Non-invasive model predicting clinically-significant portal hypertension in patients with advanced fibrosis

Background and Aims:  Hepatic venous pressure gradient (HVPG) has been established as a predictor for the development of varices, clinical decompensation and death. In the present study, the primary objectives were to determine the diagnostic accuracy of the model developed by using readily-available data in predicting the presence of significant portal hypertension and esophageal varices.
Methods:  This study included a total of 61 consecutive treatment-naive patients with advanced fibrosis (METAVIR F3, F4), established by liver biopsy. All patients underwent subsequent HVPG measurement and upper gastrointestinal endoscopy within 1 week of liver biopsy.
Results:  Seventeen patients (F3, 2/26; F4, 15/35) had clinically-significant portal hypertension (HVPG ≥ 10 mmHg). The Risk Score for predicting significant portal hypertension was 14.2 − 7.1 × log₁₀ (platelet [10⁹/L]) + 4.2 × log₁₀ (bilirubin [mg/dL]). The area under the receiver–operator curve (AUC) curve was 0.91 (95% confidence interval [CI], 0.84–0.98). The optimized cut-off value (Risk Score = −1.0) offered a sensitivity of 88% (95% CI, 62–98%) and a specificity of 86% (95% CI, 72–94%). The AUC of the Risk Score in predicting varices was 0.82 (95% CI, 0.67–0.98). The cut-off had a sensitivity of 82% (95% CI, 48–97%) and a specificity of 76% (95% CI, 62–86%).
Conclusion:  A predictive model that uses readily-available laboratory results may reliably identify advanced fibrosis patients with clinically-significant portal hypertension as well as esophageal varices. However, before accepted, the results of the current study certainly should be validated in larger prospective cohorts.     

Reappraisal of repeated transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein invasion

Background and Aim:  This study aimed to evaluate the therapeutic efficacy and safety of repeated transarterial chemoembolization (TACE) with additional radiation therapy (RT) in hepatocellular carcinoma (HCC) with portal vein (PV) invasion.
Methods:  We performed survival analysis of consecutive HCC patients with PV invasion according to the treatment modalities after stratification by the degree of PV invasion and liver function retrospectively.
Results:  During 2005, 281 patients were newly diagnosed to have HCC with PV invasion at our institution. Repeated TACE or transarterial chemoinfusion (TACI) was performed in 202 (71.9%) patients and additional RT was performed for PV invasion in 43 of them. A total of 281 patients had a median survival of 5.2 months and a 2-year survival rate (YSR) of 19.2%. Repeated TACE showed significant survival benefits compared with conservative management in patients with PV branch invasion; median survival and 2-YSR was 10.2 vs 2.3 months and 33.7% vs 0% in Child–Pugh A categorized patients and 5.5 vs 1.3 months and 10.3 vs 0% in Child–Pugh B categorized patients, respectively ( P  < 0.001). In patients with PV branch invasion, the survival rate was significantly longer with TACE/TACI plus RT than with TACE/TACI alone both in Child–Pugh A categorized patients (1-YSR: 63.6 vs 35.6%, P  = 0.031) and Child–Pugh B categorized patients (1-YSR: 66.7 vs 7.7%, P  = 0.007). Repeated TACE was well tolerated in our patients, with only one dying within one month after TACE.
Conclusion:  Repeated TACE with additional RT can be performed safely and showed a significant survival benefit in HCC patients with PV branch invasion with conserved liver function.     

Histological evaluation of intracapsular venous invasion for discrimination between portal and hepatic venous invasion in hepatocellular carcinoma

Background and Aim:  Histological criteria for intracapsular venous invasion (IVI) that would allow its discrimination between portal and hepatic venous invasion in hepatocellular carcinoma (HCC) have not been established.
Methods:  We evaluated IVI immunohistochemically to discriminate between portal and hepatic venous invasion in 89 resected specimens from patients with HCC. IVI was defined as the microscopic involvement of the vessels within the fibrous capsule of HCC. The hepatic venous system was subdivided into the central vein and the sublobular/hepatic vein. Immunohistochemical analysis with the D2-40 monoclonal antibody revealed lymphatic vessels.
Results:  In non-neoplastic liver tissues, the portal veins ( n  = 4355) were accompanied by lymphatic vessels (99.7%), bile ductules (100%) and arteries (96%), whereas the central veins ( n  = 3932) and sublobular/hepatic veins ( n  = 662) were rarely accompanied by lymphatic vessels (0% and 17%, respectively) and bile ductules (12% and 33%, respectively). In total, 29 IVI foci were detected; three foci were clearly visible within vessels that contained a distinct layer of connective tissue fibers, signifying sublobular/hepatic venous invasion. As the remaining 26 foci were accompanied by lymphatic vessels (26/26 [100%]), bile ductules (21/26 [81%]) and arteries (10/26 [38%]), these foci were considered to reflect intracapsular portal venous invasion rather than venous invasion of the central vein. Intracapsular portal venous invasion was significantly associated with extratumoral portal venous invasion ( P  < 0.001).
Conclusions:  D2-40 immunoreactivity for the histological evaluation of IVI in HCC allows discrimination between portal and hepatic venous invasion for cases in which portal venous invasion predominates.     

Underlying mechanism of portal hypertensive gastropathy in cirrhosis: A hemodynamic and morphological approach

Background and Aim:  Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis.
Methods:  Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis.
Results:  The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P  = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index ( P  = 0.53 and 0.34, respectively), Child–Pugh classification ( P  = 0.73 and 0.78, respectively) or glucagon levels ( P  = 0.59 and 0.62, respectively).
Conclusions:  The present data show no correlation between the presence or the severity of PHG and portal pressure, Child–Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.     

Prognosis of hepatocellular carcinoma accompanied by microscopic portal vein invasion

AIM： To investigate the prognostic factors in patients with hepatocellular carcinoma （HCC） accompanied by microscopic portal vein invasion （PVI）.
METHODS： Of the 267 patients with HCC undergoing hepatic resection at Aso Iizuka Hospital, 71 had PVI. After excluding 16 patients with HCC that invaded the main trunk and the first and second branches of the portal vein, 55 patients with microscopic PVI were enrolled.
RESULTS： The patients with HCC accompanied by microscopic invasion were divided into two groups： solitary PVI （PVI-S： n = 44）, and multiple PVIs （PVI-M： n = 11）. The number of portal vein branches invaded by tumor thrombi was 5.4 ± 3.8 （2-16） in patients with PVI-M. In cumulative survival, PVI-M was found to be a significantly poor prognostic factor （P = 0.0019）; while PVI-M and non-anatomical resection were significantly poor prognostic factors in disease-free survival （P = 0.0213, and 0.0115, respectively）. In patients with PVI-M, multiple intrahepatic recurrence was more common than in the patients with PVI-S （P = 0.0049）. In patients with PVI-S, non-anatomical resection was a significantly poor prognostic factor in disease-free survival （P = 0.0370）. Operative procedure was not a significant prognostic factor in patients with PVI-M.
CONCLUSION： The presence of PVI-M was a poor prognostic factor in patients with HCC, accompanied by microscopic PVI. Anatomical resection is recommended in these patients with HCC. Patients with HCC and PVI-M may also be good candidates for adjuvant chemotherapy.     

Is portal hypertension associated with protein-losing enteropathy?

Background and Aim:  Hypoalbuminemia in patients with decompensated cirrhosis has traditionally been assumed to be a result of to impaired liver synthesis; however, protein-losing enteropathy (PLE) may also contribute. The aim of this study was to assess whether hypoalbuminemic cirrhotic patients with portal hypertension had evidence of PLE.
Methods:  Sixteen patients with alcoholic cirrhosis, hypoalbuminemia and portal hypertension underwent whole gut lavage with polyethylene glycol solution. The effluent obtained was analyzed for albumin, immunoglobulin (Ig)G and α1-antitrypsin (α1-AT). Serum C-reactive protein (CRP) was also measured to assess the systemic inflammatory response.
Results:  Twelve of the 16 enrolled patients had a persistently low albumin concentration at the time of lavage. Only one patient (who was subsequently found to have celiac disease) had elevated concentrations of lavage albumin, α1-AT and IgG levels. There was a significant correlation between lavage albumin and α1-AT ( r  = 0.671, P  = 0.024), and between lavage albumin and IgG ( r  = 0.614, P  = 0.045). There was no correlation between serum albumin and lavage proteins. Six patients had elevated serum CRP levels, but serum albumin or lavage protein concentrations did not correlate with serum CRP.
Conclusion:  There is no evidence of a significant PLE in patients with alcoholic cirrhosis, hypoalbuminemia and portal hypertension.     

Effect of laparoscopic splenectomy on portal hypertensive gastropathy in cirrhotic patients with portal hypertension

Aim:  This study investigated the relationship between portal hypertensive gastropathy (PHG) and splenomegaly, and the effect of laparoscopic splenectomy on PHG in cirrhotic patients with portal hypertension.
Methods:  Seventy patients with liver cirrhosis and portal hypertension were prospectively studied. Indication for laparoscopic splenectomy was bleeding tendency in 10 patients, induction of interferon in 45, treatment of hepatocellular carcinoma in seven, and treatment for endoscopic injection sclerotherapy-resistant esophagogastric varices in eight. The severity of PHG was classified into none, mild, or severe according to the classification by McCormack et al. The severity of liver disease was classified using the Child–Pugh score. All patients underwent upper gastrointestinal endoscopy before and 1 month after the operation.
Results:  The prevalence of PHG was significantly correlated with the severity of liver disease using the Child–Pugh score. The severity of PHG was significantly correlated with the resected spleen volume. One month after the operation, PHG was improved in 16 of 17 patients with severe PHG and in 12 of 32 with mild PHG. The Child–Pugh score showed a significant improvement (6.8 ± 1.4 to 6.2 ± 1.2) at 3 months after laparoscopic splenectomy ( P  < 0.0001).
Conclusions:  PHG may be associated with splenomegaly, and laparoscopic splenectomy may have a beneficial effect on PHG, at least for a short time.     

Development of portal vein invasion and its outcome in hepatocellular carcinoma treated by transcatheter arterial chemo-embolization

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. One serious complication is the invasion of the portal vein. To investigate the new invasion of the portal vein in HCC following treatment by transcatheter arterial chemo-embolization (TACE), 124 patients with HCC were screened by ultrasound, computed tomography and angiography. Fifteen patients were diagnosed with portal vein invasion (PVI) during the initial examination and were excluded from the study. Of the remaining 109 patients, 18 developed PVI. Fourteen were male and four were female. None of these 18 patients completely responded to TACE treatment and all were in recurrence. The median time for appearance of PVI after the first TACE was 212 days. The median interval between PVI and the last negative ultrasound examination was 100 days. Both were correlated with the degree of PVI. The only significant factor affecting the time until the appearance of PVI was the TACE treatment. After the development of PVI, eight patients continued with the TACE treatment, and three of these patients were also treated with portal vein local chemotherapy. The regression of PVI was observed in two patients. The median survival time after the discovery of PVI was 129 days. Factors affecting the survival time were performance state, Pugh classification, sex, the area of tumour invasion and continued treatment.     

Evaluation of Model for End Stage Liver Disease (MELD)-based systems as prognostic index for hepatocellular carcinoma

Background:  The Cancer of Liver Italian Program (CLIP) and Japan Integrated Scoring System (JIS) used the Child-Turcotte-Pugh (CTP) score to evaluate the liver function.
Aim:  We aimed to evaluate the performance of Model for End Stage Liver Disease (MELD) based CLIP and JIS to predict the prognosis of hepatocellular carcinoma (HCC).
Methods:  Consecutive patients with HCC who presented to our Hepatoma Clinic from January 2003 to April 2005 were studied. MELD-based CLIP and JIS were generated by replacing the original CTP score with MELD score at three categories (<10, 10–14 and >14).
Results:  Among 471 HCC patients (85.1% males; aged 58.8 ± 12.2 years), 73% had chronic hepatitis B, 37.4% had >1 nodule, 84.1% had tumor size >2 cm, 55.0% had Child's B cirrhosis, 12.7% underwent tumor resection and 20.6% received locoregional therapy. The cumulative survival at 3 and 6 months were 67% and 55%, respectively. For 3-month survival, the area under the receiver operating characteristic curves (AUC) of MELD-CLIP (0.69) and MELD-JIS (0.69) were superior to the original systems (0.64, P  = 0.004 and 0.64, P  = 0.0018, respectively). For 6-month survival, AUC of MELD-CLIP (0.64) and MELD-JIS (0.62) were also superior to the original systems (0.54, P  = 0.003 and 0.59, P  = 0.002, respectively). The MELD-based systems performed best among patients who received locoregional therapy to HCC. Advanced cirrhosis (hypoalbuminemia, hyperbilirubinemia, ascites, coagulopathy and elevated creatinine), and cancer (portal vein thrombosis, elevated alpha-fetoprotein, large and multiple tumors) were associated with higher mortality.
Conclusions:  MELD-based systems performed better than Child-Pugh based systems as prognostic indexes for HCC.     

Evaluation of newly developed combination therapy of intra-arterial 5-fluorouracil and systemic pegylated interferon α-2b for advanced hepatocellular carcinoma with portal venous invasion: preliminary results

Aim:  Prognosis is extremely poor for advanced hepatocellular carcinoma (HCC) in patients with portal invasion. The present study evaluated the efficacy of combined intra-arterial 5-fluorouracil (5-FU) and systemic pegylated interferon (PEG-IFN)α-2b in patients with advanced HCC.
Methods:  The subjects comprised nine HCC patients with portal vein thrombosis treated using subcutaneous administration of PEG-IFNα-2b (50–100 µg on day 1 of every week, for 4 weeks) and intra-arterial infusion of 5-FU (250 mg/day for 5 h on days 1–5 of every week, for 4 weeks). For four patients with hepatitis C virus (HCV) infection, oral administration of ribavirin (400–800 mg/day) was added. At the end of every cycle, response to therapy was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
Results:  Partial response (PR) was observed in seven of nine patients, with stable or progressive disease in the remaining two patients. Tumors were resectable in three patients displaying PR after treatment. Tumor markers decreased significantly after therapy. Serum HCV-RNA titers were markedly decreased and became undetectable in all patients with HCV infection. National Cancer Institute–Common Toxicity Criteria: version 3.0 (NCI-CTC) grade 3 thrombocytopenia was seen in one case at the end of treatment, but was resolved with cessation of treatment. Other adverse effects were manageable.
Conclusion:  Combination therapy with intra-arterial 5-FU and systemic PEG-IFNα-2b may be useful as a palliative treatment for patients with advanced HCC. A prospective controlled trial using a larger population of patients with advanced HCC is needed to evaluate this new combination therapy.     

Abnormality of the hepatic vein waveforms in cirrhotic patients with portal hypertension and its prognostic implications

Background and Aim:  We investigated the prognostic significance of changes in the Doppler hepatic vein (HV) waveforms in cirrhotic patients with portal hypertension and the mechanisms of these changes.
Methods:  A total of 103 consecutive patients were included in this study and their HV waveforms were classified into four types: type I, triphasic waveform; type II, biphasic waveform; type III, biphasic waveform with reduced phasic oscillations; and type IV, a flat waveform.
Results:  Type I was observed in 34, type II in 40, type III in 23, and type IV in six patients. The 5-year survival rates were 90%, 89%, 41%, and 0% in type I, II, III, and IV, respectively. Five variables including the Child–Pugh score, albumin, bilirubin, ascites, and HV waveform significantly correlated with the survival in a univariate analysis. A multivariate analysis only identified the HV waveform (type III and IV) to be an independent prognostic value. Even in Child–Pugh class B patients, the 5-year survival rate for type III or IV was as poor as 26% in comparison to 92% for type I or II. In contrast, in Child–Pugh class C patients, the 5-year survival rate for type I or II was as good as 63% in comparison to 25% for type III or IV. Furthermore, the changes in HV waveforms correlated with the extent of hepatic fibrosis, the increase in portal perfusion per liver volume, or the decrease in portal vascular resistance.
Conclusions:  Analyzing the HV waveforms was thus found to be a simple method for accurately assessing the prognosis in cirrhotic patients with portal hypertension.     

Predictive factors for hepatocellular carcinoma in type 1 autoimmune hepatitis

OBJECTIVE:  Hepatocellular carcinoma (HCC) is an uncommon but serious occurrence in autoimmune hepatitis. Our objective was to determine predictors for this neoplasm to improve screening strategies.
METHODS:  Two hundred twenty-seven patients underwent hepatic ultrasonography and serum alpha fetoprotein determinations at 6–12-month intervals.
RESULTS:  Nine patients developed HCC (4%), and each had cirrhosis ≥73 months prior to the malignancy (mean, 110 ± 7 months). By univariate Cox analysis, features at accession associated with a higher risk of HCC were: male gender (Hazard Ratio [HR] 7.0, 95% Confidence Interval [CI] 1.87–26.1, P = 0.004), history of blood transfusion (HR 5.6, 95% CI 1.51–21.1, P = 0.01), thrombocytopenia (HR 7.3, 95% CI 1.89–28.3, P = 0.004), ascites (HR 23.8, 95% CI 4.65–121.8, P = 0.0001), esophageal varices (HR 7.9, 95% CI 1.96–31.8, P = 0.004), and any sign of portal hypertension (HR 19.1, 95% CI 3.91–93.3, P = 0.0003). Features after accession associated with a higher risk of malignancy were: treatment for ≥3 yr (HR 7.6, 95% CI 1.25–18.2, P = 0.02), worsening laboratory tests during corticosteroid therapy (HR 7.6, 95% CI 1.81–32.1, P = 0.006), and cirrhosis for ≥10 yr (HR 8.4, 95% CI 1.69–41.9, P = 0.009).
CONCLUSIONS:  Male gender, features of portal hypertension, history of blood transfusions, immunosuppressive treatment for ≥3 yr, treatment failure, and cirrhosis of ≥10 yr duration identify patients at risk for HCC. These risk factors should focus screening in autoimmune hepatitis.     

Small airways obstruction syndrome in clinical practice

Background and objective:   Small airways obstruction syndrome (SAOS) is a particular pulmonary function test (PFT) pattern showing decreased VC and FEV₁ but a normal FEV₁/VC ratio and TLC. The significance of this syndrome in clinical practice has not been comprehensively investigated.
Methods:   This study retrospectively identified all patients who had performed PFT that showed a SAOS pattern at a university teaching hospital over 1 year. A simple algorithm for differential diagnosis was developed and validated.
Results:   Of the 3207 PFT performed, 153 (4.8%) showed a pattern indicating SAOS. Among these, a final diagnosis was confirmed for 85 (63.4%) of the patients. The causes of SAOS included both restrictive and obstructive lung diseases with the leading causes being early interstitial lung disease ( n  = 20; 23.3%), chest wall deformity ( n  = 12; 14.1%) and asthma ( n  = 10; 11.6%). Using a cut-off point of TLC of <95% predicted value to identify restrictive ventilatory defects ( P  = 0.002) and of ≥95% predicted combined with RV/TLC ≥55% to identify obstructive ventilatory defects ( P  < 0.001), a simplified algorithm with good accuracy (86.6%) was identified. Validation in an independent group showed accuracy of 91%.
Conclusions:   The PFT pattern called SAOS is not uncommon. The most common causes of SAOS were early interstitial lung disease, chest wall deformity and asthma. A diagnostic algorithm was proposed, which may help physicians' decision-making in their daily practice.     

The preoperative positivity for serum hepatitis B e antigen did not affect overall survival after curative resection of hepatitis B virus-related hepatocellular carcinoma

Background and Aim:  Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified.
Methods:  A total of 190 Hepatitis B surface antigen-positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease-free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (≤14 months) and late (>14 months) intrahepatic recurrence.
Results:  The 5-year disease-free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease-free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson–Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post-recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence.
Conclusions:  The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long-term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated.     

Long-term outcome following successful pulmonary vein isolation: pattern and prediction of very late recurrence

Background:  Despite encouraging results of pulmonary vein isolation (PVI) ablation for atrial fibrillation (AF), it is unclear whether there is genuine cure or there is an important attrition rate. We sought to determine the long-term outcome of the initial responders who experienced a prolonged AF-free complete response.
Methods:  From a series of 350 consecutive patients who underwent PVI for AF, 264 patients (75%) (males 71%, age 57 ± 12 years, paroxysmal AF 87%) who demonstrated ≥1 year AF-free follow-up on no antiarrhythmic drugs were followed for 1–5 years.
Results:  During 28 ± 12 months follow-up, 23 of 264 (8.7%) patients had recurrence of AF. The actuarial recurrence at 2 years postablation was 5.8% and increased to 25.5% at 5 years. Compared with long-term responders, more patients with late recurrence had hypertension (HR = 2.18, P = 0.009) and hyperlipidemia (HR = 4.01, P = 0.0005). Among 18 patients with recurrent AF necessitating repeat PVI, 15 (83%) required re-isolation of > 1 PV and 28 of 45 (58%) PVs showed reconnection. All PVs were re-isolated and five (28%) patients had additional linear ablation. All 15 patients became AF-free again.
Conclusions:  Although most patients following PVI remain AF-free, some patients develop "late" recurrence of AF. The "late" recurrence patients are more likely to have hypertension and hyperlipidemia. Most late recurrences are associated with PV reconnections. Our observations emphasize the importance of continued long-term vigilance for AF recurrence, and also raise concerns regarding the need for long-term anticoagulation therapy.     

Correlation of routinely used coagulation parameters and presence of portal vein thrombosis in patients with liver cirrhosis

Aim:  Portal vein thrombosis (PVT) is a serious complication in patients with liver cirrhosis. In patients with advanced stages of liver cirrhosis plasmatic coagulation and platelet count are often reduced. However, patients with normal coagulation status might carry a high risk for developing PVT. A correlation between coagulation status used in clinical routine and the incidence of PVT in patients with liver cirrhosis has been evaluated in the present retrospective analysis.
Methods:  88 patients with liver cirrhosis were identified by screening a database. Of these patients, 23 suffered from PVT. Patients were classified according to the Child–Pugh classification. Patients were subdivided into early stages (Child A) and advanced stages (Child B/C) of liver cirrhosis.
Results:  In patients with Child–Pugh A cirrhosis, there was no difference in activated partial thromboplastin time (apTT), international normalized ratio (INR), and platelet count between the PVT ( n  = 7) and the control group ( n  = 35). In contrast, the median apTT and INR were significantly lower in patients with Child B/C cirrhosis and PVT ( n  = 16) in comparison with patients without PVT (37 s vs 43 s [ P  = 0.017] and 1.25 vs 1.40 [ P  = 0.022]), respectively. Platelet count did not differ significantly in patients with advanced liver cirrhosis and PVT from those without PVT.
Conclusion:  Patients with advanced liver cirrhosis and PVT displayed lower apTT and INR compared with those without PVT. Therefore, patients with advanced liver cirrhosis and almost normal coagulation parameters might be at particular risk of developing PVT. The results suggest that regular monitoring using Doppler-ultrasound should be carried out in these patients, especially when liver transplantation is intended.     

Incidence and clinical presentation of portal vein thrombosis in cirrhotic patients

BACKGROUND: Portal vein thrombosis (PVT) is due to many risk factors, but its pathogenesis is still not clearly understood. To identify the risk factors for PVT, we analyzed the clinical characteristics and complications associated with PVT in cir-rhotic patients.
METHODS: We studied patients with liver cirrhosis who were admitted to our unit from April 2009 to December 2014. The patients were divided into the PVT and non-PVT groups, and were compared by variables including gender, age, the etiology of cirrhosis, stage of cirrhosis, complications, imaging, and treatment.
RESULTS: PVT was found in 45 (9.8%) of 461 cirrhotic pa-tients admitted to our hospital. Most patients (45.9%) had hepatitis B virus (HBV)-related cirrhosis, with a similar dis-tribution of etiologies between the groups. However, there was no positive relationship between PVT and etiologies of cirrhosis. Most patients (71.5%) were in the stage of hepatic decompensation. No statistically signiifcant differences were found in complications including esophageal varices, ascites, and hepatic encephalopathy between the groups. However, there was a signiifcant positive correlation between hepatocel-lular carcinoma (HCC) and PVT (P<0.01). In 30 patients with PVT, thrombosis occurred in the portal vein and/or portal branches, 37.8% were diagnosed on ultrasound.
CONCLUSIONS: The incidence of PVT was 9.8%, mainly in patients with HBV-related cirrhosis. The development of PVT was associated with the severity of liver disease and HCC.     

Adult to pediatric living donor liver transplantation for portal cavernoma

Aim:  Portal cavernoma (PC) is an important cause of non-cirrhotic portal hypertension with severe complications, such as variceal hemorrhage in pediatric patients. With the development of new surgical techniques, living donor liver transplantation (LDLT) has recently been recognized as a viable but challenging treatment option for PC. The purpose of the present study was to summarize the efficacy of LDLT in PC patients and to carry out a follow-up study of pediatric recipients.
Methods:  The primary indication for LDLT in our research was PC with severe variceal bleeding and liver function decompensation. Three patients were diagnosed with PC following evaluation with computed tomography angiography and abdominal color Doppler ultrasonography (CDU).
Results:  Various surgical techniques, including jump bypass grafting for portal vein anastomosis, were carried out according to the range and degree of cavernous transformation within the splenic vein and superior mesenteric vein. Postoperative CDU confirmed the early integrity of the portal vein (PV) in each patient. PV rethrombosis occurred in one patient 7 days after LDLT, despite anticoagulation therapy with coumadin. Two of the three patients had no further episodes of variceal hemorrhage during the 2-year follow-up period.
Conclusions:  The present study is the first report of the successful use of LDLT to treat pediatric PC patients. We conclude that LDLT is effective for the majority of pediatric patients with PC.     

Neural cadherin overexpression is a predictive marker for early postoperative recurrence in hepatocellular carcinoma patients

Background and Aim:  Recent studies have disclosed alterations in neural and/or epithelial cadherin (E-cadherin) expression in several epithelial tumors. However, the clinical relevance of these phenomena in hepatocellular carcinoma (HCC) remains to be established. In this study, we investigated the expression patterns of neural and epithelial cadherins and their clinical implications in HCC.
Methods:  Immunohistochemical staining for neural and epithelial cadherins was performed on tumor and adjacent non-tumor tissue sections of 52 HCC patients subjected to curative surgical resection. Clinical, radiological, and histopathological characteristics were analyzed, relative to the degree of neural and E-cadherin expression.
Results:  The neural cadherin (N-cadherin) expression was upregulated in 67% of HCC tissues, compared to adjacent non-tumoral liver tissues. Patients expressing high levels of N-cadherin experienced more frequent tumor recurrences within 2 years (50% vs 12.5%; P  = 0.01) after surgical resection. Consequently, the cumulative overall survival rate tended to be lower in patients overexpressing N-cadherin ( P  = 0.08). The N-cadherin overexpression was the only independent predictive factor for postoperative recurrence within 2 years in both univariate and multivariate analyses (odds ratio: 8.5; 95% confidence interval: 1.625–44.46; P  = 0.011). No correlation was evident between E-cadherin expression patterns and clinicopathological parameters.
Conclusion:  The overexpression of N-cadherin is significantly related to postoperative recurrence within 2 years after surgical resection in HCC. Therefore, immunohistochemical staining for N-cadherin may be effectively applied as a predictive marker for early postoperative recurrence in HCC.