Hepatitis B Delta: assessment of the knowledge and practices of hepato-gastroenterologists practicing in non-academic settings in France.

BACKGROUND: Data on the management of Hepatitis B-Delta (HB-D) by hepatogastroenterologists (HGs) practicing in nonacademic hospitals or private practices are unknown in France. OBJECTIVE: We aimed to evaluate the knowledge and practices of HGs practicing in nonacademic settings regarding HB-D. METHODS: A Google form document was sent to those HGs from May to September 2021. RESULTS: A total of 130 HGs (mean age, 45 years) have participated in this survey. Among HBsAg-positive patients, Delta infection was sought in only 89% of cases. Liver fibrosis was assessed using FibroScan in 77% of the cases and by liver biopsy in 81% of the cases. A treatment was proposed for patients with >F2 liver fibrosis in 49% of the cases regardless of transaminase levels and for all the patients by 39% of HGs. Responding HGs proposed a treatment using pegylated interferon in 50% of cases, bulevirtide in 45% of cases and a combination of pegylated interferon and bulevirtide in 40.5% of cases. Among the criteria to evaluate the treatment efficacy, a decrease or a normalization of transaminases was retained by 89% of responding HGs, a reduction of liver fibrosis score for 70% of them, an undetectable delta RNA and HBsAg for 55% of them and a 2 log 10 decline in delta viremia for 62% of the cases. CONCLUSION: Hepatitis Delta screening was not systematically performed in HBsAg-positive patients despite the probable awareness and knowledge of the few responders who were able to prescribe treatments of hepatitis delta.

Hepatitis delta virus: Disease assessment and stratification.

Hepatitis D virus (HDV) causes one of the most severe forms of hepatitis in people with chronic hepatitis B (CHB) infection. Timely and accurate assessment of hepatitis delta virus (HDV) and disease stratification is mandatory for thorough pre-therapeutic evaluation for prioritizing treatment and outcome prediction. Viral biomarkers associated with HDV and hepatitis B virus (HBV) are crucial to aid in diagnosis, and monitoring of serum viral nucleic acids for both viruses is recommended. Liver biopsy remains the gold standard for staging of liver fibrosis and grading of histological activity and should remain central for diagnostic purposes, but is also of importance for research to enhance our understanding of HDV. The emergence of novel non-invasive tests for the assessment of liver fibrosis in HDV patients coupled with the well-recognized potential complications of liver biopsy has resulted in reduced utility of liver biopsy in clinical practice. Preliminary data suggest that these emerging non-invasive modalities appear to be reliable, and their use is supported, similar to other viral hepatitis. Nevertheless, further validation is required before their widespread adoption into clinical practice.

The Delta Delta: Gaps in screening and patient assessment for hepatitis D virus infection.

Hepatitis D virus (HDV) infection is highly prevalent in patients with chronic hepatitis B (CHB). AASLD guidelines recommend a risk-based screening approach. Our aim was to ascertain if the risk-based approach leads to appropriate HDV screening, identify targets to improve screening rates, and study HDV clinical burden. CHB patients screened for HDV from 01/2016 to 12/2021 were identified. Level of training and specialty of providers ordering HDV screening tests were determined. HDV seropositive (HDV+) patient charts were reviewed for the presence of individual risk factors per the AASLD guidelines to determine if they met screening criteria. The severity of liver disease at the time of HDV screening was compared between the HDV+ group and a matched (based on age, hepatitis B e antigen status, BMI and sex) HDV seronegative (HDV-) group. During the study period, 1444/11,190 CHB patients were screened for HDV. Most screening tests were ordered by gastroenterology (90.2%) specialists and attending physicians (80.5%). HDV+ rate was 88/1444 (6%), and 72 HDV+ patients had complete information for analysis. 18% of HDV+ patients would be missed by a risk-based screening approach due to unreported or negative risk factors (see Table). A significantly higher number of HDV+ patients had developed significant fibrosis (p = 0.001) and cirrhosis (p < 0.01) by the time of screening than HDV- (n = 67) patients. In conclusion, targeted interventions are needed towards trainees and primary care clinics to improve screening rates. Current risk-based criteria do not appropriately screen for HDV. It is time for universal screening of HDV in CHB patients.

The Epidemiology of Hepatitis D Virus in North Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Hepatitis D virus (HDV) infection has been considered a serious neglected pandemic, particularly in developing countries. The virus causes a more severe disease than mono infection with hepatitis B virus (HBV). The epidemiology of HDV is not well documented in North Africa, which is known to be endemic for HBV. In this study, we explored the prevalence of HDV infection and also attempted to identify factors associated with hepatitis D positive status among chronic hepatitis B patients in North Africa. METHODS: The electronic databases PubMed, Embase, Scopus, Science Direct, Web of Science, and Google Scholar were comprehensively searched for all papers published between January 1, 1998, and December 31, 2017, using appropriate strategies containing all related keywords, including North Africa, names of countries in the region, and all permutations of hepatitis D virus. The estimated prevalence of HDV in North Africa was calculated as an average of the pooled infection prevalence in each country weighted by the ratio of the country's hepatitis D virus population to the study's sample size in the survey data analysis. FINDINGS: A total of 312 studies were identified and 32 were included in this study, with a total sample of 4907 individuals screened for HDV. There was considerable variability in the prevalence estimates of HDV within the countries of the region. The overall prevalence of HDV in the general population of North Africa was 5·01% (95% CI: 1·25-8·27) and in liver disease patients it was 20.7% (95% CI:9.87-44.53). Genotype-1 was the most prominent genotype reported in five published studies. Ten studies reported on HDV RNA in participants who were seropositive for HDV, and four studies highlighted the impact of demographic factors (sex and age). No study showed the impact of risk factors on the prevalence of HDV in North Africa. INTERPRETATION: This review provides a comprehensive assessment of the burden of HDV in Northern Africa. There were significant differences in seroprevalence, study population, and diagnostic testing between the countries in the region. The results presented here will alert health professionals to implement clear policies based on evidence to diminish the burden of HDV infection. Such measures may include but are not restricted to improving the laboratory diagnostic tests and initiating patient data registries and blood screening. Further epidemiological and research studies are needed to explore the risk factors, coinfections, and approaches to increase testing for HDV, particularly in high-risk subpopulations, such as intravenous drug users and immigrants, and to define the consequences of HDV infection in North Africa.

Roadmap to control HBV and HDV epidemics in China.

PURPOSE: Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected individuals are also infected with hepatitis D virus (HDV) which has a 5-10 times higher mortality rate than HBV mono-infection. The aim of this manuscript is to devise strategies that can not only control HBV infections but also HDV infections in China under the current health care budget in an optimal manner. METHODS: Using a mathematical model, an annual budget of $10billion was optimally allocated among five interventions namely, testing and HBV adult vaccination, treatment for mono-infected and dually-infected individuals, second line treatment for HBV mono-infections, and awareness programs. RESULTS: We determine that the optimal strategy is to test and treat both infections as early as possible while applying awareness programs at full intensity. Under this strategy, an additional 19.8million HBV, 1.9million HDV infections and 0.25million lives will be saved over the next 10years at a cost-savings of $79billion than performing no intervention. Introduction of second line treatment does not add a significant economic burden yet prevents 1.4million new HBV infections and 15,000 new HDV infections. CONCLUSION: Test and treatment programs are highly efficient in reducing HBV and HDV prevalence in the population. Under the current health budget in China, not only test and treat programs but awareness programs and second line treatment can also be implemented that minimizes prevalence and mortality, and maximizes economic benefits.

Recognizing the impact of endemic hepatitis D virus on hepatitis B virus eradication.

BACKGROUND: Hepatitis delta virus (HDV) in conjunction with hepatitis B virus (HBV) increases adult morbidity and mortality. A number of studies have performed cost-benefit analyses for HBV interventions, but they have ignored the impact of HDV on these outcomes. METHODS: Using a mathematical model of HBV-HDV epidemiology, we compare health benefits and cost outcomes of four interventions: testing with HBV adult vaccination (diagnosis), diagnosis with antiviral treatment for HBV infections (mono-infections), diagnosis with antiviral treatment for HBV-HDV infections (dual-infections), and awareness programs. The relationship between optimal levels and outcomes of each of these interventions and HDV prevalence in HBV infected individuals ranging from 0 to 50% is determined. RESULTS: Over a 50 year period under no intervention, HBV prevalence, per capita total cost and death toll increase by 2.25%, -$11 and 2.6-fold respectively in moderate HDV endemic regions compared to mono-infected regions; the corresponding values for high HDV endemic regions are 4.2%, -$21 and 3.9-fold. Optimal interventions can be strategized similarly in mono and dually endemic regions. Only implementation of all four interventions achieves a very low HBV prevalence of around 1.5% in a moderate HDV endemic region such as China, with 2.8 million fewer deaths compared to no intervention. Although the policy of implementation of all four interventions costs additional $382 billion compared to no intervention, it still remains cost-effective with an incremental cost-effectiveness ratio of $1400/QALY. Very high efficacy awareness programs achieve less prevalence with fewer deaths at a lower cost compared to treatment and/or vaccination programs. CONCLUSION: HDV substantially affects the performance of any HBV-related intervention. Its exclusion results in over-estimation of the effectiveness of HBV interventions.

Hepatitis delta virus testing, epidemiology and management: a multicentre cross-sectional study of patients in London.

BACKGROUND: Hepatitis delta virus (HDV) testing is recommended for all patients with hepatitis B virus (HBV) infection. HDV infection is associated with severe liver disease and interferon is the only available treatment. OBJECTIVES: To determine the rate of anti-HDV antibody testing in HBV patients; and to describe the epidemiology, clinical characteristics and management of HDV-infected patients at four hospitals in London. STUDY DESIGN: The anti-HDV testing rate was estimated by reviewing clinical and laboratory data. Cross-sectional data collection identified HDV-infected patients who had attended the study centres between 2005 and 2012. RESULTS: At a centre with clinic-led anti-HDV testing, 40% (67/168) of HBV patients were tested. Recently diagnosed HBV patients were more likely to be screened than those under long-term follow-up (62% vs 36%, P=0.01). At a centre with reflex laboratory testing, 99.4% (3543/3563) of first hepatitis B surface antigen positive samples were tested for anti-HDV. Across the four study centres there were 55 HDV-infected patients, of whom 50 (91%) had immigrated to the UK and 27 (49%) had evidence of cirrhosis. 31 patients received interferon therapy for HDV with an end of treatment virological response observed in 10 (32%). CONCLUSIONS: The anti-HDV testing rate was low in a centre with clinic-led testing, but could not be evaluated in all centres. The HDV-infected patients were of diverse ethnicity, with extensive histological evidence of liver disease and poor therapeutic responses. Future recommendations include reflex laboratory testing algorithms and a prospective cohort study to optimise the investigation and management of these patients.

Hepatitis delta: epidemiology, diagnosis and management 36 years after discovery.

With recent studies showing increased prevalence of hepatitis delta (HDV) even in the US, Australia, and some countries in Europe, and very high prevalence in endemic regions, HDV infection is far from being a disappearing disease. Although immigrants from endemic countries have been shown to have increased risk, studies have clearly shown that the disease is not solely appearing in traditional high-risk groups. Recent studies provide increasing evidence that sexual transmission may be an important factor in HDV infection spread. Based on the totality of evidence showing increased disease progression and substantially increased risk of cirrhosis in HDV-infected CHB patients, and the current studies showing higher than expected prevalence, it is time to call for HDV screening of all CHB patients. HDV viral load detection and measurement should be considered in all patients whether or not they are anti-HDV-positive. With universal screening of CHB patients for HDV, earlier diagnosis and consideration of treatment would be possible. Current treatment of HDV is IFN-based therapy with or without HBV antivirals, but current research indicates the possibility that prenylation inhibitors, entry inhibitors, HBsAg release inhibitors, or other therapies currently in the pipeline may provide more effective therapy in the future. In addition, universal screening would serve the important public health goal of allowing patients to be educated on their status and on the need for HDV-negative patients to protect themselves against superinfection and for HDV-infected patients to protect against transmission to others. Further studies and global awareness of HDV infection are needed.

Epidemiology, pathogenesis and management of hepatitis D: update and challenges ahead.

Hepatitis D is caused by infection with the hepatitis D virus (HDV) and is considered to be the most severe form of viral hepatitis in humans. Hepatitis D occurs only in individuals positive for the HBV surface antigen (HBsAg) as HDV is a defective RNA viroid that requires HBsAg for transmission. At least eight different HDV genotypes have been described and each has a characteristic geographic distribution and a distinct clinical course. HDV and HBV coinfection can be associated with complex and dynamic viral dominance patterns. Chronic HDV infection leads to more severe liver disease than HBV monoinfection and is associated with accelerated fibrosis progression, earlier hepatic decompensation and an increased risk for the development of hepatocellular carcinoma. So far, only IFN-alpha treatment has proven antiviral activity against HDV in humans and has been linked to improved long-term outcomes. Studies conducted in the past 2 years on the use of PEG-IFN-alpha show that a sustained virologic response to therapy, measured in terms of undetectable serum HDV RNA levels, can be achieved in about one quarter of patients with hepatitis D. Novel alternative treatment options including prenylation inhibitors are awaiting clinical development for use in hepatitis D.