Masahiko Koda

FibroIndex, a practical index for predicting significant fibrosis in patients with chronic hepatitis C

Diagnosis of the stage of liver fibrosis in chronic hepatitis C is essential for making a prognosis and deciding on antiviral therapy. In the present study a simple model consisting of routine laboratory tests was constructed and then validated in cross‐sectional and longitudinal investigations. Consecutive treatment‐naive patients with chronic hepatitis C who had undergone liver biopsy were divided into 2 cohorts: an estimation set (n = 240) and a validation set (n = 120). A longitudinal set consisted of 30 patients who had undergone a liver biopsy twice, before and after IFN treatment. The FibroIndex was derived from the platelet count, AST, and gamma globulin measurements in the estimation set. The areas under the ROC curves of the FibroIndex for predicting significant fibrosis were 0.83 and 0.82 for the validation set, better than those of the Forns index and the aminotransferase‐to‐platelet ratio index (APRI). Using the best cutoff values, whether significant fibrosis was present was diagnosed with high positive predictive values, and 35% of patients could avoid liver biopsy. In the longitudinal set, there was a significant decrease in the FibroIndex of 14 patients whose fibrosis stage improved, and a significant increase in that of 5 patients whose fibrosis stage deteriorated. Change in the FibroIndex correlated significantly with variation in fibrosis stage. There was no such correlation with the Forns index or the APRI. Conclusion: The FibroIndex is a simple and reliable index for predicting significant fibrosis in chronic hepatitis C and could also be used as a surrogate marker during antifibrotic treatment for chronic hepatitis C. (HEPATOLOGY 2007;45:297–306.)

Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma

Percutaneous ethanol injection therapy has been used widely for small hepatocellular carcinoma. This study was undertaken to determine factors predictive of local recurrence or new nodular recurrence in patients with small hepatocellular carcinoma treated with percutaneous ethanol injection.

Combination therapy with transcatheter arterial chemoembolization and percutaneous ethanol injection compared with percutaneous ethanol injection alone for patients with small hepatocellular carcinoma

To assess whether the effectiveness of a combination of transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) is superior to PEI alone in the treatment of patients with small hepatocellular carcinoma (HCC), a randomized controlled study was performed.

Diagnostic value of serum type IV collagen test in comparison with platelet count for predicting the fibrotic stage in patients with chronic hepatitis C

Background and Aim: The serum type IV collagen test is now used as a diagnostic aid for the detection of liver fibrosis and cirrhosis. Recently, a platelet count has been reported to be a useful marker for assessing the fibrotic stage in chronic hepatitis C. The aim of this study was to compare the usefulness of the serum type IV collagen test and platelet count for diagnosing the fibrotic stage in chronic hepatitis C patients.

Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C.

Purpose. Chronic hepatitis C is an insidiously progressive disease, in which repeated assessment of liver histology is required. Various serum fibrotic markers have now been introduced. Our present aim was to assess, by receiver operating characteristic analysis, the usefulness of serum fibrotic markers for diagnosing fibrotic staging and necroinflammatory grading in chronic hepatitis C. Methods. Serum levels of procollagen type III N-terminal peptide (PIIINP), 7S fragment of type IV collagen (PIVNP), hyaluronan (HA), matrix metalloproteinase (MMP)-1, MMP-2, and tissue inhibitor of metalloproteinases (TIMP)-1 were measured in 169 patients with chronic hepatitis C. Results. The accuracy of these tests for discriminating stages greater than F2 from stages less than F1 was superior to that for discriminating stage F3 from stages less than F2. The most useful test for predicting stages greater than F2 was the serum HA test (cutoff value, 50 ng/ml; sensitivity, 75%; specificity, 80%), and the next-most useful was the serum MMP-2 test (cutoff value, 550 ng/ml; sensitivity, 75%; specificity, 70%). The usefulness of these tests for discriminating moderate grade from grades less than mild was superior to that for discriminating grades more than mild from minimal grade. The most useful test for predicting moderate grade was the serum HA test (cutoff value, 60 ng/ml; sensitivity, 77%; specificity, 74%), and the second-most useful was the serum PIVNP test (cutoff value, 6.5 ng/ml; sensitivity, 74%; specificity, 75%). The combination of the most useful and next-most useful test results increased the accuracy of the diagnosis of staging and grading. Conclusions. These serum fibrotic markers, especially the serum HA test, would be clinically useful for assessing staging and grading in patients with chronic hepatitis C.

Clinical significance of serum hyaluronan in patients with chronic viral liver disease

In order to elucidate the clinical significance of serum hyaluronan in chronic viral hepatitis, serum hyaluronan concentrations were measured using a sandwich enzyme binding assay in 115 patients with chronic viral hepatitis. These findings were examined in relation to the results of laboratory liver tests, levels of serum markers for fibrosis and liver histological findings. Serum hyaluronan levels increased with the progress of liver disease, particularly in liver cirrhosis. There were no significant differences in serum hyaluronan levels among the cirrhotic patients according to Childs grade. Multivariate analysis showed that the significant independent predictors of serum hyaluronan were serum aspartate aminotransferase (P= 0.020), serum alanine aminotransferase (P= 0.008), serum cholinesterase (P< 0.001), particularly serum type IV collagen 7S domain (P< 0.0001), and the histological degree of liver fibrosis (P< 0.0001). These findings suggest that elevated serum hyaluronan levels are closely related to the severity of liver fibrosis. We assessed the predictive value of serum hyaluronan in differentiating cirrhosis from chronic hepatitis, constructing receiver operating curves; we found that serum hyaluronan was a better test for diagnosing cirrhosis than serum type IV collagen 7S domain and laboratory liver tests.

Complications of radiofrequency ablation for hepatocellular carcinoma in a multicenter study: An analysis of 16 346 treated nodules in 13 283 patients

Aim:  We surveyed multiple centers to identify types and frequency of complications and mortality rate associated with radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC).

Myocardial injury in patients with chronic hepatitis C infection.

BACKGROUND & AIMS The existence of a direct pathogenic link between hepatitis C virus (HCV) infection and myocardial injury has not been confirmed. We investigated the association between myocardial conditions and HCV in patients with HCV-related chronic hepatitis using thallium-201 myocardial scintigraphy. METHODS In 217 consecutive cases of chronic HCV infection without overt heart disease, we performed electrocardiography (ECG), echocardiography, serum tests on myocardial injury and thallium-201 myocardial scintigraphy. Myocardial injury was confirmed by severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. SS was followed prior to and after interferon (IFN) therapy in 200 patients with chronic hepatitis C. RESULTS An abnormal ECG was found in 9% of the patients with chronic hepatitis C. Abnormal SS was found in 87% of the chronic hepatitis C patients. Independent factors related to higher pretreatment SS were histology activity index score, serum HCV RNA titer, and indocyanine green disappearance rate. After IFN therapy, SS was improved in patients with sustained virologic response. Among relapsers, SS improved at the initial disappearance of HCV RNA, but it worsened with the reappearance of HCV RNA. SS in non-viral responders did not change with IFN therapy. CONCLUSIONS Myocardial perfusion defects were found in 87% of the patients with chronic hepatitis C and improved with viral eradication with IFN therapy.

Comparison of serum 7S fragment of type IV collagen and serum central triple-helix of type IV collagen for assessment of liver fibrosis in patients with chronic viral liver disease

BACKGROUND/AIMS A competitive radioimmunoassay for serum 7S fragment of type IV collagen (7S collagen) using a polyclonal antibody against 7S collagen and a sandwich enzyme immunoassay for serum central triple-helix of type IV collagen (IV collagen) using two monoclonal antibodies against the pepsin-solubilized type IV collagen may be used as diagnostic aids for liver fibrosis in clinical medicine. We compared the clinical usefulness for assessing liver fibrosis of serum 7S collagen and IV collagen tests in chronic viral liver diseases, and also examined the elution pattern of 7S collagen- and IV collagen-related antigens in serum by gel filtration analysis. METHODS Serum 7S collagen and IV collagen levels were assayed in 151 patients with chronic viral liver disease and 30 healthy control subjects. RESULTS Gel filtration on the Sephacryl S400HR column revealed that the 7S collagen antigenicity in serum was heterogeneous, whereas the IV collagen antigen in serum was uniform in size. Serum levels of 7S collagen and IV collagen showed increases closely correlated with the severity of liver disease. The abnormal percentage of 7S collagen in three patient groups was similar to that of IV collagen in the corresponding groups. Serum 7S collagen and IV collagen levels were strongly correlated with the histological degree of liver fibrosis; the correlation coefficients were r = +0.675 for 7S collagen and r = +0.665 for IV collagen. When we assessed the ability of each test to detect cirrhosis with a receiver operating curve, the serum 7S collagen test was a slightly better marker than the serum IV collagen test. For the detection of cirrhosis, serum 7S collagen was 83% sensitive and 88% specific at a cutoff value of 9 ng/ml, and serum IV collagen was 80% sensitive and 81% specific at a cutoff value of 160 ng/ml. CONCLUSIONS These findings suggested that serum 7S collagen and IV collagen tests are similarly useful for assessing liver fibrosis in patients with chronic viral liver disease, although the former is slightly better for diagnosing cirrhosis than the latter.

Hepatic vascular and bile duct injury after ethanol injection therapy for hepatocellular carcinoma

Three patients with serious hepatic vascular injury after percutaneous ethanol injection therapy for hepatocellular carcinoma (HCC) are described. In two cases, immediately after ethanol injection, liver function tests deteriorated and computed tomography (CT) showed a wedge-shaped low-density area due to liver infarction. In the other case, 1 year after ethanol injection, the intrahepatic bile duct in the right lobe was dilated and the right hepatic lobe atrophied. Endoscopic retrograde cholangiography showed stenosis of the main right hepatic duct. Since complications include both acute and delayed vascular injury after ethanol injection, patients should be followed for a long period after treatment.