Relationship between metformin use and lactic acidosis in advanced chronic kidney disease: The REMIND-TMU study.

BACKGROUND: Evidence of metformin-associated lactic acidosis (MALA) in advanced chronic kidney disease (CKD) has been limited due to high mortality rate but rare incidence rate. The mechanism of increased MALA in advanced CKD is mainly based on the hypothesis of decreased drug elimination, which might also be confounded by increased comorbidities as CKD progresses. The goal of the study is to analyze the incidence and associated factors of lactic acidosis between metformin user and non-user with advanced CKD. METHODS: This study used a three million population-based, propensity score-matched cohort from 2008 to 2016. The primary outcome was laboratory-defined lactic acidosis. Relationships between the probability of lactic acidosis and various estimated glomerular filtration rate (eGFR) values in advanced CKD patients were also presented in regression analysis. RESULTS: Adults with type 2 diabetes whose eGFR was <30 mL/min/1.73 m2 were enrolled in this study. After the process of propensity score matching, 7707 patients were divided into metformin and non-metformin groups. In linear regression model, metformin significantly increased the risk of lactic acidosis (p=0.0204) as the eGFR declined in advanced CKD over a mean follow up of over 600 days even after confounder adjustment with age, sex and comorbidities. CONCLUSIONS: Metformin was associated with a significant increased risk of laboratory-defined lactic acidosis (p=0.0204) even after adjusting confounder such as age, sex and underlying comorbidities. This "REMIND" study reminds us that metformin-associated lactic acidosis is mainly caused by decreased drug renal elimination other than underlying comorbidities in advanced CKD patients.

Survival After Treatable Hepatocellular Carcinoma Recurrence in Liver Recipients: A Nationwide Cohort Analysis.

BACKGROUND: Survival after post-transplant recurrence of HCC is dismal, and almost all treatments for recurrent HCC are off-labeled, without an extensive large-scale analysis. We aimed to delineate their post-recurrence courses and define benchmarks for comparing future treatment effectiveness. METHODS: Three national databases, including health insurance, catastrophic illness, and the cause of death, were linked for cohort establishment and data collection during the period from 2005 to 2016. Patients with HCC recurrence ≥6 months after transplant surgery and under treatment were recruited for survival analysis. Selection of treatment strategies for HCC recurrence after liver transplant was based on the same criteria for those without liver transplant. RESULTS: Of 2,123 liver transplant recipients, 349 developed HCC recurrence ≥6 months after liver transplant, and the median recurrence time was 17.8 months post-transplant. Within 2 years of treatment, 61% patients showed recurrence (early recurrence group), and survival in these patients was poorer than in the late recurrence group. According to a multivariable analysis, the transplant era before 2008 and radiofrequency ablation were associated with good prognosis, whereas receiving sorafenib and radiotherapy was associated with poor prognosis. The effect of transplant era became insignificant after stratification by recently receiving pretransplant transarterial chemoembolization. CONCLUSION: Timing of recurrence and interventions used were associated with the outcomes of patients with post-transplant HCC recurrence. These data provide the benchmark and indicate the critical period and high-risk factors for further therapeutic trial consideration.