Acute cholangitis

clinical syndrome characterized by fever, jaundice, and abdominal pain that develops as a result of stasis and infection in the biliary tract.

or ascending cholangitis

typically ascend from the duodenum;-sphincter of oddi, IgA and bile mucous
Biliary obstruction raises intrabiliary pressure increases permeability bile ductules
 hematogenous spread from the portal vein is a rare

biliary calculi (28 to 70 percent), benign stenosis (5 to 28 percent), and malignancy (10 to 57 percent)
common complication of stent placement for malignant biliary obstruction (18 percent in one series)

Bile is sterile.

 Bacteriology — Culture of bile, ductal stones, and blocked biliary stents

• Escherichia coli (25 to 50 percent), followed by Klebsiella (15 to 20 percent) and Enterobacter species (5 to 10 percent).
•  +, Enterococcus species (10 to 20 percent).
• Anaerobes, such as Bacteroides and Clostridia, are usually present as part of a mixed infection. 

fever, abdominal pain, and jaundice (Charcot's triad),  50 to 75 percent
 Confusion and hypotension can occur in patients with suppurative cholangitis, producing Reynolds's pentad, which is associated with significant morbidity and mortality

ALT if > 2000 reflects microabscess liver and hepatocyte necrosis.
Raised amylase suggests pancreatitis

 Diagnostic criteria (the Tokyo guidelines) - two or more of the following:

• A history of biliary disease
• Fever and/or chills
• Jaundice
• Abdominal pain

 definite if Charcot's triad (fever, abdominal pain, and jaundice) or
 all present:

• Evidence of an inflammatory response (abnormal white blood cell count, elevated C-reactive protein)
• Abnormal liver tests
• Biliary dilation

 In patients with Charcot's triad and abnormal liver tests, we proceed directly to ERCP to confirm the diagnosis and provide biliary drainage.
If without Charcot's triad, we recommend transabdominal ultrasonography to look for common bile duct dilatation or stones. Then followed  (within 24 hours) by ERCP to provide biliary drainage
 If  ultrasound is normal, we proceed with MRCP to look for bile duct stones or alternative diagnoses
If cannot undergo MRCP, we will proceed with ERCP if the liver tests are suggestive of biliary obstruction
 If the liver tests are normal or if high risk ERCP, we will proceed with EUS to look for evidence of bile duct stones or obstruction.
If this subsequent testing fails to demonstrate biliary obstruction, an evaluation for alternative explanations for the patient's symptoms should be performed

 the diagnosis confirmed by ERCP

The differential diagnosis of fever and abdominal pain includes:

• Biliary leaks-asso with lap cholecystectomy
• Acute diverticulitis 
• Cholecystitis 
• Appendicitis
• Pancreatitis 
• Liver abscess 
• Infected choledochal cysts 
• Recurrent pyogenic cholangitis 
• Mirizzi syndrome 
• Intestinal perforation 
• Right lower lobe pneumonia/empyema
•  
• In general, antibiotics should be continued for 7 to 10 days 

 Biliary drainage — Endoscopic sphincterotomy with stone extraction and/or stent insertion. If fails can proceed with percutaneous transhepatic cholangiography or open surgical decompression
 Biliary drainage can then be performed on an elective basis (within 24 to 48 hours).

 If the patient does not improve over the first 24 hours, urgent biliary decompression is required.
Risk factors include impacted stones, active smoker status, age >70 years, and additional stones within the GB

 signs of acute suppurative cholangitis, such as:

• Persistent abdominal pain
• Hypotension despite adequate resuscitation
• Fever greater than 39ºC (102ºF)
• Mental confusion (a predictor of poor outcome

ERCP — 90 -95% after sphincterotomy. Prior to injection of contrast,  decompress the biliary system to reduce the risk of inducing bacteremia. Occlusive cholangiography should not be performed in patients with acute cholangitis since it can promote the development of septicemia

 Stones more than 2 cm  require lithotripsy. Intrahepatic stones can sometimes be removed with choledochoscopy.
 Endoscopic drainage has lower overall rates of mortality and morbidity compared with surgical decompression ( 4.7 to 10% VS 10 to 50 %)
 
If coagulopathies that prevent sphincterotomy, or large stones, or too ill, can insert nasobiliary catheter.

Placing a stent  without first performing a sphincterotomy appears to permit adequate drainage and may be another option for patients with coagulopathies

 PTC involves transhepatic insertion of a needle into a bile duct, followed by injection of contrast material to opacify the bile ducts. PTC permits a number of therapeutic interventions, including drainage of infected bile, extraction of biliary tract stones, dilation of benign biliary strictures, or placement of a stent across a malignant stricture.
Or placement of a percutaneous cholecystostomy tube in patients with an intact gallbladder.

 surgical exploration of the common bile duct for stone removal. Elective surgery carries a very low morbidity and mortality. If emergent surgery -choledochotomy with placement of a large-bore T tube has a lower mortality than cholecystectomy with common bile duct exploration.

Failure to perform a cholecystectomy, even after a sphincterotomy has been performed, is associated with high recurrence rates.

 Patients who are pregnant — same-antibiotic choices should take into account potential fetal toxicity . fetal shielding should be used.

mortality rates for patients with severe acute cholangitis remain high (20 to 30 percent)

PREVENTING RECURRENCE —  cholecystectomy is generally recommended.

If  benign stenosis, as is seen following bile duct injuries, endoscopic therapy or surgical repair may be required.
if malignant stenoses- typically with stent placement, though the specific therapy chosen will depend on the patient's life expectancy and the likelihood of stent occlusion.

Splenic abscess

 -results from endocarditis 4.7 % or seeding from some other site of infection-
- recurrent or persistent despite antimicrobial therapy and left upper quadrant pain with or without splenomegaly
- may be accompanied by a left-sided pleural effusion
- splenic infarction if due to septic emboli

 CT scan infarct VS abscess
antibiotic therapy and splenectomy. 
CT-guided percutaneous aspiration is occasionally successful

Toxic megacolon

total or segmental nonobstructive colonic dilatation plus systemic toxicity

The most widely used criteria for the clinical diagnosis of toxic megacolon are:

• Radiographic evidence of colonic distension
• PLUS at least three of the following:

• Fever >38ºC
• Heart rate >120 beats/min
• Neutrophilic leukocytosis >10,500/microL
• Anemia
• PLUS at least one of the following:
• Dehydration
• Altered sensorium
• Electrolyte disturbances- Metabolic alkalosis secondary to volume depletion and potassium loss is associated with a poor prognosis. Metabolic acidosis suggests the presence of ischemic colitis.
• Hypotension

non toxic- congenital megacolon (Hirschsprung's disease), idiopathic or acquired megacolon occurring with chronic constipation of any etiology, and intestinal pseudoobstruction





mucosal inflammation leads sequentially to the release of inflammatory mediators and bacterial products, increased inducible nitric oxide synthase, generation of excessive nitric oxide, and colonic dilatation.

extent of dilatation appears to be correlated with the depth of inflammation and ulceration. Damage to the myenteric plexus.

These include hypokalemia, antimotility agents, opiates, anticholinergics, antidepressants, barium enema, and colonoscopy. Discontinuing or rapid tapering of corticosteroids, sulfasalazine, or 5-ASA compounds also may contribute to the development of megacolon

Knowledge of prior attacks of IBD, the extent and type of disease, details of prior therapy, extraintestinal manifestations of IBD, recent travel, occupational exposure (eg, day care workers), antibiotic or chemotherapy use, use of antimotility agents, and HIV/AIDS status are very helpful

Radiography — Plain abdominal radiographs

• The transverse or right colon is usually the most dilated, frequently greater than 6 cm and occasionally up to 15 cm on supine films . Repositioning  results in redistribution of air in the colon,
• Multiple air-fluid levels, colonic haustral pattern is either absent or severely disturbed.
• Deep mucosal ulcerations may appear as air-filled crevices 

 only for mecanical obstruction- Barium enema or colonoscopy is often required to diagnose the level and type of obstruction.
-diarrhea is unusual and air is absent in the colon below the point of obstruction.

High resolution ultrasonography can be used to accurately determine the extent and activity of severe ulcerative colitis and assess the response to therapy; it may also permit the early detection of toxic megacolon .

CT can determinie the etiology of megacolon. -diffuse colonic thickening
- useful in patients with AIDS who may have several intercurrent intraabdominal processes.
- identify complications of megacolon, such as perforation or vascular compromise

Limited endoscopy without bowel preparation is useful if IBD has not previously been diagnosed or an infective process is suspected, particularly CMV or acute bacillary dysentery. 

full colonoscopy is extremely risky

medical treatment- preventing surgery in up to 50 percent of patients. However, a surgical consultation should be obtained upon admission,

- bowel rest and a nasogastric tube (or long intestinal tube)  to decompress the gastrointestinal tract. Enteral feeding if patient shows signs of improvement to hasten mucosal healing and stimulate normal motility.
- ICU. Complete blood counts, electrolytes, and serial abdominal plain films are reviewed every 12 hours initially and then daily as the patient improves. Anemia, dehydration, and electrolyte deficits, particularly hypokalemia, may aggravate colonic dysmotility and should be treated aggressively.

(TPN) is of limited value

All antimotility agents, opiates, and anticholinergics should be discontinued.

prophylaxis for both gastric stress ulcerations and deep venous thrombosis (pneumatic compression stockings).

Antibiotic to reduce septic complications and in anticipation of peritonitis from perforation. We generally use ampicillin-gentamicin-metronidazole or a third-generation cephalosporin with metronidazole.

 Intravenous corticosteroids (hydrocortisone 100 mg or equivalent every six to eight hours or by continuous infusion) - ulcerative colitis or Crohn's disease; this does not increase the risk of perforation .  dexamethasone has been shown in experimental studies to decrease the colonic diameter by diminishing the expression of inducible NO synthase. methylprednisolone - its lower sodium retaining and potassium wasting properties, while others prefer prednisolone since the parenteral dose is equal to the oral dose. Steroids are not used in toxic megacolon due to C. difficile colitis or infective colitis.

Sulfasalazine and 5-ASA compounds have no role in patients with toxic megacolon due to IBD and should be initiated only after the attack begins to resolve.

Cyclosporine is useful in the treatment of severe colitis refractory to steroid therapy, but the experience in toxic megacolon is limited.

Some authors recommend intermittent rolling maneuvers or the knee-elbow position to help redistribute gas in the colon and thereby promote decompression- in patient not toxic

 persistent fever after 48 to 72 hours of steroid therapy should raise the possibility of localized perforation or abscess.

 Free perforation, massive hemorrhage, increasing transfusion requirements, worsening signs of toxicity, and progression of colonic dilatation are absolute indications for surgery.

surgical studies recommend colectomy if there is persistent colonic distention after 48 to 72 hours. However, we recommend prolongation of medical therapy up to seven days if the patient appears to be clinically improving despite persistent megacolon and there is no perforation

- severe C. difficile colitis, the first step is to stop the offending antibiotic, followed by vancomycin 500 mg four times daily orally or via a nasogastric tube NOT IV and intravenous metronidazole at a dose of 500 mg every eight hours. Fecal concentrations of metronidazole in the therapeutic range are achieved with this regimen because of biliary excretion of the drug.

Surgery — Subtotal colectomy with end-ileostomy - lower morbidity and mortality than single stage proctocolectomy and allows subsequent re-anastomosis. Early surgery without perforation results has much lower mortality than after perforation (8 VS 40 %)

Clinical manifestations, diagnosis, and treatment of the Budd-Chiari syndrome

thrombosis of the hepatic veins and/or the intrahepatic or suprahepatic inferior vena cava

237 patients( in US, the Netherlands, and France) between 1984 and 2001:

• The median age was 35 (range 13 to 76)
• 67 % were female
• An overt myeloproliferative disorder 23%(the majority of whom had polycythemia vera)
•  ascites (84 %) and hepatomegaly (76 %); 11 patients (5%) were asymptomatic
•  hepatic veins (62 %) inferior vena cava (7 %) or both (31 %); 34 patients (14 %) had associated portal vein thrombosis

• Acute – 20 % (five with fulminant hepatic failure), pregnancy , present with severe right upper quadrant pain,jaundice, ascites, variceal bleed, enceph
•  high levels of ALT (≥5 times the upper limit of normal) reflected acute, severe but potentially reversible ischemic injury, a slow decline in ALT levels (<50 percent of starting concentration within three days) predicted a poor outcome
• Subacute < six months and no evidence of liver cirrhosis) – 40%
• Chronic (> six months with evidence of portal hypertension and cirrhosis) – 40%, may be associated with hypertrophy of the caudate lobe of the liver, compressing inferior vena cava
• Jaundice is rare

  ultrasonography with Doppler studies, CT or MRA (MRI angiography).

 The portal and splenic circulation should also be evaluated. Occlusion of the portal vein in patients with Budd-Chiari syndrome limits therapeutic options and has a poor prognosis

 Splenomegaly is uncommon, 30%, and venous collaterals may be seen on the anterior abdominal wall,  on the back suggest occlusion of the vena cava. Signs of RHF suggest an underlying cardiac cause of fluid accumulation

SAAG >1.1

Venography — The gold standard , which is performed by accessing the hepatic venous circulation percutaneously, either via the internal jugular vein, cephalic vein, or femoral vein.

 Arteriography —  when planning a surgical approach to decompress the congested liver


  
Liver biopsy —AASLD

• There is confusion regarding the diagnosis (an uncommon situation given the multitude of available imaging tests).
• In patients with subacute presentations- if show significant fibrosis/cirrhosis may provide an impetus for transplant evaluation. if centrizonal congestion may benefit from shunt surgery.

The goals of therapy are to:

• Prevent the propagation of the clot
• Restore patency of thrombosed veins
• Decompress the congested liver
• Address and prevent complications related to fluid retention, malnutrition, and portal hypertension

Medical- AASLD
- treat fluid retention like in cirrosis, compression stocking, shunt
- improve nutrition status
-treat underlying condition-hypercoagulability- warfarin; myeloproliferative- aspirin + hydroxyurea

 237 patients treated at four centers 1984- 2001 72 % received anticoagulation.
worse prognosis included the presence of encephalopathy, ascites, an INR >2.3, and higher bilirubin concentrations
a benefit of anticoagulation on survival (RR 0.14, 95% CI 0.02 to 1.21) could only be demonstrated in patients with class I disease (ie, less severe disease).

Addition -prognosis was worse in patients who presented with clinical features suggesting chronic disease.

Recommendation:  chronic or subacute Budd-Chiari syndrome with well compensated liver disease at the time of presentation. However, additional measures to decompress the liver should be considered

Surgical portosystemic shunting had no apparent benefit on survival.

radiologic procedures (such as angioplasty, transjugular intrahepatic portosystemic shunt [TIPS] placement, and stenting) and surgical intervention (including shunting procedures and liver transplantation).
TIPS- used for patients who do not respond to dilation of a hepatic venous outflow stricture or in whom a dilatable lesion cannot be found. is
- temporizing measure prior to liver transplantation in patients with acute, fulminant Budd-Chiari syndrome.
-Placement of TIPS in these patients, if not performed properly, can result in complication such as portal vein thrombosis

Monitor closely for disease progression LFT. OGDS looking for varices and liver biopsies annually, tapering 2-3years depending upon the overall health status of the patient. Bleeding complications appear to be common in patients maintained on anticoagulation,

Thrombolytic therapy — Systemic and locally administered - no study,  the bleeding risk is similar.
Not for chronic, but for subacute and acute.
use in: clot well defined in venography, recent, no CI
not in: who have extensive clot involving the intrahepatic vena cava and hepatic veins or a clot of unknown age.


Liver transplantation —for who are not candidates for radiologic or surgical decompression or who have decompensated cirrhosis. Patients who developed the Budd-Chiari syndrome as a result of protein S, protein C, or antithrombin III deficiency may also be cured of their clotting tendency by liver transplantation, since the transplanted liver produces normal amounts of these enzymes.

AASLD GUIDELINE 2009

• Correct  risk factor(s)
• Initiate anticoagulation therapy immediately. Use LMWH targeting anti-Xa activity to 0.5-0.8 int. unit/mL. Change to oral anticoagulation agent INR 2-3
• Maintain permanent anticoagulation therapy unless a major contraindication is present or complication occurs.
• Treat complications of portal hypertension as recommended for other types of liver disease.
• Check for a venous obstruction amenable to percutaneous angioplasty/stenting in all symptomatic patients and treat accordingly.
• In patients without ongoing improvement on anticoagulation therapy (with or without angioplasty), consider transjugular intrahepatic portosystemic shunt (TIPS).
• Consider liver transplantation if TIPS insertion fails or does not improve the patient's condition and in those with fulminant hepatic failure.
• Coordinate care with a transplant center.
• Monitor patients with longstanding, well controlled Budd-Chiari syndrome for the late development of hepatocellular cancer and transformation of underlying myeloproliferative disease

Invasive liver abscess syndrome caused by Klebsiella pneumoniae

Definition- K. pneumoniae primary liver abscess as liver abscess that occurs in the absence of hepatobiliary disease. Almost all of these infections are monomicrobial

In a review of 160 cases from Taiwan,

• Fever (93 percent)
• Right upper quadrant tenderness (71 percent)
• Nausea, vomiting, diarrhea, or abdominal pain (38 percent)
• Leukocytosis (70 percent)
• Elevations in serum alanine and aspartate aminotransferases (59 and 68 percent)
• Elevations in alkaline phosphatase (78 percent)
• Elevations in bilirubin (26 percent)

 more likely to be solitary and more likely to be monomicrobial

minority of patients -develops metastatic infection at other sites  - metastatic infection are endophthalmitis, meningitis and brain abscess , Other manifestations include lumbar or cervical spondylitis and discitis, septic pulmonary emboli, lung abscess, psoas abscess, splenic abscess, necrotizing fasciitis, neck abscess, and osteomyelitis

  The differential diagnosis of fever and right upper quadrant abdominal pain includes other hepatobiliary disease, colitis, or pneumonia.

necrosis of hepatic tumor can appear similar to a highly suppurative abscess on CT.
diffusion-weightedMRI  may be useful

Although aminoglycosides penetrate abscess cavities poorly, in theory they may eradicate bloodstream organisms early in the course of infection, potentially decreasing risk for metastatic complications. unproven

In general, treatment should be continued until CT imaging demonstrates complete or near complete resolution of the abscess cavity. Some abscesses with a thick capsule
 other clinical findings, such as normalization of inflammatory markers, sterile cultures, and the finding of a clear cavity without debris or other content on imaging, can be helpful to distinguish this from persistent infection.

 Treatment of metastatic infection — In addition to systemic antibiotics, local therapy or debridement may be required in patients with metastatic infection. As an example, patients with Klebsiella endophthalmitis should receive intravitreal antibiotics and vitrectomy.

Prognosis-  Taiwan:

• 160 cases of KLA, mortality rate was 11 %and relapse  4.4 %. significantly higher (41%) in 22 patients with polymicrobial liver abscess,
•   metastatic endophthalmitis - have impaired vision or blindness. patients with meningitis may have persistent neurologic abnormalities

Pyogenic liver abscess

1.peritonitis due to leakage of intraabdominal bowel contents that subsequently spread to liver via the portal circulation
2.or via direct spread from biliary infection. Gallstone/malignancy
3.from arterial hematogenous seeding in the setting of systemic infection. staph/strep

 commonly involve the right lobe of the liver, probably because it is larger and has greater blood supply. Liver abscess may also be accompanied by pylephlebitis.

 Risk factors include diabetes, underlying hepatobiliary or pancreatic disease, and liver transplant  Geographic and host factors - primary invasive liver abscess syndrome due to K. pneumoniae has been described in East Asia.

 Association with colorectal neoplasia — Several studies from Asia

MICROBIOLOGY —Most pyogenic liver abscesses are polymicrobial; mixed enteric facultative and anaerobic species are the most common pathogens. Anaerobes are probably under-reported because they are difficult to culture

• The Streptococcus milleri or S. anginosus group (including S. constellatus and S. intermedius) should search for simultaneous metastatic infections at other locations.
• S. aureus, S. pyogenes, and other Gram positive cocci - in patients who underwent transarterial embolization for hepatocellular carcinoma,  
• Candida species -chemotherapy and presents with recovery of neutrophil counts following a neutropenic episode.
• Klebsiella pneumoniae 
• Tuberculous liver abscesses are uncommon but should be considered when typical pyogenic organisms are not recovered from cultures 
• Burkholderia pseudomallei (the agent of Melioidosis) should be considered in patients from endemic areas (Southeast Asia and Northern Australia). 
• Amebiasis, in patients who are from or have traveled to an endemic area within the past six months. 

DIAGNOSIS — 

CT usually shows a fluid collection with surrounding edema. stranding / loculated subcollections. Pyogenic VS  amebic abscess by imaging studies 

Abscesses VS tumors and cysts. Tumors-solid radiographic /calcification. Necrosis and bleeding within a tumor may lead to a fluid-filled appearance;-difficult to differentiate,
Cysts appear as fluid collections without surrounding stranding or hyperemia.

An elevated right hemidiaphragm, right basilar infiltrate, or right-sided pleural effusion can be seen in 25- 355 of cases

 MRI and tagged white blood cell scans are less useful for distinguishing abscess from other causes of liver mass.

Microbial cultures — from CT or ultrasound-guided aspiration -gram stain and culture (both aerobic and anaerobic-specifically requested

Blood cultures + in up to 50% of case
Cultures obtained from existing drains are NOT adequate for guiding antimicrobial therapy, since they are often contaminated with skin flora and other organisms.

include leukocytosis, hypoalbuminemia, and anemia (normochromic, normocytic).

TREATMENT —

Drainage — Drainage techniques include CT-guided or ultrasound-guided percutaneous drainage (with or without catheter placement), surgical drainage, or drainage by ERCP.

single abscesses  ≤5 cm, either percutaneous catheter drainage or needle aspiration is acceptable - remain in place until drainage is minimal (7days). Repeat needle aspiration may be required in up to half of cases if a catheter is not left in situ.

diameter >5 cm, catheter drainage is preferred over needle aspiration. success 100% VS 50%
surgical intervention over percutaneous drainage -no difference in mortality, morbidity, duration of fever or complication rates. treatment failure 7 VS 28 %
Surgical drainage

• Multiple abscesses
• Loculated abscesses
• Abscesses with viscous contents obstructing the drainage catheter
• Underlying disease requiring primary surgical management
• Inadequate response to percutaneous drainage within seven days

Multiple or loculated abscesses may be successfully managed by percutaneous drainage;

ERCP can be useful for drainage of liver abscesses in patients with previous biliary procedures whose infection communicates with the biliary tree.




 Recovery of more than one organism should suggest polymicrobial infection including anaerobes, even if no anaerobes are isolated in culture. In such circumstances, anaerobic coverage should be continued.

Duration of therapy — 

no RCT 

difficult to drain or slow to resolve - require longer courses of therapy.

 temperature,WBC and CRP.
Follow-up imaging if persistent clinical symptoms or if drainage is not proceeding as expected; radiological abnormalities resolve more slowly than clinical and biochemical markers.

4-6w:  good response to initial drainage 2-4w of parenteral therapy,
 incomplete drainage 4-6weeks of parenteral therapy. The remainder of the course can then be completed with oral therapy. If culture results are not available, reasonable empiric oral antibiotic choices include amoxicillin-clavulanate alone or a fluoroquinolone (ciprofloxacin or levofloxacin) plus metronidazole.