Editor's Note: Interventional therapy is an emerging clinical discipline that forms a crucial part of minimally invasive medicine, standing alongside traditional internal medicine and surgery as a key clinical specialty. This field focuses on treating various diseases using advanced imaging techniques such as DSA, ultrasound, and CT to create small, millimeter-sized access points through the skin. These access points allow the insertion of specialized needles and catheters directly into affected organs or tissues, enabling the delivery of drugs, embolic agents, or stents without the need for open surgery. To keep colleagues informed about the latest advancements in interventional treatment for liver diseases, Hepatology Digest has partnered with Dr. Xuefeng Luo from West China Hospital of Sichuan University, to launch the “Interventional Therapy in Hepatobiliary Diseases” column. This column will share the latest research in interventional therapy on a monthly basis, promote standardized treatment concepts, and monitor developments in the field, aiming to benefit experts, researchers, and frontline healthcare workers.
In this first installment of the “Interventional Therapy in Hepatobiliary Diseases” column, Dr. Xuefeng Luo has chosen the recently released French guidelines on Transjugular Intrahepatic Portosystemic Shunt (TIPS) as the opening topic. He provides a detailed interpretation of these guidelines, which will be presented in two parts for readers’ reference.
TIPS has become a vital treatment option for managing or preventing complications of portal hypertension. Initially introduced in the early 1990s, TIPS was primarily indicated for refractory bleeding. It is now also recommended for treating ascites, preventing rebleeding, and managing vascular diseases of the liver. The number of patients undergoing TIPS worldwide has significantly increased. The expansion of indications, involvement of multiple stakeholders, the need for precise patient selection, the relationship between TIPS and liver transplantation, and the lack of standardized preoperative evaluation, surgical procedures, and postoperative follow-up prompted the French Hepatology Society to develop these guidelines.
Hepatology Digest: In this first installment, you bring us insights into the latest TIPS guidelines released by France in 2024. Could you briefly introduce the key contents of these new guidelines?
Dr. Xuefeng Luo: The French 2024 TIPS guidelines consist of 16 chapters, covering patient selection, indications for TIPS, the TIPS procedure, and postoperative follow-up. They provide an in-depth discussion on variceal bleeding, ascites, rebleeding prevention, and vascular diseases of the liver. Additionally, the guidelines address some of the hot topics that have received significant attention in recent years, such as the relationship between TIPS and cardiac function, renal function, and hepatocellular carcinoma (HCC).
In the past, many liver cancer patients in China were diagnosed at an advanced stage, with few cases involving TIPS treatment. Clinically, there were many challenges: how should liver cancer be managed? Can these patients undergo TIPS treatment? Is it necessary? Due to the short survival time of these patients, there has been limited exploration in this area.
Now, with the application of various local and systemic treatment methods, the survival time of liver cancer patients has been significantly extended. As a result, we are also changing our treatment approach, considering which carefully selected patients might benefit from TIPS treatment. Although this new guideline may not provide strong or precise recommendations, it suggests that this is a direction for future clinical research. Perhaps in the future, Chinese doctors will be able to answer some of these questions.
Hepatology Digest: When dealing with acute variceal bleeding or ascites, how should these conditions be managed according to the new guidelines? How do these recommendations compare with the TIPS expert consensus in China?
Dr. Xuefeng Luo: When developing guidelines in China, we often refer to excellent clinical research from Europe and the United States, so generally, there are no fundamental differences between the new French guidelines and the Chinese TIPS expert consensus. However, there are some differences in management philosophies.
In the treatment of variceal bleeding, significant progress has been made. In the past, TIPS was often limited to patients with severe bleeding that was unresponsive to endoscopic treatment, at which point intervention occurred relatively late. Although bleeding was controlled after TIPS, complications such as renal impairment, chronic liver failure, and severe infections still led to poor patient outcomes.
Therefore, the current treatment approach favors early intervention. We aim to stratify the risk immediately after the onset of acute bleeding, differentiating patients at high risk of treatment failure based on liver function scores, endoscopic findings, and hepatic venous pressure gradients, and prioritizing TIPS treatment for these patients. For those at lower risk, traditional standardized treatment protocols are continued. The key shift in treatment philosophy is early identification and early intervention.
Additionally, in the salvage treatment of variceal bleeding, we have observed regional differences. For example, in China, we widely use balloon tamponade for salvage or temporary treatment, while in Europe, balloon tamponades are often unavailable, leading to a preference for self-expanding esophageal stents for hemostasis. These resource differences necessitate corresponding adjustments in clinical management, meaning we cannot entirely replicate foreign guidelines.
Hepatology Digest: The guidelines from the United States, China, and Europe recommend TIPS primarily as a secondary treatment for variceal bleeding and ascites related to portal hypertension. One major reason for this is the risk of overt hepatic encephalopathy associated with TIPS. In the new French guidelines, what is the recommendation level for TIPS in the treatment of refractory/recurrent ascites? What is the clinical significance for China?
Dr. Xuefeng Luo: Over the past decade, the clinical indications for TIPS have significantly expanded compared to the past. This expansion is not due to individual physicians’ enthusiasm but because they observed clear clinical benefits in many patients, particularly in terms of prolonged survival.
Currently, the clinical indications for TIPS in managing ascites, bleeding, and liver vascular diseases are clearly expanding. This expansion is primarily due to three factors: (1) TIPS can significantly extend patient survival compared to traditional treatments, thanks to our success in risk stratification and individualized management. We can identify high-risk patients who benefit from longer survival through TIPS treatment. (2) The management of TIPS-related complications has improved significantly compared to the past. One major limitation of TIPS was the high risk of hepatic encephalopathy, with 20% to 30% of patients experiencing cognitive, emotional, or behavioral abnormalities. However, through preoperative and postoperative medication management, the risk of TIPS-associated hepatic encephalopathy has significantly decreased, and patients’ quality of life, treatment adherence, and acceptance have substantially improved. (3) Advances in equipment and devices have also supported the widespread use of TIPS. Initially, we used bare stents to establish TIPS, which had poor patency, requiring repeated interventional treatments. Later, polytetrafluoroethylene-covered stents, TIPS-specific stents, and diameter-controllable TIPS stents were adopted. We now use TIPS stents that start with the smallest diameter and gradually expand, which are more suitable for Chinese patients and more cost-effective. These improvements allow us to tailor individualized pressure-lowering strategies for each patient, maximizing clinical benefits.
Thus, it can be said that clinical research has driven the expansion of TIPS clinical applications, and these applications, in turn, have raised new research questions.
French TIPS Guidelines Recommendations
2024 French Guidelines: Indications and Modalities of Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Larrue H, Allaire M, Weil-Verhoeven D, et al. French guidelines on TIPS: Indications and modalities. Liver International. Published online May 17, 2024. doi:10.1111/liv.15976
Part 1: Preoperative Evaluation and Preparation for Elective TIPS
1. Once a TIPS indication is confirmed, patients should be referred to a center capable of performing TIPS for preoperative evaluation.
(G2+, strong agreement)
2. If TIPS is technically complex or carries a high risk of complications, it is recommended to consult the liver transplant team.
(Expert opinion, strong agreement)
3. For cirrhotic patients with an indication for elective TIPS, liver transplantation should be evaluated pre-TIPS or if the condition worsens post-TIPS.
(G2+, strong agreement)
4. TIPS is generally not recommended for cirrhotic patients with severe liver damage unless they are being considered for liver transplantation, where individual analysis is warranted.
(G2−, strong agreement)
5. Preoperative evaluation for elective TIPS should include an assessment of the risk factors for post-TIPS hepatic encephalopathy.
(G1+, strong agreement)
6. A history of overt hepatic encephalopathy, its triggers, minimal hepatic encephalopathy, and liver function should be assessed before elective TIPS.
(G1+, strong agreement)
7. Screening for renal impairment, hyponatremia, sarcopenia, and large portosystemic shunts should be conducted pre-elective TIPS.
(G2+, strong agreement)
8. Preoperative imaging (CT or MRI) is recommended for elective TIPS. If the preoperative imaging was done more than a month prior, recent imaging, such as ultrasound, is also acceptable for reference.
(Expert opinion, strong agreement)
9. If there is extensive/recent portal vein thrombosis, anticoagulation treatment should be initiated before elective TIPS.
(G1+, strong agreement)
10. Vascular invasion or infiltrative hepatocellular carcinoma (HCC) should be considered contraindications for elective TIPS.
(G2+, strong agreement)
11. Bile duct dilation or polycystic liver disease are relative contraindications for TIPS.
(Expert opinion, strong agreement)
12. Specialized anesthesia evaluation is recommended before elective TIPS.
(G1+, strong agreement)
13. There is insufficient evidence to recommend correcting coagulopathy before TIPS.
(Expert opinion, strong agreement)
14. Prophylactic antibiotics are not required during TIPS.
(Expert opinion, strong agreement)
15. If infection is present or suspected, TIPS should be delayed.
(Expert opinion, strong agreement)
16. Cardiac function should be evaluated before elective TIPS in all patients.
(G1+, strong agreement)
17. Patients with severe or symptomatic right or left heart failure, untreated valvular heart disease, or severe pulmonary hypertension (mPAP ≥45 mmHg) should not undergo TIPS.
(G2+, strong agreement)
18. Screening for hepatopulmonary syndrome (HPS) should be performed before elective TIPS, using transesophageal echocardiography (TEE).
(G1+, strong agreement)
19. Severe pulmonary hypertension (mPAP ≥45 mmHg) confirmed by right heart catheterization and persistent after standard treatment is a contraindication for TIPS.
(G1+, strong agreement)
20. For cirrhotic patients with an indication for elective TIPS, treatment of the underlying cause of cirrhosis is recommended.
(Expert opinion, strong agreement)
21. There is no sufficient evidence to support an upper age limit as a contraindication for TIPS.
(Expert opinion, strong agreement)
Part 2: Rescue/Salvage TIPS for Acute Variceal Bleeding
1. Patients with portal hypertension-related refractory bleeding or early rebleeding should consider rescue/salvage TIPS to improve survival rates.
(G1+, strong agreement)
2. Given the feasibility and potential delay of TIPS, tamponade treatment may be used as a bridge, with a preference for self-expanding esophageal stents.
(G2+, strong agreement)
3. For patients excluded from liver transplantation, if they meet any of the following criteria, rescue TIPS may be ineffective:
o Multiple organ failure
o Child-Pugh score ≥14
o MELD score ≥30 and/or lactate ≥12 mmol/L after initial fluid resuscitation (Expert opinion, strong agreement)
Part 3: Prioritized TIPS for Acute Variceal Bleeding
1. For cirrhotic patients with variceal bleeding due to esophageal or gastroesophageal varices type 1, if:
o Child-Pugh C <14
o Child-Pugh B >7 with active bleeding during the initial endoscopy Covered stent TIPS should be performed within 72 hours, ideally within 24 hours.
(G1+, strong agreement)
2. Patients with ACLF or hepatic encephalopathy on admission should undergo prioritized TIPS if they meet the above criteria.
(G2+, strong agreement)
3. To date, there is no specific age, MELD score, or serum creatinine threshold that would render prioritized TIPS ineffective.
(Expert opinion, strong agreement)
4. Patients with a history of severe heart failure, significant valvular disease, uncontrolled sepsis, or anatomical abnormalities that prevent shunt creation should not undergo prioritized TIPS.
(Expert opinion, strong agreement)
5. Pre-TIPS, at least a Doppler ultrasound or cross-sectional imaging is recommended to assess for visceral vein thrombosis and hepatocellular carcinoma, and guide treatment.
(Expert opinion, strong agreement)
6. Extensive or occlusive portal vein thrombosis should be discussed with an experienced operator.
(Expert opinion, strong agreement)
7. There is insufficient scientific evidence to recommend prioritized TIPS beyond the 72-hour window.
(Expert opinion, strong agreement)
Part 4: TIPS for Rebleeding Prevention
1. Due to the lack of survival benefit and the increased risk of hepatic encephalopathy, TIPS is not recommended as a first-line treatment for secondary prevention of variceal rebleeding (esophageal or gastroesophageal varices type 1).
(G1−, strong agreement)
2. TIPS can be considered for patients who develop portal hypertension-related bleeding despite standard secondary prevention.
(Expert opinion, strong agreement)
3. For patients with recurrent ascites who cannot receive standard secondary prevention therapy (e.g., intolerance, contraindications, or non-compliance with NSBB or EBL), TIPS is recommended.
(Expert opinion, strong agreement)
4. For patients with portal vein thrombosis, TIPS is recommended as secondary prevention.
(G1+, strong agreement)
5. For secondary prevention of bleeding from type 2 gastroesophageal varices or isolated gastric varices, TIPS is not recommended as first-line treatment.
(Expert opinion, strong agreement)
6. TIPS can be considered for ectopic variceal bleeding as secondary prevention. Assessment of whether to combine variceal embolization during TIPS is necessary.
(Expert opinion, strong agreement)
7. Patients with portal hypertensive gastropathy who require repeated transfusions despite NSBB combined with endoscopic therapy should consider TIPS.
(G2+, strong agreement)
8. Patients with gastric antral vascular ectasia (GAVE) who experience recurrent bleeding may not be suitable for TIPS.
(G2−, strong agreement)
Part 5: TIPS for Vascular Diseases of the Liver
1. Before elective TIPS for Budd-Chiari syndrome (BCS), it is recommended to use liver-specific contrast-enhanced MRI to assess the nature of liver nodules.
(Expert opinion, strong agreement)
2. Treatment of BCS or portal vein cavernous transformation should be conducted by experienced physicians with expertise in liver vascular diseases.
(Expert opinion, strong agreement)
3. TIPS should be considered for BCS patients who fail medical therapy or where angioplasty (with or without stenting) is ineffective or not feasible.
(Expert opinion, strong agreement)
4. For fulminant BCS, TIPS should be considered. Once a TIPS indication is present, liver transplantation should be immediately evaluated.
(G2+, strong agreement)
5. Due to the presence of BCS, long-term anticoagulation therapy should continue after TIPS.
(G2+, strong agreement)
6. For patients with non-cirrhotic BCS or chronic portal vein thrombosis post-TIPS, early Doppler ultrasound is recommended, followed by every 6 months to monitor for thrombosis or TIPS failure.
(Expert opinion, strong agreement)
7. For patients with chronic portal vein thrombosis or cavernous transformation with severe portal hypertension-related complications (e.g., recurrent variceal bleeding despite endoscopic and drug therapy, symptomatic portal hypertensive cholangiopathy), portal vein recanalization with or without TIPS is recommended.
(Expert opinion, strong agreement)
8. TIPS is recommended for patients with portal sinusoidal vascular diseases (PSVD) with refractory gastrointestinal bleeding, repeated bleeding despite standardized secondary prevention, or recurrent/obstinate ascites.
(Expert opinion, strong agreement)
9. For cirrhotic patients with portal vein thrombosis, waiting for liver transplantation, TIPS is recommended if the thrombosis progresses or does not improve after anticoagulation therapy.
(Expert opinion, strong agreement)
10. For cirrhotic patients with portal vein thrombosis who continue to have complications of portal hypertension (ascites or recurrent variceal bleeding) despite adequate anticoagulation therapy, TIPS or portal vein recanalization is recommended.
(Expert opinion, strong agreement)
11. The benefits of long-term anticoagulation therapy post-TIPS in cirrhotic patients have not been confirmed.
(Expert opinion, strong agreement)
Part 6: TIPS for Recurrent/Refractory Ascites
1. All patients with recurrent ascites (≥3 large volume paracenteses) or refractory ascites should consider TIPS for ascites relief.
(G1+, strong agreement)
2. Once recurrent or refractory ascites is identified, early TIPS is recommended to improve transplant-free survival.
(G2+, strong agreement)
3. All patients with refractory hepatic hydrothorax should consider TIPS for pleural effusion relief. Patients with high post-TIPS complication risks should prioritize liver transplantation evaluation.
(G2+, strong agreement)
Part 7: TIPS and the Kidneys
1. Regardless of liver transplantation plans, TIPS may not be suitable for patients with type 1 hepatorenal syndrome/acute kidney injury due to the high mortality rate still associated with liver failure.
(G2−, strong agreement)
2. TIPS can be considered for patients with type 2 hepatorenal syndrome/acute kidney injury associated with refractory or recurrent ascites.
(G2+, strong agreement)
In the next issue, Dr. Xuefeng Luo will present the remaining sections (8-16) of the French TIPS guidelines and his analysis. Stay tuned!
