Cell Culture Models for the Study of Hepatitis D Virus Entry and Infection

Chronic hepatitis D is one of the most severe and aggressive forms of chronic viral hepatitis with a high risk of developing hepatocellular carcinoma (HCC). It results from the co-infection of the liver with the hepatitis B virus (HBV) and its satellite, the hepatitis D virus (HDV). Although current therapies can control HBV infection, no treatment that efficiently eliminates HDV is available and novel therapeutic strategies are needed. Although the HDV cycle is well described, the lack of simple experimental models has restricted the study of host–virus interactions, even if they represent relevant therapeutic targets. In the last few years, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key cellular entry factor for HBV and HDV has allowed the development of new cell culture models susceptible to HBV and HDV infection. In this review, we summarize the main in vitro model systems used for the study of HDV entry and infection, discuss their benefits and limitations and highlight perspectives for future developments.     

Age-Sensitive Design of Online Health Information: Comparative Usability Study

Background

Older adults’ health maintenance may be enhanced by having access to online health information. However, usability issues may prevent older adults from easily accessing such information. Prior research has shown that aging is associated with a unique pattern of cognitive changes, and knowledge of these changes may be used in the design of health websites for older adults.

Objective

The goal of the current study was to examine whether older adults use of a health information website was affected by an alternative information architecture and access interface (hierarchical versus tag-based).

Methods

Fifty younger adults (aged 18-23) and 50 older adults (aged 60-80) navigated a health information website, which was organized hierarchically or used tags/keywords, to find answers to health-related questions while their performance was tracked. We hypothesized that older adults would perform better in the tag-based health information website because it placed greater demands on abilities that remain intact with aging (verbal ability and vocabulary).

Results

The pattern of age-related differences in computer use was consistent with prior research with older adults. We found that older adults had been using computers for less time (F _1,98= 10.6, P= .002) and used them less often (F _1,98= 11.3, P= .001) than younger adults. Also consistent with the cognitive aging literature, younger adults had greater spatial visualization and orientation abilities (F _1,98= 34.6, P< .001 and F _1,98= 6.8, P= .01) and a larger memory span (F _1,98= 5.7, P= .02) than older adults, but older adults had greater vocabulary (F _1,98= 11.4, P= .001). Older adults also took significantly more medications than younger adults (F _1,98= 57.7, P< .001). In the information search task, older adults performed worse than younger adults (F _1,96= 18.0, P< .001). However, there was a significant age × condition interaction indicating that while younger adults outperformed older adults in the hierarchical condition (F _1,96= 25.2, P< .001), there were no significant age-related differences in the tag-based condition, indicating that older adults performed as well as younger adults in this condition.

Conclusions

Access to online health information is increasing in popularity and can lead to a more informed health consumer. However, usability barriers may differentially affect older adults. The results of the current study suggest that the design of health information websites that take into account age-related changes in cognition can enhance older adults’ access to such information.     

Hospice utilization in advanced cervical malignancies: An analysis of the National Inpatient Sample

ObjectiveHospice services improve quality of life and outcomes for patients and caretakers, compared to inpatient mortality. This study identifies factors that exert the strongest influence on end-of-life care modalities in patients with cervical cancer.MethodsAdmissions with a diagnosis of cervical cancer that were discharged to hospice or died in-hospital were identified in the National Inpatient Sample years 2007–2011, excluding admissions coded for hysterectomy. Logistic regression models were used to examine differences in age, race, length of stay, primary payer, hospital region, admission type, hospital bedsize, hospital teaching status, income quartile, and Elixhauser comorbidity index score between the groups.Results2073 admissions with a diagnosis of cervical cancer resulting in hospice discharge (n = 1290) or inpatient death (n = 783) were identified. Age (P = 0.01), hospital region (P = 0.01), length of hospitalization (P < 0.01), Elixhauser comorbidity index score (P = 0.03), and urban vs. rural location (P = 0.01) had a significant impact on disposition in univariate analysis. Admissions of patients categorized as Asian/Pacific Islander (OR = 2.24, 95% CI 1.11–4.49), hospitalizations lasting 0–3 days (OR = 1.57, 95% CI 1.21–2.03), and admissions in rural areas (OR = 1.62, 95% CI 1.12–2.36) had higher rates of in-hospital death compared to the reference groups. Patients aged 18–45 years (OR = 0.69, 95% CI 0.52–0.90) and those treated in the South (OR 0.59, 95% CI 0.45–0.77) and West (OR = 0.50, 95% CI 0.30–0.81) had lower odds ratios of inpatient mortality.ConclusionModalities of care in terminal cervical cancer vary among sociodemographic and clinical factors. This data underscores the continued push for improved end-of-life care among cervical cancer patients and can guide clinicians in appropriate targeted counseling to increase utilization of hospice resources.     

The value of comprehensive genomic sequencing to maximize the identification of clinically actionable alterations in advanced cancer patients: a case series

Purpose: We present seven cases of advanced cancer patients who initially underwent tumor testing utilizing smaller, panel-based tests, followed by a variety of therapeutic treatments which ultimately resulted in progression of their disease. These cases demonstrate the value of utilizing WES/RNA seq and characterization following disease progression in these patients and the determination of clinically targetable alterations as well as acquired resistance mutations.Materials and Methods: All patients are part of an IRB approved observational study. WES and RNA sequencing were performed, using GEM ExTra^® on tumor and blood samples obtained during routine clinical care. To accurately determine somatic versus germline alterations the test was performed with paired normal testing from peripheral blood.Results: The presented cases demonstrate the clinical impact of actionable findings uncovered using GEM ExTra^® in patients with advanced disease who failed many rounds of treatment. Unique alterations were identified resulting in newly identified potential targeted therapies, mechanisms of resistance, and variation in the genomic characterization of the primary versus the metastatic tumor.Conclusions: Taken together our results demonstrate that GEM ExTra^® maximizes detection of actionable mutations, thus allowing for appropriate treatment selection for patients harboring both common and rare genomic alterations.     

Impact of the new kidney allocation system A2/A2B → B policy on access to transplantation among minority candidates

Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case‐control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients. Cases were defined as recipients of A2/A2B kidneys, whereas controls were all remaining recipients of non‐A2/A2B kidneys. A2i DDKT trends were compared from the pre‐KAS (1/1/2013‐12/3/2014) to the post‐KAS period (12/4/2014‐2/28/2017) using multivariable logistic regression. Post‐KAS, there was a 4.9‐fold increase in the likelihood of A2i DDKT, compared to the pre‐KAS period (odds ratio [OR] 4.92, 95% confidence interval [CI] 3.67‐6.60). However, compared to whites, there was no difference in the likelihood of A2i DDKT among minorities post‐KAS. Although KAS resulted in increasing A2/A2B→B DDKT, the likelihood of A2i DDKT among minorities, relative to whites, was not improved. Further discussion regarding A2/A2B→B policy revisions aiming to improve DDKT access for minorities is warranted.     

Population level outcomes and cost‐effectiveness of hepatitis C treatment pre‐ vs postkidney transplantation

Direct‐acting antivirals approved for use in patients with end‐stage renal disease (ESRD) now exist. HCV‐positive (HCV+) ESRD patients have the opportunity to decrease the waiting times for transplantation by accepting HCV‐infected kidneys. The optimal timing for HCV treatment (pre‐ vs posttransplant) among kidney transplant candidates is unknown. Monte Carlo microsimulation of 100 000 candidates was used to examine the cost‐effectiveness of HCV treatment pretransplant vs posttransplant by liver fibrosis stage and waiting time over a lifetime time horizon using 2 regimens approved for ESRD patients. Treatment pretransplant yielded higher quality‐adjusted life years (QALYs) compared with posttransplant treatment in all subgroups except those with Meta‐analysis of Histological Data in Viral Hepatitis stage F0 (pretransplant: 5.7 QALYs vs posttransplant: 5.8 QALYs). However, treatment posttransplant was cost‐saving due to decreased dialysis duration with the use of HCV‐infected kidneys (pretransplant: $735 700 vs posttransplant: $682 400). Using a willingness‐to‐pay threshold of $100 000, treatment pretransplant was not cost‐effective except for those with Meta‐analysis of Histological Data in Viral Hepatitis stage F3 whose fibrosis progression was halted. If HCV+ candidates had access to HCV‐infected donors and were transplanted ≥9 months sooner than HCV‐negative candidates, treatment pretransplant was no longer cost‐effective (incremental cost‐effectiveness ratio [ICER]: $107 100). In conclusion, optimal timing of treatment depends on fibrosis stage and access to HCV+ kidneys but generally favors posttransplant HCV eradication.