Correlation of Kupffer cell function and hepatocyte function in chronic viral hepatitis evaluated with superparamagnetic iron oxide-enhanced magnetic resonance imaging and scintigraphy using technetium-99m-labelled galactosyl human serum albumin.

Kupffer cells contribute to the pathogenesis of liver injury in chronic liver disease, yet it is difficult to assess Kupffer cell function either ex vivo or in vivo, since supporting data are limited. The aim of this study was to clarify the relation between Kupffer cell function and hepatocyte function by analyzing the correlation between conventional indices of hepatic functional reserve and both superparamagnetic iron oxide-enhanced MRI (SPIO-MRI) and technetium-99m-galactosyl human serum albumin scintigraphy (Tc-99m-GSA) in patients with chronic viral hepatitis. Consecutive 46 patients (16 patients with chronic hepatitis and 30 patients with cirrhosis) who underwent both SPIO-MRI and Tc-99m-GSA were examined. The patients were aged 46-83 years (median 70) and included 29 men and 17 women. Spearman correlation coefficient was used to analyze the correlations between functional reserve indices and both reduction percentages of liver-to-muscle signal intensity ratio (reduction-%LMR), as a surrogate parameter of Kupffer cell function and Tc-99m-GSA parameters. The usefulness of each parameter as a marker to differentiate Child-Pugh A from Child-Pugh B/C was evaluated using receiver operating characteristic (ROC) analysis. The reduction-%LMR correlated more closely with Child-Pugh score (r=0.77; P<0.001) than did Tc-99m-GSA parameters. For predicting Child-Pugh B/C, ROC analysis revealed that reduction-%LMR (AUC=0.91, P<0.001) was the most useful parameter and at a cutoff value of 50% or less, sensitivity, specificity, positive and negative predictive values were 0.79, 0.91, 0.94 and 0.71, respectively. SPIO-MRI may be a helpful non-invasive method for the evaluation of hepatic functional reserve, and this study suggests that Kupffer cell function is closely correlated with hepatocyte function in patients with chronic viral hepatitis.

The ratio of serum placenta growth factor to soluble vascular endothelial growth factor receptor-1 predicts the prognosis of hepatocellular carcinoma.

Angiogenesis plays crucial roles in development and progression of hepatocellular carcinoma (HCC). Placenta growth factor (PLGF), belonging to vascular endothelial growth factor (VEGF) family, is involved in angiogenesis associated with cancer. Soluble VEGF receptor-1 (sVEGFR1) has been thought to be an intrinsic negative regulator for PLGF. We investigated whether serum PLGF and serum sVEGFR1 is associated with prognosis of HCC. Serum PLGF and sVEGFR1 levels were measured in 145 patients with HCC using enzyme-linked immunosorbent assay. The levels of these factors and the ratio of PLGF to sVEGFR1 were analyzed in relation with clinical parameters. The higher level of sVEGFR1 and the lower ratio of PLGF/sVEGFR1 were significantly associated with poor survival in HCC. Cox regression analysis revealed that the lower ratio of PLGF/sVEGFR1 independently correlated to prognosis of patients with HCC. The ratio of PLGF/sVEGFR1 was independent prognostic indicator for HCC. The ratio of PLGF/sVEGFR1 should be addressed in anti-angiogenic therapy for HCC.

Serum C-reactive protein levels predict survival in hepatocellular carcinoma.

BACKGROUND/AIMS: C-reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship between the serum levels of high sensitivity CRP (H-CRP) and the prognosis of HCC patients. METHOD: We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H-CRP (serum H-CRP levels >/=3.0 mg/L, n=47) and those negative for H-CRP (serum H-CRP levels <3.0 mg/L, n=43). We also determined the relationship between serum H-CRP and prognosis in HCC patients. RESULTS: The survival rate of patients of the H-CRP-positive group was lower than that of H-CRP-negative patients. Tumour stage (stages 3 or 4), total bilirubin >/=1.2 mg/dL, albumin (Alb) <3.5 g/dL, des-gamma-carboxy prothrombin >/=40 mAU/mL, positive H-CRP and initial treatment (transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy or best supportive care) were identified as significant poor prognostic factors by univariate analysis, while positive H-CRP [hazard ratio (HR), 1.58; P=0.048], Alb<3.5 g/dL (HR, 2.10; P=0.004), tumour stage (stages 3 or 4; HR, 3.05; P=0.001) and initial treatment (HR, 1.88; P=0.029) were considered to be significant determinants of poor prognosis by multivariate Cox proportional hazards analysis. CONCLUSIONS: The prognosis of H-CRP-positive patients was poorer compared with H-CRP-negative patients. This study confirmed that H-CRP, like CRP, is a marker of poor prognosis in HCC patients.

Temporary indwelling catheter system via the left brachial artery: evaluation in 83 patients with hepatic tumors.

OBJECTIVE: The purpose of our study was to evaluate retrospectively the usefulness and complications associated with a temporary indwelling catheter system through the brachial artery for patients with liver tumors. CONCLUSION: The temporary indwelling catheter system via the left brachial artery can be used not only for CO2-enhanced sonographically guided aspiration biopsy, radiofrequency ablation, and percutaneous ethanol injection, but also for short-term hepatic arterial infusion chemotherapy and transcatheter arterial chemoembolization.

Value of fusing PET plus CT images in hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma patients with extrahepatic metastases: preliminary findings.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). METHODS: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. RESULTS: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. CONCLUSIONS: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

Prophylactic lamivudine administration prevents exacerbation of liver damage in HBe antigen positive patients with hepatocellular carcinoma undergoing transhepatic arterial infusion chemotherapy.

BACKGROUND AND AIMS: Exacerbation of liver damage during transhepatic arterial infusion chemotherapy (THAIC) is a critical complication in patients with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). We previously reported that HBe antigen positivity was the associating factor for the exacerbation of liver damage. In the present study, we investigated the effect of lamivudine administration for exacerbation of liver damage in such patients. PATIENTS AND METHODS: Seventeen patients with HBV-related hepatocellular carcinoma who received THAIC were reviewed. Eight of these patients received lamivudine administration. Nine patients did not receive lamivudine administration. All patients were HBe antigen positive. Liver function tests, liver enzymes, HBV-DNA levels, HBe antigen, HBe antibody, and mutation in the precore and core-promoter regions of HBV DNA were evaluated. RESULTS: In the lamivudine-treated group, HBV-DNA levels were significantly reduced and did not increase throughout chemotherapy. Lamivudine did not induce any changes in precore or core-promoter regions. Although levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), total bilirubin, and prothrombin time (PT) in the lamivudine-treated group did not change, levels of ALT, AST and total bilirubin increased, and PT were prolonged in the untreated group by chemotherapy. No patients receiving lamivudine administration showed exacerbation of liver damage. Exacerbation of liver damage was detected in six patients without lamivudine administration. Of these, three patients died of progressive liver failure due to reactivation of HBV. CONCLUSION: These results indicate that prophylactic lamivudine administration reduces HBV-DNA levels and prevents exacerbation of liver damage throughout the period of chemotherapy in HBe antigen positive patients with hepatocellular carcinoma.