Management of Dyslipidemia as a Cardiovascular Risk Factor in Individuals with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the United States and is associated with an increased risk of cardiovascular disease (CVD) and cardiovascular (CV) mortality, independent of traditional cardiovascular risk factors. CVD is one of the most common causes of death among individuals with NAFLD and management of NAFLD must extend beyond liver disease to include CVD risk modification. Clinicians should assess CVD risk with the Framingham Risk Score (FRS) and screen for CVD risk factors including dyslipidemia, diabetes mellitus (DM), hypertension, tobacco use and the metabolic syndrome (MetS). CVD risk factors, particularly dyslipidemia, require aggressive medical management to reduce the high risk of CVD events and death in individuals with NAFLD

Nonalcoholic steatohepatitis is associated with an atherogenic lipoprotein subfraction profile

Background: Nonalcoholic steatohepatitis (NASH) carries an increased risk of cardiovascular disease (CVD) relative to the general population. We sought to evaluate whether differences in lipoprotein subfractions in obese patients with and without NASH contributes to this difference in CVD risk. Findings: Ion mobility analysis was performed on 78 individuals with obesity undergoing weight loss surgery. All individuals had standard of care liver biopsies performed during surgery. Patients with NASH had significantly smaller peak LDL diameter (P = 0.02, 219.0 Å vs. 222.6 Å), and levels of IDL2 (P = 0.01, 104. nmol/L vs. 133.4 nmol/L) and HDL2b (P = 0.05, 676.7 nmol/L vs. 880.1 nmol/L) compared to those without NASH. NASH patients had significantly higher LDL-IVb levels than those without NASH (P = 0.02, 49.0 nmol/L vs. 37.1 nmol/L). The inverse association of LDL peak diameter with NASH remained significant after adjustment for diabetes (P = 0.02). HDL2b levels were inversely correlated with hepatocyte ballooning and NASH and these remained significant after adjustment for diabetes (P = 0.0017 and P = 0.007, respectively). IDL2 levels were inversely correlated with NASH, hepatocyte ballooning and fibrosis stage but these were not significant after adjustment for diabetes. Conclusions: The lipoprotein subfraction profile in subjects with NASH is characterized by small peak LDL diameter, reduced HDL2b levels and elevated LDL-IVb levels. These changes may contribute to the increased CVD seen in patients with NASH

Serum Vitamin D Levels Are Not Predictive of the Progression of Chronic Liver Disease in Hepatitis C Patients with Advanced Fibrosis

In animal models and human cross-sectional studies, vitamin D deficiency has been associated with liver disease progression. Vitamin D supplementation has been suggested as a treatment to prevent disease progression. We sought to evaluate the role of vitamin D levels in predicting chronic liver disease development. We conducted a nested case-control study of vitamin D levels in subjects with (cases) and without (controls) liver histologic progression or clinical decompensation over the course of the HALT-C Trial. Vitamin D levels were measured at 4 points over 45 months. 129 cases and 129 aged-matched controls were included. No difference in baseline vitamin D levels were found between cases and controls. (44.8 ng/mL vs. 44.0 ng/mL, P = 0.74). Vitamin D levels declined in cases and controls over time (P = 0.0005), however, there was no difference in the level of decline (P = 0.37). Among study subjects with diabetes mellitius, baseline vitamin D levels were higher in cases, 49.9 ng/mL, than controls, 36.3 ng/mL. (P = 0.03) In addition, baseline vitamin D levels were higher in black case subjects, 32.7 ng/mL, than in black control subjects, 25.2 ng/mL (P = 0.08) No difference in vitamin D levels was found between patients with and without progression of hepatitis C-associated liver disease over 4 years. Our data do not suggest any role for vitamin D supplementation in patients with advanced chronic hepatitis C and raise the possibility that higher vitamin D levels may be associated with disease progression

The MELD-Plus: A generalizable prediction risk score in cirrhosis

Background and aims Accurate assessment of the risk of mortality following a cirrhosis-related admission can enable health-care providers to identify high-risk patients and modify treatment plans to decrease the risk of mortality. Methods: We developed a post-discharge mortality prediction model for patients with a cirrhosis-related admission using a population of 314,292 patients who received care either at Massachusetts General Hospital (MGH) or Brigham and Women’s Hospital (BWH) between 1992 and 2010. We extracted 68 variables from the electronic medical records (EMRs), including demographics, laboratory values, diagnosis codes, and medications. We then used a regularized logistic regression to select the most informative variables and created a risk score that comprises the selected variables. To evaluate the potential for generalizability of our score, we applied it on all cirrhosis-related admissions between 2010 and 2015 at an independent EMR data source of more than 18 million patients, pooled from different health-care systems with EMRs. We calculated the areas under the receiver operating characteristic curves (AUROCs) to assess prediction performance. Results: We identified 4,781 cirrhosis-related admissions at MGH/BWH hospitals, of which 778 resulted in death within 90 days of discharge. Nine variables were the most effective predictors for 90-day mortality, and these included all MELD-Na’s components, as well as albumin, total cholesterol, white blood cell count, age, and length of stay. Applying our nine-variable risk score (denoted as “MELD-Plus”) resulted in an improvement over MELD and MELD-Na scores in several prediction models. On the MGH/BWH 90-day model, MELD-Plus improved the performance of MELD-Na by 11.4% (0.78 [95% CI, 0.75–0.81] versus 0.70 [95% CI, 0.66–0.73]). In the MGH/BWH approximate 1-year model, MELD-Plus improved the performance of MELD-Na by 8.3% (0.78 [95% CI, 0.76–0.79] versus 0.72 [95% CI, 0.71–0.73]). Performance improvement was similar when the novel MELD-Plus risk score was applied to an independent database; when considering 24,042 cirrhosis-related admissions, MELD-Plus improved the performance of MELD-Na by 16.9% (0.69 [95% CI, 0.69–0.70] versus 0.59 [95% CI, 0.58–0.60]). Conclusions: We developed a new risk score, MELD-Plus that accurately stratifies the short-term mortality of patients with established cirrhosis, following a hospital admission. Our findings demonstrate that using a small set of easily accessible structured variables can help identify novel predictors of outcomes in cirrhosis patients and improve the performance of widely used traditional risk scores

Host Genetics Predict Clinical Deterioration in HCV-Related Cirrhosis

Single nucleotide polymorphisms (SNPs) in the epidermal growth factor (EGF, rs4444903), patatin-like phospholipase domain-containing protein 3 (PNPLA3, rs738409) genes, and near the interleukin-28B (IL28B, rs12979860) gene are linked to treatment response, fibrosis, and hepatocellular carcinoma (HCC) in chronic hepatitis C. Whether these SNPs independently or in combination predict clinical deterioration in hepatitis C virus (HCV)-related cirrhosis is unknown. We genotyped SNPs in EGF, PNPLA3, and IL28B from liver tissue from 169 patients with biopsy-proven HCV cirrhosis. We estimated risk of clinical deterioration, defined as development of ascites, encephalopathy, variceal hemorrhage, HCC, or liver-related death using Cox proportional hazards modeling. During a median follow-up of 6.6 years, 66 of 169 patients experienced clinical deterioration. EGF non-AA, PNPLA3 non-CC, and IL28B non-CC genotypes were each associated with increased risk of clinical deterioration in age, sex, and race-adjusted analysis. Only EGF non-AA genotype was independently associated with increased risk of clinical deterioration (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.31–6.25) after additionally adjusting for bilirubin, albumin, and platelets. Compared to subjects who had 0–1 unfavorable genotypes, the HR for clinical deterioration was 1.79 (95%CI 0.96–3.35) for 2 unfavorable genotypes and 4.03 (95%CI 2.13–7.62) for unfavorable genotypes for all three loci (Ptrend<0.0001). In conclusion, among HCV cirrhotics, EGF non-AA genotype is independently associated with increased risk for clinical deterioration. Specific PNPLA3 and IL28B genotypes also appear to be associated with clinical deterioration. These SNPs have potential to identify patients with HCV-related cirrhosis who require more intensive monitoring for decompensation or future therapies preventing disease progression

The Association Between IGF-1 Levels and the Histologic Severity of Nonalcoholic Fatty Liver Disease

Objectives: The mechanisms responsible for the development of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) are incompletely understood. Growing evidence suggests that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) may have roles in the development and progression of NAFLD. We hypothesized that lower serum IGF-1 levels would be associated with increased liver fat accumulation, inflammation, and fibrosis in a group of meticulously phenotyped obese subjects with liver biopsies. Methods: A retrospective, cross-sectional study was performed at Massachusetts General Hospital, Boston, MA, USA and St. Mary's Hospital, Richmond, VA, USA. Liver biopsies were performed in 142 subjects during NAFLD work-up or bariatric surgery and were graded by a single, blinded pathologist. Main outcome measures included liver histology and serum IGF-1. Results: Mean age was 52±10 years and body mass index (BMI) was 43±9 kg/m2. Mean serum IGF-1 was lower in subjects with lobular inflammation (112±47 vs. 136±57 ng/ml, P=0.01), hepatocyte ballooning (115±48 vs. 135±57 ng/ml, P=0.05), higher fibrosis stage (stage 2–4 vs. 0–1; 96±40 vs. 125±51 ng/ml, P=0.005), and NASH (109±45 vs. 136±57 ng/ml, P=0.002). All results remained significant after controlling for age, BMI, and a diagnosis of diabetes, and all but hepatocyte ballooning (trend, P=0.06) remained significant after excluding individuals with cirrhosis. Steatosis was not significantly associated with mean serum IGF-1 levels. Conclusions: Low serum IGF-1 levels are associated with increased histologic severity of NAFLD when rigorously controlled for age, BMI, the presence of diabetes, and after the exclusion of subjects with cirrhosis. Further investigation is warranted to determine the differential effects of GH and IGF-1 on the development and progression of NAFLD, which could further elucidate pathophysiology and identify therapeutic targets

Comparing Outcomes of Two Types of Bariatric Surgery in an Adolescent Obese Population: Roux-en-Y Gastric Bypass vs. Sleeve Gastrectomy

Background: Obesity is prevalent among adolescents and is associated with serious health consequences. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) are bariatric procedures that cause significant weight loss in adults and are increasingly being performed in adolescents with morbid obesity. Data comparing outcomes of RYGB vs. SG in this age-group are scarce. This study aims to compare short-term (1–6 months) and longer-term (7–18 months) body mass index (BMI) and biochemical outcomes following RYGB and SG in adolescents/young adults. Methods: A retrospective study using data extracted from medical records of patients 16–21 years who underwent RYGB or SG between 2012 and 2014 at a tertiary care academic medical center. Results: Forty-six patients were included in this study: 24 underwent RYGB and 22 underwent SG. Groups did not differ for baseline age, sex, race, or BMI. BMI reductions were significant at 1–6 months and 7–18 months within groups (p < 0.0001), but did not differ by surgery type (p = 0.65 and 0.09, for 1–6 months and 7–18 months, respectively). Over 7–18 months, within-group improvement in low-density lipoprotein (LDL) (−24 ± 6 in RYGB, p = 0.003, vs. −7 ± 9 mg/dl in SG, p = 0.50) and non-high-density lipoprotein (non-HDL) cholesterol (−23 ± 8 in RYGB, p = 0.02, vs. −12 ± 7 in SG, p = 0.18) appeared to be of greater magnitude following RYGB. However, differences between groups did not reach statistical significance. When divided by non-alcoholic steatohepatitis stages (NASH), patients with Stage II–III NASH had greater reductions in alanine aminotransferase levels vs. those with Stage 0–I NASH (−45 ± 18 vs. −9 ± 3, p = 0.01) after 7–18 months. RYGB and SG groups did not differ for the magnitude of post-surgical changes in liver enzymes. Conclusion: RYGB and SG did not differ for the magnitude of BMI reduction across groups, though changes trended higher following RYGB. Further prospective studies are needed to confirm these findings

Thank You to Our 2019 Peer Reviewers

On behalf of the journal, AGU, and the scientific community, the editors would like to sincerely thank those who reviewed the manuscripts for Geophysical Research Letters in 2019. The hours reading and commenting on manuscripts not only improve the manuscripts but also increase the scientific rigor of future research in the field. We particularly appreciate the timely reviews in light of the demands imposed by the rapid review process at Geophysical Research Letters. With the revival of the “major revisions” decisions, we appreciate the reviewers’ efforts on multiple versions of some manuscripts. With the advent of AGU’s data policy, many reviewers have helped immensely to evaluate the accessibility and availability of data associated with the papers they have reviewed, and many have provided insightful comments that helped to improve the data presentation and quality. We greatly appreciate the assistance of the reviewers in advancing open science, which is a key objective of AGU’s data policy. Many of those listed below went beyond and reviewed three or more manuscripts for our journal, and those are indicated in italics.Key PointThe editors thank the 2019 peer reviewersPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162718/2/grl60415.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162718/1/grl60415_am.pd

Seroprevalence following the second wave of pandemic 2009 H1N1 influenza in Pittsburgh, PA, USA

Background: In April 2009, a new pandemic strain of influenza infected thousands of persons in Mexico and the United States and spread rapidly worldwide. During the ensuing summer months, cases ebbed in the Northern Hemisphere while the Southern Hemisphere experienced a typical influenza season dominated by the novel strain. In the fall, a second wave of pandemic H1N1 swept through the United States, peaking in most parts of the country by mid October and returning to baseline levels by early December. The objective was to determine the seroprevalence of antibodies against the pandemic 2009 H1N1 influenza strain by decade of birth among Pittsburgh-area residents. Methods and Findings: Anonymous blood samples were obtained from clinical laboratories and categorized by decade of birth from 1920-2009. Using hemagglutination-inhibition assays, approximately 100 samples per decade (n = 846) were tested from blood samples drawn on hospital and clinic patients in mid-November and early December 2009. Age specific seroprevalences against pandemic H1N1 (A/California/7/2009) were measured and compared to seroprevalences against H1N1 strains that had previously circulated in the population in 2007, 1957, and 1918. (A/Brisbane/59/2007, A/Denver/1/ 1957, and A/South Carolina/1/1918). Stored serum samples from healthy, young adults from 2008 were used as a control group (n = 100). Seroprevalences against pandemic 2009 H1N1 influenza varied by age group, with children age 10-19 years having the highest seroprevalence (45%), and persons age 70-79 years having the lowest (5%). The baseline seroprevalence among control samples from 18-24 year-olds was 6%. Overall seroprevalence against pandemic H1N1 across all age groups was approximately 21%. Conclusions: After the peak of the second wave of 2009 H1N1, HAI seroprevalence results suggest that 21% of persons in the Pittsburgh area had become infected and developed immunity. Extrapolating to the entire US population, we estimate that at least 63 million persons became infected in 2009. As was observed among clinical cases, this sero-epidemiological study revealed highest infection rates among school-age children. © 2010 Zimmer et al