Weight Loss in Short-Term Interventions for Physical Activity and Nutrition Among Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

Introduction: Reaching, enrolling, and retaining participants in lengthy lifestyle change interventions for weight loss is a major challenge. The objective of our meta-analysis was to investigate whether lifestyle interventions addressing nutrition and physical activity lasting 6 months or less are effective for weight loss. Methods: We searched for peer-reviewed studies on lifestyle change interventions of 6 months or less published from 2012 through 2023. Studies were screened based on inclusion criteria, including randomized controlled trials (RCTs) for adults with overweight or obesity. We used a random-effects model to pool the mean difference in weight loss between intervention and control groups. We also performed subgroup analyses by intervention length and control type. Results: Fourteen RCTs were identified and included in our review. Half had interventions lasting less than 13 weeks, and half lasted from 13 to 26 weeks. Seven were delivered remotely, 4 were delivered in person, and 3 used combined methods. The pooled mean difference in weight change was -2.59 kg (95% CI, -3.47 to -1.72). The pooled mean difference measured at the end of the intervention was -2.70 kg (95% CI, -3.69 to -1.71) among interventions lasting less than 13 weeks and -2.40 kg (95% CI, -4.44 to -0.37) among interventions of 13 to 26 weeks. Conclusion: Short-term multicomponent interventions involving physical activity and nutrition can achieve weight loss for adults with overweight or obesity. Offering short-term interventions as alternatives to long-term ones may reach people who otherwise would be unwilling or unable to enroll in or complete longer programs.

Outcomes after kidney transplant alone in patients with cirrhosis-A case-control study.

BACKGROUND: Guidelines recommend kidney transplant alone (KTA) in compensated cirrhosis based on a few small studies, but this is not widely performed despite its potential benefit to patients and the organ supply. Our aim was to determine the outcomes of KTA in patients with compensated cirrhosis. STUDY DESIGN: From 1/2012 to 12/2021, outcomes in KTA recipients with compensated cirrhosis were retrospectively compared to patients with chronic liver disease (CLD) but no cirrhosis. Patients with compensated cirrhosis were also compared to a matched cohort (based on age, time on hemodialysis, sex, and ethnicity) of KTA recipients without CLD. The outcomes included patient survival, allograft failure, allograft rejection, serious infection, liver decompensation, and length of stay (LOS). RESULTS: Over 9 years, 1562 KTAs were performed, with 150 (9.6%) patients having CLD mostly due to chronic hepatitis C, and a median follow-up of 3.5 years. 32/150 (21%) had compensated cirrhosis at the time of KTA with a mean MELD-Na of 22 (1.5). Matched controls (n = 189) were identified. We found no differences in patient survival (p = .07), allograft failure (p = .6), allograft rejection (p = .43), rates of serious infection (p = .31), as well as LOS (p = .61) among patients with compensated cirrhosis compared to patients with CLD but no cirrhosis, but with higher rates of liver decompensation (p = .004). Similarly, compared to patients without CLD, patients with cirrhosis had similar rates of patient survival (p = .20), allograft failure (p = .27), allograft rejection (p = .62) and LOS (p = .19) but with higher rates of serious infections (p = .001). CONCLUSIONS: Our study supports the safety and efficacy of KTA in patients with compensated cirrhosis.

Association of HSD17B13 and PNPLA3 With Liver Enzymes and Fibrosis in Hispanic/Latino Individuals of Diverse Genetic Ancestries.

BACKGROUND & AIMS: Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease-associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record-linked biobank in New York City. METHODS: This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. RESULTS: Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P = .002), AST level (P < .001), and FIB-4 score (P = .045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P < .001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P = .006). CONCLUSIONS: Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals.

Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis.

BACKGROUND: Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation. METHODS: In this retrospective study among 5 ACCELERATE-AH sites, we randomly sampled patients evaluated and then declined for liver transplantation for alcohol-associated hepatitis. All had Model of End-Stage Liver Disease (MELD) >20 and <6 months of abstinence. Recompensation was defined as MELD <15 without variceal bleeding, ascites, or overt HE requiring treatment. Multilevel mixed effects linear regression was used to calculate probabilities of recompensation; multivariable Cox regression was used for mortality analyses. RESULTS: Among 145 patients [61% men; median abstinence time and MELD-Na was 33 days (interquartile range: 13-70) and 31 (interquartile range: 26-36), respectively], 56% were declined for psychosocial reasons. Probability of 30-day, 90-day, 6-month, and 1-year survival were 76% (95% CI, 68%-82%), 59% (95% CI, 50%-66%), 49% (95% CI, 40%-57%), and 46% (95% CI, 37%-55%), respectively. Probability of 1-year recompensation was low at 10.0% (95% CI, 4.5%-15.4%). Among patients declined because of clinical improvement, 1-year probability of recompensation was 28.0% (95% CI, 5.7%-50.3%). Among survivors, median MELD-Na at 30 days, 90 days, and 1-year were 29 (interquartile range: 22-38), 19 (interquartile range : 14-29), and 11 (interquartile range : 7-17). Increased MELD-Na (adjusted HR: 1.13, p <0.001) and age (adjusted HR: 1.03, p <0.001) were associated with early (≤90 d) death, and only history of failed alcohol rehabilitation (adjusted HR: 1.76, p =0.02) was associated with late death. CONCLUSIONS: Liver recompensation is infrequent among severe alcohol-associated hepatitis patients declined for liver transplantation. Higher MELD-Na and age were associated with short-term mortality, whereas only history of failed alcohol rehabilitation was associated with long-term mortality. The distinction between survival and liver recompensation merits further attention.

Early Liver Transplantation for Severe Alcohol-Associated Hepatitis and a History of Prior Liver Decompensation.

INTRODUCTION: In the published studies of early liver transplantation (LT) for alcohol-associated hepatitis (AH), patients with a prior liver decompensation are excluded. The appropriateness of this criteria is unknown. METHODS: Among 6 American Consortium of Early Liver Transplantation for Alcohol-Associated Hepatitis sites, we included consecutive early LT for clinically diagnosed AH between 2007 and 2020. Patients were stratified as first vs prior history of liver decompensation, with the latter defined as a diagnosis of ascites, hepatic encephalopathy, variceal bleeding, or jaundice, and evidence of alcohol use after this event. Adjusted Cox regression assessed the association of first (vs prior) decompensation with post-LT mortality and harmful (i.e., any binge and/or frequent) alcohol use. RESULTS: A total of 241 LT recipients (210 first vs 31 prior decompensation) were included: median age 43 vs 38 years ( P = 0.23), Model for End-Stage Liver Disease Sodium score of 39 vs 39 ( P = 0.98), and follow-up after LT 2.3 vs 1.7 years ( P = 0.08). Unadjusted 1- and 3-year survival among first vs prior decompensation was 93% (95% confidence interval [CI] 89%-96%) vs 86% (95% CI 66%-94%) and 85% (95% CI 79%-90%) vs 78% (95% CI 57%-89%). Prior (vs first) decompensation was associated with higher adjusted post-LT mortality (adjusted hazard ratio 2.72, 95% CI 1.61-4.59) and harmful alcohol use (adjusted hazard ratio 1.77, 95% CI 1.07-2.94). DISCUSSION: Prior liver decompensation was associated with higher risk of post-LT mortality and harmful alcohol use. These results are a preliminary safety signal and validate first decompensation as a criterion for consideration in early LT for AH patients. However, the high 3-year survival suggests a survival benefit for early LT and the need for larger studies to refine this criterion. These results suggest that prior liver decompensation is a risk factor, but not an absolute contraindication to early LT.

Leveraging health systems data to characterize a large effect variant conferring risk for liver disease in Puerto Ricans.

The integration of genomic data into health systems offers opportunities to identify genomic factors underlying the continuum of rare and common disease. We applied a population-scale haplotype association approach based on identity-by-descent (IBD) in a large multi-ethnic biobank to a spectrum of disease outcomes derived from electronic health records (EHRs) and uncovered a risk locus for liver disease. We used genome sequencing and in silico approaches to fine-map the signal to a non-coding variant (c.2784-12T>C) in the gene ABCB4. In vitro analysis confirmed the variant disrupted splicing of the ABCB4 pre-mRNA. Four of five homozygotes had evidence of advanced liver disease, and there was a significant association with liver disease among heterozygotes, suggesting the variant is linked to increased risk of liver disease in an allele dose-dependent manner. Population-level screening revealed the variant to be at a carrier rate of 1.95% in Puerto Rican individuals, likely as the result of a Puerto Rican founder effect. This work demonstrates that integrating EHR and genomic data at a population scale can facilitate strategies for understanding the continuum of genomic risk for common diseases, particularly in populations underrepresented in genomic medicine.

COVID-19 Aftershocks on Alcohol-Associated Liver Disease: An Early Cross-Sectional Report From the U.S. Epicenter.

Experts have forewarned about the coronavirus disease 2019 (COVID-19) pandemic environment fomenting the rising incidence of alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). We performed a cross-sectional study of ALD at our liver transplantation (LT) center, located in the initial U.S. epicenter, New York City. Centered around the "stay at home" order date in New York state, March 22, 2020, we defined three time periods: "pre-COVID" (January 1, 2020-March 21, 2020), "COVID-quarantine" (March 22, 2020-April 22, 2020), and "declining-COVID" (April 23, 2020-August 25, 2020). We found a 62% increase in interhospital patient transfers for ALD from pre-COVID (20 of 93, 21%) to the declining-COVID period (43 of 127, 34%). Our inpatient liver census with ALD also increased: 38% pre-COVID, 45% COVID-quarantine, and 49% declining-COVID. Among 30 patients with severe alcoholic hepatitis (AH) not responding to medical therapy since March 22, 2020, 9 underwent early LT for AH (16% of the total number of early LT during our 8-year program). Three of 9 early-LT recipients reported specific COVID-related stressors. All 25 previous LT recipients with established abstinence pre-COVID maintained abstinence at follow-up visits during the declining-COVID period. Of the 6 recipients with sustained alcohol use within 6 months before March 22, 2020, half regained abstinence during the declining-COVID period. Our findings help confirm the predictions of rising AUD and ALD as an immediate consequence of the COVID-19 pandemic. This aftershock particularly affected ethnically diverse patients with ALD with high inpatient mortality, reflecting the disproportionate impact of COVID-19 on underserved and minority populations. Alcohol relapse did not occur in long-term early LT for AH recipients during the time of COVID-19. This lends further support to AH being a viable indication for LT, with recipients able to demonstrate ongoing resilience in the face of this unprecedented universal stressor.

Current and Future Biomarkers in Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is a clinical syndrome of jaundice, abdominal pain, and anorexia due to prolonged heavy alcohol intake, and is associated with alterations in gene expression, cytokines, immune response, and the gut microbiome. Currently, we have limited biomarkers to diagnose and prognosticate in AH, but there are many novel noninvasive biomarkers under development. We evaluate the currently used algorithms to risk-stratify in AH (such as the Maddrey modified discriminant function), and discuss novel biomarkers in development, such as breath biomarkers, microRNAs, cytokeratin-18 fragments, and the AshTest. We also review the characteristics of an ideal biomarker in AH.

Liver Injury in Patients Hospitalized with Coronavirus Disease 2019 Correlates with Hyperinflammatory Response and Elevated Interleukin-6.

Liver injury is commonly seen in coronavirus disease 2019 (COVID-19); however, the mechanism behind liver injury, particularly in patients with severe and critical COVID-19, remains unclear, and the clinical course is poorly described. We conducted a single-center retrospective cohort study of consecutive patients hospitalized with severe and critical COVID-19 with or without liver injury and who underwent immunologic testing (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-1ß). Liver injury was defined as peak aminotransferases ≥3 times the upper limit of normal (40 U/L) or ≥120 U/L. Patients with liver injury were compared to those who had normal aminotransferases throughout the hospital course. We studied 176 patients: 109 with liver injury and 67 controls. Patients with liver injury were more likely to be men (71.6% vs. 37.3%, P < 0.001). Peak inflammatory markers and IL-6 were higher in the liver injury group: C-reactive protein (CRP), 247 vs. 168 mg/L, P < 0.001; lactate dehydrogenase (LDH), 706 vs. 421 U/L; ferritin, 2,973 vs. 751 ng/mL, P < 0.001; IL-6, 121.0 vs. 71.8 pg/mL, P < 0.001. There was no difference in the levels of IL-8, TNF-α, and IL-1ß. The liver injury group had a longer length of stay in the hospital and more severe COVID-19 despite having less diabetes and chronic kidney disease. Conclusion: An exaggerated hyperinflammatory response (cytokine storm) characterized by significantly elevated CRP, LDH, ferritin, and IL-6 levels and increasing severity of COVID-19 appears to be associated with the occurrence of liver injury in patients with severe/critical COVID-19.

Estimated number of eligible Part B beneficiaries for the medicare diabetes prevention program at the county level and by urban-rural classification.

INTRODUCTION: Diabetes imposes large health and financial burdens on Medicare beneficiaries. Type 2 diabetes can be prevented or delayed through lifestyle modification programs. In 2018, Medicare began to offer the Medicare Diabetes Prevention Program (MDPP), a lifestyle intervention, to eligible beneficiaries nationwide. The number of MDPP-eligible beneficiaries is not known, but this information is essential in efforts to expand the program and increase enrollment. This study aimed to estimate the number and spatial variation of MDPP-eligible Part B beneficiaries at the county level and by urban-rural classification. METHODS: Data from 2011-2016 National Health and Nutrition Examination Surveys and a survey-weighted logistic regression model were used to estimate proportions of prediabetes in the United States by sex, age, and race/ethnicity based on the MDPP eligibility criteria. The results from the predictive model were applied to 2015 Medicare Part B beneficiaries to estimate the number of MDPP-eligible beneficiaries. The National Center for Health Statistics' Urban-Rural Classification Scheme for Counties from 2013 were used to define urban and rural categories. RESULTS: An estimated 5.2 million (95% CI = 3.5-7.0 million) Part B beneficiaries were eligible for the MDPP. By state, estimates ranged from 13,000 (95% CI = 8,500-18,000) in Alaska to 469,000 (95% CI = 296,000-641,000) in California. There were 2,149 counties with ≤1,000 eligible beneficiaries and 11 with >25,000. Consistent with demographic patterns, urban counties had more eligible beneficiaries than rural counties. CONCLUSIONS: These estimates could be used to plan locations for new MDPPs and reach eligible Part B beneficiaries for enrollment.

Smoking and Liver Disease.

Cigarette smoking is the leading cause of preventable disease and death in the United States, causing approximately 480,000 deaths per year, which is equivalent to 1 in 5 deaths being attributable to tobacco use. The adverse effects of cigarette smoking on the lungs and cardiovascular system are well described; however, the detrimental effects of smoking on the liver are not as well defined. Smoking affects the liver via 3 separate mechanisms: toxic (both direct and indirect), immunologic, and oncogenic. There is an emerging body of evidence of an association between cigarette smoking and progression of fibrosis in chronic liver diseases such as nonalcoholic fatty liver disease and primary biliary cholangitis. Smoking is associated with accelerated development of hepatocellular carcinoma in patients with chronic hepatitis B or C virus infection. Tobacco smoking adversely affects lung function, which increases physical limitations and may preclude liver transplantation. Following liver transplantation, smoking is associated with several adverse outcomes, including increased risk of de novo malignancy, vascular complications, and nongraft-associated mortality. The respiratory illness caused by the novel coronavirus disease 2019 serves as a good example of the complex interplay between the lungs and the liver. It is evident that cigarette smoking has important negative effects on a multitude of liver diseases and that patients' smoking cessation must be prioritized. The data are limited, and more research is needed to better understand how smoking affects the liver. This article summarizes what is known about the pathologic effects of cigarette smoking on common liver diseases.

No evidence for higher rates of hepatocellular carcinoma after direct-acting antiviral treatment: a meta-analysis.

AIM: Hepatitis C virus (HCV) is the leading cause of hepatocellular carcinoma (HCC) in the United States. Achieving sustained viral response with interferon (IFN) treatment reduces the risk from 3%-5% to 0.5%-1% annually. Several studies reported unexpectedly high rates of HCC after treatment with direct-acting antivirals (DAAs). The aim of our study was to compare HCC rates in DAA-, IFN-treated and untreated populations. METHODS: A literature search was conducted using ScienceDirect, Ovid®, Web of Science and MEDLINE through January 2019. Studies were included if they measured rates of de novo or recurrent HCC (following curative treatment) in HCV-infected persons. We included 138 studies (n = 177,512). Simple pooling of data and meta-analysis were performed, using the random effects method. RESULTS: Mean age was higher in the DAA-treated vs. IFN-treated group (58.4 years vs. 52.6 years; P = 0.0073), as were diabetes prevalence (34.5% vs. 11.7%; P ≤ 0.001) and incident cirrhosis (47.8% vs. 34.2%, P = 0.0017). The incidence rate of de novo HCC was 2.01/100 person-years (py) (95%CI: 1.38, 2.67) in the DAA group and 1.45/100py (95%CI: 0.98, 1.94) in the IFN-treated group. HCC recurred at 16.76/100py (95%CI: 10.75, 22.91) in the DAA-treated group vs. 20.04/100py (95%CI: 2.58, 45.21) after IFN. After adjusting for factors such as age and cirrhosis, the hazard ratio was 0.58 (95%CI: 0.20, 1.07) for HCC occurrence and 0.59 (95%CI: 0.24, 1.03) for HCC recurrence after DAA treatment compared to IFN-based treatment. CONCLUSION: We did not find evidence for increased rates of HCC in DAA-treated compared with IFN-treated patients. Compared to those treated with IFN, older patients with additional risk factors for HCC were treated with DAAs. This imbalance appears to explain the higher numerical incidence of HCC among DAA-treated patients.

Autoimmune Kidney Diseases Associated with Chronic Viral Infections.

Autoimmune kidney diseases triggered by viruses are an important cause of kidney disease in patients affected by chronic viral infection. Hepatitis B virus (HBV) infection is associated with membranous nephropathy and polyarteritis nodosa. Hepatitis C virus (HCV) infection is a major cause of cryoglobulinemic glomerulonephritis. Patients with human immunodeficiency virus (HIV) may develop HIV-associated nephropathy, a form of collapsing focal segmental glomerulosclerosis, or various forms of immune-complex-mediated kidney diseases. This article summarizes what is known about the pathogenesis, diagnosis, and management of immune-mediated kidney diseases in adults with chronic HBV, HCV, and HIV infections.

Prolonged cenicriviroc therapy reduces hepatic fibrosis despite steatohepatitis in a diet-induced mouse model of nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease projected to become the leading cause of cirrhosis and liver transplantation in the next decade. Cenicriviroc (CVC), a dual chemokine receptor 2 and 5 antagonist, prevents macrophage trafficking and is under clinical investigation for the treatment of human NASH fibrosis. We assessed the efficacy and durability of short and prolonged CVC therapy in a diet-induced mouse model of NASH, the choline deficient, L-amino acid-defined, high-fat diet (CDAHFD) model. C57BL/6 mice received 4 or 14 weeks of standard chow or the CDAHFD. CVC (10 mg/kg/day and 30 mg/kg/day for 4 weeks and 20 mg/kg/day and 30 mg/kg/day for 14 weeks) was initiated simultaneously with the CDAHFD. At 4 and 14 weeks, livers were harvested for histology and flow cytometric analyses of intrahepatic immune cells. High-dose CVC (30 mg/kg/day) therapy in CDAHFD mice for 4 or 14 weeks inhibited intrahepatic accumulation of Ly6Chigh bone marrow-derived macrophages. Prolonged CVC therapy (14 weeks) yielded no significant differences in the total intrahepatic macrophage populations among treatment groups but increased the frequency of intrahepatic anti-inflammatory macrophages in the high-dose CVC group. Despite ongoing steatohepatitis, there was significantly less fibrosis in CDAHFD mice receiving high-dose CVC for 14 weeks based on histologic and molecular markers, mirroring observations in human NASH CVC trials. CVC also directly inhibited the profibrotic gene signature of transforming growth factor-ß-stimulated primary mouse hepatic stellate cells in vitro. Conclusion: CVC is a novel therapeutic agent that is associated with reduced fibrosis despite ongoing steatohepatitis. Its ability to alter intrahepatic macrophage populations and inhibit profibrogenic genes in hepatic stellate cells in NASH livers may contribute to its observed antifibrotic effect. (Hepatology Communications 2018;2:529-545).

Treatment of hepatitis C virus infection in patients with mixed cryoglobulinemic syndrome and cryoglobulinemic glomerulonephritis.

Cryoglobulinemia is a common extrahepatic manifestation of infection with hepatitis C virus (HCV). When signs and symptoms of systemic vasculitis or glomerulonephritis occur in the presence of circulating cryoglobulins, this syndrome is called "mixed cryoglobulinemia syndrome" (MCS). Historically, interferon-based therapies in HCV have been associated with lower rates of viral cure in patients with MCS than in the general HCV-infected population. The advent of direct-acting antiviral therapies have revolutionized the treatment of HCV, dramatically increasing rates of cure. Early studies of first-generation protease inhibitors (telaprevir and boceprevir) in combination with interferon and ribavirin demonstrated HCV cure rates of 67% and complete clinical response rates of vasculitis symptoms in 60% of patients with MCS; however, regimens were poorly tolerated by patients, 22% discontinued treatment early. More recently, all-oral, interferon-free regimens have become available and combination therapies are now being approved for patients with and without renal impairment. Patients with HCV-MCS achieved sustained virologic response in 297 out of 313 patients (95%) treated with direct-acting antiviral therapy, and 85% had a complete or partial clinical response of MCS symptoms. Current direct-acting antiviral therapies are well tolerated in patients with HCV-MCS and only 1.6% discontinued treatment early. Patients with cryoglobulinemic glomerulonephritis also had an excellent cure rate (94%). The majority improved; 17/52 (33%) experienced full remission and 15/52 (29%) experienced partial remission. There were no reports of worsening kidney function in patients treated with direct-acting antiviral therapies. Less than 5% of patients with HCV-MCS treated with IFN-free direct-acting antiviral therapy required immunosuppression. However, patients with severe vasculitis appear to still require concomitant immunosuppression.

The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study.

Recent studies have reported higher rates of hepatocellular carcinoma (HCC) in individuals treated with direct-acting antivirals (DAAs). However, making definitive conclusions has been challenging because of the heterogeneous populations and methodologies of these reports. We investigated whether DAA use is associated with higher rates of incident HCC compared to treatment with interferon (IFN)-based regimens. We performed a retrospective, population-based cohort study using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database. In a cohort of 17,836 persons, sustained virological response (SVR) was achieved by 66.6% and 96.2% of the IFN and DAA groups, respectively. Among all treated persons, risk of HCC was not higher in the DAA group compared to the IFN group (hazard ratio, 1.07; 95% confidence interval, 0.55, 2.08). Among persons with cirrhosis who achieved SVR, neither the HCC incidence rate nor HCC-free survival were significantly different in the DAA group compared to the IFN group (21.2 vs. 22.8 per 1,000 person-years; P = 0.78 and log-rank P = 0.17, respectively). Untreated persons with cirrhosis had a significantly higher HCC incidence rate (45.3 per 1,000 person-years) compared to those treated with either IFN or DAAs (P = 0.03). Both groups of treated persons had significantly lower probability of HCC development compared to untreated persons (log-rank, P = 0.0004). CONCLUSION: DAA treatment is not associated with a higher risk of HCC in persons with cirrhosis with chronic HCV infection in the short term. Previously reported higher rates of HCC associated with DAA treatment may be explained by both the presence of relatively fewer baseline HCC risk factors in persons treated with IFN as well as selection bias, given that DAA regimens were used to treat persons at higher risk for developing HCC. (Hepatology 2018;67:2244-2253).

Early Results of States' Efforts to Support, Scale, and Sustain the National Diabetes Prevention Program.

The Centers for Disease Control and Prevention (CDC) developed a cooperative agreement with health departments in all 50 states and the District of Columbia to strengthen chronic disease prevention and management efforts through the implementation of evidence-based strategies, such as CDC's National Diabetes Prevention Program. The National Diabetes Prevention Program supports organizations to deliver the year-long lifestyle change program that has been proven to prevent or delay the onset of type 2 diabetes among those at high risk. This article describes activities, barriers, and facilitators reported by funded states during the first 3 years (2013-2015) of a 5-year funding cycle.