Chronic Hepatitis D Research Articles

Prediction of Hepatocellular Carcinoma and Liver-related Events in Anti-hepatitis D Virus-positive Individuals

Chronic hepatitis D (CHD) is the most severe form of chronic viral hepatitis, with a high risk of developing hepatocellular carcinoma (HCC) and liver-related mortality. Risk stratification is needed to guide HCC surveillance strategies and to prioritize treatment with antiviral agents. We conducted a multicenter retrospective cohort of anti-hepatitis D virus (HDV)-positive individuals managed at sites in the Netherlands and the United Kingdom. We studied the 5-year cumulative incidences of HCC and liver-related events (first of HCC, liver transplantation, and liver-related mortality), in the overall cohort and among relevant subgroups. We analyzed 269 anti-HDV-positive individuals with a median follow-up of 4.3 years in which 47 first events occurred. The 5-year cumulative incidences of HCC and liver-related events were 3.8% and 15.6% in the overall cohort. The 5-year cumulative incidence of HCC and liver-related events for individuals without cirrhosis was 0% and 0.9% compared with 12% and 41.3% for individuals with cirrhosis (P < .001). The 5-year cumulative incidence of HCC and liver-related events was 0% and 2.1% among individuals with low PAGE-B scores, compared to 3.2% and 21.1% with intermediate and 25.4% and 45.5% with high-risk scores (P < .001). We found comparable results for the Fibrosis-4 score. Findings were consistent regardless of cirrhosis or detectable HDV RNA (P < .001). Anti-HDV-positive individuals are at high risk of adverse liver-related outcomes. The incidence of HCC was negligible among individuals without cirrhosis and among individuals with low baseline PAGE-B and/or Fibrosis-4 scores. Therefore, these scores can be used to guide HCC surveillance strategies and potentially also for treatment prioritization.

Clinical and economic value of bulevirtide in the treatment of chronic hepatitis D

Background/AimsBulevirtide (Hepcludex®) is the first drug approved for the treatment of chronic hepatitis D (CHD), unlike the current off-label treatment (PEG-IFN-α), limited in clinical practice and associated with post-treatment relapses. In a hypothetical cohort of CHD patients in Spain, the study aim was to compare the efficiency of bulevirtide with PEG-IFN-α in terms of clinical events avoided and associated cost savings. MethodsA validated economic model reflecting the natural history of the disease was used to project lifetime liver complications and costs for two hypothetical cohorts treated with bulevirtide or PEG-IFN-α. The model considered progression to complications such as decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplantation (LT), and death. The efficacy rates used at 24 and 48 weeks were defined as the combined response rate for bulevirtide and undetectable HDV RNA to PEG-IFN-α. The numbers of clinic events and associated costs were evaluated from the perspective of the National Healthcare System. ResultsIn a hypothetical cohort of 3882 patients, bulevirtide reduced the numbers of complications events in comparison to PEG-IFN-α (152 DCC, 113 HCC, 11 LT, and 321 deaths over a lifetime). This was associated with a reduction of event-related costs of €11,837,044 (DCC €1,138,059; HCC €1,503,583; LT €7,834,291; and death €1,361,111). ConclusionIn patients with CHD, bulevirtide could prevent a significant number of clinical events compared to PEG-IFN-α and contribute to cost savings through these reduction in liver complications. Further testing for hepatitis D virus is needed so that more patients can benefit from bulevirtide.

Efficacy of Pegylated Interferon-alpha-2a in Chronic Hepatitis Delta: Experience from a Tertiary Care Hospital in Karachi.

Chronic hepatitis D (CHD) along with chronic hepatitis B (CHB) is an important cause of morbidity and mortality in patients with cirrhosis. It is a potentially curable infection that has long awaited a good treatment option. To ascertain the efficacy of pegylated interferon (PEG-IFN)-alpha-2a in patients suffering from CHD. A tertiary care hospital experience from Pakistan. The study included 207 CHD polymerase chain reaction (PCR)-positive patients treated with PEG-IFN-alpha-2a between July 2020 and October 2022. Virological response rate (PCR negative) at weeks 24 and 48 was the primary endpoint. Secondary outcomes included partial response (>2 log reduction in PCR) and treatment failure rate (<2 log reduction in PCR). A total of 187 patients started PEG-IFN therapy, and 148 patients completed the assigned 48 weeks of therapy. Patients' mean age was 25.7 years with 65% being males. The virological response rate was 40.5% at week 24 and 32.4% at week 48. The partial response rate was 24% at both weeks 24 and 48. The treatment failure rate was 36% at week 24 and 44% at week 48. Hemoglobin, white blood cell (WBC) count, and total bilirubin were found to be predictive of treatment response. Side effects led to treatment discontinuation among eighteen patients and one patient died due to hepatic failure. Therapy with PEG-IFN-alpha-2a shows suboptimal outcomes in patients with CHD. There is a strong need for more effective alternate therapies for CHD patients. Butt N, Usmani MT, Hussain R, et al. Efficacy of Pegylated Interferon-alpha-2a in Chronic Hepatitis Delta: Experience from a Tertiary Care Hospital in Karachi. Euroasian J Hepato-Gastroenterol 2024;14(1):51-55.

Characterizing Hepatitis Delta in Spain and the gaps in its management

Background and aimsChronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated hepatitis delta prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. MethodMulticenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. ResultsWe identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3–12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. ConclusionOne-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.

A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort

Background and AimsWe aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. MethodsThis was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. ResultsOf 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. ConclusionsCHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Liver stiffness measurement as a noninvasive method for the diagnosis of liver cirrhosis in patients with chronic hepatitis D virus infection.

Noninvasive tests (NITs) have been proposed as an alternative to liver biopsy for diagnosing liver cirrhosis. The evidence of NIT performance in patients with chronic hepatitis D (CHD) is limited. To evaluate the diagnostic performance of liver stiffness measurement (LSM) and other NITs in CHD patients. We evaluated the diagnostic performance of LSM by transient elastography for the detection of liver cirrhosis in a retrospective, multicentre cohort of 144 CHD patients with paired (±6 months) LSM and liver biopsies. Cirrhosis was diagnosed histologically in 22 patients (15.3%). Mean LSM was significantly higher in patients with cirrhosis compared to those without fibrosis (23.4 vs 10.2 kPa, p < 0.0001) or with intermediate fibrosis (23.4 vs 13.5 kPa, p < 0.0001). In the detection of liver cirrhosis, LSM was superior to other NITs (AUROCs: 0.89 [LSM], 0.87 [D4FS], 0.74 [APRI], 0.73 [FIB-4], and 0.69 [AAR]). The optimal cut-off for identifying patients with liver cirrhosis was ≥15.2 kPa (Se 91%, Sp 84%, PPV 50%, NPV 98%). The ideal cut-off for diagnosing non-advanced liver fibrosis (Metavir ≤2) was <10.2 kPa (Se 55%, Sp 86%, PPV 90%, NPV 45%), correctly identifying 90% of patients. Data were validated in an independent cohort of 132 CHD patients. LSM is a useful tool for identifying patients at risk for liver cirrhosis and is superior to other NITs. The cut-offs of <10.2 and < 15.2 kPa reliably diagnose non-advanced liver fibrosis and exclude cirrhosis in the majority of patients. However, LSM cannot completely replace liver biopsy in CHD patients.

Long-Term Treatment with Bulevirtide in Patients with Chronic Hepatitis D and Advanced Chronic Liver Disease.

Bulevirtide (BLV) is approved for the treatment of chronic hepatitis D (CHD). Because only limited long-term experience has been reported, we aimed to evaluate the efficacy and safety of BLV treatment in patients with advanced chronic liver disease (ACLD). We performed a retrospective analysis of patients with CHD who received BLV 2 mg/day for >12 months at a tertiary center. Virological response (VR) was defined as a reduction in hepatitis delta virus-ribonucleic acid (HDV-RNA) ≥2 log10 from baseline or HDV-RNA negativity and biochemical response (BR) as gender-specific normalization of transaminases. We identified 14 patients (9 men, 5 women; median age of 48 years; interquartile range (IQR) of 37-55), of whom 12 (86%) had suggested or assumed ACLD according to Baveno VI criteria. The median duration of BLV treatment was 26 months (IQR 17-27). During treatment, the mean HDV-RNA level decreased from log10 5.58 IU/ml to levels between log10 2.19 IU/ml and log10 3.19 IU/ml. HDV-RNA negativity was achieved in up to 63% after 24 months. VR and BR were 86% and 43% after 12 months, 90% and 60% after 18 months, 75% and 75% after 24 months, and 100% and 50% after 30 months, respectively. Two nonpersisting viral breakthroughs were observed after 24 months of treatment. The Child Pugh score and model of end-stage liver disease (MELD) scores remained stable or improved in 12 patients (86%). Only one patient developed hepatic decompensation after 24 months of treatment with ascites requiring large-volume paracentesis which was not associated with viral breakthrough, portal vein thrombosis, or hepatocellular carcinoma. Treatment with BLV beyond one year is effective and safe for patients with CHD and ACLD. Liver function remained stable or improved during treatment in the vast majority of patients, and only one case of hepatic decompensation occurred during a median follow-up of 26 months.

Лечение хронического гепатита D в Краснодарском крае – опыт реальной практики

Objective. To analyze the results of treatment of patients with chronic hepatitis D (CHD) in Krasnodar Krai in the conditions of real practice using bulevirtide, an HBV/HDV entry inhibitor. Patients and methods. Interim treatment outcomes were studied in 11 patients with CHD, predominantly at the cirrhotic stage (82%), with the presence of portal hypertension (55%), liver failure (n = 3), and hepatocellular carcinoma (n = 2, detected during treatment). Patients received bulevirtide as monotherapy (n = 7) or in combination with peginterferon (n = 4); evaluation periods ranged from 24–96 weeks of treatment. Results. All patients with known baseline HDV RNA level (n = 5) achieved virologic response, HDV RNA level reduction was -1.8 and -5.5 log10 after 24 and 96 weeks of monotherapy, -2.0–4.9 log10 after 24–72 weeks of combined therapy, with aviremia in 1 patient. In patients with unknown baseline HDV RNA level (n = 6) its dynamics during treatment corresponded to virologic response in 4 patients (decrease from -1.5 to -4.0 log10 in the period from 12/24/48 to 72 weeks of monotherapy, with aviremia in 1 patient). Efficacy improved as treatment continued to 72–96 weeks in 5 of 7 patients (4 received monotherapy, 1 received combination therapy). The overall virologic response rate was 82%, aviremia 18%, and biochemical response (ALT level reduction/normalization) 55%/45%, respectively. All patients with liver dysfunction (n = 3) showed virological and biochemical response, including aviremia and ALT normalization (1 and 2 patients, respectively). Treatment was characterized by good tolerability, absence of severe and serious adverse reactions, cases of treatment withdrawal, stability of liver function indices, including cirrhosis with dysfunction. In 1 patient after hepatectomy for HCC there was a temporary deterioration of liver function with the transition of class A to class B according to Child-Pugh, unrelated to treatment. Conclusion. Interim results of HDV treatment in real practice have demonstrated efficacy, safety and good tolerability of bulevirtide in monotherapy or combination therapy, including in patients with liver dysfunction. Further development of an optimal treatment algorithm is necessary, taking into account the results of ongoing studies, in order to improve patient prognosis and achieve cure of HDV infection. Key words: bulevirtide, hepatocellular carcinoma, decompensated cirrhosis, monotherapy, combination therapy, chronic hepatitis D, liver cirrhosis

Опыт противовирусной терапии хронического гепатита D в Республике Саха (Якутия)

Objective. To analyze the results of antiviral therapy of patients with chronic hepatitis D (CHD) in the Republic of Sakha (Yakutia). Patients and Methods. Interim treatment outcomes over 48 weeks were studied in 36 patients receiving bulevirtide monotherapy (30 patients) and in combination with peginterferon alfa (6 patients); 11 of these patients were followed for more than 48 weeks, up to 54–118 weeks (5 and 6 patients, respectively). Results. After 48 weeks of treatment, there was a decrease in the median HDV RNA level from 7.1 log10 to 4.6 log10, with a median reduction of 2.2 log10 ( p &lt; 0.001) (2.1 log10 with monotherapy (p &lt; 0.001), 4.1 log10 with combination therapy), a virologic response rate of 64% (53% and 100%, respectively); and an aviremia rate of 18% (2 patients in each group). The median ALT level decreased from 63.0 to 33.0 U/L, the frequency of detection of normal ALT level increased from 24 to 67% (in the monotherapy group – from 18 to 69%). When treatment was continued for more than 48 weeks (up to 54–118 weeks), maintenance and/or improvement of virologic and biochemical response was observed in the majority of patients. The treatment was characterized by good tolerability, absence of serious adverse events, cases of treatment withdrawal, worsening of liver function indices in cirrhosis. Conclusion. Analysis of interim results of bulevirtide application in real practice demonstrated efficacy, safety and good tolerability of treatment, both in combination therapy and monotherapy, including in compensated liver cirrhosis. Further accumulation of treatment experience is necessary in order to develop an optimal treatment algorithm. Key words: bulevirtide, chronic hepatitis D, combined therapy, cirrhosis, monotherapy

Non-Invasive Prediction Scores for Hepatitis B Virus- and Hepatitis D Virus-Infected Patients-A Cohort from the North-Eastern Part of Romania.

Approximately 62-72 million people are infected worldwide with HDV. Patients with chronic hepatitis D (CHD) have a higher risk of developing cirrhosis or hepatocellular carcinoma (HCC) and an increased mortality rate compared to those with chronic hepatitis B (CHB). The stage of liver fibrosis or the risk of developing HCC can also be estimated by non-invasive scores, which are cost effective, easier to apply, and reproducible. In this study, we aimed to evaluate the predictive value of four non-invasive scores (FIB-4, APRI, AST/ALT ratio, and aMAP) in assessing severe fibrosis/cirrhosis and the presence of HCC in patients with HBV/HDV superinfection, as compared with HBV mono-infection. Our 8-year retrospective analysis revealed that HDV-infected patients had a 2-3 times higher risk of developing cirrhosis and HCC than HBV-mono-infected subjects. High AST and ALT baseline levels qualified as independent predictors for cirrhosis development in both groups. The following fibrosis scores, FIB-4, APRI score, and AAR, were significantly increased when cirrhosis was present at baseline and showed a good prediction for developing cirrhosis in the CHD group. The aMAP score, a risk predictor for HCC, showed significantly higher values in patients with HCC in both groups. Nonetheless, non-invasive scores should always be considered for monitoring patients with CHB and CHD, but only when associated with other diagnosis methods.

The Circulating miRNA Profile of Chronic Hepatitis D and B Patients Is Comparable but Differs from That of Individuals with HBeAg-Negative HBV Infection.

miRNAs circulating in whole serum and HBsAg-particles are differentially expressed in chronic hepatitis B (CHB) and HBeAg-negative-HBV infection (ENI); their profiles are unknown in chronic hepatitis D (CHD). Serum- and HBsAg-associated miRNAs were analyzed in 75 subjects of 3 well-characterized groups (CHB 25, CHD 25, ENI 25) using next-generation sequencing (NGS). Overall miRNA profiles were consonant in serum and HBsAg-particles but significantly different according to the presence of hepatitis independently of Hepatitis D Virus (HDV)-co-infection. Stringent (Bonferroni Correction < 0.001) differential expression analysis showed 39 miRNAs upregulated in CHB vs. ENI and 31 of them also in CHD vs. ENI. miRNA profiles were coincident in CHB and CHD with only miR-200a-3p upregulated in CHB. Three miRNAs (miR-625-3p, miR-142-5p, and miR-223-3p) involved in immune response were upregulated in ENI. All 3 hepatocellular miRNAs of MiR-B-Index (miR-122-5p, miR-99a-5p, miR-192-5p) were overexpressed in both CHB and CHD patients. In conclusion, CHD and CHB patients showed highly similar serum miRNA profiling that was significantly different from that of individuals with HBeAg-negative infection and without liver disease.

Impact of hepatitis D reflex testing on the future disease burden: A modelling analysis.

Chronic hepatitis D (CHD) is a severe form of viral hepatitis that leads to liver cirrhosis and hepatocellular carcinoma. CHD is underdiagnosed, and this study aimed to assess the impact of hepatitis D reflex testing in HBsAg-positive individuals in Spain over the next 8 years. Two scenarios were compared: the current situation (7.6% of HBsAg-positive patients tested for anti-HDV) and reflex testing for all positive samples. A decision tree model was designed to simulate the CHD care cascade. Implementing reflex testing would increase anti-HDV detection to 5498 cases and HDV-RNA to 3225 cases. Additionally, 2128 more patients would receive treatment, with 213 achieving undetectable HDV-RNA levels. The cost per anti-HDV case detected would be €132. In the median time of the analysis, liver complications (decompensated cirrhosis, HCC and liver-related deaths) would be reduced by 35%-38%, implying an estimated cost savings of 36 million euros associated with the management of such complications. By 2030, implementing anti-HDV reflex testing would reduce the clinical and economic burden of CHD by 35%-38%.

Pegylated interferon in the treatment of chronic delta hepatitis: the experience from real-world clinical practice

Rationale: The high prevalence of hepatitis D virus (HDV) infection in the Republic of Dagestan, significantly exceeding that in the European part of the Russian Federation, as well as the limited choice of therapeutic options, have led to the need to analyze the accumulated experience of interferon therapy in the real clinical practice to further select possible treatment regimens.&#x0D; Aim: To evaluate the efficacy of pegylated interferon alpha (Peg-IFN-) in patients with chronic hepatitis D (CHD) in real world clinical practice.&#x0D; Materials and methods: In a retrospective study, the efficacy, safety and tolerability of Peg-IFN- were analyzed in 34 patients with CHD living in the Republic of Dagestan. Main virological parameters (anti-HDV antibodies (anti-HDV), HDV RNA and HBV DNA), alanine aminotransferase levels, changes over time in liver density by elastometry, and clinical parameters (hematology and urine tests, clinical chemistry, thyroid function tests) were assessed at 24 and 48 weeks of therapy, as well as at 48 weeks after its completion.&#x0D; Results: The treatment with Peg-IFN- for 48 weeks resulted in a virological response, defined as a HDV RNA decrease by more than 2 lg copies/mL, in 32% (11/34) of the patients. A sustained virological response, defined as undetectable HDV RNA at 48 weeks after the end of therapy, was not observed in any case. Treatment with interferon was associated with a decrease in liver density by average 4.1 kPa by week 48 on therapy. Normalization of alanine aminotransferase levels after 48 weeks of treatment was observed in 59% (20/34) of the patients; however, sustained biochemical response was achieved in none of them. Serious adverse events of high or moderate severity that resulted in the discontinuation of therapy were observed in 12% (4/34) of the cases.&#x0D; Conclusion: The results obtained indicate low efficacy of Peg-IFN- in the treatment of CHD in the Dagestan patients. Further research is needed to refine optimal interferon therapy regimens, to search for predictors of treatment response, and to evaluate the impact of interferon treatment regimens on the risk of hepatic complications, clinical outcomes, and patient survival. However, the most obvious solution to the problem of CHD therapy is the development and implementation of interferon-free treatment regimens.

Clinical long-term outcome of hepatitis D compared to hepatitis B monoinfection

Background and aimsHepatitis D virus (HDV) infection causes the most severe form of chronic viral hepatitis. However, it is still unclear to what extent the underlying cirrhosis may contribute to disease progression. The aim of this study was to compare the long-term outcome of HDV infection with HBV monoinfection in a single-center cohort of both non-cirrhotic and cirrhotic patients.MethodWe retrospectively studied 175 patients with chronic hepatitis D (CHD) who were followed for at least 6 months (median of 6.3 (0.6–23.6) years). In addition, we selected 175 patients with HBV monoinfection (CHB) who were matched for gender, age, region of origin, HBeAg status, and bilirubin. Liver-related clinical end points were defined as hepatic decompensation (ascites, encephalopathy, variceal bleeding), liver transplantation, HCC, or liver-related death.ResultsClinical complications developed earlier (4.6 vs. 6.2 years) and more frequently (35.4% vs. 12.6%, p < 0.01) in CHD patients. In a multivariate Cox regression, HDV infection was independently associated with the development of end points (p < 0.01; HR: 3.0; 95% CI 1.4–6.4). However, in cirrhotic patients there were no significant differences between HBV and HDV in the development of end points. Besides, CHB patients with cirrhosis developed more frequently HCC (35.5%) than CHD patients with cirrhosis (18.5%).ConclusionOur results confirmed that HDV leads to a faster progression to cirrhosis compared to HBV. However, once cirrhosis is present, not HDV but the underlying cirrhosis is the dominate intrinsic risk factor for the development of liver-related end points and for the progression to HCC.

HBsAg protein composition and clinical outcomes in chronic hepatitis D and variations across HBeAg-negative chronic HBsAg carriers

HBsAg proteins are useful to identify HBV inactive carriers (ICs), but data on chronic hepatitis D (CHD) are scarce. This study aimed to describe HBsAg composition in CHD, its changes during the evolution, and the potential association with clinical outcomes. In addition, we assess the composition of HBsAg across different HBV genotypes and validate previous results on HBsAg proteins in an independent HBV cohort. Quantitative HBsAg, medium HBsAg proteins (MHBs), and large HBsAg proteins (LHBs) were measured in two cohorts. The first cohort consisted of patients with CHD. A cross-sectional study of samples from two European institutions (N =46) was conducted. Outcomes were assessed in a retrospective-prospective study of those patients with a follow-up of >1 year (n=36), and the longitudinal evolution of HBsAg proteins in those with samples >5 years apart (n=12) was analysed. The second cohort consisted of patients with HBeAg-negative HBV, and a cross-sectional study was performed (N=141). Forty-one (89%) patients with CHD had detectable HDV-RNA, and the presence of HDV-RNA was associated with higher LHBs proportion (p=0.010). Baseline MHBs (p=0.051) and MHBs proportion (p=0.086) tended to be higher in those developing clinical outcomes (9/36, 25%) after a median follow-up of 5.9 years. Patients in which HDV-RNA became spontaneously undetectable during follow-up (5/31, 16.1%) tended to present lower MHBs proportion (p= 0.085). In the longitudinal study, changes in LHBs proportion were observed (p=0.041), whereas MHBs proportion remained stable (p=0.209). Regarding HBV, ICs showed lower LHBs proportion (p=0.027). LHBs and MHBs differed significantly according to HBV genotype, regardless of the HBV phase. Patients with CHD with detectable HDV-RNA presented higher LHBs proportion than those with undetectable HDV-RNA. A trend toward having higher baseline MHBs proportion was observed in patients who developed clinical outcomes or remained with detectable HDV-RNA. This study validates the different HBsAg composition in HBV ICs and reveals the HBV-genotype influence in HBsAg composition. The composition of HBsAg in chronic hepatitis D differs in patients with detectable and undetectable HDV viral load and may help predict the likelihood of achieving undetectable HDV viraemia and the development of clinical events such as decompensation. The composition of the surface antigen is also useful to distinguish inactive carriers of HBV, and it varies according to HBV genotype.

Non-organ-specific autoantibodies with unspecific patterns are a frequent para-infectious feature of chronic hepatitis D.

Infections with hepatotropic viruses are associated with various immune phenomena. Hepatitis D virus (HDV) causes the most severe form of viral hepatitis. However, few recent data are available on non-disease-specific and non-organ-specific antibody (NOSA) titers and immunoglobulin G (IgG) levels in chronic hepatitis D (CHD) patients. Here, we examined the NOSA titers and IgG levels of 40 patients with CHD and different disease courses and compared them to 70 patients with chronic hepatitis B (CHB) infection. 43% of CHD patients had previously undergone treatment with pegylated interferon-α (IFN-α). The antibody display of 46 untreated patients diagnosed with autoimmune hepatitis (AIH) was used as a reference. The frequency of elevated NOSA titers (CHD 69% vs. CHB 43%, p < 0.01), and the median IgG levels (CHD 16.9 g/L vs. CHB 12.7 g/L, p < 0.01) were significantly higher in CHD patients than in patients with CHB, and highest in patients with AIH (96%, 19.5 g/L). Also, the antinuclear antibody pattern was homogeneous in many patients with AIH and unspecific in patients with viral hepatitis. Additionally, f-actin autoantibodies were only detectable in patients with AIH (39% of SMA). In CHD patients, IgG levels correlated with higher HDV viral loads, transaminases, and liver stiffness values. IgG levels and NOSA were similar in CHD patients irrespective of a previous IFN-α treatment. In summary, autoantibodies with an unspecific pattern are frequently detected in CHD patients with unclear clinical relevance.

OS-030 - Treatment with siRNA JNJ-73763989 plus nucleos (t)ide analogue (NA) decreases HBsAg and HDV RNA levels in patients with chronic hepatitis D (CHD): part 1 of the REEF-D study

OS-030 - Treatment with siRNA JNJ-73763989 plus nucleos (t)ide analogue (NA) decreases HBsAg and HDV RNA levels in patients with chronic hepatitis D (CHD): part 1 of the REEF-D study

Bulevirtide monotherapy is safe and well tolerated in patients with chronic hepatitis D (CHD): An integrated safety analysis of 48-week data

Bulevirtide monotherapy is safe and well tolerated in patients with chronic hepatitis D (CHD): An integrated safety analysis of 48-week data

Efficacy of bulevirtide as monotherapy for chronic hepatitis D (CHD): Week 48 results from an integrated analysis

Efficacy of bulevirtide as monotherapy for chronic hepatitis D (CHD): Week 48 results from an integrated analysis

NOVEL ENTRY INHIBITORS FOR VIRAL HEPATITIS D TREATMENT: BULEVIRTIDE

Chronic hepatitis D virus infection is the most severe form of viral hepatitis. Hepatitis delta virus (HDV) is a faulty RNA virus that needs hepatitis B virus surface antigen (HBsAg) for the completion of its life cycle. Hepatitis B virus (HBV) receptor, sodium taurocholate cotransporting polypeptide (NTCP), is used by HDV to infect hepatocytes. The replication of the HDV genome, which is a circular single-stranded RNA and encodes for a single HDAg that occurs in two forms (S-HDAg and L-HDAg), is carried out by the host RNA polymerases. Antiviral therapy is urgently needed to protect patients from hepatocellular carcinoma or end-stage liver disease and poses an important public health issue in many countries. There is still a need for efficient pharmacological therapies for chronic hepatitis D (CHD). A good strategy to stop new infections is to stop virus from entering cells. A new virion entry inhibitor called bulevirtide is now a promising treatment for both infections because it prevents the virion from entering the hepatocyte through the hepatic sodium/taurocholate cotransporting polypeptide Before bulevirtide's conditional approval by the EMA (European Medicines Agency) in July 2020 for the treatment of chronic HDV infection in adult patients with compensated liver disease, therapy options were restricted to the off-label use of pegylated interferon alfa. (NTCP) receptor. We will outline the most recent discoveries about the HDV life cycle that have prompted the development of noveldrug bulevirtide.