Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis

Portal vein thrombosis(PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs(low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs(DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time.

Use of non-selective beta blockers in cirrhosis:The evidence we need before closing(or not) the window

Non selective beta blockers(NSBBs)are used in primary and secondary prophylaxis of portal hypertensionrelated bleeding in patients with cirrhosis.The efficacy of NSBBs treatment is predicted by hemodynamic response in term of reduction of the hepatic venouspressure gradient(HVPG)below 12 mm Hg or at least20%of the basal value.Nevertheless a relevant number of patients who do not achieve this HVPG reduction during NSBBs therapy do not bleed during follow up;this evidence suggests an additional non-hemodynamic advantage of NSBBs treatment to modify the natural history of cirrhosis.Recent studies have questioned the efficacy and safety of NSBBs in patients with advanced stage of liver disease characterized by refractory ascites and/or spontaneous bacterial peritonitis.These studies have suggested the existence of a defined and limited period to modify the natural history of cirrhosis by NSBBs:the"window hypothesis".According with this hypothesis,patients with cirrhosis benefit from the use of NSBBs from the appearance of varices up to the development of an advanced stage of cirrhosis.Indeed,in patients with refractory ascites and/or spontaneous bacterial peritonitis the hemodynamic effects of NSBBs may expose to a high risk of further complications such as renal insufficiency and/or death.Methodological concerns and contrasting results counterbalance the evidence produced up to now on this issue and are the main topic of this editorial.

Urea cycle disorders:A case report of a successful treatment with liver transplant and a literature review

The urea cycle is the final pathway for nitrogen metabolism. Urea cycle disorders(UCDs) include a variety of genetic defects, which lead to inefficient urea synthesis. Elevated blood ammonium level is usually dominant in the clinical pattern and the primary manifestations affect the central nervous system. Herein, we report the case of a 17-year-old girl who was diagnosed with UCD at the age of 3. Despite a controlled diet, she was hospitalized several times for acute attacks with recurrent life risk. She came to our attention for a hyperammonemic episode. We proposed an orthotopic liver transplant(OLT) as a treatment; the patient and her family were in complete agreement. On February 28, 2007, she successfully received a transplant. Following the surgery, she has remained well, and she is currently leading a normal life. Usually for UCDs diet plays the primary therapeutic role, while OLT is often considered as a last resort. Our case report and the recent literature data on the quality of life and prognosis of traditionally treated patients vs OLT patients, support OLT as a primary intervention to prevent life-threatening acute episodes and chronic mental impairment.