Hepatitis B Surface Antigen (Hbsag) Decrease and Serum Interferon-Inducible Protein-10 Levels as Predictive Markers for Hbsag Loss during Treatment with Nucleoside/Nucleotide Analogues

Jaroszewicz, Jerzy; Ho, Huy; Markova, Antoaneta; Deterding, Katja; Wursthorn, Karsten; Schulz, Sandra; Bock, C.‐Thomas; Tillmann, Hans L.; Manns, Michael P.; Wedemeyer, Heiner; Cornberg, Markus

doi:10.3851/imp1866

Cited by 81 publications

(85 citation statements)

References 39 publications

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“…The role of host immune response for HBsAg clearance was recently reported by J. Jaroszewicz et al (34) who showed that high baseline interferon-inducible protein-10 (IP-10) levels as well as elevation of baseline ALT >5x predicts HBsAg-loss during NUC therapy. As HBsAg seroclearance remains a rare event with NA, the adding of immunomodulators to NUC is an essential therapeutic strategy to increase this important event.…”

Section: Discussionmentioning

confidence: 99%

Inosine Pranobex (Isoprinosine) – a Potential Adjuvant in the Management of Chronic HBV Infection

Krastev¹,

Nikolova²,

Jelev³

et al. 2015

MedInform

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After achieving a durable on-treatment virological response with NUC (nucleos(t)ide analogues), adding an immunomodulating agent seems to have beneficial effect on the course of chronic HBV disease. Methods: Nine patients were investigated (5 -HBeAg(-) and 4 -HBeAg(+). All patients achieved durable on-treatment virological response with NA and then Isoprinosine was added for a period of 21 to 27 months. Serum HBsAg and HBV DNA levels were evaluated at a 3-month interval. Aim: The aim of the present study was to evaluate the effect of adjuvant immunomodulation with Isoprinosine in patients with chronic HBV infection who achieved durable suppression of HBV DNA on-treatment with NUC. Results: In HBeAg-negative patients an initial increase of qHBsAg was observed in 4/5 of patients after the adding of Isoprinosine. On month 15 of combined therapy a reduction of more than 50% from the baseline HBsAg level was found in 4/5 of patients (P=0.043). In HBeAg-positive patients there was no significant reduction of HBsAg during the follow-up. A reduction of HBsAg levels (about 30%) from the baseline was established in 3/4 patients at month 18. In the remaining one patient a reduction of 70% was established at month 27. There was an initial increase of HBsAg in 3/4 patients. In 3/4 of the patients there was a negativation of HBeAg. Conclusion: After adding Isoprinosine to NA, HBeAg-loss was achieved in 3/4 of HBeAg positive patients. HBsAg decline was more pronounced in HBeAg-negative subjects, which was not observed in NUC monotherapy. Isoprinosine in combination with NUC is safe and well tolerated. .

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Section: Discussionmentioning

confidence: 99%

Inosine Pranobex (Isoprinosine) – a Potential Adjuvant in the Management of Chronic HBV Infection

Krastev¹,

Nikolova²,

Jelev³

et al. 2015

MedInform

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“…A decline in HBsAg may also be induced by immunomodulation with IFN-α [15,20], whereas this rarely occurs during treatment with HBV reverse transcriptase inhibitors [21,22]. We and others have recently suggested that high levels of IFN-γ-inducible protein of 10 kDa (IP-10) may be useful to identify patients who achieve an HBsAg decline during treatment with nucleoside or nucleotide analogues (NA) [23,24]. Serum IP-10 has been discussed as a marker for an activated endogenous interferon system that might predict response to exogenous IFN-α treatment in patients with viral hepatitis.…”

Section: Introductionmentioning

confidence: 97%

Dominance of hepatitis C virus (HCV) is associated with lower quantitative hepatitis B surface antigen and higher serum interferon-γ-induced protein 10 levels in HBV/HCV-coinfected patients

Wiegand

Jaroszewicz

Potthoff

et al. 2015

Clinical Microbiology and Infection

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Different viral dominance patterns have been documented in coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) based on HBV DNA and HCV RNA quantification. In most cases, HCV is dominant and suppresses HBV replication. In vitro studies revealed that there is most probably no direct interference between HBV and HCV replication. We hypothesized that indirect mechanisms mediated by host immune responses might be responsible for the different dominance patterns. In this study we analysed quantitative hepatitis B surface antigen (HBsAg) as a marker for immune control of HBV and interferon γ-induced protein 10 (IP-10) as host marker for the endogenous interferon in 85 patients with HBV/HCV coinfection. Levels of HBsAg were closely associated with viral dominance patterns in 85 HBV/HCV-coinfected patients. HBsAg levels were lowest in patients with HCV dominance, even lower compared with HBV-monoinfected patients undergoing treatment with nucleos(t)ide analogues (NA) but comparable to low replicative HBsAg carriers. An increase in HCV RNA during follow up was associated with HBsAg decline. Patients with HCV dominance had significantly higher serum IP-10 levels compared with HBV-dominant patients or HBV-monoinfected patients treated with NA. Lower HBsAg and higher IP-10 levels in HCV-dominant HBV/HCV-coinfected patients suggest that HCV suppresses HBV DNA replication and also HBsAg production by immune mechanisms.

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“…Thus, HBeAg seroconversion was shown to be predictable by a decrease in the levels of HBeAg after 6 months of entecavir treatment [33]. Higher serum levels of the interferon-inducible protein 10 have recently been shown to be associated with a greater decrease in HBsAg levels during treatment with entecavir in a cohort of 114 European patients, an observation which had also been previously made in a smaller cohort of patients receiving treatment with different NAs [34,35]. Other viral markers like core-related antigen or cytokines such as interleukin-22 which show an association to response to NA treatment are currently being investigated [36].…”

Section: Prediction Of Response To Na Treatmentmentioning

confidence: 60%

Antiviral Therapy of Chronic Hepatitis B

Bömmel

Berg²

2014

Intervirology

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Since the licensing of lamivudine in 1999, the treatment of chronic hepatitis B has been revolutionized by the introduction of oral nucleoside and nucleotide analogues (NAs), which act as inhibitors of the HBV polymerase. The effectiveness of the first of these substances was limited by incomplete response and resistance development in many patients, but today, highly potent substances are available that make a reliable and durable suppression of HBV replication, a reduction of necroinflammatory activity in the liver, and even a reversion of liver fibrosis achievable for almost all patients. Beyond that, NA treatment can prevent the development of hepatocellular carcinoma in many patients. HBeAg seroconversion appears in approximately 50% of all HBeAg-positive patients during NA treatment. However, the ideal treatment endpoint, the serologic loss of HBsAg, remains a rare event almost exclusively achievable for HBeAg-positive patients. After cessation of the treatment, HBV replication tends to relapse in most patients, which is why the duration of NA treatment is indefinite. Future treatment strategies should aim at tailoring individual NA treatment regimens to increase HBs loss rates and optimize treatment duration.

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Hepatitis B Surface Antigen (Hbsag) Decrease and Serum Interferon-Inducible Protein-10 Levels as Predictive Markers for Hbsag Loss during Treatment with Nucleoside/Nucleotide Analogues

Abstract: Monitoring qHBsAg after successful HBV DNA suppression might be useful to identify patients who clear HBsAg, implicating finite NA treatment. The role of IP-10 as predictive marker for HBsAg loss should be further evaluated.

Cited by 81 publications

References 39 publications

Inosine Pranobex (Isoprinosine) – a Potential Adjuvant in the Management of Chronic HBV Infection

Inosine Pranobex (Isoprinosine) – a Potential Adjuvant in the Management of Chronic HBV Infection

Dominance of hepatitis C virus (HCV) is associated with lower quantitative hepatitis B surface antigen and higher serum interferon-γ-induced protein 10 levels in HBV/HCV-coinfected patients

Antiviral Therapy of Chronic Hepatitis B

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