What does quantitative HBsAg level mean in chronic hepatitis D infection?

Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial

The aim of this study was to evaluate whether patients with chronic hepatitis delta virus (HDV) infection treated with alpha interferon and subsequent loss of hepatitis B surface antigen (HBsAg) eliminate HDV. HDV RNA was detected in 26 of 28 patients with chronic delta hepatitis using the polymerase chain reaction. Seventeen patients in whom HDV RNA was detected were treated with alpha interferon; in 65%, HDV RNA remained detectable during treatment or reappeared after stopping therapy whereas in three patients HDV RNA remained absent (17.5%). HDV RNA became and remained undetectable in serum and liver of two of these three patients who lost HBsAg from serum and in one patient who was intermittently HBsAg negative during therapy. After loss of HBsAg, hepatitis B virus (HBV) DNA was still detectable in the liver, but not HBV RNA, indicating absent or very low HBV replication. Three patients were lost to follow up (17.5%). Two nontreated patients with chronic HDV infection also lost HBsAg during follow up; HDV RNA also became undetectable in their serum. Thus, HDV replication does not persist after the loss of HBsAg. Clearance of HBsAg may be a useful guide to when therapy can be stopped.

Study of reactivation of chronic hepatitis delta infection

Hepatitis delta virus (HDV) superinfection of woodchuck chronic carriers of woodchuck hepatitis virus (WHV) results in acute and chronic disease. The different courses of disease mimicked the outcome of human HDV superinfection, making woodchucks valuable models for clinical studies of HDV. Ten of 11 woodchuck chronic carriers of WHV superinfected with HDV developed acute HDV infection with markers of viral replication in the serum and liver. One animal (DW128) had no serological markers of acute HDV infection. Nine of 11 (82%) superinfected animals developed chronic HDV infection. An unusual course of chronic HDV infection occurred in one woodchuck (DW128): no serum markers of acute or chronic HDV infection appeared but HDV RNA was detected in the liver, indicating that chronic HDV infection can occur without serological markers.

Hepatitis delta virus (HDV) infection is the most severe form of chronic viral hepatitis: HDV-infected individuals are more likely to die from advanced liver disease compared with hepatitis B virus...

Detection of hepatitis delta virus RNA by a nonradioactive in situ hybridization procedure

The intrahepatic distribution of hepatitis delta virus RNA was studied by in situ hybridization in 33 formalin-fixed, paraffin-embedded biopsies from 17 chronic hepatitis B virus carriers superinfected with hepatitis delta virus. The findings were correlated with the expression of the hepatitis delta antigen, the duration of the hepatitis delta virus infection and the eosinophilic degeneration of the hepatocytes. Intranuclear hepatitis delta virus RNA and antigen were found in 28 specimens, whereas the remaining five were negative for both markers. Hepatitis delta virus RNA and antigen were mostly found within the same cell. In 20 specimens, however, a variable number of hepatocytes showed the presence of hepatitis delta virus RNA alone. The percentage of these over the total number of infected cells was higher in the specimens taken within 1 year from the acute delta hepatitis, whereas their absence was invariably associated with a long-established hepatitis delta virus infection. Interestingly, the vast majority of hepatocytes undergoing eosinophilic degeneration, a change significantly associated with hepatitis delta virus infection, did not show the presence of either hepatitis delta virus RNA or the viral antigen, suggesting a lack of association, at the cellular level, between viral replication and cytopathological change. The specificity of the detection of hepatitis delta virus RNA was confirmed by negative findings in nine specimens from seven chronic hepatitis B virus carriers without evidence of past or current hepatitis delta virus infection. The loss in sensitivity due to the formalin fixation was estimated to be 50% of that obtained in frozen biopsies, as determined by counting autoradiographic grains over infected cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Serological markers of hepatitis delta virus (HDV) infection were found in 18 (12%) of 146 consecutive patients with chronic hepatitis B, and the characteristics of patients who had antibody to HDV (anti-HDV-positive) were analyzed. During one to 15 years of follow-up, histological deterioration was documented in 77% of anti-HDV-positive patients; however, in hepatitis B surface antigen (HBsAg) carriers without HDV infection, histology deteriorated in 30% but improved or remained unchanged in the majority of patients (P less than .01). In seven (70%) of the 10 anti-HDV-positive patients who showed transition from chronic active hepatitis to cirrhosis, this event was observed within the first two years of follow-up. The probability of evolution to cirrhosis was significantly higher in anti-HDV-positive patients than in patients without antibody to HDV (P less than .001). These findings indicate that HDV infection in patients with chronic hepatitis B is associated with a more-rapid progression to cirrhosis compared with HBsAg carriers with chronic hepatitis and no evidence of HDV infection.

BackgroundHepatitis B virus (HBV) is detected in extrahepatic tissues of individuals with HBV infection. Whether nails and hair contain HBV has been unknown.MethodsWe examined two patient groups: those with chronic HBV infection alone (n = 71), and those with both chronic HBV and hepatitis delta virus (HDV) infections (n = 15). HBV DNA in the patients’ fingernails and hair were measured by real-time PCR. Hepatitis B surface antigen (HBsAg) of fingernails was evaluated by an enzyme immunoassay. HDV RNA in fingernails was measured by real-time PCR. Immunochemical staining was performed on nails. We used chimeric mice with humanized livers to evaluate the infectivity of nails.ResultsOf the 71 pairs of HBV-alone nail and hair samples, 70 (99%) nail and 60 (85%) hair samples were positive for β-actin DNA. Of those 70 nail samples, 65 (93%) were HBV DNA-positive. Of the 60 hair samples, 49 (82%) were HBV DNA-positive. The serum HBV DNA level of the nail HBV DNA-positive patients was significantly higher than that of the nail HBV DNA-negative patients (p < 0.001). The hair HBV DNA-positive patients’ serum HBV DNA level was significantly higher compared to the hair HBV DNA-negative patients (p < 0.001). The nail HBV DNA level was significantly higher than the hair HBV DNA level (p < 0.001). The nails and hair HBV DNA levels were correlated (r = 0.325, p < 0.05). A phylogenetic tree analysis of the complete genome sequence of HBV isolated from nails and hair identified the infection source. Of the 64 nail samples, 38 (59%) were HBsAg-positive. All 15 pairs of chronic HBV/HDV infection nail and hair samples were β-actin DNA-positive. However, nail HBV DNA was detected in two patients (13%). None of the 15 patients were positive for hair HBV DNA. Nail HDV RNA was detected in three patients (20%). Of the 15 patients, eight (53%) were nail HBsAg-positive. HBsAg and hepatitis delta (HD) antigen were detected in the nails by immunochemical staining. Chimeric mice were not infected with PBS containing HBsAg and HBV DNA elucidated from nails.ConclusionsNails and hair were the reservoir of HBV DNA. Moreover, nails can contain HBsAg, HDV RNA, and HD antigen.

The hepatitis delta virus (HDV) nucleocapsid consists of a genomic-length RNA of 1.7 kb and approximately equimolar amounts of the small and large forms of the hepatitis delta antigen (S-HDAg and L-HDAg, respectively). Since HDV RNA particles contain not only a genomic RNA species encoding S-HDAg but also an RNA species encoding L-HDAg, which is produced by an RNA-editing process, the question arises as to whether RNAs encoding either L-HDAg or S-HDAg can initiate replication. To study this, two cDNA-free transfection methods were employed: HDV RNA cotransfected with either the S-HDAg-encoding mRNA species or the ribonucleocapsid protein complex, comprising HDV RNA and recombinant S-HDAg. Results showed that the genomic-sense RNA encoding S-HDAg could promote HDV replication, whereas the L-HDAg-encoding RNA species was unable to replicate under the same conditions. The antigenomic RNA species encoding either S-HDAg or L-HDAg could not replicate by either of these procedures. In addition, L-HDAg alone could not promote replication of the genomic RNA but, by supplementing an equal amount of S-HDAg, replication occurred. These data indicate that L-HDAg-encoding RNA species are probably not involved in the initiation of HDV RNA synthesis; instead, their main function may be to serve as template for producing L-HDAg, which regulates HDV RNA synthesis and virion assembly. These results suggest that the genomic RNA species encoding S-HDAg is the only functional genome for HDV infection and explain why the presence of the edited HDV RNA encoding L-HDAg does not interfere with HDV infection.

Hepatitis delta virus (HDV) infection is associated with severe hepatic complications and rapid progression towards liver cirrhosis and hepatocellular carcinoma. Accurate measurement of HDV RNA is critical for monitoring therapeutic responses, especially during treatment with novel therapies such as bulevirtide (BLV). This study compared the analytical performance of two HDV RNA quantification assays, Bosphore (Anatolia) and AltoStar® (Altona), focusing on their sensitivity, specificity, and potential implications for clinical management. Sixty-one clinical samples from twenty-four patients, including fifteen HDV-infected patients receiving BLV treatment and nine controls, were tested using each assay. Of 30 samples identified as HDV-negative by the Bosphore assay, 17 (56.7%) were HDV-positive with AltoStar®, demonstrating the superior sensitivity (p < 0.0001) of the latter assay. Quantitative analyses revealed consistently higher viral load measurements with AltoStar® compared to Bosphore, with a difference of 1.23 Log IU/mL and a moderate correlation (r2 = 0.7385) between assays. Each assay demonstrated a high specificity, with no false positives detected among control samples. However, our findings suggest that differences in assay sensitivity could impact the evaluation of virological response, highlighting the risk of false-negative results in chronically HDV-infected patients with low-level viremia. This emphasizes the need for careful assay selection to accurately monitor treatment outcomes.

Famciclovir treatment of chronic delta hepatitis

Pathogenesis of and New Therapies for Hepatitis D

Quantitative longitudinal evaluations of hepatitis delta virus RNA and hepatitis B virus DNA shows a dynamic, complex replicative profile in chronic hepatitis B and D

erosion.Pathologic diagnosis of Mycobacterium infection from bony specimens was recorded for 35 (92%) patients.For 29 (76%), diagnosis was conducted by molecular study, including 25 (66%) by the national reference mycobacterial laboratory.For 4 patients, diagnosis was confirmed by culture of M. bovis.Osteomyelitis/osteitis for 5 patients was considered BCG related according to pathologic diagnosis of Mycobacterium infection, BCG vaccination history, and lack of a history of contact with a person with tuberculosis.Thirty-two (84%) children underwent surgery (excision, debridement, open biopsy), 4 children received arthrotomy (3 ankle and knee joint), and 2 children underwent only aspiration biopsy.All patients received isoniazid and rifampin therapy; 33 patients also received pyrazinamide, and 6 received additional ethambutol therapy.Medications were adjusted after diagnoses changed from tuberculosis to BCG infection.Two patients had major sequelae, both involving the thoracic spine and causing severe kyphosis.Adverse reactions after BCG vaccination depend on the BCG dose, vaccine strain, vaccine administration method, injection technique, and recipient's underlying immune status (5).The vaccine strain and manufacturing process in Taiwan did not change during the study period.Findings were not associated with a specific batch of vaccine, inoculation age, underlying disease, or Salmonella spp.infection.Patients had no common birth place, hospital, or area of residence.We believe the increased number of cases resulted mainly from policy changes and laboratory facility improvements.A surgical approach to obtain a specimen is indicated.However, because medical treatment usually yields a good outcome (6), extensive debridement should be avoided.Although some patients with lower extremity involvement initially limped, most were able to walk well later.Vertebral involvement is rare.Unlike previously reported cases (7,8), both patients reported here who had vertebral involvement had sequelae.For young children with suspected vertebral tuberculosis but no tuberculosis contact history, a biopsy specimen for BCG studies is preferable to spondylectomy.Although no definite immunologic deficit was found in these BCG osteomyelitis/osteitis patients, 2 other compensated infants with disseminated BCG during the same period in Taiwan had identified immunodeficiency (9).Studies are ongoing by the Taiwan Centers for Disease Control to evaluate medical treatment duration, long-term outcomes, and more detailed immune genetic tests.