Yusuf Bayraktar

The role of natural anticoagulant deficiencies and factor V Leiden in the development of idiopathic portal vein thrombosis.

One of the causes of portal hypertension is portal vein thrombosis (PVT). The aim of this study was to determine whether natural anticoagulant deficiencies, activated protein C resistance (APCR), and factor V Leiden play a role in the development of PVT, leading to cavernous transformation of the portal vein (CTPV). Twenty-three patients with idiopathic CTPV (group 1) seen at Hacettepe University Hospital during the past 12 years were identified and prospectively studied. These 23 patients underwent a detailed hematological evaluation including measurement of protein S, protein C, antithrombin III, activated protein C resistance (APCR), and factor V Leiden gene mutation. Additionally, all patients were tested for anticardiolipin antibodies (ACA), IgG, IgM, and lupus anticoagulant (LA). Natural anticoagulants and APCR were measured using available commercial kits, and factor V Leiden mutation (R506Q) was detected by Mnl I digestion of an amplified factor V DNA fragment. All parameters were measured at least 6 months after the diagnosis of CTPV was established. No patient was on anticoagulant or antiaggregant treatment while tested. The findings in these 23 patients were compared with those in 20 healthy control subjects (group 2), in whom all tests mentioned above were also performed. In 23 patients (group 1), who had no recognizable factor for portal vein thrombosis, considerably natural anticoagulant deficiencies and factor V Leiden mutation positivity were found when we compare them to those healthy controls (group 2). The protein C levels of six patients (26%), the protein S levels of 10 patients (43.5%), and the antithrombin III levels of five patients (26%) were lower than in control subjects. Two patients were found to have combined protein S and antithrombin III deficiency, and one had combined protein S and C deficiency and APCR. APCR was detected in seven of the 23 patients, and six of these seven patients were found to have R506Q factor V Leiden mutations. In group 1, ACA IgG levels were higher in four patients (17%) and ACA IgM level was higher in one (4%) compared with the control group. LA was positive in only one patient in group 1. Natural anticoagulant deficiencies and factor V Leiden mutation are strongly associated with PVT. The natural anticoagulant deficiencies and APCR (almost totally caused by R506Q mutation) produce a favorable medium for thrombus generation. PVT seems to be related to the natural anticoagulant deficiencies and factor V Leiden R506Q mutation. A combination of these defects increases the incidence of PVT and these factors should be evaluated carefully in patients with idiopathic CTPV.

Endoscopic therapy in the management of hepatobiliary hydatid disease.

Hydatid disease constitutes a serious public health problem throughout the world, especially in endemic areas, despite the use of various kinds of preventive measures. Currently, there are three treatment options for hepatic hydatid disease including surgery, PAIR (puncture, aspiration, injection, and re-aspiration), and chemotherapy with benzimidazole compounds. Each of these therapeutic modalities has limitations depending on the individual case. The authors review the use of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in the management of hepatobiliary hydatid disease (HHD) to clarify its place in the treatment algorithm among surgical, medical, and percutaneous measures. ERCP in the preoperative period: (1) defines the cystobiliary relationship to help in surgery planning, (2) permits evaluation for acute conditions like cholangitis and obstruction so that subsequent surgery can be performed on an elective basis, (3) may give permanent cure specifically in cases of frank intrabiliary rupture if evacuation of biliary tract and cystic cavity is manageable, and (4) when combined with preoperative endoscopic sphincterotomy may decrease the incidence of the development of postoperative external fistula. ERCP in the postoperative period: (1) can help to clarify the causes of ongoing or recurrent symptoms or laboratory abnormalities, (2) may help to resolve the obstruction or cholangitis due to residual material in biliary ducts, (3) may provide the chance to manage postoperative external biliary fistulae, and (4) may be a realistic solution for secondary biliary strictures. Considering the current literature and adding this experience, the authors propose a new treatment algorithm in HHD including medical, surgical, PAIR, and ERCP-related therapies. To illustrate the algorithm, a case is presented of a patient who had a persistent external biliary fistula in the postoperative period and was managed successfully by endoscopic approach.

Is Congenital Hepatic Fibrosis a Pure Liver Disease

OBJECTIVES:An association between congenital hepatic fibrosis (CHF) and several different conditions is being increasingly recognized. We aimed to investigate, prospectively, these associated disorders and the clinical consequences for patients with CHF.MATERIALS AND METHODS:CHF was diagnosed using liver biopsy, abdominal ultrasound (US), Doppler US, upper endoscopy, and abdominal computed tomography (CT) in 19 patients (13 women, 6 men). CT portography and splenoportography with digital subtraction angiography were performed if indicated. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to investigate the extent of portal vein involvement of the common bile duct if it existed, to remove a stone located in the common bile duct when documented, and to confirm the diagnosis of Carolis syndrome. Cranial MRI was done when clinical findings suggested brain involvement.RESULTS:The mean age of the patients was 29.47 ± 12.06, ranging from 13 to 57. CHF-associated diseases were Carolis syndrome, polycystic kidney disease, cavernous transformation of the portal vein, Jouberts syndrome, von Meyenburg complex, polydactyly, medullary sponge kidney, and pancreatic duct atrophy. In two cases, cholangiocarcinoma had developed. There was only one case with pure CHF. Portosystemic shunt, TIPS, or splenectomy were performed in some cases to control bleeding from esophageal varices. Papillotomy and stone extraction from the common bile duct were performed in four patients with Carolis syndrome complicated by cholangitis. Three patients died of complications of CHF. Two patients with Carolis syndrome underwent liver transplantation.CONCLUSION:In this prospective study, it seems that CHF is not a pure liver disease but rather a multiorgan disorder involving the brain, portal vein, kidneys, and bile ducts. In most cases, the clinical picture includes other organ involvement, rather than purely the liver parenchyma.

Arterial thrombosis leading to intestinal infarction in a patient with Behçet’s disease associated with protein C deficiency

Behçets disease may be a possible cause of both occlusive and aneurysmal arterial involvement as well as recurrent venous thrombosis. A case of Behçets disease complicated with vascular involvement leading to intestinal infarction is presented. A 41-yr-old man suffering from Behçets disease for 15 yr presented with a 2-day history of severe abdominal pain and bloody diarrhea. Intestinal infarction secondary to thrombosis of the superior mesenteric artery had been diagnosed during surgical exploration 3 yr previously. He was started on anticoagulation with nutritional support. The patient was readmitted with severe diarrhea and malabsorbtion symptoms 3 yr after intestinal resection. A thrombus located in the posterior wall of the infrarenal portion of aorta was detected by aortography and ultrasonography. Although thrombosis is a relatively common complication of Behçets disease caused by vasculitis, protein C deficiency, which is a pertinent laboratory finding in this case, might be a secondary factor in the thrombotic event. This is the first case reported of mesenteric artery thrombosis leading to bowel infarction and abdominal aorta thrombosis associated with protein C deficiency.

JAK2V617F Mutation in Patients with Portal Vein Thrombosis

In a retrospective cohort, we investigated the presence of the JAK2V617F mutation in chronic non-cirrhotic portal vein thrombosis (PVT) patients, irrespective of the presence or absence of myeloproliferative diseases (MPDs). We identified 25 patients in whom thrombophilia workup was completed. The diagnoses of MPDs were made according to the World Health Organization (WHO) criteria. JAK2V617F mutation analysis was performed by allele-specific polymerase chain reaction (PCR). There were 9 male and 16 female patients. Prior to JAK2V617F analysis, there were one or more thrombophilic risk factors in 19 patients (76%). The JAK2V617F mutation analysis revealed the presence of this mutation (all in the heterozygote state) in six patients (24%; two male, four female). Five of the six cases with prior clinical diagnosis of MPDs were found to have wild-type JAK2. We found that the addition of JAK2V617F analysis into the thrombophilia workup in patients with chronic PVT contributes to a 4% increase in the diagnosis of thrombophilic conditions.

How can portal vein cavernous transformation cause chronic incomplete biliary obstruction

Biliary disease in the setting of non-cirrhotic portal vein thrombosis (and similarly in portal vein cavernous transformation) can become a serious problem during the evolution of disease. This is mostly due to portal biliary ductopathy. There are several mechanisms that play a role in the development of portal biliary ductopathy, such as induction of fibrosis in the biliary tract (due to direct action of dilated peribiliary collaterals and/or recurrent cholangitis), loss of biliary motility, chronic cholestasis (due to fibrosis or choledocholithiasis) and increased formation of cholelithiasis (due to various factors). The management of cholelithiasis in cases with portal vein cavernous transformation merits special attention. Because of a heterogeneous clinical presentation and concomitant pathophysiological changes that take place in biliary anatomy, diagnosis and therapy can become very complicated. Due to increased incidence and complications of cholelithiasis, standard treatment modalities like sphincterotomy or balloon sweeping of bile ducts can cause serious problems. Cholangitis, biliary strictures and hemobilia are the most common complications that occur during management of these patients. In this review, we specifically discuss important issues about bile stones related to bile duct obstruction in non-cirrhotic portal vein thrombosis and present evidence in the current literature.

Budd-Chiari syndrome: analysis of 30 cases.

The authors report their experience with 30 adult patients with Budd-Chiari syndrome (BCS), which is a rare and serious disorder, characterized by hepatic outflow obstruction caused by many different conditions. The diagnosis was based on the clinical data, ultrasonography (US), vena cavography and hepatic venography, computed tomography (CT), and liver bi opsy. Behçets disease (BD) was found in 10 patients with BCS as an underlying disease. Two patients used oral contraceptive drugs, 2 had liver tumor hepato cellular carcinoma and liver lymphoma, and 1 patient had chronic lymphocytic leukemia. Despite full investigation, the authors could not find any obvious un derlying cause in the other 15 patients. The results suggest that (1) BCS must be considered as a possible complica tion in patients with Behçets disease when they have hepatomegaly even if there were no cardinal manifestations of the disease at the time of admission, and BD is the most common etiologic factor in BCS (33%) in Turkey, where the inci dence of Behçets disease is relatively high. (2) Anti-aggregant treatment seems to be effective in many instances. (3) There were space-occupying lesion-like appearances in the liver of 7 cases by CT and US examination in the acute stage, and these disappeared on the follow-up CT and US in 5 patients but continued in 2. BCS should thus be differentiated from other liver lesions. (4) There were other great-vessel involvements in 43% of the cases, mostly venous, but only 1 pulmonary arterial occlusion.

The use of deferoxamine infusions to enhance the response rate to interferon-α treatment of chronic viral hepatitis B

Summary An individuals iron status may affect the response rate achieved with the use of interferon (IFN) as therapy for chronic viral hepatitis. A total of 27 patients with chronic hepatitis B viral infection, who had elevated serum ferritin levels, were randomized to receive either IFN 5 MU, three times weekly by subcutaneous injection alone (n= 14) or in combination with cycles of deferoxamine at a dose of 80 mg kg‐1 per cycle (n= 13) administered over 3 consecutive days, to reduce their iron and maintain a serum ferritin level less than 250 ng ml‐1. All deferoxamine‐treated patients were on a low iron‐containing diet. An IFN response was defined as a normalization of the serum alanine aminotransferase (ALT) level and seroconversion from hepatitis B e antigen (HBeAg) positivity to hepatitis B e antibody (HBeAb) positivity. The deferoxamine‐treated group experienced a reduction in their serum ferritin level to 226 ± 73 ng ml‐1 as a result of the deferoxamine treatment. Six of the 13 (46%) deferoxamine‐treated patients and two of the 14 (14%) control patients normalized their ALT levels. Seven of the 13 (54%) deferoxamine but only 14% of the IFN‐treated group seroconverted to HBeAb positivity. A greater rate of histological improvement and loss of hepatitis B virus (HBV) DNA was seen in the deferoxamine‐treated group. Two of the deferoxamine‐treated patients were treated only once, two were treated twice, seven were treated three times and two were treated four times to achieve a ferritin level below 250 ng ml‐1.

Potential role of lycopene in the treatment of hepatitis C and prevention of hepatocellular carcinoma.

Hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC) are growing health problems around the world. Oxidative stress plays a significant role in the initiation and progression of hepatocellular damage and possibly in the development of HCC in HCV infected patients. In vitro, animal and clinical studies suggest that lycopene, a nonprovitamin A carotenoid and a potent antioxidant, may attenuate the liver injury and possibly prevent the development of HCC. In this article, we discuss the relationship between HCV infection and oxidative stress and review the potential role of lycopene in the treatment of HCV and prevention of HCC.

The etiologic distribution of thrombophilic factors in chronic portal vein thrombosis.

Goals We aimed to prospectively investigate the full etiologic contributors to portal vein thrombosis. Background Portal vein thrombosis in the absence of liver disease is a rare cause of portal hypertension with a different clinical course and management strategy. The etiologic distribution of this interesting clinical picture is important as far as diagnostic and management issues are concerned. Study After the application of exclusion criteria, 59 patients were included in the study who had normal liver functions, normal liver histology and studied the thrombophilia factors of both acquired factors and congenital factors like protein C, protein S, antithrombin levels with the mutations. Results In all, 23.7% of the patients were found to have acquired thrombophilia factors like myeloproliferative disorders and cyst hydatid disease, whereas 22.1% of the patient population was found to harbor no identifiable cause of thrombophilia, which we termed as idiopathic. One or more causes of thrombophilia were identified in 46 patients. There were 27 patients with protein C deficiency, 18 patients with protein S deficiency. The antithrombin deficiency was found in 17 patients. The factor V Leiden mutation was found in 7 patients. There was 1 patient with homozygote mutation, whereas the remaining 6 patients were heterozygotes. There were 3 patients with prothrombin mutation who were heterozygote for this mutation. Conclusions Complete investigation of thrombophilia is crucial to delineate the outline of thrombophilic risk factors to estimate the rethrombosis risk and for further management concerns.