IFNL4 genotype and other personal characteristics to predict response to 8-week sofosbuvir-based treatment for chronic hepatitis C.

Background: Shorter duration therapy for hepatitis C virus (HCV) infection might reduce treatment costs and increase the number of patients treated and cured. We determined factors associated with treatment response after an 8-week sofosbuvir-based therapy and developed a simple model to predict an individual's likelihood of treatment success.

Methods: Among 2907 patients who received ledipasvir/sofosbuvir for 8 weeks, we determined failure rates by demographic and clinical characteristics, and IFNL4-∆G/TT genotype.

Cancers Attributable to Infections in the US in 2017: A Meta-Analysis.

Importance: Infections are largely modifiable causes of cancer. However, there remains untapped potential for preventing and treating carcinogenic infections in the US.

Objective: To estimate the percentage and number of incident cancers attributable to infections in the US among adults and children for the most recent year cancer incidence data were available (2017).

Decreasing incidence of hepatocellular carcinoma among most racial groups: SEER-22, 2000-2019.

Background: Hepatocellular carcinoma (HCC) incidence was rising in the United States. Previously, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program through 2017, we found that overall incidence had begun to decline, although not in Black and American Indian/Alaska Native (AI/AN) populations. Utilizing expanded SEER data encompassing ~50% of the population, we examined secular trends and demographic differences in HCC incidence through 2019.

Risk of hepatocellular carcinoma in people with HIV in the United States, 2001-2019.

Background: People with HIV have higher risk of hepatocellular carcinoma than the general population, partly because of higher prevalence of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV).

Methods: We calculated standardized incidence ratios for hepatocellular carcinoma in people with HIV by comparing rates from people with HIV in the HIV/AIDS Cancer Match Study, a population-based HIV and cancer registry linkage, to those in the general population. We used multivariable Poisson regression to estimate adjusted incidence rate ratios among people with HIV and linked the Texas HIV registry with medical claims data to estimate adjusted odds ratios (AORs) of HBV and HCV in hepatocellular carcinoma patients with logistic regression.

Genotype Frequencies in Asian Populations Support Shorter Duration Therapy with Sofosbuvir-Based Hepatitis C Virus Regimens to Increase the Number Cured.

Globally, ∼56.8 million people are chronically infected with hepatitis C virus (HCV), with about half residing in Asia. The cost and efficiency of delivering regimens based on direct-acting antiviral agents for HCV are important considerations in implementing these curative treatments.

Hepatitis B virus and hepatitis D virus infection in women with or at risk for HIV infection in the United States.

Hepatitis D virus (HDV) requires co-infection with hepatitis B virus (HBV). Human immunodeficiency virus (HIV) shares transmission routes with these viruses. Among 4,932 US women infected with or at-risk for HIV during 1994-2015, HBV surface antigen (HBsAg) positivity was more common in women with HIV (2.

No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.

Background: IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers.

Methods: We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990.

Association between Immunologic Markers and Cirrhosis in Individuals from a Prospective Chronic Hepatitis C Cohort.

Background: Chronic hepatitis C virus (HCV) infection can affect immune response and inflammatory pathways, leading to severe liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). Methods: In a prospective cohort of chronically HCV-infected individuals, we sampled 68 individuals who developed cirrhosis, 91 controls who did not develop cirrhosis, and 94 individuals who developed HCC. Unconditional odds ratios (ORs) from polytomous logistic regression models and canonical discriminant analyses (CDAs) were used to compare categorical (C) baseline plasma levels for 102 markers in individuals who developed cirrhosis vs.

The role of IFNL4 in liver inflammation and progression of fibrosis.

The discovery that genetic variation within the interferon lambda locus has a profound effect on the outcome of hepatitis C virus (HCV) treatment and spontaneous clearance of HCV is one of the great triumphs of genomic medicine. Subsequently, the IFNL4 gene was discovered and proposed as the causal gene underlying this association. However, there has been a lively debate within the field concerning the causality, which has been further complicated by a change in naming.

The Impact of IFNλ4 on the Adaptive Immune Response to SARS-CoV-2 Infection.

Genetic polymorphisms at the loci are known to influence the clinical outcome of several different infectious diseases. Best described is the association between the genotype and hepatitis C virus clearance. However, an influence of the genotype on the adaptive immune system was suggested by several studies but never investigated in humans.

Association between immunologic markers and cirrhosis in individuals with chronic hepatitis B.

Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs.

Intracellular Accumulation of IFN-λ4 Induces ER Stress and Results in Anti-Cirrhotic but Pro-HCV Effects.

polymorphisms are inversely associated with the risk of chronic hepatitis C virus (HCV) infection and cirrhosis, two major risk factors for developing hepatocellular carcinoma (HCC). To further explore these inverse associations and their molecular underpinnings, we analyzed polymorphisms represented by the genotype (presence of rs368234815-dG or rs12979860-T alleles) in HCV patients: 2969 from Japan and 2931 from Taiwan. genotype was associated with an increased risk of HCV-related HCC (OR=1.

Immunologic markers and risk of hepatocellular carcinoma in hepatitis B virus- and hepatitis C virus-infected individuals.

Background: Clinical and experimental studies suggest immunologic proteins contribute to hepatocellular carcinoma (HCC) development.

Aim: To evaluate circulating immunologic markers and HCC risk.

Methods: From a Taiwanese cohort of chronically hepatitis B virus (HBV)-infected individuals followed over time (REVEAL-HBV), we sampled 175 who developed HCC, 117 cirrhosis only, and 165 non-cirrhotic controls.

Death certificates compared to SEER-Medicare data for surveillance of liver cancer mortality due to hepatitis B or hepatitis C infection.

Hepatocellular carcinoma (HCC) is often caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. To investigate the completeness of death certificates for recording viral hepatitis in HCC death, we compared the proportion of HCC deaths with hepatitis virus infection reported on death certificates to that reported as claims in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database among individuals ≥66 years of age. For 2001-2015, we tabulated proportions of HCC deaths with HBV or HCV infection in each database overall, and by demographic factors.

Declining US Hepatocellular Carcinoma Rates, 2014-2017.

Liver cancer is a prominent cause of cancer death in the United States. Rates of hepatocellular carcinoma (HCC), the most common histologic subtype, increased for decades, until recent years when rates flattened, and then potentially declined. Previously, we reported that US HCC rates in 2016 were 4% lower than 2015; however, it was unclear from those data whether that finding reflected a true downward trend.

Intradisciplinary Nursing Communication Post Hospital Merger: A Quality Improvement Project Using Online Communities of Practice in the Intensive Care Unit.

After hospital mergers, unit work environments are at risk of being unhealthy due to poor intradisciplinary two-way communication in times of change. This quality improvement project explored the impact a 4-week, social-media-based, intradisciplinary communication strategy had on a postmerger intensive care unit work environment. The sample (N = 14) included 11 bedside nurses and three administrative nurses working in a 22-bed southwestern US ICU.

A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

Background: Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors.

Methods: To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group.

Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection.

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance.

Prediagnostic serum polychlorinated biphenyl concentrations and primary liver cancer: A case-control study nested within two prospective cohorts.

Background: Polychlorinated biphenyls (PCBs) were used in electrical equipment and a range of construction materials. Although banned in the United States and most of Europe in the 1970s, they are highly persistent in the environment and bioaccumulate. Whether PCBs are associated with liver cancer risk at general population levels is unknown.