The Transjugular Intrahepatic Portosystemic Shunt (TIPS) procedure is a common intervention used to manage complications of severe liver disease, such as recurrent variceal bleeding and refractory fluid accumulation (ascites). The procedure involves placing a stent within the liver to create a direct channel between the portal vein and the hepatic vein, effectively lowering high blood pressure in the portal circulation. While successful in alleviating portal hypertension, this redirection of blood flow bypasses the liver’s detoxification system. This leads to a significant risk of increased ammonia levels in the bloodstream, a condition known as hyperammonemia. Hyperammonemia is the primary cause of Hepatic Encephalopathy (HE), a neurological complication affecting a notable percentage of patients after shunt placement.
How the TIPS Procedure Leads to High Ammonia Levels
The underlying cause of high ammonia levels following a TIPS procedure is the intentional rerouting of blood flow away from the liver’s primary filtering cells. The gastrointestinal tract produces ammonia as a byproduct of protein and amino acid metabolism, which is absorbed into the portal bloodstream. Normally, this ammonia-rich blood travels directly to the liver. The liver uses the urea cycle, a series of biochemical reactions, to convert toxic ammonia (NH3) into harmless urea, which is then safely excreted by the kidneys.
The TIPS procedure creates a bypass that shunts portal blood directly into the systemic circulation, allowing a large volume of ammonia-laden blood to skip the liver’s detoxification process entirely. This influx of unfiltered blood causes the rapid rise in systemic ammonia concentrations (hyperammonemia). The degree of shunting is substantial, and reduced blood flow through the liver tissue can also impair the remaining capacity of liver cells to detoxify any ammonia that still passes through. The increased pressure gradient reduction achieved by the shunt, while beneficial for portal hypertension, directly contributes to hepatic encephalopathy, which occurs in an estimated 30% to 50% of patients after TIPS placement. The ammonia that escapes liver filtration travels through the bloodstream and crosses the blood-brain barrier, where it acts as a neurotoxin, disrupting normal brain function. Factors such as the size of the shunt or the patient’s underlying liver function influence the severity and timing of hyperammonemia.
Identifying Symptoms of Hepatic Encephalopathy
Hepatic Encephalopathy (HE) presents a wide range of neurological and psychiatric symptoms. These symptoms are often subtle at first, categorized as minimal HE (MHE). Early signs include a shortened attention span, difficulty with fine motor skills like handwriting, and mild sleep disturbances such as insomnia or excessive daytime sleepiness.
As the condition progresses into overt HE, the symptoms become more obvious and are classified using the West Haven Criteria. Patients may exhibit increased lethargy, noticeable confusion, and distinct personality changes. A telltale physical sign is asterixis, often described as a flapping tremor, where the patient is unable to hold their wrists extended, causing a rapid, involuntary movement. Severe stages of overt HE involve profound disorientation and marked changes in consciousness. Speech may become confused or slurred, and the patient’s level of wakefulness decreases significantly. In the most serious cases, the patient can become unresponsive and progress into a coma, requiring immediate medical attention.
Treatment and Management of Post-TIPS Hyperammonemia
The management of post-TIPS hyperammonemia focuses on reducing the amount of ammonia produced in the gut and increasing its removal from the body.
Pharmacological Treatment
Pharmacological treatment typically begins with lactulose, a non-absorbable disaccharide and the standard therapy for Hepatic Encephalopathy. Lactulose works primarily in the colon, where gut bacteria metabolize it into short-chain organic acids. This process lowers the pH of the colon, which chemically converts ammonia (NH3) into the non-absorbable ammonium ion (NH4+). The ammonium ion is then trapped within the colon and cannot be reabsorbed into the bloodstream. Furthermore, lactulose acts as an osmotic laxative, increasing the frequency of bowel movements and physically accelerating the excretion of nitrogenous compounds. The goal is to titrate the dose of lactulose to ensure two to three soft bowel movements each day, which indicates effective ammonia clearance.
A second line of treatment often involves the non-absorbable oral antibiotic rifaximin, which is frequently used in combination with lactulose. Rifaximin targets and reduces the population of ammonia-producing bacteria within the gut. Since it is minimally absorbed into the bloodstream, its effects are localized to the gastrointestinal tract, minimizing systemic side effects. Combining rifaximin with lactulose has been shown to increase clinical effectiveness and reduce the risk of HE recurrence compared to lactulose alone.
Dietary Adjustments
Dietary adjustments are a significant component of managing post-TIPS hyperammonemia, particularly regarding protein intake. While historically protein restriction was common, current recommendations emphasize maintaining adequate caloric intake and avoiding severe protein deprivation, as this can lead to muscle wasting (sarcopenia). Skeletal muscle plays a role in ammonia detoxification by converting it into glutamine, so preserving muscle mass is beneficial. Patients may be advised to consume smaller, more frequent portions of protein throughout the day and to favor vegetable or dairy-based proteins over red meat, which can be easier to metabolize.
Interventional Options
When medical and dietary management fails to control severe or recurrent HE, the situation is defined as refractory hepatic encephalopathy. The primary mechanical intervention is a shunt revision, where the diameter of the TIPS stent is reduced to restrict blood flow through the bypass. Reducing the shunt size forces more blood back through the liver tissue, partially restoring the organ’s ability to clear ammonia from the portal circulation. In rare cases, if all other treatments are unsuccessful, the shunt may need to be completely closed or the patient may be evaluated for liver transplantation.