Youichi Morimoto

Measurement of Spleen Stiffness by Acoustic Radiation Force Impulse Imaging Identifies Cirrhotic Patients With Esophageal Varices

BACKGROUND & AIMS We evaluated whether spleen stiffness (SS), measured by acoustic radiation force impulse imaging, can identify patients who have esophageal varices (EVs); those without EVs would not require endoscopic examination. METHODS In a prospective study, we measured SS and liver stiffness (LS) in 340 patients with cirrhosis undergoing endoscopic screening for EVs and 16 healthy volunteers (controls) at the Kurashiki Central Hospital in Okayama, Japan. The diagnostic accuracy of SS for the presence of EVs was compared with that of other noninvasive parameters (LS, spleen diameter, and platelet count). Optimal cutoff values of SS were chosen to confidently rule out the presence of varices. RESULTS Patients with cirrhosis had significantly higher SS and LS values than controls (P < .0001 and P < .0001, respectively). Levels of SS were higher among patients with EVs (n = 132) than controls, and values were highest among patients with high-risk EVs (n = 87). SS had the greatest diagnostic accuracy for the identification of patients with EVs or high-risk EVs compared with other noninvasive parameters, independent of the etiology of cirrhosis. An SS cutoff value of 3.18 m/s identified patients with EVs with a 98.4% negative predictive value, 98.5% sensitivity, 75.0% accuracy, and 0.025 negative likelihood ratio. An SS cutoff value of 3.30 m/s identified patients with high-risk EVs with a 99.4% negative predictive value, 98.9% sensitivity, 72.1% accuracy, and 0.018 negative likelihood ratio. SS values less than 3.3 m/s ruled out the presence of high-risk varices in patients with compensated or decompensated cirrhosis. SS could not be measured in 16 patients (4.5%). CONCLUSIONS Measurements of SS can be used to identify patients with cirrhosis with EVs or high-risk EVs. A cutoff SS was identified that could rule out the presence of varices and could be used as an initial noninvasive screening test; UMIN Clinical Trials Registry number, UMIN000004363.

Comparison of Combined Transcatheter Arterial Chemoembolization and Radiofrequency Ablation with Surgical Resection by Using Propensity Score Matching in Patients with Hepatocellular Carcinoma within Milan Criteria

PURPOSE To retrospectively compare the outcome of combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained. From January 2000 to December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107 men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who underwent TACE-RFA or SR were enrolled if they met the following inclusion criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to three nodules smaller than 3 cm without vascular invasion or extrahepatic metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS) and disease-free survival (DFS) rates were compared after adjustment with propensity score matching. RESULTS After this adjustment, OS rates were comparable between the groups (P = .393), but DFS was superior in the SR group (P < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS and DFS rates in the SR group were significantly higher than those in the TACE-RFA group (P < .001 and P = .008, respectively). However, adjustment with propensity score matching yielded comparable OS and DFS rates between the two groups (P = .348 and P = .614, respectively). CONCLUSION TACE-RFA may be a viable alternative treatment for early-stage HCC when SR is not feasible.

Portal Hypertension in Patients with Liver Cirrhosis: Diagnostic Accuracy of Spleen Stiffness.

PURPOSE To evaluate the accuracy of spleen stiffness (SS) and liver stiffness (LS) measured by using acoustic radiation force impulse imaging in the diagnosis of portal hypertension in patients with liver cirrhosis, with the hepatic venous pressure gradient (HVPG) as a reference standard. MATERIALS AND METHODS Institutional review board approval and informed consent were obtained for this prospective single-center study. From February 2012 to August 2013, 60 patients with liver cirrhosis (mean age, 70.8 years; age range, 34-88 years; 34 men, 26 women) with HVPG, LS, and SS measurements and gastrointestinal endoscopy and laboratory data were included if they met the following criteria: no recent episodes of gastrointestinal bleeding, no history of splenectomy, no history of partial splenic embolization, no history of β-blocker therapy, and absence of portal thrombosis. The efficacy of the parameters for the evaluation of portal hypertension was analyzed by using the Spearman rank-order correlation coefficient and receiver operating characteristic (ROC) curve analysis. RESULTS The correlation coefficient between SS and HVPG (r = 0.876) was significantly better than that between LS and HVPG (r = 0.609, P < .0001). The areas under the ROC curve of SS for the identification of clinically important portal hypertension (HVPG ≥ 10 mm Hg), severe portal hypertension (HVPG ≥ 12 mm Hg), esophageal varices (EVs), and high-risk EVs were significantly higher (0.943, 0.963, 0.937, and 0.955, respectively) than those of LS, spleen diameter, platelet count, and platelet count to spleen diameter ratio (P < .05 for all). SS could be used to accurately rule out the presence of clinically important portal hypertension, severe portal hypertension, EVs, and high-risk EVs (negative likelihood ratios, 0.051, 0.056, 0.054, and 0.074, respectively). CONCLUSION SS is reliable and has better diagnostic performance than LS for identifying portal hypertension in liver cirrhosis.

Outcomes after curative treatment for cryptogenic cirrhosis-associated hepatocellular carcinoma satisfying the Milan criteria.

Background and Aim:  The prognosis of cryptogenic cirrhosis‐associated hepatocellular carcinoma (CC‐HCC) was reported to be poor because many of them were discovered at the advanced stage. The aim of this study is to reveal the clinical features of early CC‐HCC.

Measurement of Spleen Stiffness With Acoustic Radiation Force Impulse Imaging Predicts Mortality and Hepatic Decompensation in Patients With Liver Cirrhosis

BACKGROUND & AIMS: Hepatic venous pressure gradient can predict mortality and hepatic decompensation in patients with cirrhosis. Measurement of hepatic venous pressure gradient requires an invasive procedure; therefore, prognostic markers are needed that do not require invasive procedures. We investigated whether measurements of spleen stiffness, made by acoustic radiation force impulse (ARFI) imaging, associated with mortality and decompensation in patients with cirrhosis, compared with liver stiffness and other markers. METHODS: We measured spleen stiffness in 393 patients diagnosed with cirrhosis (based on histologic or physical, laboratory, and radiologic findings) at a hospital in Japan from September 2010 through August 2013 (280 patients with compensated and 113 patients with decompensated cirrhosis). Patients underwent biochemical, ARFI, ultrasonography, and endoscopy evaluations every 3 or 6 months to screen for liver‐related complications until their death, liver transplantation, or the end of the study period (October 2015). The primary outcome was the accuracy of spleen stiffness in predicting mortality and decompensation, measured by Cox proportional hazards model analysis. We compared spleen stiffness with other noninvasive parameters using the Harrell’s C‐index analysis. RESULTS: During a median follow‐up period of 44.6 months, 67 patients died and 35 patients developed hepatic decompensation. In the multivariate analysis, spleen stiffness was an independent parameter associated with mortality, after adjustment for levels of alanine aminotransferase and serum sodium, and the model for end‐stage liver disease score (P < .001). Spleen stiffness was associated independently with decompensation after adjustment for Child–Pugh score and model for end‐stage liver disease score (P < .001). Spleen stiffness predicted mortality and decompensation with greater accuracy than other parameters (C‐indexes for predicting mortality and decompensation were 0.824 and 0.843, respectively). A spleen stiffness cut‐off value of 3.43 m/s identified the death of patients with a 95.3% negative predictive value and 75.8% accuracy. A spleen stiffness cut‐off value of 3.25 m/s identified patients with decompensation with a 98.8% negative predictive value and 68.9% accuracy. CONCLUSIONS: Spleen stiffness, measured by ARFI imaging, can predict death of patients with cirrhosis with almost 76% accuracy and hepatic decompensation with almost 70% accuracy. It might be a useful noninvasive test to predict patient outcome. UMIN Clinical Trials Registry no. UMIN000004363.

Prediction of oesophageal variceal bleeding by measuring spleen stiffness in patients with liver cirrhosis

Letter to the Editor We read with interest the guidelines by Tripathi et al 1 and the leading article by Rosselli et al ,2 reporting the role of transient elastography for the diagnosis of oesophageal varices (OV). Before screening endoscopy, non-invasive measures are needed to ascertain cirrhotic patients at high risk for oesophageal variceal bleeding (OVB) to decrease the number receiving unnecessary prophylactic treatments. In our recent study,3 spleen stiffness (SS) evaluated by acoustic radiation force impulse (ARFI) imaging was shown to be closely correlated with the presence of OV. This study aimed to evaluate SS determined by ARFI imaging as a predictor of OVB. We measured SS in 446 cirrhotic patients and followed them prospectively at Kurashiki Central Hospital between 2010 and 2014. We examined the diagnostic accuracy of SS for predicting OVB …

Diagnostic Accuracy of Laparoscopic Liver Biopsy in Chronic Liver Diseases, Comparison of Laparoscopic and US‐Guided Liver Biopsy Results

Liver biopsies were carried out using three different needles, a Vim‐Silverman needle 2.5 mm in outer caliber, an 18‐Gauge (18G) Majima needle, and a 17‐Gauge (17G) Majima needle. The biopsies were obtained from nearby locations on the liver surface under laparoscopic observation, to ascertain differences in histological diagnosis according to the size of the biopsy specimen. The biopsy specimens obtained with the Vim‐Silverman needle were wider than those obtained with the other two needles. The agreement in histological diagnoses of the liver, obtained with the Vim‐Silverman needle versus the 18G Majima needle, was 26.0%, while that between the Vim‐Silverman needle and the 17G Majima needle was 40.0%. Histological diagnosis tended to be underestimated in small biopsy specimens in advanced chronic liver diseases. A questionnaire survey, conducted in 92 hospitals affiliated with Okayama University Medical School, revealed US‐guided liver biopsy to be the practice of choice in 57 of 92 (62.0%) hospitals, and 18G needles were used in US‐guided liver biopsy in 35 of 78 (45.2%) hospitals.

Repeated Laparoscopy of 27 Patients with Chronic Non‐A, Non‐B Hepatitis Showing a Complete Response to IFN Therapy

The laparoscopies and liver histology results of 27 patients with chronic non‐A, non‐B hepatitis who had a complete response to the longterm administration of IFN‐alpha were studied. When comparing the liver surface before IFN therapy, code number 1 using Shimadas classification, i. e., whitish markings, increased from 14.0% to 57.9%, code number 2, i. e., dilated vessels, decreased from 34.9% to 10.6%, code number 4, i. e., reddish markings, decreased from 11.6% to 2.6%, and code number 7, i. e., patchy markings, decreased from 16.3% to 2.6%. Improvement of the liver edge dullness and a decrease of the liver consistency after the IFN therapy were also observed in 40. 7%, and 14. 8% of the patients, respectively. Liver histology after the therapy showed normal liver or liver fibrosis in chronic hepatitis patients, and liver cirrhosis with active hepatitis developed into liver cirrhosis without activity. The hepatitis activity index score decreased significantly after the therapy. The present report seems to be the first which describes detailed changes of the liver surface before and after IFN therapy in patients with chronic non‐A, non‐B hepatitis who had a complete response to the therapy

Dynamic relationship between urea and glutamine synthesis in the mechanism of ammonia detoxication: A tracer study using15NH4Cl in fulminant hepatic failure rats

SummaryFulminant hepatic failure (FHF) was produced in rats with intraperitoneal injection of Dgalactosamine.15NH4C1 (50 mg/kg of body weight) was injected into the rats via the tail vein. Arterial blood was drawn before and 5,15, 30, 60 min after the injection of15NH4C1.15N-ammonia, -urea, and-glutamine (amide and amino) were determined by gas chromatography and mass spectrometry. The plasma15N-ammonia level was higher but decreased more rapidly in the FHF rats than in the control rats. This suggests that in FHF rats, the systemic vascular pool of ammonia is enlarged and ammonia clearance from blood is increased. The incorporation of15N into urea was significantly different between the two groups. In FHF rats, the plasma urea-15N level rose 5 min after the injection, decreased at 15 min and was elevated again up to 60 min after injection. This biphasic change suggests that in FHF rats the incorporation of15N into the extrahepatic glutamine pool is accelerated up to 15 min and that after 30 min a larger volume of glutamine-amide-15N is transferred to the urea cycle.

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development

AIM To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients. METHODS CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy. RESULTS Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/mL before therapy and in non-SVR patients showing AFP ≥ 5 ng/mL before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/mL before therapy and no decrease in AFP to < 5 ng/mL 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/mL before therapy and decreased AFP (P = 0.043). AFP ≥ 5 ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/mL before therapy than in those showing AFP ≥ 5 ng/mL. CONCLUSION The criteria of AFP < 5 ng/mL before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.