Hepatic Encephalopathy and Post TIPS HE
Hepatic encephalopathy is a complex neurological disorder that arises as a consequence of liver dysfunction. It is characterized by a range of cognitive and motor impairments, stemming from the liver’s compromised ability to metabolize toxins and maintain metabolic balance. Central to its pathogenesis is the accumulation of ammonia, a neurotoxic substance, which infiltrates the bloodstream and exerts detrimental effects on the brain. This condition often manifests in individuals with advanced liver disease, particularly those with cirrhosis. Additionally, factors such as portal hypertension, neuroinflammation, and disruptions in neurotransmitter systems play pivotal roles in the development and progression of hepatic encephalopathy. Understanding the intricate interplay of these elements is crucial in managing and mitigating the impact of this debilitating condition.
Type and Grade of Hepatic Encephalopathy (HE):
| Type and Grade | Description |
|---|---|
| Type of HE (A, B, or C) | Type A: Reduced liver detoxification in acute liver failure Type B: Bypass of hepatic detoxification via portosystemic shunt Type C: Combination in cirrhosis |
| Clinical Grade of HE | Grade 0: Normal state of consciousness Grade 1: Mental slowdown with slight disturbed motor skills Grade 2: Increased fatigue, apathy, ataxia, flapping tremor, slurred speech Grade 3: Marked disorientation, rigor, stupor Grade 4: Coma |
| Time Course of HE | 1. Episodic (more than 6 months apart), 2. Recurrent (within 6 months), and 3. Persistent (continuous) |
| Existence of Precipitating Factors | Presence or absence of triggers like infections, gastrointestinal bleeding, etc. |
Pathogenesis and Molecular Mechanisms of Hepatic Encephalopathy:
| Pathogenic Factor | Description | Molecular Mechanism |
|---|---|---|
| Portal Hypertension | Increased pressure in the portal venous system due to liver dysfunction | 1. Increased resistance in the hepatic circulation leads to elevated portal pressure. 2. Diversion of blood through portosystemic shunts, bypassing the liver's detoxification processes. |
| Ammonia Toxicity | Accumulation of ammonia, a neurotoxic substance, in the blood and brain | 1. In the liver, impaired urea cycle and glutamine synthesis lead to ammonia buildup. 2. Elevated ammonia levels in the blood lead to increased entry into the brain via the blood-brain barrier. |
| Glutamate Excitotoxicity | Dysregulation of glutamate neurotransmission | 1. Glutamine increase permeability of Blood brain barrier. 2. Generalized swelling of astrocytes (due to increase ammonia level) 3. Release of cytokines (e.g., TNF-α, IL-1β) leading to neuroinflammation and neuronal dysfunction. |
| GABAergic System Dysfunction | Alterations in gamma-aminobutyric acid (GABA) neurotransmission | 1. Increased activity of GABA due to poor clearance from Liver. 2. GABA binds to post-synaptic membrane at benzodiazepines binding site (therefore, BZD can trigger HE) |
Risk Factors Following TIPS for Post-TIPS HE:
| Risk Factors | Description |
|---|---|
| Age | Older age associated with increased risk |
| Child–Pugh Score/Class | Higher scores or class associated with higher risk (CTP B or C) |
| MELD Score | Higher scores associated with increased risk |
| History of HE Pre-TIPS | Presence of HE before TIPS placement |
| Portosystemic Pressure Gradient | Lower PPG associated with increased risk |
| Sarcopenia | Presence of sarcopenia (muscle loss) associated with increased risk |
| Use of Proton Pump Inhibitors | Use of PPIs associated with increased risk |
| Comorbidities (e.g., Diabetes) | Presence of specific comorbidities may increase risk |
| Statin | Protective Effect (risk reduction by 20%) |
Post-TIPS Hepatic Encephalopathy Management:
| HE Severity | Management Strategies |
|---|---|
| Mild HE | Dietary adjustments, lactulose therapy, monitoring for progression. |
| Severe Overt HE | Consider stent lumen reduction or occlusion, but caution is needed to avoid life-threatening hemodynamic alterations. |
| Persistent Overt HE | Evaluate for large spontaneous portosystemic shunts and consider embolization. Monitor for response to interventions. |
| Management Strategy | Description |
|---|---|
| Standard Medications | Low-protein diet, nonabsorbable antibiotics, disaccharides (historical) |
| Non-Pharmacological Treatments | Probiotics, Fecal Microbiota Transplants (FMT), Nutritional Management |
| Shunt Modification | Partial or complete occlusion of TIPS to reduce shunt volume |
| Response to Shunt Modification | Assessment of improvement in HE after shunt modification |
| Non-Responder Prognosis | Poor prognosis, may require liver transplantation |
Shunt Reduction Technique for TIPSS:
| Shunt Reduction Technique | Description/Considerations |
|---|---|
| Customized Stent-Graft Hourglass Configuration | On-table customization for shunt reduction. |
| Parallel Placement of Stent Graft and Balloon-Expandable Stent | Balloon-expandable stent used to compress stent-graft. |
| Stent-Reduction with Sutures | Hourglass configuration created with sutures. |
| Controlled-Expansion Stents | Stents with adjustable diameter for precise regulation of blood flow. |
| Effect of Stent Diameter | 8 mm sized covered stents may reduce HE compared to 10 mm sized stents |