Noninvasive estimation of liver fibrosis and response to interferon therapy by a serum fibrogenesis marker, YKL-40, in patients with HCV-associated liver disease

AIM: To evaluate the clinical utility of serum fibrosis markers,including YKL-40, in patients with HCV-associated liver disease.METHODS: A total of 109 patients with HCV-associated liver disease were enrolled. We measured serum type Ⅳ collagen, amino-terminal peptide of type Ⅲ procollagen (PⅢP),hyaluronic acid (HA), YKL-40 levels and biochemical.Parameters by RIA or ELISA. Eighty-eight patients underwent liver biopsy, and 67 of 109 patients received interferon (IFN)therapy. We also investigated the relationship between the concentrations of serum fibrosis markers and histological fibrosis scores (METAVIR), and evaluated the changes of the levels of fibrosis markers before and after the IFN therapy.RESULTS: The increase in serum levels of all markers,particularly HA, was correlated with the progression of liver fibrosis (for type Ⅳ collagen, F= 9.076, P＜0.0001; for PⅢP,F= 9.636, P＜0.0001; for HA, F= 13.128, P＜0.0001; and for YKL-40, F= 8.016, P＜0.0001). YKL-40 had strong correlation with HA (r= 0.536, P＜0.0001). Based on the receiver operating curve (ROC), the ability of serum HA exceeded the abilities of other serum markers to determine fibrosis score 4 from fibrosis score 0-3 (AUC = 0.854). While YKL-40 was superior to other fibrosis markers for predicting severe fibrosis (F2-F4) from mild fibrosis (F0-F1) (YKL-40, AUC = 0.809;HA, AUC = 0.805). After IFN therapy, only YKL-40 values significantly decreased not only in the responder group,but also in the nonresponder group (P = 0.03).CONCLUSION: YKL-40 may be a useful non-invasive serum marker to estimate the degree of liver fibrosis and to evaluate the efficacy of IFN therapies in patients with HCV-associated liver disease.

Portal hypertensive colopathy in patients with liver cirrhosis

AIM: In patients with liver cirrhosis and porlal hypertension, portal hypertensive colopathy is thought to be an important cause of lower gastrointestinal hemorrhage. In this study, we evaluated the prevalence of colonic mucosal changes in patients with liver cirrhosis and its clinical significance. METHODS: We evaluated the colonoscopic findings and liver function of 47 patients with liver cirrhosis over a 6-year period. The main cause of liver cirrhosis was post-viral hepatitis (68%) related to hepatitis B (6%) or C (62%)infection. All patients underwent upper gastrointestinal endoscopy to examine the presence of esophageal varices, cardiac varices, and congestive gastropathy, as well as a full colonoscopy to observe changes in colonic mucosa. Portal hypertensive colopathy was defined endoscopically in patients with vascular ectasia, redness, and blue vein. Vascular ectasia was classified into two types: type 1, solitary vascular ectasia; and type 2, diffuse vascular ectasia.RESULTS: Overall portal hypertensive colopathy was present in 31 patients (66%), including solitary vascular ectasia in 17 patients (36%), diffuse vascular ectasia in 20 patients (42%), redness in 10 patients (21%) and blue vein in 6 patients (12%). As the Child-Pugh class increased in severity, the prevalence of portal hypertensive colopathy rose. Child-Pugh class B and C were significantly associated with portal hypertensive colopathy. Portal hypertensive gastropathy, esophageal varices, ascites and hepatocellular carcinoma were not related to occurrence of portal hypertensive colopathy. Platelet count was significantly associated with portal hypertensive colopathy, but prothrombin time, serum albumin level, total bilirubin level and serum ALT level were not related to occurrence of portal hypertensive colopathy. CONCLUSION: As the Child-Pugh class worsens and platelet count decreases, the prevalence of portal hypertensive colopathy increases in patients with liver cirrhosis. A colonoscopic examination in patients with liver cirrhosis is indicated, especially those with worsening Child-Pugh class and/or decreasing platelet count, to prevent complications such as lower gastrointestinal bleeding.

Functional expression of a proliferation-related ligand in hepatocellular carcinoma and its implications for neovascularization

AIM: To detect the expression of a proliferation-related ligand on human hepatocellular carcinoma (HCC) cell lines (SK-Hep1, HLE and HepG2) and in culture medium.METHODS: APRIL expression was analyzed by Western blotting in HCC cell lines. Effects of APRIL to cell count and angiogenesis were analyzed, too.RESULTS: Recombinant human APRIL (rhAPRIL) increased cell viability of HepG2 cells and, in HUVEC, rhAPRIL provided slight tolerance to cell death from serum starvation. Soluble APRIL (sAPRIL) from HLE cells increased after serum starvation, but did not change in SK-Hep1 or HepG2 cells. These cells showed down-regulation of VEGF after incubation with anti-APRIL antibody.Furthermore, culture medium from the HCC cells treated with anti-APRIL antibody treatment inhibited tube formation of HUVECs.CONCLUSION: Functional expression of APRIL might contribute to neovascularization via an upregulation of VEGF in HCC.

Basket pattern blood flow signals discovered in a case of splenic hamartoma by power Doppler ultrasonography

We present the gray-scale ultrasonography (GSUS), power Doppler ultrasonography (PDUS), abdominal computed tomography (CT), and magnetic resonance imaging (MRI) findings for a case of splenic hamartoma in a 27-year-old man, showing a ψ 50 mm homogeneous, iso- and hypo-echoic splenic mass with evidence of a small plural cystic lesion.This splenic hamartoma showed increased vascularity on power Doppler sonograms. PDUS showed multiple circular blood flow signals inside the mass (i.e. a basket pattern),which was consistent with the small plural cystic lesion shown by GSUS. Spectral analysis also confirmed arterial and venous flow. CT scans showed that the mass had lowdensity relative to the normal spleen and MRI showed that the mass was isodense, relative to the normal spleen.Therefore, CT and MRI are not useful for the diagnosis of splenic hamartoma. Ultrasonography can be used to diagnose splenic hamartoma without administration of a contrast material and therefore is an indispensable method for the diagnosis of splenic hamartoma.

Risk factors for the recurrence of hepatocellular carcinoma after radiofrequency ablation of hepatocellular carcinoma in patients with hepatitis C

AIM: To analyze the risk factors of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation (RFA) treatment with HCV-associated hepatitis. METHODS: Twenty-six patients with HCV-associated HCC who were followed-up for more than 12 mo were selected for this study. Risk factors for distant intrahepatic recurrences of HCC were evaluated for patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule. Twelve clinical and tumoral factors were examined: Age, gender, nodule diameter, number of primary HCC nodule, Child-Pugh classification, serum platelet, serum albumin, serum AST, post RFA AST, serum ALT, post RFA ALT, post RFA treatment.RESULTS: Distant recurrences of HCC in remnant liver after RFA were observed in 14 cases and in the number of primary HCC nodules (P = 0.047), and the serum platelets (P = 0.030), the clear difference came out by the recurrence group and the non-recurrence group. The cumulative recurrence rates after 1 and 2 years were30.8% and 86.8%, respectively for primary multinodular HCC, and 15.4% and 29.5% respectively, for primary uninodular HCC. In addition the 1-year recurrence rates for patients with serum albumin more than 3.4 g/dL and less than 3.4 g/dL were 23.1% for both, but the 2-years recurrence rates were 89.0% and 23.1%, respectively. The number of primary HCC nodules (relative risk, 6.970; P = 0.016) were found to be a statistically significant predictor for poor distant intrahepatic recurrence by univariate analysis.CONCLUSION: Patients who have multiple HCC nodules, low serum platelets and low serum albumin accompanied by HCV infection, should be carefully followed because of the high incidence of new HCC lesions in the remnant liver, even if coagulation RFA is complete.

Augmentation of tumor necrosis factor family-induced apoptosis by E3330 in human hepatocellular carcinoma cell lines via inhibition of NFκB

AIM: To investigate the reduction of cell viability in human hepatocellular carcinoma (HCC) cell lines induced by inhibition of nuclear factor κB (NFκB). METHODS: HLE, SKHep1, and HepG2 were incubated and E3330 was used to compare the stimulation of some chemotherapeutic drugs with that of TNF family, Fas ligand, TNFα and TNF-related apoptosis-inducing ligand (TRAIL) at the point of the reduction of cell viability by inhibiting NFκB. RESULTS: E3330 decreased NFκB levels in HLE cells stimulated by TNF and TRAIL. The cytotoxicity of the combination of TRAIL, TNFα, Fas ligand, and E3330 increased synergistically in a dose-dependent manner compared to either E3330 alone in all HCC cell lines by MTT assay. However, the combination of some chemotherapeutic drugs and E3330 did not decrease the cell viability. CONCLUSION: Inhibition of NFκB sensitizes human HCC cell lines to TNF-mediated apoptosis including TRAIL, and TRAIL-based tumor therapy might be a powerful potential therapeutic tool in the treatment of human HCC.

An anomaly in persistent right umbilical vein of portal vein diagnosed by ultrasonography

AIM: To detect the anomaly in the persistent right umbilical vein (PRUV) of portal vein (PV) with deviation of the ligamentum tere and left-sided gallbladder.METHODS: A total of 5783 candidates for routine analysis were evaluated for hepatic vascular abnormalities by ultrasonography.RESULTS: Ten candidates (0.17%) had a portal vein anomaly with a rightward-deviated ligamentum tere.The blood-flow velocity in the PRUV of the portal vein (17.7±3.0 cm/s) of the 10 cases was similar to that of the right anterior portal trunk (17.6±4.1 cm/s). However,the vessel diameter of the PRUV (ψ12.4±4.4 mm) was larger than the right anterior portal trunk (ψ6.1±0.9 mm).Therefore, flow volume in the anomalous portion (0.97±0.30 L/min) was more than that in the right anterior portal trunk (0.18±0.05 L/min).CONCLUSION: The anomaly plays an important role in intra-hepatic PV flow.

Relative predictive factors for hepatocellular carcinoma after HBeAg seroconversion in HBV infection

AIM: To determine the predictive factors forhepatocellular carcinoma (HCC) development in patientsafter spontaneous or therapeutic HBeAg seroconversion.METHODS: In 48 patients who seroconverted to anti-HBe positive during follow-up, the background factors forHCC development were analyzed.RESULTS: HCC was developed in six patients duringfollow-up (average follow-up after HBeAg seroconversion:10.9±5.4 years). The incidence of HCC evaluated byKaplan-Meier analysis was significantly higher in patientswith abnormal aspartate aminotransferase (AST＞40 IU/L) level, lower platelet counts (PLT＜10×104/μL),lower albumin level (Alb＜30 g/L), positive HBV-DNA or older age at seroconversion (＞40 years). However, lower platelet count was the only predictive factor for HCC development shown by multivariate proportional-hazard analysis.CONCLUSION: Active hepatitis or advanced hepatitis at HBeAg seroconversion or progressive hepatitis even after HBeAg seroconversion would be the risk factors for HCC development. These predictive factors should be taken into account in determining the frequency of biochemical study or imaging studies for HCC surveillance.

Hemodynamics in the portal vein evaluated by pulse wave Doppler ultrasonography in patients with chronic hepatitis C treated with interferon

AIM: To employ pulse wave Doppler ultrasonography to evaluate the changes in portal blood flow velocity in patients with chronic hepatitis C (CHC) receiving interferon (IFN)treatment.METHODS: The subjects in this study were 14 patients (13 men and 1 woman) with CHC who received IFN treatment. Portal blood flow velocity was measured in the vessels at the porta hepatis at four time points: before IFN administration (pre-IFN), 2 wk after the start of administration (wk 2), 24 wk after the start of administration (wk 24, i.e.,the end of IFN administration), and 24 wk after the end of administration (wk 48).RESULTS: The patients with CHC in whom IFN treatment resulted in complete elimination or effective elimination of viruses showed a significant increase in portal blood flow velocity at the end of IFN treatment compared with that before IFN treatment. In contrast, when IFN was ineffective, no significant increase in portal bloocl flow velocity was observed at wk 24 or 48 compared with the pre-IFN value. In addition,the patients with CHC in whom IFN was ineffective showed significantly lower portal blood flow velocity values than control subjects at all measurement time points.CONCLUSION: Pulse wave Doppler ultrasonography is a noninvasive and easily performed method for evaluating the effects of IFN treatment in patients with CHC. This technique is useful for measuring portal blood flow velocity before and 24 wk after IFN administration in order to evaluate the changes over time, thus assessing the effectiveness of IFN treatment.

1.5 Harmonic Imaging Sonography with microbubble contrast agent improves characterization of hepatocellular carcinoma

AIM: To investigate the usefulness of 1.5 Harmonic Imaging Sonography with the use of the contrast agent Levovist for the diagnosis of hepatocellular carcinoma (HCC) and for the evaluation of therapeutic response.METHODS: Phantom experiments were performed to compare the contrast effects of 2nd harmonic imaging and 1.5 Harmonic Imaging Sonography. 1.5 Harmonic Imaging Sonography was employed to examine 36 patients with HCC (42 nodules) before and after the treatment and to compare against the findings obtained using other diagnostic imaging modalities. RESULTS: In 1.5 Harmonic Imaging Sonography, the tumor vessels of HCCs were clearly identified during the early phase, and late-phase images clearly demonstrated the differences in contrast enhancement between the tumor and surrounding hepatic parenchyma. Blood flow within the tumor was detected in 36 nodules (85.7%)during the early phase and in all 42 nodules (100%) during the late phase using 1.5 Harmonic Imaging Sonography,in 38 nodules (90.5%) using contrast-enhanced CT, in 34nodules (81.0%) using digital subtraction angiography (DSA), and in 42 nodules (100%) using US CO2angiography.Following transcatheter arterial embolization, 1.5Harmonic Imaging Sonography detected blood flow and contrast enhancement within the tumors that were judged to contain viable tissue in 20 of 42 nodules (47.6%).However, 6 of these 20 cases were not judged in contrastenhanced CT. 1.5 Harmonic Imaging Sonography was compared with the US CO2 angiography findings as the gold standard, and the sensitivity and specificity of these images for discerning viable and nonviable HCC after transcatheter arterial embolization were 100% and 100%,respectively.CONCLUSION: 1.5 Harmonic Imaging Sonography permits the vascular structures of HCCs to be identified and blood flow within the tumor to be clearly demonstrated.Furthermore, 1.5 Harmonic Imaging Sonography is potentially useful for evaluating the therapeutic effects of transcatheter arterial embolization on HCC.

Primary biliary cirrhosis after aortoiliac reconstruction surgery using a Y-graft: A case report

Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by anti-mitochondrial antibodies and destruction of intra-hepatic bile ducts. Though little is known about the etiology of PBC, some reports suggest that xenobiotics and viral infections may induce PBC. We describe a case of PBC after the aortoiliac reconstruction surgery using a Y-graft.

Remission of bronchial asthma after viral clearance in chronic hepatitis C

A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

Cardiac metastases of gallbladder carcinoma

This report describes the case of a 68-year-old woman diagnosed with advanced gallbladder cancer, whose autopsy revealed multiple metastases, including cardiac metastases.

The right hepatic artery syndrome

Various benign and malignant conditions could cause biliary obstruction. Compression of extrahepatic bile duct (EBD) by right hepatic artery was reported as a right hepatic artery syndrome but all cases were compressed EBD from stomach side. Our case compressed from dorsum was not yet reported, so it was thought to be a very rare case. We present here the first case of bile duct obstruction due to the compression of EBD from dorsum by right hepatic artery.

尼可地尔:一种抗心绞痛的钾离子通道开放剂,在慢性冠状动脉疾病患者的左室收缩和舒张功能方面的作用

尼可地尔（硝化2-乙基烟酰胺）是一种强效冠状血管舒张剂，并且它还是一种具有钾离子通道开放作用的烟酰胺衍生物。化学结构上，尼可地尔是一种硝化物。目前为止，尚不明确的是尼可地尔是否能够改善冠状血管疾病患者的左心室机能障碍，尤其是舒张期的左心室机能障碍。本研究的目的是明确尼可地尔对冠状血管疾病患者左心室功能方面的作用，并且与硝酸甘油和硝苯地平做比较。