Luciano Tarantino

The risk of venous thromboembolism in patients with cirrhosis: A systematic review and meta-analysis

Some studies suggest that patients with cirrhosis have an increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Unfortunately, available data on this association are contrasting. It was the objective of this study to perform a systematic review and meta-analysis of literature to evaluate the risk of venous thromboembolism (VTE) associated with cirrhosis. Studies reporting on VTE risk associated with cirrhosis were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Eleven studies (15 data-sets) showed a significantly increased VTE risk in 695,012 cirrhotic patients as compared with 1,494,660 non-cirrhotic controls (OR: 1.703; 95 %CI: 1.333, 2.175; P<0.0001). These results were confirmed when specifically considering the risk of DVT (7 studies, OR: 2.038; 95 %CI: 1.817, 2.285; P<0.0001) and the risk of PE (5 studies, OR: 1.655; 95 %CI: 1.042, 2.630; p=0.033). The increased VTE risk associated with cirrhosis was consistently confirmed when analysing nine studies reporting adjusted risk estimates (OR: 1.493; 95 %CI: 1.266, 1.762; p<0.0001), and after excluding studies specifically enrolling populations exposed to transient risk factors for VTE (OR: 1.689; 95 %CI: 1.321, 2.160; p<0.0001). Meta-regression models suggested that male gender may significantly impact on the risk of VTE associated with cirrhosis. Results of our meta-analysis suggest that cirrhotic subjects may exhibit an increased risk of VTE. This should be considered to plan specific prevention strategies in this clinical setting.

Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma

Portal vein thrombosis (PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma (HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound (US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography (CT) and contrast-enhanced magnetic resonance (MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography (PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound (CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement (wash in - wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is a very reliable technique with a high intrinsic sensitivity for portal vein patency assessment. More expensive and sophisticated techniques (i.e., CT, MRI, PET, and PET-CT) should only be indicated in undetermined cases at CEUS.

Preservation of nutritional-status in patients with refractory ascites due to hepatic cirrhosis who are undergoing repeated paracentesis.

Background and Aim:  Refractory ascites in liver‐cirrhosis is associated with a poor prognosis. We performed a prospective study to investigate whether aggressive nutritional‐support could improve outcomes in cirrhotic patients.

Viral hepatitis and anti-phospholipid antibodies positivity: A systematic review and meta-analysis

BACKGROUND Anti-phospholipid antibodies positivity is associated with several clinical conditions, including infectious diseases. AIMS We performed a meta-analysis evaluating the association of hepatitis B and C with anti-phospholipid antibody positivity and with anti-phospholipid antibody-related thrombotic complications. METHODS Studies evaluating the association of viral hepatitis with anti-cardiolipin, anti-β2 glycoprotein-I and lupus anticoagulant antibodies and anti-phospholipid antibody-related thrombotic events were systematically searched. RESULTS 20 studies (2319 cases, 1901 controls) were included. The analyses showed that viral hepatitis is associated with the presence of anti-cardiolipin and anti-β2 glycoprotein-I antibodies. The association with anticardiolipin antibodies was confirmed in both hepatitis B (OR 11.22, 95% CI: 6.68-18.84) and hepatitis C (OR 11.26, 95% CI: 6.82-18.59). Similarly, compared to controls, anti-β2 glycoprotein-I antibodies were found more frequently in hepatitis B (OR 14.07, 95% CI: 3.06-64.66) and hepatitis C (OR 5.64, 95% CI: 1.69-18.77). Moreover, 11 studies (257 cases, 1079 controls) showed a higher prevalence of venous and/or arterial thrombosis in patients with hepatitis and anti-cardiolipin antibody positivity compared hepatitis alone (OR 3.29, 95% CI: 1.79-6.07). This result was consistently confirmed in hepatitis C (OR 3.64, 95% CI: 1.78-7.46) but not in hepatitis B. CONCLUSIONS Viral hepatitis is significantly associated with anti-phospholipid antibody positivity and with anti-phospholipid antibody-related thrombotic complications.

Validation of an extension of the international non-invasive criteria for the diagnosis of hepatocellular carcinoma to the characterization of macroscopic portal vein thrombosis

Background and Aim:  We aimed to validate the non‐invasive criteria for the characterization of portal vein thrombosis (PVT) in patients with cirrhosis and hepatocellular carcinoma (HCC). In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non‐invasive diagnosis of HCC, as a criterion for characterizing macroscopic PVT (EASL/AASLD extension criteria).

The risk of coronary artery disease and cerebrovascular disease in patients with hepatitis C: A systematic review and meta-analysis

BACKGROUND/OBJECTIVES Some studies suggest that patients with hepatitis C virus (HCV) infection have an increased risk of coronary artery disease (CAD) and cerebrovascular disease. Unfortunately, available data on this association are widely variable. We have performed a systematic review and meta-analysis of literature to evaluate the risk of cardio-cerebrovascular disease (CCD) associated with HCV. METHODS Studies reporting on CCD risk associated with HCV were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. RESULTS Twenty-seven studies (34 data-sets) showed a significantly increased CCD risk in 297,613 HCV patients as compared with 557,814 uninfected controls (OR: 1.428; 95% CI: 1.214, 1.681). These results were confirmed when separately considering the risk of CAD (20 studies, OR: 1.382; 95% CI: 1.103, 1.732) and of cerebrovascular disease (13 studies, OR: 1.485; 95% CI: 1.079, 2.044). Similar results were confirmed when analyzing 21 studies reporting adjusted risk estimates (OR: 1.448; 95% CI: 1.218, 1.722) and when, after excluding studies defining CAD as positive angiographic or electrocardiographic evidence, we specifically included the 17 studies reporting on acute CCD-related events (OR: 1.357; 95% CI: 1.103, 1.670). Moreover, 4 studies evaluating CCD-related deaths showed a higher risk in HCV patients than controls (OR: 1.772; 95% CI: 1.448, 2.168; P<0.0001). Meta-regression models suggested a direct association between prevalence of cirrhosis and difference in CCD risk between HCV patients and controls. CONCLUSIONS Results of our large meta-analysis suggest that HCV-infected subjects experience an increased risk of CCD. This should be considered to plan specific cardiovascular prevention strategies in this clinical setting.

The risk of venous thromboembolism in patients with hepatitis C. A systematic review and meta-analysis.

Some studies suggest that patients with hepatitis C virus (HCV) infection have an increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Unfortunately, available data on this association are contrasting. A systematic review and meta-analysis of literature studies was performed to evaluate the risk of venous thromboembolism (VTE) associated with HCV. Studies reporting on VTE risk associated with HCV were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Six studies (10 data-sets) showed a significantly increased VTE risk in 100,364 HCV patients as compared with 8,471,176 uninfected controls (odds ratio [OR]: 1.900; 95 % confidence interval [CI]: 1.406, 2.570; p<0.0001). These results were confirmed when specifically considering the risk of DVT (6 studies, OR: 1.918; 95 %CI: 1.351, 2.723; p<0.0001), whereas a trend towards an increased risk of PE was documented in HCV patients (4 studies, OR: 1.811; 95 %CI: 0.895, 3.663; p=0.099). The increased VTE risk associated with HCV infection was consistently confirmed when analysing four studies reporting adjusted risk estimates (OR: 1.876; 95 %CI: 1.326, 2.654; P<0.0001), and after excluding studies specifically enrolling populations exposed to transient risk factors for VTE (4 studies, OR: 1.493; 95 %CI: 1.167, 1.910; p=0.001). Meta-regression models suggested that age and male gender may significantly impact on the risk of VTE associated with HCV-positivity. Results of our meta-analysis suggest that HCV-infected subjects may exhibit an increased risk of VTE. However, further high quality studies are needed to extend and confirm our findings.

The risk of osteoporosis in patients with liver cirrhosis: a meta-analysis of literature studies

Data about the association between cirrhosis and osteoporosis are contrasting. Thus, we have performed a meta‐analysis of literature studies on this topic.

Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study

AIM To treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those patients. METHODS Six patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae®, IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months thereafter. RESULTS Post-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after ECT. CONCLUSION In patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

Electrochemotherapy of cholangiocellular carcinoma at hepatic hilum: A feasibility study

AIM We evaluated feasibility, safety and efficacy of Electrochemotherapy (ECT) in a prospective series of patients with unresectable Perihilar-Cholangiocarcinoma (PHCCA). PATIENTS AND METHODS Five patients with PHCCA underwent ECT. Three patients underwent percutaneous ECT of a single PHCCA nodule. One patient underwent resection of a nodule in the IV segment and intraoperative ECT of a large PHCCA in the VIII segment. Another patient underwent percutaneous ECT of a large PHCCA recurrence after left lobectomy and RF ablation of a synchronous metastasis in the VI segment. ECT was performed under US guidance. Efficacy was evaluated by contrast-enhanced multiple-detector-computed-tomography (MDCT) 4 weeks after treatment. Follow-up entailed MDCT every 6 months thereafter. RESULTS No major complication occurred. Follow-up ranges from 10 to 30 months. Four weeks post-treatment CT showed complete response in 3 cases. These patients are still alive, and follow-up CT controls demonstrated no local or distant intrahepatic recurrences and no biliary duct dilation in 2 cases and local recurrence at 18 months follow-up control in 1 patient. In the remaining 2 cases, 4-weeks-post-treatment CT showed incomplete response (>90%). In these patients follow-up CT demonstrated local progression of the disease at 6 months. One of them had bilateral external biliary drainages and died because of tumor progression at 16-months-follow-up. The other patient, died at 10 months follow-up for cardiovascular failure not related to the hepatobiliary disease. CONCLUSIONS ECT is feasible, safe and effective therapy to improve prognosis and quality of life of patients with unresectable PHCCA.