OBJECTIVE -To determine the association between nonalcoholic fatty liver disease and the risk for development of diabetes.RESEARCH DESIGN AND METHODS -We conducted an observational cohort study in male workers Ն40 years old in a Japanese company from 1997 to 2005. We excluded workers with alcohol intake Ն20 g/day and those with impaired glucose tolerance by a 75-g oral glucose tolerance test. The remaining 3,189 workers were classified into fatty liver (FL) and non-FL group based on the findings of abdominal ultrasonography. Both groups were followed for the development of diabetes. Hazard ratio (HR) was determined in Cox proportional hazard analysis. A nested case-control study was conducted to determine the odds ratio (OR).RESULTS -The average age of participants was 48.0 years at the entry, and the average follow-up period was 4.0 years. The incidence of diabetes in the FL group was 2,073 per 100,000 person-years (65 cases), whereas 452 per 100,000 person-years (44 cases) in the non-FL group. The age-and BMI-adjusted HR of diabetes associated with FL was 5.5 (95% CI 3.6 -8.5, P Ͻ 0.001). In the nested case-control analysis, the OR adjusted for age and BMI was 4.6 (3.0 -6.9, P Ͻ 0.001).CONCLUSIONS -Nonalcoholic fatty liver disease significantly increases the risk of diabetes in middle-aged Japanese men. Diabetes Care 30:2940-2944, 2007N onalcoholic fatty liver disease (NAFLD) has become the most common disease of chronic liver damage, with increased prevalence of obesity, diabetes, and metabolic syndrome in the U.S. (1-3). The prevalence of NAFLD is increasing in Japan because of the westernization of the lifestyle, such as a high-fat and high-calorie diet and less physical activity (4). The high prevalence of fatty liver in association with type 2 diabetes has been reported (5,6).NAFLD is characterized by significant lipid deposition in hepatocytes in patients without history of excessive alcohol intake and is often associated with obesity (7), type 2 diabetes (8,9), dyslipidemia (10), and hypertension (11). Although they are often categorized as the insulin resistance syndrome or the metabolic syndrome (12), each of these individual abnormalities carries a risk of cardiovascular disease. In addition, diabetes, insulin resistance, and increased plasma fatty acids are considered to increase the risk for NAFLD (13,14), and each of these metabolic factors is also characteristic of type 2 diabetes. It has been reported that NAFLD influences severity of hepatic insulin resistance in type 2 diabetes (15). Moreover, NAFLD was correlated with hepatic insulin resistance independently of obesity and intra-abdominal adiposity among nonobese men without type 2 diabetes (16).Increased prevalence of NAFLD in relation to the development of diabetes has been reported in a cross-sectional study (17), and a close relationship between liver enzymes and diabetes has been reported in cohort studies (18 -23). However, the former does not prove a causal relationship, and the latter does not directly pay attention to NAFLD. There is...

A 66‐year‐old man was admitted to our department due to cholestatic liver injury. He had received five cycles of pembrolizumab for small‐cell lung cancer. Imaging showed the possibility of sclerosing cholangitis (SC) with hemobilia. Histologically, CD8+ T cells had infiltrated the biliary epithelium of the extrahepatic bile duct. We reached the diagnosis of secondary SC induced by pembrolizumab. Although we treated him with high‐dose corticosteroids, laboratory data showed only a moderate response. Clinicians should recognize that immune checkpoint inhibitors can sometimes cause severe and irreversible SC.

Background A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear. Objective This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC. Patients and Methods This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA ( n = 186) or LEN ( n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed. Results After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007). Conclusions ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-022-00921-x.

A 74-year-old man was hospitalized due to hematemesis. Upper gastrointestinal endoscopy revealed a very large and dark red mass in the cardiac region of the stomach that extended from the upper esophagus. A biopsy specimen showed hemorrhagic tissue and no malignant cells. The tumor-like region ulcerated at 5 days after the administration of intravenous lansoprazole at a dose of 30 mg twice a day and resolved with scar formation at 2 months after a change to oral rabeprazole at a dose of 10 mg/day.We diagnosed the patient with gastroesophageal submucosal hematoma. Gastroesophageal submucosal hematoma is a rare complication. In this case, we could follow the process of its disappearance by endoscopy.

criterion of fasting plasma glucose (FPG) for the diagnosis of diabetes mellitus in 1997 (1). The point was to diagnose diabetes with a reduced cut-off value of FPG (126 mg/dl) that corresponds to the 2-h plasma glucose (2-h PG) value of 200 mg/dl in the oral glucose tolerance test (OGTT). More recently, the Japan Diabetes Society published a report on the classification and diagnostic criteria of diabetes mellitus (2). Hyperglycemia due to liver cirrhosis (specific mechanismand diseases) was included in the classification and the same cutoff value of FPGwas adopted. However, here we report findings indicating that the FPGlevel is insufficient for the diagnosis of diabetes in patients with liver cirrhosis. FPG and 2-h PG during OGTTswere analyzed in 60 subjects with compensated liver cirrhosis by hepatitis C virus (HCV). Diagnosis of diabetes was done according to WHOcriteria (3) and HCV-positive cirrhosis was diagnosed by 1) the existence of HCVantibody, 2) liver deformity shown by an ultrasonography and/or a CT scan, 3) decreased synthetic liver function shown by serum albumin and prothrombin time, 4) absence of icterus, ascites or esophageal varices. The mean age was 67±8 years (mean±SD), and BMI, 22.5±3. 1 kg/m2. Scatterplots of FPGand 2-h PG and linear regression analysis showed that FPG of 107 mg/dl (95% CI: 71-143 mg/dl) was a corresponding value for 2-h PG of 200 mg/dl. The sensitivity and specificity to diagnose diabetes with FPGwere calculated. In addition, accuracy, defined as the sum of true-positive and true-negative subjects divided by the total number of the subjects, was determined. The sensitivity was 0.64 and 0.50, the specificity was 0.87 and 0.97, and the accuracy was 0.78 and 0.80, for the 107 and 126 mg/dl cutoff points, respectively. The 2 FPG cut-off points showed similar accuracy. In addition, 9 out of 42 patients whose FPGs were normal (<1 10 mg/dl) were classified as diabetic. Wetherefore assume that the FPGcriterion is not applicable for cirrhotic patients.Patients with cirrhosis have been shownto be insulin resistant both in muscle and liver tissues (4). This maycause a more marked elevation in 2-h PG levels. If cirrhotic patients are suspected to have postprandial hyperglycemia, an OGTTwould be recommended at lower FPG levels (<1 10 mg/dl). Another point we like to emphasize is that the patients with compensated liver cirrhosis are usually asymptomatic and without detailed blood test and special examinations, they would be regarded as normal individuals. It is highly recommendedthat subjects with occult liver disease undergo a screening for diabetes. Furthermore, since the recent development of the treatment has remarkably improved the prognosis of cirrhosis, diabetic vascular complications in cirrhosis with long-standing postprandial hyperglycemia cannot be overlooked.

A 56-year-old woman with rheumatoid arthritis treated with methotrexate (MTX) was admitted to our hospital due to multiple liver tumors. Contrast-enhanced computed tomography (CT) revealed multiple hypovascular masses, and 18F-fluorodeoxyglucose positron emission tomography CT showed diffuse abnormal accumulation in the liver only. We therefore made a diagnosis of MTX-related primary hepatic lymphoma (MTX-PHL) exhibiting features of diffuse large B-cell lymphoma. Although MTX has been reported to increase the risk of lymphoproliferative disorders, MTX-PHL has not been reported previously. The present case is the first case in which MTX appears to have been involved in the development of PHL.

A 37-year-old man was diagnosed with Wilson disease at the age of 14. His first manifestations were neurological. He was treated with trientine for more than 10 years and suffered from anemia and liver dysfunction. Wilson disease is a genetic disorder characterized by accumulation of copper in the body. Excess copper is toxic, but copper is an essential trace element. Copper-binding ceruloplasmin is important for iron metabolism. Excess copper chelating treatment-induced anemia and iron deposition in the liver was suspected. Proper monitoring of copper status is important for the management of Wilson disease.

Aims: Antiplatelet therapy has been reported to reduce liver fibrosis and hepatocellular carcinoma (HCC), and has exhibited antitumor properties in other cancers. However, the effects of antiplatelet therapy after diagnosis of HCC are unknown. We investigated the effects of antiplatelet therapy on prognosis, tumor progression, liver function and safety in HCC patients. Methods: We retrospectively analyzed 772 HCC patients. Antiplatelet therapy was defined as the regular intake of aspirin or clopidogrel from HCC diagnosis through to an endpoint of either overall survival (OS) or liver-related death. Overall survival, liver-related death, tumor progression, Child–Pugh deterioration and hemorrhage were analyzed for patients who either had or had not undertaken antiplatelet therapy. Results: The numbers of patients who did and did not undertake antiplatelet therapy were 111 and 661, respectively. Patients who undertook antiplatelet therapy were older and had better liver function at diagnosis. Antiplatelet therapy resulted in significant improvements in OS (p < 0.01) and lower risk of liver-related death (p < 0.01). Multivariate Cox regression analysis revealed that antiplatelet therapy had a significant negative association with liver-related death (hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.44–0.93, p = 0.02). In patients who underwent transcatheter arterial chemoembolization (TACE) as the first treatment, antiplatelet therapy prevented tumor progression (p < 0.01) and Child–Pugh deterioration (p < 0.01). Antiplatelet therapy did not increase the risk of hemorrhagic events. Conclusions: Antiplatelet therapy reduced liver-related death and improved OS safely in HCC patients.