Editor's note: Portal hypertension is defined as a pathologically elevated pressure in the portal venous system. While the most common cause is cirrhosis, it can also occur without cirrhosis, known as non-cirrhotic portal hypertension, which can be caused by various factors. The "8th Academic Conference of the Chinese Research Hospital Association Liver Disease (Traditional Chinese and Western Medicine) Professional Committee" , jointly organized by the Chinese Research Hospital Association Liver Disease (Traditional Chinese and Western Medicine) Professional Committee and the China Hepatitis Prevention and Treatment Foundation, recently concluded. During the conference, "Hepatology Digest" interviewed Dr.Jidong Jia, the Chairman of the Liver Disease Professional Committee of the Chinese Medical Association Digestive Physicians Branch, and the Director of the Liver Disease Center at Beijing Friendship Hospital affiliated to Capital Medical University. He discussed in-depth the diagnostic and therapeutic strategies for non-cirrhotic portal hypertension.
“Hepatology Digest”: In recent years, what are the major advances in the research of portal hypertension in China?
Dr. Jidong Jia: Portal hypertension refers to a group of clinical syndromes caused by an elevated pressure in the portal venous system due to various reasons. It is a common clinical issue in hepatology, involving various clinical disciplines. In China, there have been three main advances in the field of portal hypertension research in recent years.
Firstly, there is a deepening understanding of the etiology of portal hypertension. In addition to the traditional cause of cirrhosis, the etiology of non-cirrhotic portal hypertension has also received increasing attention.
Secondly, the techniques for measuring portal vein pressure have become more widespread. Non-invasive methods which assess portal vein pressure indirectly include Doppler ultrasound imaging, liver spleen stiffness measurement, spiral CT portal vein imaging, magnetic resonance angiography, radionuclide imaging, and artificial intelligence technology. Invasive methods for measuring portal pressure include classic portal vein catheterization (direct puncture of the portal vein system during surgery), endoscopic-guided puncture for portal vein pressure measurement, and percutaneous transhepatic portal vein puncture guided by ultrasound. Measuring hepatic vein pressure gradient (HVPG), the difference between wedged hepatic vein pressure and free hepatic vein pressure, is also used to indirectly reflect portal vein pressure. HVPG, considered the “gold standard” for assessing the degree of sinusoidal portal hypertension, is subclinical portal hypertension when between 5-10 mmHg and clinically significant portal hypertension (CSPH) when ≥10 mmHg.
Thirdly, as our understanding of the etiology and pathophysiology of portal hypertension deepens, we have gained rich experience in the treatment modalities such as medication, endoscopy, intervention, and surgery, making treatment choices more rational and standardized.
“Hepatology Digest”: In routine clinical practice, what examinations are mainly used for the diagnosis and assessment of portal hypertension? How can non-cirrhotic portal hypertension be accurately identified?
Dr. Jidong Jia: In routine clinical practice, patients with portal hypertension often seek medical attention due to manifestations such as hepatosplenomegaly, decreased platelet count, and other related symptoms. Some may only seek medical attention when complications like esophagogastric variceal bleeding or ascites occur. The diagnosis of portal hypertension can be categorized into two main scenarios.
Firstly, for patients with known liver diseases such as chronic hepatitis B, chronic hepatitis C, alcoholic cirrhosis, non-alcoholic fatty liver disease/metabolic-associated fatty liver disease, etc., it is essential to observe signs of portal hypertension, such as decreased platelet count, enlarged spleen, and the presence of esophagogastric varices. On the other hand, for those without known liver diseases but presenting with manifestations directly related to portal hypertension (such as hepatosplenomegaly, decreased platelet count, or esophagogastric varices), a systematic differential diagnosis of the underlying cause is required.
It is important to note that while cirrhosis is the most common cause of portal hypertension, accounting for over 90%, approximately 10% of cases of portal hypertension are non-cirrhotic, referred to as “non-cirrhotic portal hypertension.” The causes of non-cirrhotic portal hypertension are diverse and complex, and they should not be overlooked. The related diseases causing non-cirrhotic portal hypertension can be classified based on the affected region of the portal venous system (pre-hepatic, intra-hepatic, or post-hepatic). Intra-hepatic causes can be further divided into pre-sinusoidal, sinusoidal, and post-sinusoidal. Pre-sinusoidal and pre-hepatic portal hypertension include anomalies in portal vein development, various conditions leading to portal vein thrombosis, congenital liver fibrosis, idiopathic non-cirrhotic portal hypertension (portal sinus vascular disease), and splenomegaly due to various blood or rheumatic immune diseases. Sinusoidal portal hypertension includes cirrhosis caused by various reasons. Post-sinusoidal and post-hepatic portal hypertension causes mainly include hepatic sinus obstruction syndrome, Budd-Chiari syndrome (including hepatic vein thrombosis caused by various prothrombotic factors), hepatic vein sclerosis (caused by chronic radiation damage, vitamin A excess, etc.), primary malignant vascular tumors (such as epithelioid hemangioendothelioma, angiosarcoma), granulomatous venous inflammation (caused by diseases like sarcoidosis, mycobacterial infections), and heart diseases (such as constrictive pericarditis).
On the basis of a comprehensive understanding and proficiency in these causes, a correct diagnosis can be made through the integration of medical history, physical examination, imaging studies, pathology, and routine and special laboratory tests (such as genetic testing).
“Hepatology Digest”: Currently, there are various treatment options for portal hypertension, including medications, endoscopy, intervention, and surgery. Could you discuss how to rationally choose and formulate the best treatment strategy in clinical practice?
Dr. Jidong Jia: Regarding portal hypertension, we emphasize the importance of etiological diagnosis, and similarly, the treatment also emphasizes etiological treatment. The initiating factor of cirrhotic portal hypertension lies in the increased portal vein pressure due to changes in liver structure or function. Therefore, etiological treatment should be integrated throughout the treatment process. For example, for patients with chronic hepatitis B or C, antiviral therapy should be employed; for patients with alcoholic fatty liver disease or metabolic-associated fatty liver disease, alcohol cessation (all patients with cirrhosis due to any cause should quit drinking), dietary control, and increased exercise are recommended; for patients with autoimmune hepatitis, standardized immunosuppressive therapy should be implemented.
Secondly, treatment for portal hypertension itself is targeted, involving medication, endoscopy, intervention, and liver transplantation.
The first step is medication, aimed at controlling various complications of cirrhotic portal hypertension. It can serve as primary prevention for esophagogastric variceal bleeding, acute bleeding treatment, and secondary prevention. For example, non-selective beta-blockers are mainly used for patients with moderate to severe esophagogastric varices at high risk of bleeding. Currently, both domestically and internationally, carvedilol is widely recommended because it can block beta and alpha receptors simultaneously, and its advantage lies in not requiring heart rate monitoring, as long as the blood pressure is maintained above 90/60 mmHg.
The second step, if digestive tract bleeding has already occurred, emergency endoscopic hemostasis and secondary prevention of bleeding can also be considered. Endoscopic treatment is usually implemented on the basis of medication, and the combination of non-selective beta-blockers with endoscopic treatment is the preferred secondary prevention strategy for esophagogastric variceal rupture.
The third step, if the above treatment modalities fail or there are signs of refractory bleeding or refractory ascites, interventional therapy can be considered. Interventional therapy mainly include transjugular intrahepatic portosystemic shunt (TIPS), balloon-occluded retrograde transvenous obliteration (BRTO), percutaneous transhepatic portal vein shunt, and direct portosystemic shunt through the inferior vena cava. Taking TIPS as an example, with the improvement of stent materials and manufacturing technology, the incidence of post-covered stent TIPS lumen restenosis is now very low, and complications such as hepatic encephalopathy after controlled inner diameter stent TIPS have also been significantly reduced, making it gradually a long-term treatment option. The overall trend is more proactive than in the past, and the treatment threshold is more suitable for current circumstances. Recent studies have shown that TIPS treatment can reduce the risk of bleeding, ascites, and other complications.
The fourth step is liver transplantation, which is the last line of defense for various end-stage liver diseases.
It is important to re-emphasize that for non-cirrhotic portal hypertension, identifying and actively treating the underlying cause is crucial. Particularly for hematologic diseases, rheumatic diseases, and tumor diseases, appropriate treatment should be given based on a clear understanding of the etiology.
TAG：Interview; Non-Cirrhotic Portal Hypertension
