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.