Akihide Masumoto

Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis

The predictive role of antinuclear antibodies (ANAs) remains elusive in the long‐term outcome of primary biliary cirrhosis (PBC). The progression of PBC was evaluated in association with ANAs using stepwise Cox proportional hazard regression and an unconditional stepwise logistic regression model based on the data of 276 biopsy‐proven, definite PBC patients who have been registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). When death of hepatic failure/liver transplantation (LT) was defined as an end‐point, positive anti‐gp210 antibodies (Hazard ratio (HR) = 6.742, 95% confidence interval (CI): 2.408, 18.877), the late stage (Scheuers stage 3, 4) (HR = 4.285, 95% CI:1.682,10.913) and male sex (HR = 3.266, 95% CI: 1.321,8.075) were significant risk factors at the time of initial liver biopsy. When clinical progression to death of hepatic failure/LT (i.e., hepatic failure type progression) or to the development of esophageal varices or hepatocellular carcinoma without developing jaundice (Total bilirubin < 1.5 mg/dL) (i.e., portal hypertension type progression) was defined as an end‐point in the early stage (Scheuers stage 1, 2) PBC patients, positive anti‐gp210 antibodies was a significant risk factor for hepatic failure type progression [odds ratio (OR) = 33.777, 95% CI: 5.930, 636.745], whereas positive anti‐centromere antibodies was a significant risk factor for portal hypertension type progression (OR = 4.202, 95% CI: 1.307, 14.763). Histologically, positive anti‐gp210 antibodies was most significantly associated with more severe interface hepatitis and lobular inflammation, whereas positive anticentromere antibodies was most significantly associated with more severe ductular reaction. Conclusion: These results indicate 2 different progression types in PBC, hepatic failure type and portal hypertension type progression, which may be represented by positive‐anti‐gp210 and positive‐anticentromere antibodies, respectively. (HEPATOLOGY 2007;45:118–127.)

β1 Integrins Play an Essential Role in Adhesion and Invasion of Pancreatic Carcinoma Cells

Summary: To investigate the role of β1 integrins in pancreatic carcinoma invasion, we analyzed the relationship between the activity of β1 integrins and the invasive ability of human pancreatic carcinoma cell lines. AsPC1, BxPC3, PANC1, SU8686, KP1NL, KP2, and H48N cells had high expression of β1 an

Development of Sjögren's syndrome during treatment with recombinant human interferon-alpha-2b for chronic hepatitis C

A 63-year-old woman with type C chronic active hepatitis developed Sjögrens syndrome after being treated with recombinant interferon-alpha-2b. After 3 months interferon-alpha administration, serum levels of γ-globulin (4.5 g/dl) and titers of antinuclear and anti-SS-A antibodies were greatly increased, anti-SS-B antibody appeared, and the erythrocyte sedimentation rate was elevated. Although no xerostomia was exhibited, the patient experienced conjunctival dryness. Schirmers test showed reduced lacrimal gland function and a gum test showed reduced salivary gland function. Sialography revealed scattered pools of retained contrast media with a diameter of around 1–2 mm. Based on these findings, a diagnosis of Sjögrens syndrome was made. This present case may provide important information regarding the pathogenesis of Sjögrens syndrome.

Plasma nitrite/nitrate concentrations as a tumor marker for hepatocellular carcinoma.

Since plasma concentrations of nitrite/nitrate, the stable end-products of nitric oxide, increase in patients with hepatocellular carcinoma (HCC) correlatively to tumor volume, we examined the ability of plasma nitrite/nitrate to discriminate between those patients with HCC and those without and compared the diagnostic performance of the parameter with that of serum alpha-fetoprotein (AFP) concentrations. Plasma nitrite/nitrate and serum AFP concentrations were measured using a Griess reaction and a solid phase enzyme immunoassay, respectively. Eighty-nine patients with chronic liver diseases (CLD) with (n=39) or without HCC (n=50) and 50 healthy control subjects participated in the study. A receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value and accuracy. The areas under ROC curves for nitrite/nitrate and AFP were calculated to be 0.758 and 0.812, respectively, which were not significantly different. There was no correlation between the concentrations of plasma nitrite/nitrate and serum AFP. The sensitivity, the specificity, and diagnostic efficiency were 79.5, 72.0, and 75.3%, respectively, for nitrite/nitrate, and 74.4, 76.0, and 75.3%, respectively, for AFP. Based on a partial ROC curve, the clinical utility of plasma nitrite/nitrate as a tumor marker approximated that of serum AFP, but exceeded in AFP-negative patients. Indeed, nitrite/nitrate was positive in 70% of AFP-negative HCC patients. The simultaneous determinations of serum AFP and plasma nitrite/nitrate concentrations gave significant improvement in detection of HCC in CLD patients compared with that of serum AFP alone.

Recurrent subcutaneous abscess of the sternal region in ulcerative colitis.

ABSTRACTAn 18-yr-old female patient with extensive ulcerative colitis suffered from several episodes of recurrent aseptic subcutaneous abscesses of the sternal region with a course paralleling that of her colitis. The abscess seemed to occur secondarily to osteomyelitis of the sternum, which is a manifestation of the synovitis, acne, pustulosis, hyperostosis, and osteomyelitis (SAPHO) syndrome.

Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma: Japanese subgroup analysis of the REACH trial

AbstractBackgroundREACH evaluated ramucirumab in the second-line treatment of patients with advanced hepatocellular carcinoma. In the intent-to-treat population (nxa0=xa0565), a significant improvement in overall survival (OS) was not observed. In patients with an elevated baseline α-fetoprotein (AFP) level (400xa0ng/mL or greater), an improvement in OS was demonstrated. An analysis of the Japanese patients in REACH was performed.MethodsAn analysis was performed with the subset of the intent-to-treat population enrolled in Japan (nxa0=xa093).ResultsThe median OS was 12.9xa0months for the ramucirumab arm (nxa0=xa045) and 8.0xa0months for the placebo arm (nxa0=xa048) [hazard ratio (HR) 0.621 (95xa0% confidence interval (CI) 0.391–0.986); Pxa0=xa00.0416]. The median progression-free survival was 4.1xa0months for the ramucirumab arm and 1.7xa0months for the placebo arm [HR 0.449 (95xa0% CI 0.285–0.706); Pxa0=xa00.0004]. The objective response rates were 11xa0% for the ramucirumab arm and 2xa0% for the placebo arm (Pxa0=xa00.0817). The grade 3 or higher treatment-emergent adverse events occurring in more than 5xa0% of patients with a higher incidence for the ramucirumab arm (nxa0=xa044) than for the placebo arm (nxa0=xa047) were ascites (7% vs 2xa0%), hypertension (7xa0% vs 2xa0%), and cholangitis (7xa0% vs 0xa0%). In patients with a baseline AFP level of 400xa0ng/mL or greater, the median OS was 12.9xa0months for the ramucirumab arm (nxa0=xa020) and 4.3xa0months for the placebo arm (nxa0=xa022) [HR 0.464 (95xa0% CI 0.232–0.926); Pxa0=xa00.0263].ConclusionsIn the Japanese patients in REACH, ramucirumab treatment improved OS, including in patients with a baseline AFP level of 400xa0ng/mL or greater; improvements in progression-free survival and objective response rate were also demonstrated. The safety profile of ramucirumab was acceptable and well tolerated in Japanese patients.n ClinicalTrials.gov identifier NCT01140347.

Effects of lamivudine on serum albumin levels correlate with pretreatment HBV-DNA levels in cirrhotic patients

BackgroundLamivudine treatment has been recently demonstrated to increase the serum albumin levels in cirrhotic patients with hepatitis B virus (HBV) infection, but the precise mechanism remains unclear. We hypothesized that the improvement of hypoalbuminemia by lamivudine may be attributable to the reduction of HBV replication itself, rather than to cessation of hepatitis. In order to confirm this hypothesis, in this study we evaluated factors which correlated with the increase in serum albumin levels. Fifty-four patients (Child-Pugh A/B/C, 35/9/10) with HBV-related liver cirrhosis who had been treated with lamivudine for more than 12 months were evaluated. We analyzed the correlation between the increase in serum albumin levels at month 12 after starting treatment (Δ-albumin) and various pretreatment variables. We also analyzed the correlation between Δ-albumin and the reduction in serum levels of HBV-DNA (Δ-HBV-DNA) or alanine aminotransferase (Δ-ALT) at month 12.ResultsThe average Δ-albumin was 0.38 g/dL and only serum HBV-DNA levels before treatment correlated significantly with Δ-albumin. We also analyzed the correlation in patients whose alanine aminotransferase levels were normalized after 12 months so that the possible influence of breakthrough hepatitis could be excluded. Even among this subgroup of patients, there was no significant correlation between Δ-albumin and either pretreatment alanine aminotransferase levels or Δ-ALT. In contrast, in patients whose serum HBV-DNA was undetectable at month 12, we found a significant correlation between Δ-albumin and both pretreatment serum HBV-DNA levels and Δ-HBV-DNA.ConclusionOur results demonstrated that albumin levels are associated with pretreatment HBV-DNA but not with alanine aminotransferase levels.

Efficacy of tolvaptan for the patients with advanced hepatocellular carcinoma

AIM To investigate the factors influenced the efficacy of tolvaptan (TLV) in liver cirrhosis. METHODS We retrospectively enrolled 61 consecutive patients with refractory hepatic ascites. All of them had been treated with furosemide and spironolactone before admission, and treated with TLV for 7 d in our hospital. The effect of TLV was defined by the rate of body weight loss, and the factors that influenced TLV efficacy were analyzed using multiple regression. RESULTS Coexistent hepatocellular carcinoma (HCC) was the only significant predictive variable that attenuated the efficacy of TLV. In stratified analysis, high doses of furosemide decreased the efficacy of TLV in patients with HCC, and increased efficacy in those without HCC. In the latter, a high Child-Pugh-Turcotte score had a positive influence and a high concentration of lactate dehydrogenase had a negative influence on the effectiveness of TLV. CONCLUSION Development of ascites may differ between patients with liver failure and those with HCC progression. A sufficient preceding dose of furosemide decreases diuretic effect of TLV.

Prognostic factors associated with mortality in patients with gastric fundal variceal bleeding

AIM To determine the prognostic factors associated with mortality in patients with gastric fundal variceal (GFV) bleeding. METHODS In total, 42 patients were endoscopically diagnosed with GFV bleeding from January 2000 to March 2014. We retrospectively reviewed the patients medical records and assessed their history, etiology of liver cirrhosis, disease conditions, treatment options for GFV bleeding, medications administered before and after onset of GFV bleeding, blood test results (hemoglobin, albumin, and bilirubin concentrations), and imaging results (including computed tomography and abdominal ultrasonography). We also assessed the prognostic factors associated with short-term mortality (up to 90 d) and long-term mortality in all patients. RESULTS Multivariate analysis showed that prophylactic administration of antibiotics was an independent prognostic factor associated with decreases in short-term mortality (OR = 0.08, 95%CI: 0.01-0.52) and long-term mortality (OR = 0.27, 95%CI: 0.08-0.91) in patients with GFV bleeding. In contrast, concurrent hepatocellular carcinoma (HCC) and regular use of proton pump inhibitors (PPI) were independent prognostic factors associated with increases in short-term mortality (HCC: OR = 15.4, 95%CI: 2.08-114.75; PPI: OR = 12.76, 95%CI: 2.13-76.52) and long-term mortality (HCC: OR = 7.89, 95%CI: 1.98-31.58; PPI: OR = 10.91, 95%CI: 2.86-41.65) in patients with GFV bleeding. The long-term overall survival rate was significantly lower in patients who regularly used PPI than in those who did not use PPI (P = 0.0074). CONCLUSION Administration of antibiotics is associated with decreased short- and long-term mortality, while concurrent HCC and regular PPI administration are associated with increased short- and long-term mortality.

The prognostic role of lactate dehydrogenase serum levels in patients with hepatocellular carcinoma who are treated with sorafenib: the influence of liver fibrosis

BACKGROUNDnSerum lactate dehydrogenase (LDH) levels could be a prognostic factor for sorafenib-treated patients with several types of solid tumor because it reflects hypoxic circumstances in aggressive tumors. For hepatocellular carcinoma (HCC), however, the prognostic role of LDH has been controversial. Liver fibrosis can potentially cause hypoxia in the liver, which has not been previously studied in the patients with advanced HCC. Thus, we aimed to analyze the prognostic role of LDH based on the degree of fibrosis.nnnMETHODSnEighty-nine consecutive patients with HCC (Child-Pugh class A) who were treated using sorafenib were enrolled into this study. Pretreatment characteristics and changes in hepatic functional tests based on early response to sorafenib and serum LDH levels were analyzed. The degree of fibrosis was estimated using the aspartate aminotransferase (AST) to platelet ratio index (APRI), and the tumor response was evaluated after 3 months of sorafenib treatment.nnnRESULTSnOverall, five patients discontinued sorafenib within 4 weeks. For the other 84 patients, those with progressive disease (PD) had significantly high pretreatment LDH levels, which correlated with the APRI score but not with the tumor stage. Multivariate logistic analysis revealed that older age and lower pretreatment LDH levels were independent prognostic factors for a better response to sorafenib. In patients who discontinued sorafenib early, three experienced acute liver failure accompanied with an increase in serum LDH.nnnCONCLUSIONSnWe demonstrated that baseline serum LDH levels in HCC patients were affected by liver fibrosis but not by the tumor stage, and these LDH levels could be a marker for early response to sorafenib. A marked increase in serum LDH levels during sorafenib administration might also indicate subsequent acute liver failure. Close observation of serum LDH levels before and during sorafenib treatment could be useful in managing treatment of patients receiving this therapy.