but have a suspicion of acute cholangitis. It is used as a non-invasive tool to localize lesions within the biliary tree. Common MR findings seen in acute cholangitis include increased peri-ductal signal intensity, transient peri-ductal signal difference, abscess, thrombosis and ragged duct.

## Other diagnostic studies
Other tests in diagnosis of ascending cholangitis include ERCP which is a gold standard test in diagnosis of acute cholangitis. It is used both for diagnostic and therapeutic purposes, however, it is preferred a therapeutic drainage method. ERCP has a higher rate of complications as compared to other endoscopic procedures.

# Treatment

## Medical Therapy
The main goal of treatment of acute cholangitis is treating both causes of acute cholangitis that are the biliary infection and biliary obstruction. Therefore, both antibiotic therapy and biliary drainage are important components of therapy in addition to supportive care.  Empiric antibiotics of choice usually include piperacillin-tazobactam, ticarcillin-clavulanate, ceftriaxone plus metronidazole or ampicillin-sulbactam. The urgency of treatment depends on the illness severity. About 80 percent of patients with mild cholangitis respond well to medical therapy and 10-15 percent who do not respond need surgical or endoscopic intervention. Markers for these people are persistent abdominal pain, hypotension, fever >102 F, and confusion.. Sick patients should be promptly resuscitated and transferred to the intensive care unit for further management and immediate decompression should be done.

## Surgery
Surgical or endoscopic drainage may be needed in addition to the medical therapy in patients with moderate to severe ascending cholangitis or those with mild cholangitis not responding to medical treatment. Different procedures of biliary drainage include ERCP, PTC, EUS- guided drainage and open surgical drainage. If attempts at an endoscopic papillotomy or percutaneous transhepatic drainage of the common bile duct are unsuccessful, surgical exploration should be carried out to control sepsis. Clinical studies show that emergency surgery for patients suffering from acute cholangitis results in improved postoperative morbidity and mortality rates.

## Primary Prevention
There are no established measures for the primary prevention of cholangitis in otherwise healthy people.

## Secondary Prevention
Secondary prevention strategies for cholangitis include continued treatment of predisposing causes in appropriate patients to avoid the recurrence of cholangitis :
- If the biliary infection was developed due to instrumentation of biliary tract, Appropriate antiniotics should be given in addition to biliary drainage to treat the infection:
- If the cause of ascending cholangitis is a gallstones/cholelithiais/choledocholithiasis - Initially endoscopic papilotomy/sphincterotomy should be done for biliary drainage and stone removal followed by elective  laparoscopic cholecystectomy as drainage and stone extraction from bile duct will not reduce the risk of recurrence of cholangitis.

## Cost-effectiveness of therapy
According to some studies, early ERCP is considered safe as well as cost effective in the treatment of mild to moderate ascending cholangitis. It reduces the duration of hospital stay and antibiotics are needed for fewer days thus making it a cost effective intervention.