Laboratory monitoring and antiviral treatment for chronic hepatitis B among routine care patients in the United States

We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. \u27Recommended monitoring\u27 was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the \u27definite\u27 category, and 34.1% (208/610 patients) in the \u27equivocal\u27 category, of whom 109 moved up to \u27definite\u27 status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in \u27definite\u27 patients. Routine monitoring rates were high prior to treatment in \u27definite/ treated\u27 patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in \u27definite/ untreated\u27 patients (ALT: 48%; DNA: 32%). Among \u27equivocal/ treated\u27 patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among \u27treatment ineligible\u27 patients was similar to those in the \u27equivocal\u27 and untreated \u27definite\u27 groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with \u27definite\u27 indications for antiviral therapy remained untreated

Trends in Cirrhosis and Mortality by Age, Sex, Race, and Antiviral Treatment Status Among US Chronic Hepatitis B Patients (2006-2016)

BACKGROUND: Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. METHODS: Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. RESULTS: Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. CONCLUSIONS: From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB

Epitope-positive truncating MLH1 mutation and loss of PMS2: implications for IHC-directed genetic testing for lynch syndrome

We assessed mismatch repair by immunohistochemistry (IHC) and microsatellite instability (MSI) analysis in an early onset endometrial cancer and a sister’s colon cancer. We demonstrated high-level MSI and normal expression for MLH1, MSH2 and MSH6. PMS2 failed to stain in both tumors, strongly implicating a PMS2 defect. This family did not meet clinical criteria for Lynch syndrome. However, early onset endometrial cancers in the proband and her sister, a metachronous colorectal cancer in the sister as well as MSI in endometrial and colonic tumors suggested a heritable mismatch repair defect. PCR-based direct exonic sequencing and multiplex ligation-dependent probe amplification (MLPA) were undertaken to search for PMS2 mutations in the germline DNA from the proband and her sister. No mutation was identified in the PMS2 gene. However, PMS2 exons 3, 4, 13, 14, 15 were not evaluated by MLPA and as such, rearrangements involving those exons cannot be excluded. Clinical testing for MLH1 and MSH2 mutation revealed a germline deletion of MLH1 exons 14 and 15. This MLH1 germline deletion leads to an immunodetectable stable C-terminal truncated MLH1 protein which based on the IHC staining must abrogate PMS2 stabilization. To the best of our knowledge, loss of PMS2 in MLH1 truncating mutation carriers that express MLH1 in their tumors has not been previously reported. This family points to a potential limitation of IHC-directed gene testing for suspected Lynch syndrome and the need to consider comprehensive MLH1 testing for individuals whose tumors lack PMS2 but for whom PMS2 mutations are not identified

Allometry and Ecology of the Bilaterian Gut Microbiome.

Classical ecology provides principles for construction and function of biological communities, but to what extent these apply to the animal-associated microbiota is just beginning to be assessed. Here, we investigated the influence of several well-known ecological principles on animal-associated microbiota by characterizing gut microbial specimens from bilaterally symmetrical animals (Bilateria) ranging from flies to whales. A rigorously vetted sample set containing 265 specimens from 64 species was assembled. Bacterial lineages were characterized by 16S rRNA gene sequencing. Previously published samples were also compared, allowing analysis of over 1,098 samples in total. A restricted number of bacterial phyla was found to account for the great majority of gut colonists. Gut microbial composition was associated with host phylogeny and diet. We identified numerous gut bacterial 16S rRNA gene sequences that diverged deeply from previously studied taxa, identifying opportunities to discover new bacterial types. The number of bacterial lineages per gut sample was positively associated with animal mass, paralleling known species-area relationships from island biogeography and implicating body size as a determinant of community stability and niche complexity. Samples from larger animals harbored greater numbers of anaerobic communities, specifying a mechanism for generating more-complex microbial environments. Predictions for species/abundance relationships from models of neutral colonization did not match the data set, pointing to alternative mechanisms such as selection of specific colonists by environmental niche. Taken together, the data suggest that niche complexity increases with gut size and that niche selection forces dominate gut community construction.IMPORTANCEThe intestinal microbiome of animals is essential for health, contributing to digestion of foods, proper immune development, inhibition of pathogen colonization, and catabolism of xenobiotic compounds. How these communities assemble and persist is just beginning to be investigated. Here we interrogated a set of gut samples from a wide range of animals to investigate the roles of selection and random processes in microbial community construction. We show that the numbers of bacterial species increased with the weight of host organisms, paralleling findings from studies of island biogeography. Communities in larger organisms tended to be more anaerobic, suggesting one mechanism for niche diversification. Nonselective processes enable specific predictions for community structure, but our samples did not match the predictions of the neutral model. Thus, these findings highlight the importance of niche selection in community construction and suggest mechanisms of niche diversification

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Juggling the contradictions: An exploration of White college students\u27 understanding of meritocracy and racial inequality

This qualitative study investigates the ways in which White college students make sense of meritocracy in relation to racial inequality in the contemporary United States. Through in-depth individual interviews and qualitative methods of analysis, participants reveal their beliefs about how people achieve success in the U.S., their explanations of the economic disparity between Black and White Americans, and their perspectives on meritocracy in contemporary U.S. society. Twenty traditionally-aged White undergraduate college students at a large public University in the Northeast took part in the study. The sample was stratified by gender, year in school and engagement with issues of racism. White students who had experience with issues of racism through academic courses, or who had taken active roles in student organizations that addressed racism were identified as “engaged.” White students who had not been actively involved in such courses or co-curricular activities were identified as “not-engaged.” Based on their gender or year in school, there were no differences in White students\u27 perspectives on either meritocracy or racial inequality. Prior engagement with racism, however, was strongly related to striking differences in White students\u27 perspectives on meritocracy and their explanations for racial inequality. Engaged White students were much more likely than not-engaged White students to espouse a structuralist stratification perspective about both success and racial inequality, and to assert that the United States is not a meritocracy. Most of the not-engaged White students relied on individualist explanations for both the achievement of success and the causes of racial inequality. Of particular note is the way that many not-engaged White students seemed to be involved in a cognitive juggling act, trying to work with the contradictions between their ideology of meritocracy and their awareness of racial discrimination. The findings raise implications about the role that merit and racial ideology play in forming White students\u27 understanding of individual achievement and racial inequality in the United States. The study includes suggestions for new ways of conceptualizing anti-racism teaching to emphasize the role of meritocratic ideology and it suggests future research on developmental processes that may challenge traditionally-aged White undergraduate college students\u27 reliance on merit ideology

Pathways from climate change to emotional wellbeing: A qualitative study of Kenyan smallholder farmers living with HIV.

Climate change is associated with adverse mental and emotional health outcomes. Social and economic factors are well-known drivers of mental health, yet comparatively few studies examine the social and economic pathways through which climate change affects mental health. There is additionally a lack of research on climate change and mental health in sub-Saharan Africa. This qualitative study aimed to identify potential social and economic pathways through which climate change impacts mental and emotional wellbeing, focusing on a vulnerable population of Kenyan smallholder farmers living with HIV. We conducted in-depth, semi-structured interviews with forty participants to explore their experience of climate change. We used a thematic analytical approach. We find that among our study population of Kenyan smallholder farmers living with HIV, climate change is significantly affecting mental and emotional wellbeing. Respondents universally report some level of climate impact on emotional health including high degrees of stress; fear and concern about the future; and sadness, worry, and anxiety from losing ones home, farm, occupation, or ability to support their family. Climate-related economic insecurity is a main driver of emotional distress. Widespread economic insecurity disrupts systems of communal and family support, which is an additional driver of worsening mental and emotional health. Our study finds that individual adaptive strategies used by farmers in the face of economic and social volatility can deepen economic insecurity and are likely insufficient to protect mental health. Finally, we find that agricultural policies can worsen economic insecurity and other mental health risk factors. Our proposed conceptual model of economic and social pathways relevant for mental health can inform future studies of vulnerable populations and inform health system and policy responses to protect health in a changing climate

RISK FACTORS FOR SARS-COV-2 INFECTION AMONG PATIENTS WITH CHRONIC VIRAL HEPATITIS

Background: We investigated factors associated with risk of SARS-CoV-2 infection among an established cohort of chronic hepatitis B and C (CHB/ CHC) patients at a large, vertically integrated health system located in southeastern Michigan (which includes Detroit), a racially-diverse area that experienced a significant outbreak of COVID-19 during March–May 2020. Methods: Patient characteristics and clinical conditions were collected for the period prior to date of first positive SARS-CoV-2 test, or March 11, 2020 for those who were not SARS-CoV-2 infected. Variables included: age; gender; race; insurance type; household income; BMI; CHC vs. CHB; AST; ALT; liver fibrosis status (as measured by APRI/ FIB4); diagnosis of liver cirrhosis; Charlson-Deyo comorbidity index; select individual comorbidities; and history of antiviral therapy. Patients coinfected with both CHB and CHC were excluded. Logistic regression, univariate followed by multivariable modeling, was performed. Variables with p-values \u3c0.05 were retained in the final model. Results: A total of 13,556 patients with a history of chronic viral hepatitis were included; 94 had a positive SARS-CoV-2 result. In univariate comparisons, there was a significant difference between groups (p\u3c0.05) with regard to type of hepatitis infection (C vs. B), age, race, BMI, insurance type, household income, comorbidity index, AST, ALT, APRI, presence of cirrhosis, type 2 diabetes, chronic heart disease, renal disease, peripheral vascular disease, history of receipt of antiviral therapy, and achievement of sustained viral response (CHC). In the final multivariable model, increased risk of SARS-CoV-2 infection was associated with CHC vs CHB (adjusted Odds Ratio [aOR])=4.00, 95% confidence interval [CI] 1.89–8.47), presence of cirrhosis (aOR=1.66, 95%CI 1.08–2.55), normal AST at baseline (aOR=2.50, 95%CI 1.46–4.27), higher comorbidity index (aOR=1.40, 95%CI 1.19–1.67), Black/ African American vs white race (aOR=18.0, CI 6.59–45.5), and BMI (BMI 25–30 vs \u3c25: aOR=3.82, CI 1.95–7.49; BMI \u3e30 vs \u3c25: aOR=2.85, CI 1.46–5.56). Conclusion: In a cohort of chronic viral hepatitis patients drawn from a geographic area that experienced a significant COVID-19 outbreak, Black/ African American race, BMI\u3e25, cirrhosis, CHC (active or post-SVR) vs. CHB, and higher comorbidity index were associated with higher risk of SARS-CoV-2 infection

IMPACT OF HISTORY OF CHRONIC VIRAL HEPATITIS AND LIVER FIBROSIS ON RISK OF HOSPITALIZATION AND DEATH AMONG PATIENTS WITH SARS-COV-2 INFECTION

Background: We investigated factors associated with Covid-19 related hospitalization and death among patients with and without a history of chronic viral hepatitis B or C (CHB/CHC) in a single large, integrated health system located in metropolitan Detroit, Michigan, an area that experienced a significant outbreak of SARS-Cov-2 in Spring 2020. Methods: Baseline data were collected before date of first positive SARS-CoV-2 test or Covid-related hospitalization, whichever was earlier. Risk of hospitalization was analyzed with logistic regression; risk of death with Cox regression. Variables with p-values \u3c0.05 were retained in the final multivariable models. Results: Of 6661 patients that tested SARS-CoV-2 positive from March 12–April 26, 2020, 94 (1.4%) had a history of CHB or CHC. A total of 2604 were hospitalized due to Covid-19, 55 (58.5%) with CHB or CHC and 2549 (38.8%) without CHB/CHC. Among hospitalized patients, 10 (18.2%) CHB/CHC patients and 426 (16.7%) non-hepatitis patients died. In multivariable analyses, viral hepatitis was not a risk factor for hospitalization, but approached significance for death (adjusted Hazard Ratio [aHR] 1.82, 95% Confidence Interval [CI] 0.96–3.46). In addition to recognized risk factors for Covid-19 severity such as increasing age, obesity, type 2 diabetes, and multiple co-morbidities, we found that increasing Fibrosis-4 (FIB4) score (a biomarker for liver fibrosis and cirrhosis) was associated with risk of hospitalization (adjusted Odds Ratio [aOR] 95%CI 1.32, 1.16–1.51). African American and male patients were also at higher risk of hospitalization. Notably, a number of risk factors for hospitalization were not associated with or were associated with reduced risk of death among hospitalized patients; African American patients and those with BMI ≥30 had lower mortality than White patients and those with BMI \u3c25 (aHR 0.73, 95%CI 0.60–0.89; and aHR 0.69, 95%CI 0.54–0.88) respectively. Conclusion: Increasing baseline FIB4 index is associated with higher risk of hospitalization among patients with Covid-19. History of CHB or CHC trended toward increased risk of Covid-related mortality; future studies in larger samples of patients with chronic viral hepatitis are warranted

Dynamic risk assessment for hepatocellular carcinoma in patients with chronic hepatitis C

Chronic hepatitis C (HCV) is a primary cause of hepatocellular carcinoma (HCC). Although antiviral treatment reduces risk of HCC, few studies quantify the impact of treatment on long-term risk in the era of direct-acting antivirals (DAA). Using data from the Chronic Hepatitis Cohort Study, we evaluated the impact of treatment type (DAA, interferon-based [IFN], or none) and outcome (sustained virological response [SVR] or treatment failure [TF]) on risk of HCC. We then developed and validated a predictive risk model. 17186 HCV patients were followed until HCC, death or last follow-up. We used extended landmark modelling, with time-varying covariates and propensity score justification and generalized estimating equations with a link function for discrete time-to-event data. Death was considered a competing risk. We observed 586 HCC cases across 104,000 interval-years of follow-up. SVR from DAA or IFN-based treatment reduced risk of HCC (aHR 0.13, 95% CI 0.08-0.20; and aHR 0.45, 95% CI 0.31-0.65); DAA SVR reduced risk more than IFN SVR (aHR 0.29, 95% CI 0.17-0.48). Independent of treatment, cirrhosis was the strongest risk factor for HCC (aHR 3.94, 95% CI 3.17-4.89 vs. no cirrhosis). Other risk factors included male sex, White race and genotype 3. Our six-variable predictive model had \u27excellent\u27 accuracy (AUROC 0.94) in independent validation. Our novel landmark interval-based model identified HCC risk factors across antiviral treatment status and interactions with cirrhosis. This model demonstrated excellent predictive accuracy in a large, racially diverse cohort of patients and could be adapted for \u27real world\u27 HCC monitoring