Yohei Koizumi

Liver Fibrosis in Patients with Chronic Hepatitis C: Noninvasive Diagnosis by Means of Real-time Tissue Elastography—Establishment of the Method for Measurement

PURPOSE To prospectively measure liver stiffness with real-time tissue elastography in patients with chronic hepatitis C and to compare the results with those of clinical assessment of fibrosis by using histologic stage as the reference standard. MATERIALS AND METHODS All subjects gave informed consent, and the study was approved by the institutional ethics committee. Seventy hospitalized patients (46 men, 24 women; mean age, 65.5 years ± 11.7 [standard deviation]; age range, 33-87 years) with chronic hepatitis C underwent real-time elastography between January 2009 and September 2009. Elastography was performed at four liver locations by two independent observers. The elastic ratio (ratio of the value in the intrahepatic venous small vessels divided by the value in the hepatic parenchyma) was calculated and was compared with histologic fibrosis stage at liver biopsy. The elastic ratio and clinical fibrosis markers were assessed by using receiver operating characteristic (ROC) analysis. The differences between body site and observers were assessed with κ statistics and intraclass correlation coefficients (ICCs). RESULTS Real-time tissue elastography cutoff values were 2.73 for F of 2 or greater, 3.25 for F of 3 or greater, and 3.93 for F of 4. No site differences were observed (κ = 0.835, ICC = 0.966), and the elastic ratio measurement was correlated between the two examiners (r(2) = 0.869, P < .0001). The areas under the ROC curves for elastic ratio, hyaluronic acid, type IV collagen, aspartate aminotransferase-to-platelet ratio index, FibroIndex, Forns score, and Hepascore were 0.95, 0.32, 0.73, 0.76, 0.76, 0.87, and 0.70, respectively; the elastic ratio performed better than the serum fibrosis markers and other scores. CONCLUSION Real-time tissue elastography is not invasive and could be used to evaluate liver fibrosis in patients with chronic hepatitis C. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100319/-/DC1.

Real‐time tissue elastography for evaluation of hepatic fibrosis and portal hypertension in nonalcoholic fatty liver diseases

The aim of this study was to prospectively measure liver stiffness with real‐time tissue elastography in patients with nonalcoholic fatty liver diseases (NAFLD) and to compare the result with the clinical assessment of fibrosis using histological stage. One hundred and eighty‐one prospectively enrolled patients underwent real‐time tissue elastography, with the first 106 being analyzed as the training set and the remaining 75 being evaluated as the validation set. Hepatic and splenic elastic ratios were calculated and compared with stage of histological fibrosis. Portal hypertension (PH) was assessed. Real‐time tissue elastography cut‐off values by stage in the training set were 2.47 for F1, 2.67 for F2, 3.02 for F3, and 3.36 for F4. Using these cut‐off values, the diagnostic accuracy of hepatic fibrosis in the validation set was 82.6%‐96.0% in all stages. Only portal fibrosis correlated with the hepatic elastic ratio by multivariate analysis. The area under the receiver operating characteristic curve of elastic ratio better correlated than serum fibrosis markers in both early and advanced fibrosis stages. Patients with PH, defined by splenic elasticity, had early fibrosis. Patients with severe PH were found only in the group with cirrhosis. Conclusion: Real‐time tissue elastography is useful in evaluating hepatic fibrosis and PH in patients with NAFLD. (HEPATOLOGY 2012)

Splenic Elasticity Measured with Real-time Tissue Elastography Is a Marker of Portal Hypertension

PURPOSE To prospectively correlate spleen elasticity and degree of portal hypertension estimated with the hepatic venous pressure gradient (HVPG) and to evaluate splenic elasticity as a predictor of gastroesophageal varices. MATERIALS AND METHODS The institutional review board approved this study, and patients provided written informed consent. In a pilot study of 60 patients with chronic liver damage, the authors measured liver and spleen elasticity with real-time tissue elastography (RTE), obtained serum markers related to fibrosis, examined hepatic and splenic blood flow with duplex Doppler ultrasonography, estimated HVPG, and performed upper gastrointestinal endoscopy. Then, with use of thresholds determined in the pilot study, the authors conducted a validation trial with another 210 patients, performing all studies except the measurement of HPVG. The relationship between HVPG and the other parameters was analyzed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the diagnosis of gastroesophageal varices were calculated by using cutoff values obtained from receiver operating characteristic curves. RESULTS Among the parameters associated with HVPG, correlation was closest with splenic elasticity (R = 0.854, P < .0001). When 8.24 was selected as the cutoff of splenic elasticity for predicting HVPG of more than 10 mm Hg, the accuracy of diagnosing gastroesophageal varix was 90% (sensitivity, 96%; specificity, 85%; PPV, 83%; NPV, 97%). The results of the validation trial showed that the 8.24 cutoff for splenic elasticity was associated with a diagnostic accuracy of 94.8% (sensitivity, 98%; specificity, 93.8%; PPV, 82.1%; NPV, 99.4%) for gastroesophageal varices. CONCLUSION Splenic elasticity determined with RTE is the most closely associated parameter for evaluating HVPG and is useful as a clinical marker of portal hypertension and a predictive marker of gastroesophageal varices.

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients

Background and Aim:  With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (≥ 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively.

Hepatic Elasticity in Patients With Ascites: Evaluation With Real-Time Tissue Elastography

OBJECTIVE Transient elastography is a rapid, noninvasive, and reproducible approach to assessment of liver fibrosis by measurement of liver elasticity. However, transient elastographic measurements are of limited utility in patients with ascites or severe obesity. The aim of this study was to determine whether measurements of liver stiffness with real-time tissue elastography can be altered for patients with ascites. SUBJECTS AND METHODS The subjects were 54 patients being treated at a university hospital between January and December 2009. In 42 patients, real-time tissue elastography to evaluate liver stiffness was performed before and after injection to produce artificial ascites for radiofrequency ablation. The other 12 patients had ascites due to cirrhosis, and liver stiffness was measured with real-time tissue elastography before and after control of ascites. RESULTS Elastic ratios evaluated with real-time tissue elastography did not differ significantly before and after injection for artificial ascites or before and after control of ascites. This ratio was the same for patients with and those without cirrhosis and was unaffected by distance between the body surface and the targeted liver area. Stable values thus were measured with real-time tissue elastography. CONCLUSION Liver stiffness can be measured reproducibly with real-time tissue elastography even in patients with ascites. This method has the potential of being superior to transient elastography for assessment of liver stiffness, particularly in patients with decompensated cirrhosis.

Contrast‐enhanced sonography with abdominal virtual sonography in monitoring radiofrequency ablation of hepatocellular carcinoma

Contrast‐enhanced CT is regarded as the gold standard for monitoring radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). Recently, 3‐dimensional volume data from CT have been used to create cross‐sectional multiplanar reconstruction images. Using this technique, we can reconstruct 2‐dimensional CT images identical in orientation to ultrasound (US) images, which we call virtual sonographic (VUS) images. The present prospective randomized control trial compared the number of CT scans needed to assess the efficacy of RFA of HCC using VUS‐contrast‐enhanced ultrasonography (CEUS) versus CT.

Muscle volume loss as a prognostic marker in hepatocellular carcinoma patients treated with sorafenib

To elucidate the clinical significance of muscle wasting in regard to survival of hepatocellular carcinoma (HCC) patients undergoing sorafenib treatment, we evaluated prognostic factors including muscle wasting at the start of sorafenib treatment.

Mass Reduction by Radiofrequency Ablation Before Hepatic Arterial Infusion Chemotherapy Improved Prognosis for Patients With Huge Hepatocellular Carcinoma and Portal Vein Thrombus

OBJECTIVE The prognosis for patients with advanced large hepatocellular carcinoma (HCC) with portal vein (PV) tumor thrombosis remains poor, and treatment is usually limited to hepatic arterial infusion (HAI) chemotherapy. In this study, we first performed mass reduction using radiofrequency ablation (RFA), followed by HAI chemotherapy. Prognosis after this treatment was evaluated. SUBJECTS AND METHODS HCC with PV tumor thrombosis was diagnosed in 20 patients between April 2004 and December 2008, and treatment was performed using mass-reduction therapy by RFA before HAI chemotherapy. For comparison, 33 patients treated with HAI chemotherapy without RFA were retrospectively selected as historical control subjects under the same conditions. Prognosis in each group was evaluated. RESULTS Mass-reduction therapy by RFA combined with HAI chemotherapy achieved complete response in six patients (30%), partial response in 11 patients (55%), stable disease in two patients (10%), and progressive disease in one patient (5%). Among the control subjects, complete response was seen in 0 patients (0%), partial response in 12 patients (33.3%), stable disease in 16 patients (44.4%), and progressive disease in eight patients (22.2%). The cumulative survival rates for those who received the combined therapy at 6, 12, and 24 months were 100%, 89.7%, and 78.8%, respectively. The median survival was 953 days (95% CI, 760-1,102 days). In the control subjects, the cumulative survival rates at 6, 12, and 24 months were 84.9%, 56.1%, and 16.9%, respectively (p < 0.0001). No serious adverse events were encountered in either group. CONCLUSION For patients with huge HCC and PV tumor thrombosis, mass-reduction treatment by RFA before HAI chemotherapy is safe and can improve prognosis.

Nonalcoholic Fatty Liver Disease: Portal Hypertension Due to Outflow Block in Patients without Cirrhosis

PURPOSE To prospectively evaluate whether the characteristics of hepatic blood flow change during the early stages of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS All participants provided written informed consent, and the study protocols were approved by the institutional ethics committee. A total of 121 patients with NAFLD that was diagnosed at histologic examination were enrolled. Hepatic blood flow was measured by means of Doppler ultrasonography (US), and the ratio of arterial to portal blood flow (arterioportal ratio) was calculated. Elasticity of the spleen was measured by means of real-time tissue elastography. The elastic ratio was measured as the value in the small splenic vessel divided by the value of the splenic parenchyma. The arterioportal ratio and splenic elasticity were compared in patients with all stages of fibrosis (F0-F4) and with all levels of platelet counts. Correlations among the resistive index of the hepatic artery and that of the splenic artery, the fibrosis 4 index, hepatic elasticity, arterioportal ratio, splenic elasticity, and platelet counts were analyzed. Univariate and multivariate logistic regression analyses were performed. Correlations in patients with platelet counts greater than 200 000/μL also were analyzed. RESULTS The mean ± standard deviation arterioportal ratio was significantly higher at fibrosis stage 2 (2.4 ± 0.6) than at fibrosis stage 0 (1.8 ± 0.4) in patients with NAFLD (P < .01). Increased splenic stiffness at earlier stages of fibrosis also was observed in patients with NAFLD (fibrosis stage 2, 4.4 ± 2.3; fibrosis stage 0, 3.2 ± 1.9; P < .05). In patients with NAFLD with platelet counts higher than 200 000/μL, pericellular fibrosis was the only significant predictor of hepatic hemodynamic change at multivariate analysis (odds ratio, 7.17; 95% confidence interval: 1.33, 57.13; P = .021). CONCLUSION Change in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD because of outflow block in the sinusoidal area.

Des-gamma-carboxy prothrombin identified by P-11 and P-16 antibodies reflects prognosis for patients with hepatocellular carcinoma

Serum des‐γ‐carboxy prothrombin (DCP) is an established tumor marker in patients with hepatocellular carcinoma (HCC), which can be identified by using MU‐3 antibody. The MU‐3 antibody mainly reacts with the 9–10 glutamic acid residues of DCP (conventional DCP). Since other variants of DCP with fewer glutamic acid residues can be detected using P‐11 and P‐16 antibodies (code name: NX‐PVKA), we examined the clinical characteristics associated with NX‐PVKA, and whether NX‐PVKA is a useful measure in HCC patients.