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Background and Aims: Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of U.S. HDV prevalence. We aim to provide an updated assessment of HDV prevalence in the U.S. using a comprehensive literature review and meta-analysis approach. Methods: A comprehensive literature review of articles reporting HBsAg seropreva-lence and anti-HDV prevalence was conducted to calculate country-specific rates and pooled prevalence of CHB and HDV using meta-analyses. Country-specific CHB and HDV rate estimates were combined with number of foreign-born (FB) persons in the U.S. in 2022 from U.S. Census Bureau to estimate total numbers of FB with CHB and HDV, respectively. These estimates were further combined with updated estimates of U.S.-born persons with CHB and HDV to yield the total number of persons with CHB and HDV. Results: In 2022, we estimated 1.971 million (M) (95% CI 1.547-2.508) persons with CHB; 1.547 M (95% CI 1.264-1.831) were FB and 0.424 M (95% CI: 0.282-0.678) were U.S.-born. The weighted average HDV prevalence among FB persons in the U.S. was 4.20% (64938 [95% CI 33055-97392] persons), among whom 45% emigrated from Asia, 25% from Africa, and 14% from Europe. When combined with updated estimates of U.S.-born persons with HDV, we estimate 75005 (95% CI: 42187-108393) persons with HDV in the U.S. Conclusions: Including both FB and U.S.-born persons, we estimated that 1.971M and 75005 persons were living with CHB and HDV, respectively, in the U.S. in 2022. [ABSTRACT FROM AUTHOR]

Foreign‐born (FB) persons represent a large proportion of adults with chronic hepatitis B (CHB) in Canada due to higher prevalence rates in countries of birth for FB persons. Suboptimal awareness and low rates of hepatitis delta virus (HDV) testing contribute to underdiagnosis and gaps in accurate estimates of Canada HDV prevalence. We aim to provide an assessment of CHB and HDV prevalence in Canada using a comprehensive literature review and meta‐analysis. A comprehensive literature review of articles reporting HBsAg seroprevalence and anti‐HDV prevalence was conducted to calculate country‐specific rates and pooled prevalence of CHB and HDV using meta‐analyses. Country‐specific CHB and HDV rate estimates were combined with number of FB persons in Canada in 2021 from Statistics Canada to estimate total numbers of FB with CHB and HDV, respectively. These estimates were combined with estimates of Canada‐born persons with CHB and HDV to yield the total number of persons with CHB and HDV. In 2021, we estimated 0.550 million (M) (95% CI 0.488–0.615) persons with CHB; 0.344 M (95% CI 0.288–0.401) were FB and 0.206 M (95% CI: 0.200–0.214) were Canada‐born. The weighted average HDV prevalence among FB persons in Canada was 5.19% (17,848 [95% CI 9611–26,052] persons), among whom 50% emigrated from Asia and 31% from Africa. When combined with estimates of Canada‐born persons with HDV, we estimate 35,059 (95% CI: 18,744–52,083) persons with HDV in Canada. In conclusion, we estimate 0.550 M and 35,059 persons living with CHB and HDV, respectively, in Canada in 2021. [ABSTRACT FROM AUTHOR]

Objective: Identifying digital markers of sleep disturbance—a known suicide risk factor—may aid in the detection of imminent suicide risk. This study examined sleep‐related communication and texting patterns in personal text messages (N = 86,705) of suicide attempt survivors. Method: Twenty‐six participants provided dates of past suicide attempts and 2‐week periods of positive mood, depressed mood, or suicidal ideation. Linguistic Inquiry Word Count was used to identify sleep‐related texts via a custom dictionary. Mixed effect models were fitted to test the association between suicide/mood episode type (e.g., attempt versus ideation) and three outcomes: likelihood of a text including sleep‐related content, nightly count of texts sent from midnight to 5:00 AM, and sum of unique hour bins from midnight to 5:00 AM with outgoing texts. Results: Analyses with a sleep dictionary that was manually revised to be more accurate (but not the original unedited dictionary) showed sleep‐related communication was more likely during depressed mood episodes than positive mood episodes. Otherwise, there were no significant differences in sleep‐related communication or objective texting patterns across episode type. Conclusions: Although we did not detect differences in sleep‐related communication tied to suicidal thoughts or behaviors, sleep‐related communication may differ as a function of within‐person mood level. [ABSTRACT FROM AUTHOR]

Background: The affective states most strongly associated with nonsuicidal self-injury (NSSI) remain poorly understood, particularly among veterans. This study used ecological momentary assessment (EMA) to examine relationships between affect ratings and NSSI urges and behaviors among veterans with NSSI disorder.Methods: Participants (N = 40) completed EMA entries via mobile phone for 28 days (3722 total entries). Entries included intensity ratings for five basic affective states, as well as NSSI urges and behaviors, during the past 4 hours.Results: Bivariate analyses indicated that each affect variable was significantly associated with both NSSI urges and behaviors. Angry/hostile and sad were most strongly associated with both NSSI urges and behaviors. A multivariate regression revealed that angry/hostile, disgusted with self, and happy (inversely related) were contemporaneously (within the same period) associated with NSSI behaviors, whereas all five basic affective states were contemporaneously associated with NSSI urges. In a lagged model, angry/hostile and sad were associated with subsequent NSSI urges but not behaviors.Conclusions: Findings highlight the relevance of particular affective states to NSSI and the potential utility of targeting anger in treatments for NSSI among veterans. There is a need for future EMA research study to further investigate temporal relationships between these variables. [ABSTRACT FROM AUTHOR]

Summary: Background: Hepatitis delta virus (HDV) infection is the most aggressive form of chronic viral hepatitis. Response rates to therapy with 1‐ to 2‐year courses of pegylated interferon alpha (peginterferon) treatment are suboptimal. Aims: To evaluate the long‐term outcomes of patients with chronic hepatitis D after an extended course of peginterferon. Methods: Patients were followed after completion of trial NCT00023322 and classified based on virological response defined as loss of detectable serum HDV RNA at last follow‐up. During extended follow‐up, survival and liver‐related events were recorded. Results: All 12 patients who received more than 6 months of peginterferon in the original study were included in this analysis. The cohort was mostly white (83%) and male (92%) and ranged in age from 18 to 58 years (mean = 42.6). Most patients had advanced but compensated liver disease at baseline, a median HBV DNA level of 536 IU per mL and median HDV RNA level of 6.86 log10 genome equivalents per mL. The treatment duration averaged 6.1 years (range 0.8‐14.3) with a total follow‐up of 8.8 years (range 1.7‐17.6). At last follow‐up, seven (58%) patients had durable undetectable HDV RNA in serum, and four (33%) cleared HBsAg. Overall, one of seven (14%) responders died or had a liver‐related event vs four of five (80%) non‐responders. Conclusions: With further follow‐up, an extended course of peginterferon therapy was found to result in sustained clearance of HDV RNA and favourable clinical outcomes in more than half of patients and loss of HBsAg in a third. [ABSTRACT FROM AUTHOR]

Objective: Previous studies of military veterans have produced mixed findings regarding whether combat exposure is directly related to suicidal ideation or is indirectly related to suicidal ideation via its influence on other factors. The present study used a longitudinal design to test the hypothesis that post‐traumatic stress disorder (PTSD) symptom severity mediates the effect of combat exposure on suicidal ideation in veterans. Method: Participants included 319 post‐9/11 veterans (83.4% male; 42.1% White/52.1% Black; Mage = 39.7) assessed at baseline, 6, and 12 months. Structural equation modeling and bootstrapped confidence intervals were employed to examine the direct and indirect relationships between combat exposure, suicidal ideation, and PTSD symptom severity. Results: Results from the mediation model, in which demographic variables and non‐combat trauma were included as covariates, revealed that the indirect effect of combat exposure on suicidal ideation via PTSD symptom severity was statistically significant, accounting for 64.1% of the covariance between combat exposure and suicidal ideation. Conclusions: This study provides longitudinal evidence that the effects of combat exposure on suicidal ideation are mediated by PTSD symptom severity, suggesting the importance of targeting such symptoms in treatment to mitigate suicide risk among veterans with combat exposure. [ABSTRACT FROM AUTHOR]

The Death/Suicide Implicit Association Test (IAT) is effective at detecting and prospectively predicting suicidal thoughts and behaviors. However, traditional IAT scoring procedures used in all prior studies (i.e., D-scores) provide an aggregate score that is inherently relative, obfuscating the separate associations (i.e., "Me = Death/Suicide," "Me = Life") that might be most relevant for understanding suicide-related implicit cognition. Here, we decompose the D-scores and validate a new analytic technique called the Decomposed D-scores ("DD-scores") that creates separate scores for each category ("Me," "Not Me") in the IAT. Across large online volunteer samples (N > 12,000), results consistently showed that a weakened association between "Me = Life" is more strongly predictive of having a history of suicidal attempts than is a stronger association between "Me = Death/Suicide." These findings replicated across three different versions of the IAT and were observed when calculated using both reaction times and error rates. However, among those who previously attempted suicide, a strengthened association between "Me = Death" is more strongly predictive of the recency of a suicide attempt. These results suggest that decomposing traditional IAT D-scores can offer new insights into the mental associations that may underlie clinical phenomena and may help to improve the prediction, and ultimately the prevention, of these clinical outcomes. [ABSTRACT FROM AUTHOR]

Summary: Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q‐MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case‐control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha‐foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q‐MAC, western blot and RNA assays. We evaluated separate cut‐offs of the Q‐MAC assay for predicting anti‐HDV and RNA positivity. Q‐MAC correctly identified 29/29 subjects who were western blot‐positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA‐positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA−; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV‐HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti‐HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74‐11.98) and HBV‐HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97‐134.95). In this Gambian population, HDV Q‐MAC had high sensitivity and specificity for both anti‐HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatitis delta virus (HDV) infection is the most rapidly progressive chronic viral hepatitis. Little is understood about the immune responses to HDV. This study aims to characterize the systemic immune environments of hepatitis B virus (HBV) and HDV patients at various disease stages. Methods: A total of 129 subjects were evaluated: 53 HBV, 43 HDV, and 33 healthy controls. HBV and HDV subjects were categorized by aspartate aminotransferase to platelet ratio index (APRI) into mild (APRI < 0.5), moderate, and severe (APRI > 1.0). Serum cytokines and immune markers were assessed at a single treatment‐naïve time‐point. Results: Type 1 cytokines are elevated in both HBV and HDV. Both groups show higher tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐12p40, and C–X–C motif chemokine ligand 9 when compared with controls (all P < 0.05). However, only HBV group displayed elevated γ‐interferon compared with controls. Type 2 cytokines are elevated in HBV. HBV group shows higher IL‐4, IL‐13, and C–C motif chemokine ligand (CCL) 26 compared with healthy controls and HDV. Chemokines CCL2 and CCL13 are lower in HDV. When assessing ratios, HDV displays higher γ‐interferon/IL‐4, TNF‐α/IL‐4, and TNF‐α/IL‐13 ratios than HBV and controls. Conclusion: Hepatitis B virus and HDV subjects show similarly elevated type 1 cytokines. HDV subjects display relatively lower type 2 cytokines. These differences in the systemic immune environments, particularly the predominance of type 1 responses, may contribute to the comparatively rapid progression of HDV disease. Characterization of the imbalance in type 1 and type 2 immunity unique HDV has the potential to provide immunological insights for designing therapeutic targets in HDV‐associated disease progression. [ABSTRACT FROM AUTHOR]

Background and Aims With no report on the overall prevalence and ramifications of hepatitis Delta virus ( HDV) infection in the United States for more than two decades, the characteristics of chronic hepatitis B virus ( CHB) patients coinfected with HDV, including clinical presentation, rate of hepatitis C virus tri-infection, and HDV viral load, were assessed. Methods At California Pacific Medical Center, a retrospective chart review was conducted on all CHB patients. Results Of 1191 CHB patients, 499 had been tested for HDV, with 42 (8%) determined to be coinfected; half of these were also hepatitis C virus-infected. Cirrhosis was present in 73% of the coinfected, 80% of the tri-infected, but only 22% of the monoinfected. Twenty-nine patients (69%) were Caucasian non- Hispanic; 10 (24%) were Asians and Pacific Islanders. Of 39 patients for whom HBV-DNA quantification at time of HDV presentation was available, 22 (56%) had undetectable levels; four (10%) had levels > 100 000 IU/m L. Conclusions HDV affects individuals of all ages and various ethnic groups. Although HBV viral loads are lower, rates of cirrhosis are higher in coinfected patients and higher still in the tri-infected. Our data support revising screening guidelines to advocate for all patients with HBV to be screened for HDV in order to both give the individual patient important information related to the possible need for treatment and to support the public health goal of reducing transmission by educating HDV-negative patients about the need for protection against superinfection and HDV-infected patients about the need to protect against transmission to others. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated techniques in differentiating human adipose-derived stem cells (hADSCs) into hepatocytes. Unfortunately, transdifferentiation is inefficient, and the function of these induced hepatocyte-like cells (which we termed ‘iHeps’) is low compared with that of real hepatocytes. Aims: We aimed to identify transcriptional deficiencies in iHeps that are critical to hepatocyte development, which may provide insights into improving the efficiency of transdifferentiation. Methods: hADSCs were differentiated into iHeps, and iHeps were assayed for hepatocyte-like activity. iHeps were then screened for expression of several growth factors, receptors and transcription factors (TFs) critical to liver development using reverse transcription-polymerase chain reaction (RT-PCR). Deficient TFs were transduced into hADSCs and hepatocyte function was reassessed after hepatic differentiation. Results: Differentiation of hADSCs into iHeps resulted in the upregulation of hepatic proteins. However, the levels of expression of hepatocyte-specific proteins in these iHeps were well below those of Huh 7.5 hepatoma cells, used in comparison. Five developmental TFs were notably absent on the RT-PCR screen. Lentiviral transduction of these TFs into hADSCs followed by culture in hepatocyte induction medium resulted in increased albumin expression compared with untransduced hADSCs treated in a parallel fashion. Conclusions: These five missing TFs are known to regulate hepatocyte differentiation and some are required to establish the competence of the foregut endoderm. Presumably due to their mesenchymal lineage, hADSCs do not express these endodermal TFs and are not fully competent to respond to critical developmental signals. Supplementation of these TFs may induce competency and enhance the differentiation of hADSCs into hepatocytes. [ABSTRACT FROM AUTHOR]