Tsuyoshi Mashitani

Correlations between serum bilirubin levels and diabetic nephropathy progression among Japanese type 2 diabetic patients: a prospective cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT 5]).

OBJECTIVE To assess the correlations between serum bilirubin levels and diabetic nephropathy development and progression in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Longitudinal data were obtained from 2,511 type 2 diabetic patients registered in a Japanese diabetes registry. To assess the independent correlations between serum bilirubin levels and either the development or progression of diabetic nephropathy, we used logistic regression analysis adjusted for potential confounders. RESULTS The median follow-up period was 503.4 days (range 238–777). The mean patient age, BMI, and HbA1c level was 65.2 years, 24.7 kg/m2, and 7.5% (58.5 mmol/mol), respectively. Baseline serum bilirubin levels were significantly associated with the urinary albumin-creatinine ratio at baseline (P < 0.001) and 1 year after registration (P < 0.001). Multivariable adjusted odds ratios for progression from microalbuminuria to macroalbuminuria for the second, third, and fourth quartile of serum bilirubin levels were 0.89 (95% CI 0.49–1.58), 0.93 (0.47–1.83), and 0.33 (0.13–0.84), respectively, showing a statistically significant linear trend across categories (P = 0.032). However, this trend disappeared after adjustment for hemoglobin levels. CONCLUSIONS Serum bilirubin levels were associated with diabetic nephropathy progression in type 2 diabetic patients independent of possible confounders. Serum bilirubin levels might be the link in the correlation between hemoglobin levels and nephropathy progression.

Elevated Levels of hs-CRP Are Associated With High Prevalence of Depression in Japanese Patients With Type 2 Diabetes: The Diabetes Distress and Care Registry at Tenri (DDCRT 6)

OBJECTIVE Because of the absence of data on the direct association between inflammation and depression in patients with diabetes, we examined the association between hs-CRP levels and the high prevalence of depression in adult patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Cross-sectional data were obtained from 3,573 patients with type 2 diabetes recruited from a Japanese diabetes registry. A multiple logistic regression analysis adjusted for potential confounders was used to assess independent associations between hs-CRP levels and major depression, as defined by the Patient Health Questionnaire-9. RESULTS Mean age, BMI, and HbA1c levels were 66.0 years, 24.6 kg/m2, and 7.4% (57.8 mmol/mol), respectively, and 122 patients (3.4%) suffered from major depression. In the age- and sex-adjusted model, the odds ratio (OR) for major depression was 1.86 (95% CI 1.01–3.42; P = 0.045) in the highest CRP quintile compared with that in the 3rd CRP quintile; however, this association disappeared after adjustment for other possible confounders (OR 1.58 [95% CI 0.85–2.94]; P = 0.148). Among patients with a BMI of ≥25 kg/m2, a significant association was observed between the highest hs-CRP quintile and major depression (multivariable-adjusted OR 2.69 [95% CI 1.09–7.08]; P = 0.032). CONCLUSIONS We observed a significant positive association between high hs-CRP levels and depression in patients with diabetes who had a high BMI.

Patient-reported adherence to insulin regimen is associated with glycemic control among Japanese patients with type 2 diabetes: Diabetes Distress and Care Registry at Tenri (DDCRT 3)

AIMS We investigated the association between self-reported adherence to an insulin regimen and glycemic control in Japanese patients with type 2 diabetes. METHODS Data from 1441 patients with type 2 diabetes who were treated with insulin were obtained from a diabetes registry in Japan. We obtained information on self-reported adherence to an insulin regimen. Relative risk regression analysis was employed to assess the independent association of various demographic factors with good glycemic control (HbA1c<7.0% [53 mmol/mol]) while adjusting for possible confounders. RESULTS The mean age, body mass index, and number of daily insulin injections of participants were 65.4 years, 24.7 kg/m(2), and 2.3, respectively. Of all patients, 70.6% reported high adherence to their insulin regimen. Compared with participants with higher adherence, the crude relative risk of good glycemic control was 0.82 (95% CI, 0.67-1.00) for those with middle adherence and 0.64 (95% CI, 0.31-1.31) for those with lower adherence (P=0.029 for trend). Subgroup analysis confirmed this association in patients below 65 years old, but not in those 65 years old and over. CONCLUSIONS A higher adherence to a daily insulin regimen was associated with a greater likelihood of good glycemic control in Japanese type 2 diabetes patients. This association was not seen in patients of 65 years old or over. Self-reported adherence to an insulin regimen may prove useful in titrating insulin dose in patients in the younger age group, but requires further investigation.

Development of hepatocellular carcinoma in a patient 13 years after sustained virological response to interferon against chronic hepatitis C: a case report

BackgroundAlthough several recent reports have shown that hepatocellular carcinoma (HCC) developed in patients with chronic hepatitis C (CH-C) even after having a sustained virological response (SVR) to interferon (IFN) therapy, it is not common for HCC to develop more than 10 years after SVR.Case presentationA 73-year-old Japanese man with CH-C who achieved SVR to IFN therapy 13 years ago was admitted into our hospital because of huge multiple liver tumors along with marked elevation of the tumor markers. Several diagnostic modalities strongly suggested HCC, and we performed histopathological examination. After confirming the diagnosis as well-differentiated HCC, we successfully treated these tumors with intensive combination therapies.ConclusionOur report highlights the need for careful follow-up for more than 10 years even if the patients with CH-C achieve SVR to IFN therapy.

Serum High-Sensitivity C-Reactive Protein Levels Are Associated With High Risk of Development, Not Progression, of Diabetic Nephropathy Among Japanese Type 2 Diabetic Patients: A Prospective Cohort Study (Diabetes Distress and Care Registry at Tenri [DDCRT7])

OBJECTIVE To assess the prospective association between baseline serum hs-CRP concentration and the subsequent risk of development or progression of diabetic nephropathy. RESEARCH DESIGN AND METHODS Longitudinal data were obtained from 2,518 patients with type 2 diabetes registered in a Japanese diabetes registry. To assess the independent correlations between serum baseline hs-CRP and either the development or progression of diabetic nephropathy 1 year later, the Cox proportional hazards model was used and adjusted for potential confounders. RESULTS The mean patient age, BMI, and HbA1c level were 66.1 years, 24.6 kg/m2, and 7.5% (57.6 mmol/mol), respectively. Baseline serum hs-CRP levels were significantly associated with the urinary albumin-to-creatinine ratio at baseline (P < 0.001). Multivariable adjusted hazard ratio for the development from normoalbuminuria to microalbuminuria was 1.31 (95% CI 0.80–2.17; P = 0.286), 1.55 (1.16–2.08; P = 0.003), and 1.57 (1.22–2.03; P = 0.001), respectively, for the second, third, and fourth quartiles of serum hs-CRP levels, showing a statistically significant linear trend across categories (P < 0.001). We did not observe a significant association between hs-CRP levels and the subsequent risk of diabetic nephropathy progression (P for trend = 0.575). CONCLUSIONS Serum hs-CRP levels, independent of possible confounders, were associated with a subsequent risk of developing, not progressing, diabetic nephropathy in type 2 diabetic patients. Serum hs-CRP may be useful for predicting the future risk of developing diabetic nephropathy.

Predictor variables and an equation for estimating HbA1c attainable by initiation of basal supported oral therapy.

Aims/Introduction:  A method of estimating HbA1c attained after initiation of basal supported oral therapy (BOT) has not been reported previously. The aim of the present study was to determine which characteristics of patients could influence the effectiveness of BOT introduction, and to obtain an equation to estimate HbA1c after BOT initiation.

Clinical significance of the Scheuer histological staging system for primary biliary cholangitis in Japanese patients.

Background Inadequate response to ursodeoxycholic acid (UDCA) is associated with unfavorable outcomes in patients with primary biliary cholangitis (PBC). We aimed to identify surrogate markers for predicting long-term prognosis and biochemical response to UDCA in patients with PBC. Patients and methods In this single-center, retrospective study, 99 patients with PBC were classified into responders (n=53) and nonresponders (n=46) based on reductions in the &ggr;-glutamyl transpeptidase levels at 1 year after initiating UDCA therapy (Nara criteria). We assessed whether the criteria for patentability by different countries are useful in predicting the prognosis of PBC. The accuracy of Scheuer and Nakanuma staging systems in predicting prognosis and treatment response was compared. Results Nara definition had comparable utility to the Paris-II definition for selecting patients in whom UDCA monotherapy can be safely continued. Patients at Scheuer stage 1 had a significantly better prognosis than those at Scheuer stages 3 or 4 (P<0.05 and 0.0001, respectively). Patients at Nakanuma stage 4 had decreased survival compared with those at stage 1 (P<0.05). The proportion of responders to nonresponders was significantly higher in stages 1–3 PBC than in stage 4 PBC, according to both staging systems (P<0.05 for both). All patients with Scheuer stage 4 PBC were nonresponders, whereas only 28.6% (2/7) of those with Nakanuma stage 4 PBC were responders. Conclusion The Scheuer staging system had greater utility in predicting long-term prognosis and UDCA response than the Nakanuma staging system.

Predisposing factors for hepatocellular carcinoma recurrence following initial remission after transcatheter arterial chemoembolization

Hepatocellular carcinoma (HCC) is prone to recurrence following curative treatment. The purpose of the present study was to identify the predisposing factors of HCC recurrence following complete remission achieved by transarterial chemoembolization (TACE). A retrospective cohort study of 70 consecutive patients with HCC who underwent TACE as the initial treatment was conducted. The patients were divided into two groups according to their 1-year disease-free survival (DFS) status; the early recurrence group (ER group; n=32), with HCC recurring within 1 year of initial TACE; and the non-early recurrence group (NER group; n=38), who did not experience recurrence within 1 year. The parameters identified as significantly associated with DFS time on univariate analysis were aspartate aminotransferase (AST), alanine aminotransferase and α-fetoprotein levels, as well as the tumor number (P=0.003, P=0.027, P=0.002 and P=0.005, respectively). Multivariate analysis revealed that AST levels and tumor number were significantly associated with a shorter DFS period (P=0.009 and P=0.038, respectively). The Mantel-Haenszel test revealed a significant trend of decreasing DFS with increasing tumor number. Among the patients with HCC in the ER group, locoregional recurrence occurred more frequently in those who received TACE alone compared with those treated with TACE combined with radiofrequency ablation treatment. In summary, multinodularity of HCC is the most potent predictive factor for the recurrence of HCC within 1 year of initial TACE.

Liver fibrosis progression predicts survival in patients with primary biliary cirrhosis.

The prognosis and natural history of primary biliary cirrhosis (PBC) has improved, and the clinical end‐point for PBC needs to be discovered. We aimed to identify surrogate markers for predicting long‐term prognosis in patients with PBC.

Severe Aplastic Anemia following Parvovirus B19-Associated Acute Hepatitis

Human parvovirus (HPV) B19 is linked to a variety of clinical manifestations, such as erythema infectiosum, nonimmune hydrops fetalis, and transient aplastic anemia. Although a few cases have shown HPVB19 infection as a possible causative agent for hepatitis-associated aplastic anemia (HAAA) in immunocompetent patients, most reported cases of HAAA following transient hepatitis did not have delayed remission. Here we report a rare case of severe aplastic anemia following acute hepatitis with prolonged jaundice due to HPVB19 infection in a previously healthy young male. Clinical laboratory examination assessed marked liver injury and jaundice as well as peripheral pancytopenia, and bone marrow biopsy revealed severe hypoplasia and fatty replacement. HPVB19 infection was diagnosed by enzyme immunoassay with high titer of anti-HPVB19 immunoglobulin M antibodies. Immunosuppressive therapy was initiated 2 months after the onset of acute hepatitis when liver injury and jaundice were improved. Cyclosporine provided partial remission after 2 months of medication without bone marrow transplantation. Our case suggests that HPVB19 should be considered as a hepatotropic virus and a cause of acquired aplastic anemia, including HAAA.