Causes of Post-TIPSS Hepatic Encephalopathy
Post-TIPSS hepatic encephalopathy primarily develops due to increased shunting of ammonia-rich blood from the portal circulation directly into the systemic circulation, bypassing the liver's detoxification capacity.
Pathophysiological Mechanisms
Primary Mechanism: Portosystemic Shunting
- The TIPSS procedure creates an artificial shunt between the portal and systemic circulation, allowing blood to bypass the liver's detoxification processes 1
- This leads to decreased hepatic ammonia extraction and consequently the development of hyperammonemia, even without worsening liver disease 1
Risk Factors for Post-TIPSS Encephalopathy
Patient-Related Factors:
- Age: Older patients are at higher risk 2
- Gender: Female gender carries higher risk (relative risk 3.0) 3
- Pre-existing encephalopathy: History of prior HE increases risk 1
- Diabetes: Recently recognized as a risk factor, possibly due to altered renal handling of ammonia 1
- Sarcopenia: Independently associated with development of post-TIPSS HE due to reduced muscle capacity for ammonia processing 1
- Hypoalbuminemia: Each 1 g/dL decrease increases risk by 2.2 times 3
- Non-alcoholic etiology of liver disease: Carries 9.2 times higher risk compared to alcoholic liver disease 3
- Severe intrinsic renal disease: Stage 4/5 kidney disease leads to unacceptably high rates of encephalopathy 1
Procedure-Related Factors:
- Shunt size: Larger diameter shunts create greater portosystemic shunting 1
- Degree of portosystemic shunting: Higher shunt fraction increases risk 1
Diagnostic Predictors of Post-TIPSS Encephalopathy
Several pre-TIPSS assessments can help identify patients at high risk:
- Covert hepatic encephalopathy: Predicts development of overt HE post-TIPSS 1
- Critical flicker frequency (CFF): Values >39 Hz have 100% negative predictive value for post-TIPSS overt encephalopathy 1
- Psychometric hepatic encephalopathy score (PHES): Normal scores have 90% probability of remaining free of HE post-procedure 1
- EEG with spectral analysis: Values <8 Hz are abnormal and indicate risk 1
Clinical Implications and Management
Incidence and Impact
- Post-TIPSS encephalopathy occurs in approximately 23-55% of patients 1, 3
- Episodic overt HE after TIPSS does not increase mortality, but persistent HE is associated with higher mortality 2
Prevention and Management
- Pre-procedure risk stratification is essential
- Prophylactic lactulose and rifaximin are being studied to prevent post-TIPSS HE 4
- For established HE, medical management with lactulose is effective in 78% of cases 3
- In refractory cases, shunt reduction, embolization, or occlusion may be necessary 1, 5
Contraindications to TIPSS
- Severe or uncontrolled hepatic encephalopathy is an absolute contraindication to TIPSS 1
- Significant intrinsic renal disease (stage 4/5) is not recommended for elective TIPSS due to high encephalopathy risk 1
Special Considerations
- Patients with NASH and diabetes require special attention due to higher risk 1
- Nutritional assessment is important as sarcopenia increases risk of post-TIPSS HE 1
- Pre-TIPSS testing for covert encephalopathy should include at least two abnormal psychometric tests or an abnormal PHES, and quantitative EEG when possible 1
In patients with refractory HE not responding to medical therapy, stent reduction may be necessary as a rescue measure before considering liver transplantation 5.