Association of Statins and 28-Day Mortality Rates in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

BACKGROUND: Statins may be protective in severe acute respiratory syndrome coronavirus 2 SARS-CoV-2 infection. The aim of the current study was to evaluate the effect of in-hospital statin use on 28-day mortality rates and intensive care unit (ICU) admission among patients with SARS-CoV-2, stratified into 4 groups: those who used statins before hospitalization (treatment continued or discontinued in the hospital) and those who did not (treatment newly initiated in the hospital or never initiated). METHODS: In a cohort study of 1179 patients with SARS-CoV-2, record review was used to assess demographics, laboratory measurements, comorbid conditions, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, we estimated hazard ratios (HRs) for death and ICU admission. RESULTS: Among 1179 patients, 676 (57%) were male, 443 (37%) were >65 years old, and 493 (46%) had a body mass index ≥30 (calculated as weight in kilograms divided by height in meters squared). Inpatient statin use reduced the hazard of death (HR, 0.566; P=.008). This association held among patients who did and those who did not use statins before hospitalization (HR, 0.270 [P=.003] and 0.493 [P=.04], respectively). Statin use was associated with improved time to death for patients aged >65 years but not for those ≤65 years old. CONCLUSION: Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates. Well-designed randomized control trials are needed to better define this relationship.

Effect of combined tobacco use and type 2 diabetes mellitus on prevalent fibrosis in patients with MASLD.

BACKGROUND: Several studies have investigated the independent effect of cigarette smoking or type 2 diabetes mellitus (T2DM) on MASLD. However, the interaction effect between tobacco consumption and T2DM on MASLD severity remains underexplored. In this study, we assessed the combined effect of tobacco use and T2DM on hepatic fibrosis in MASLD. METHODS: We conducted a single-center retrospective cross-sectional analysis of eligible participants from the Mass General Brigham Fibroscan© database. The participants were divided into 3 groups: those with T2DM and a history of tobacco use (primary exposure group), those with T2DM but no history of tobacco use (secondary exposure group), and those without T2DM and no history of tobacco use (reference group). An additional model was developed, which included a fourth group, participants with a history of tobacco use but no T2DM. The likelihood of fibrosis was determined using a defined fibrosis-4 index cutoff value of 1.3. In addition, we computed the estimated marginal means for liver stiffness measurement and compared the values among the exposure groups. Bivariable and multivariable logistic regression models were used to explore the associations between the exposure groups and the risk for hepatic fibrosis. RESULTS: Overall, 598 individuals were enrolled in the study. The bivariable logistic regression model revealed a significant independent association between T2DM, combined smoking and T2DM, and the outcome of interest, fibrosis. Age, sex, metabolic syndrome, aspirin use, statin use, hemoglobin A1C (A1C), and total bilirubin level were also significantly associated with fibrosis. In the adjusted fibrosis-4 multivariable model (comparing exposure groups to controls), cigarette smoking and T2DM interaction had higher odds of prevalent fibrosis (aOR, 3.04; 95% CI, 1.62-5.76), compared to those with T2DM alone (aOR 2.28; 95% CI, 1.37-3.85). The continuous liver stiffness measurement comparison across the exposure group showed an estimated marginal means of 6.26 (95% CL: 5.58-6.94), 7.54 (95% CL: 6.78-8.30), and 7.88 (6.78-8.99) for the reference group, T2DM only group, and tobacco-T2DM group, respectively. The diabetes-only group and the combined tobacco-T2DM group had statistically significant associations with liver stiffness measurement (p values: 0.013 and 0.014, respectively). CONCLUSION: Although diabetes is independently associated with hepatic fibrosis in patients with MASLD, the combination of tobacco consumption and diabetes is associated with a higher prevalence of fibrosis. Therefore, lifestyle change through tobacco use cessation in patients with diabetes could be beneficial in reducing the incidence of liver fibrosis among individuals with MASLD.

Intermittent Fasting as a Treatment for Nonalcoholic Fatty Liver Disease: What Is the Evidence?

Content available: Author Interview and Audio Recording.

Risk of Cardiovascular Disease in Individuals With Nonobese Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is independently associated with obesity and cardiovascular disease (CVD). CVD is the primary cause of mortality in the predominantly obese population of adults with NAFLD. NAFLD is increasingly seen in individuals who are lean and overweight (i.e., nonobese), but it is unclear whether their risk of CVD is comparable to those with NAFLD and obesity. Using a prospective cohort of patients with NAFLD, we compared the prevalence and incidence of CVD in individuals with and without obesity. NAFLD was diagnosed by biopsy or imaging after excluding other chronic liver disease etiologies. Logistic regression was used to compare the odds of baseline CVD by obesity status. Cox proportional hazards regression was used to evaluate obesity as a predictor of incident CVD and to identify predictors of CVD in subjects with and without obesity. At baseline, adults with obesity had a higher prevalence of CVD compared to those without obesity (12.0% vs. 5.0%, P = 0.02). During follow-up, however, obesity did not predict incident CVD (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.69-2.22) or other metabolic diseases. Findings were consistent when considering body mass index as a continuous variable and after excluding subjects who were overweight. Age (adjusted HR [aHR], 1.05; 95% CI, 1.03-1.08), smoking (aHR, 4.61; 95% CI, 1.89-11.22), and decreased low-density lipoprotein levels (aHR, 0.98; 95% CI, 0.96-1.00) independently predicted incident CVD in the entire cohort, in subjects with obesity, and in those without obesity, respectively. Conclusion: Individuals with overweight or lean NAFLD are not protected from incident CVD compared to those with NAFLD and obesity, although CVD predictors appear to vary between these groups. Patients without obesity also should undergo rigorous risk stratification and treatment.

Statins Are Associated with Improved 28-day Mortality in Patients Hospitalized with SARS-CoV-2 Infection.

BACKGROUND: Statins may be protective in viral infection and have been proposed as treatment in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. OBJECTIVE: We evaluated the effect of statins on mortality in four groups hospitalized with (SARS-CoV-2) infection (continued statin, newly initiated statin, discontinued statin, never on statin). DESIGN: In a single center cohort study of 1179 patients hospitalized with SARS-CoV-2 infection, the outcome of death, Intensive Care Unit (ICU) admission or hospital discharge was evaluated. Patients' statin use, laboratory data, and co-morbidities were determined via chart review and electronic health records. Using marginal structural models to account for timing of statin initiation and competing risks, we compared the likelihood of severe outcomes in the four statin exposure groups. SETTING: Academic medical center in the United States. PARTICIPANTS: Patients hospitalized with SARS-CoV-2 infection. MEASUREMENTS: 28-day mortality, ICU admission, or discharge. RESULTS: Among 1179 patients, 360 were never on a statin, 311 were newly initiated on a statin, 466 were continued on a statin, and 42 had a statin discontinued. In this cohort, 154 (13.1%) patients died by 28-days. With marginal structural model analysis, statin use reduced the hazard of 28-day mortality (HR 0.566 [CI 0.372, 0.862], p = 0.008). Both new initiation of statins (HR 0.493 [CI 0.253, 0.963], p=0.038) and continuing statin therapy reduced the hazard of 28-day mortality (HR 0.270 [CI 0.114, 0.637], p=0.003). Sensitivity analysis found that statin use was associated with improved mortality for patients > 65 years, but not for patients 65 years or younger. LIMITATION: Observational design. CONCLUSION: Statin therapy during hospitalization for SARS-CoV-2 infection, including new initiation and continuation of therapy, was associated with reduced short-term mortality.

Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: A meta-analysis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Effects of second-line oral antidiabetic medications on incident HCC risk in individuals with type 2 diabetes mellitus remain unclear. This study evaluated associations between sulfonylureas, thiazolidinediones, meglitinides and alpha-glucosidase inhibitors, and incident HCC risk. METHODS: We systematically reviewed all studies on PubMed, Embase and Web of Science databases. Studies were included if they documented: (1) exposure to oral antidiabetic medication classes; (2) HCC incidence; (3) relative risks/odds ratios (OR) for HCC incidence. Eight eligible observational studies were identified. We performed random-effects meta-analyses to calculate pooled adjusted ORs (aORs) and 95% confidence intervals (CI). RESULTS: Thiazolidinedione use (7 studies, 280,567 participants, 19,242 HCC cases) was associated with reduced HCC risk (aOR = 0.92, 95% CI = 0.86-0.97, I2 = 43%), including among Asian subjects (aOR = 0.90, 95% CI = 0.83-0.97), but not Western subjects (aOR = 0.95, 95% CI = 0.87-1.04). Alpha-glucosidase inhibitor use (3 studies, 56,791 participants, 11,069 HCC cases) was associated with increased HCC incidence (aOR = 1.08; 95% CI = 1.02-1.14, I2 = 21%). Sulfonylurea use (8 studies, 281,180 participants, 19,466 HCC cases) was associated with increased HCC risk in studies including patients with established liver disease (aOR = 1.06, 95% CI = 1.02-1.11, I2 = 75%). Meglitinide use (4 studies, 58,237 participants, 11,310 HCC cases) was not associated with HCC incidence (aOR = 1.19; 95% CI = 0.89-1.60, I2 = 72%). CONCLUSIONS: Thiazolidinedione use was associated with reduced HCC incidence in Asian individuals with diabetes. Alpha-glucosidase inhibitor or sulfonylurea use was associated with modestly increased HCC risk; future research should determine whether those agents should be avoided in patients with chronic liver disease.

Aspirin Use Is Associated with a Reduced Incidence of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related death worldwide, with a growing incidence and poor prognosis. While some recent studies suggest an inverse association between aspirin use and reduced HCC incidence, other data are conflicting. To date, the precise magnitude of risk reduction-and whether there are dose-dependent and duration-dependent associations-remains unclear. To provide an updated and comprehensive assessment of the association between aspirin use and incident HCC risk, we conducted a systematic review and meta-analysis of all observational studies published through September 2020. Using random-effects meta-analysis, we calculated the pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between aspirin use and incident HCC risk. Where data were available, we evaluated HCC risk according to the defined daily dose of aspirin use. Among 2,389,019 participants, and 20,479 cases of incident HCC, aspirin use was associated with significantly lower HCC risk (adjusted RR, 0.61; 95% CI, 0.51-0.73; P ≤ 0.001; I2 = 90.4%). In subgroup analyses, the magnitude of benefit associated with aspirin was significantly stronger in studies that adjusted for concurrent statin and/or metformin use (RR, 0.45; 95% CI, 0.28-0.64) versus those that did not (P heterogeneity = 0.02), studies that accounted for cirrhosis (RR, 0.49; 95% CI, 0.45-0.52) versus those that did not (P heterogeneity = 0.02), and studies that confirmed HCC through imaging/biopsy (RR, 0.30; 95% CI, 0.15-0.58) compared with billing codes (P heterogeneity < 0.001). In four studies, each defined daily dose was associated with significantly lower HCC risk (RR, 0.98; 95% CI, 0.97-0.98), corresponding to an 8.4% risk reduction per year of aspirin use. Conclusion: In this comprehensive systematic review and meta-analysis, aspirin use was associated with a significant reduction in HCC risk. These benefits appeared to increase with increasing dose and duration of aspirin use.