Interview with Dr. Shiv K. Sarin, President of APASL 2004

 

　　1APASL Daily:  What are the major risk factors for the development of portal vein thrombosis (PVT) in cirrhosis and non-cirrhosis?

 

　　Dr. Sarin: PVT in non-cirrhotics is mainly because of hypercoagulable states which are genetically determined, like being procoagulant. Besides genetic factors, local factors and systemic factors like dehydration or pancreatitis can precipitate PVT in non-cirrhotics. But in cirrhotic patients, PVT is a result of cirrhosis causing hepatic frugal flow (blood flowing away from the liver). Sluggish flow and high pressure in the liver leads to thrombosis. Also, tumor thrombi can occur. So the most important cause is hemodynamics in patients with cirrhosis and in non-cirrhotics it is procoagulant factors. Thrombosis can be acute or chronic. Chronic thrombosis is generally because of infections.

 

　　2APASL Daily:  What progress has been made in the diagnosis and treatment of PVT in recent years?

 

　　Dr. Sarin: The diagnosis of PVT has improved with the use of ultrasound Doppler and contrast-enhanced CT scans. With the Doppler, you can see where there is no or sluggish flow, and with the CT scan you will see causative material in the portal vein. There are also certain blood tests which indicate procoagulant factors. Sometimes myelodysplastic syndrome is present and a bone marrow biopsy is needed to find out if the patient has a hypercoagulable state.

 

　　In treatment also, there are many advances. If patients have a procoagulant state (i.e. hypercoagulable), they are given continuous lifelong anticoagulation starting with drugs like enoxaparin and continuing with oral drugs. In those patients with no procoagulant factors, we give them three to six months of therapy and try to recanalize. In acute thrombosis of the portal veins, it may be required to implant a stent. The stent can extend from the portal vein to the hepatic vein. A catheter can also be placed in the portal vein by instilling urokinase. There are new drugs called inhibitors of thrombin, which are very effective and can be used in all liver disease patients, but have not been fully evaluated. If the PVT is recognized early, prognosis is improved.

 

　　The most important thing is, in cirrhotics who are on a transplant list, 50% of these patients will have thrombosis of the portal vein. If we dissolve this thrombus, the patient’s ascites and jaundice may improve to the point of perhaps not requiring a transplant.

 

　　It has been shown that long-term survival improves if you give anticoagulants. Our own group has shown that giving anticoagulants is safe. If a patient has varices and portal vein thrombosis, I would suggest first blocking the varices and eradicate them and then start with enoxaparin and later switch to Acitrom (nicoumalone) or warfarin to resolve the thrombus. These patients need to be monitored every three to six months. At the end of one year, about 50% resolution of thrombosis can be achieved.

 

　　3APASL Daily:  What is the role of growth factors in the treatment of liver failure?

 

　　Dr. Sarin: In liver failure, regeneration is slow. Normally in acute liver failure, the hepatocytes can replicate by themselves. But in cirrhosis with liver failure (acute-on-chronic liver failure), the hepatocyte regeneration is very weak, so progenitor or resident stem cells are required. To stimulate them, we give growth factors which work on the bone marrow, like G-CSF or erythropoietin, and they mobilize cells from bone marrow like CD33-positive or CD34-positive cells, and those work in the liver to stimulate regeneration. In two large studies published by our group in 2012, in acute-on-chronic liver failure, patients given G-CSF every day for five days and every alternate day for the rest of the month (a twelve-dose schedule), showed improved survival compared to placebo (69% vs. 30%). A second study used two growth factors, G-CSF plus darbepoetin, in cirrhotics who were on transplant lists. Giving growth factors decreased the chance of infection from about 35% to 5% and also improved survival. This was published last year in Gastroenterology. So growth factors are very important for managing liver failure and improving liver regeneration.

 

　　4APASL Daily:  Next year’s APASL annual conference will be held in Shanghai, China. What are your hopes for that meeting?

 

　　Dr. Sarin: China is the most populated country in the world with a very heavy burden of liver disease and consequently the best liver experts are in China. With Professors Jinlin Hou, Lai Wei and Ji-Dong Jai, you have the best three people in Asia to lead the liver disease field. The 2017 meeting has my fullest support and I am sure attendance in Shanghai will exceed 6000 people and I would predict that it will be a most memorable congress. In 2018, APASL will be in New Delhi and we invite all the Chinese hepatologists to attend our meeting also. My best wishes to Jinlin Hou and to China.