HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test for antibodies against the Hepatitis Delta antigen (anti-HDV-Ab) in 4103 HBsAg-positive and 1661 HBsAg-negative, anti-HCV-positive sera from China and Germany. We found that the HDV seroprevalence in HBsAg-positive patients in China is limited to geographic hotspots (Inner Mongolia: 35/251, 13.9%; Xinjiang: 7/180, 3.9%) and high-risk intravenous drug users (HBV mono-infected: 23/247, 9.3%; HBV-HCV co-infected: 34/107, 31.8%), while none of the 2634 HBsAg carriers from other metropolitan regions were anti-HDV-Ab-positive. In Germany, we recorded an HDV seroprevalence of 5.3% in a university hospital environment. In a cohort of HBsAg-negative, anti-HCV-positive patients that were not exposed to HBV before (anti-HBc-negative), HDV was not associated with HCV mono-infection (Chinese high-risk cohort: 0/365, 0.0%; German mixed cohort: 0/263, 0.0%). However, 21/1033 (2.0%) high-risk HCV patients in China with markers of a previously cleared HBV infection (anti-HBc-positive) were positive for anti-HDV-Ab, with two of them being positive for both HDV and HCV RNA but negative for HBV DNA. The absence of anti-HDV-Ab in HCV mono-infected patients shows that HCV cannot promote HDV transmission in humans.

Hepatitis Delta Virus (HDV) is the smallest mammalian single-stranded RNA virus. It requires host cells and hepatitis B virus (HBV) to complete its unique life cycle. The present review summarizes the specific regions on hepatitis D antigen (HDAg) and hepatitis B surface antigen (HBsAg) that drive HDV to utilize host cell machinery system to produce three types of RNA and two forms of HDAg, and hijack HBsAg for its secretion and de novo entry. Previously, interferon-α was the only recommended therapy for HDV infection. In recent years, some new therapies targeting these regions, such as Bulevirtide, Lonafarnib, Nucleic acid polymers have appeared, with better curative effects and fewer adverse reactions.

Current estimates suggest 9 million to 19 million people worldwide are affected by Hepatitis D virus (HDV) infection, though significant discrepancies in diagnostic guideline implementation across regions and countries indicate these figures may not fully capture the true disease burden. HDV coinfection and superinfection with hepatitis B hasten disease progression, increasing cirrhosis and liver cancer risks, highlighting the importance of early and precise diagnosis. We present a thorough analysis of current and emerging hepatitis D diagnostic methods. Initial diagnosis involves detecting serum anti-HDV antibodies using radioisotope- or enzyme-linked immunosorbent assays. Established techniques like chemiluminescence immunoassay, quantitative microarray antibody capture, and lateral flow assays are being improved. Additional diagnostic markers include HDV antigens and RNA in the serum or liver, detectable through methods like northern and slot blots, fluorescence in situ hybridization, and quantitative real-time PCR. Droplet digital PCR allows quantifying unedited and edited HDV genomes in one sample. Next-generation sequencing offers deeper insights into HDV quasispecies for precise genotyping. Challenges persist, including qualitative diagnostic methods and need for international standards due to lab variability. This review emphasizes the urgency of establishing standardized protocols and international standards for early interventions and reducing the medical burden of chronic HDV infection.

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.

Diabetes and viral hepatitis, particularly hepatitis B (HBV) and hepatitis C (HCV), are significant global health burdens with complex interconnections. This review discusses the molecular mechanisms linking viral hepatitis to diabetes, focusing on inflammatory pathways, oxidative stress, and epigenetic modifications. Key findings highlight the role of STAT3 in promoting insulin resistance and β-cell apoptosis, the impact of ER stress and NOX-mediated oxidative stress on metabolic dysfunction, and the influence of epigenetic changes such as DNA methylation and histone acetylation on glucose homeostasis. These interconnected pathways provide insights into the pathogenesis of diabetes in hepatitis patients and suggest potential therapeutic targets for managing these co-occurring conditions. Future research directions include exploring the synergistic effects of these pathways and leveraging advanced technologies for personalized treatment strategies.