Treatment options beyond <scp>IFN</scp><i>α</i> and <scp>NUC</scp>s for chronic <scp>HBV</scp> infection: expectations for tomorrow

Baltayiannis, Gerasimos; Karayiannis, Peter

doi:10.1111/jvh.12307

Cited by 12 publications

(13 citation statements)

References 63 publications

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“…This hypothesis is based on recent suggestion that sustained inhibition of viral replication could facilitate the effect of Peg-IFN and other immunomodulators (14). Several novel immune modulatory agents, like different therapeutic vaccines or toll-like-receptor agonists, are currently in clinical development (9). The design of future clinical trials should be focused on elucidating the optimal duration of these new drugs in combination with direct antiviral agents.…”

Section: Discussionmentioning

confidence: 99%

“…HBsAg clearance and development of anti-HBs occurs in only a minority of cases not exceeding 8% after both Peg-IFN and NUC therapy (1,9). Durable HBV DNA suppression with NUC is only possible with continued treatment for many years.…”

Section: Discussionmentioning

confidence: 99%

“…New drugs based on immunomodulation are being developed such as different therapeutic vaccines and TLR agonists (9). The results from add-on Peg-IFN or other immunomodulators to NUC are limited and controversial (10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

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

Krastev¹,

Nikolova²,

Jelev³

et al. 2015

MedInform

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“…Currently, nucleos(t)ide analogues and Peg-Interferon alpha are the main classes of antivirals to treat chronic hepatitis B (CHB) [4,5]. IFN-α mediates signal transduction by binding to its receptors.…”

Section: Introductionmentioning

confidence: 99%

Interferon-stimulated gene 15 in hepatitis B-related liver diseases

et al. 2016

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This study investigates the association of Interferon-stimulated gene 15 (ISG15) polymorphisms, ISG15 serum levels and expression with HBV-related liver diseases. The ISG15 promoter and the two exons of the gene were screened for polymorphisms in 766 HBV-infected patients and in 223 controls. Soluble ISG15 levels were measured by ELISA. ISG15 mRNA expression was quantified by qRT-PCR in 36 tumor and adjacent non-tumor tissues. The exon 2 allele rs1921A was found associated with decreased progression of HBV-related liver diseases (LC vs. CHB: OR = 0.6, 95%CI = 0.4-0.8, adjusted P = 0.003; HCC vs. CHB: OR = 0.6, 95%CI = 0.4-0.9, adjusted P = 0.005). The rs1921AA genotype was associated with low levels of AST, ALT and total bilirubin, but with high prothrombin levels (P < 0.05). ISG15 serum levels were higher among HBV patients compared to controls (P < 0.0001) and positively associated with HBV-related liver diseases, with highest levels among LC patients. ISG15 levels were correlated with HBV-DNA loads (P = 0.001). In non-tumor tissues from HCC patients, ISG15 mRNA expression was increased in HBV compared to non-HBV infection (P = 0.016). The ISG15 rs1921 variant and ISG15 expression are associated with HBV-related liver diseases. Taken together, ISG15 appears to be a proviral factor involved in HBV replication and triggering progression of HBV-related liver diseases.

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“…Research efforts currently focus on the development of novel approaches with the capacity to suppress the production of multiple viral proteins, including hepatitis B surface antigen, with such agents as small interfering RNA (siRNA) agents, or to target cccDNA itself. Immunomodulatory approaches are also being investigated . The long‐term outlook for such novel approaches is favorable, but current investigational programs are early in their development.…”

Section: Routes To Elimination Of Hepatitis B and C (2015)mentioning

confidence: 99%

The extinction of chronic viral hepatitis?

Kumar

Jacobson

2015

Clinical Liver Disease

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Chronic viral hepatitis from hepatitis B virus (HBV) and hepatitis C virus (HCV) is a significant global health problem, with the World Health Organization (WHO) estimating 240 million people worldwide to be chronically infected with HBV and 170 million people infected with HCV.1,2 Patients with chronic infection are at risk for significant morbidity and mortality due to long-term complications of the disease, including cirrhosis and hepatocellular carcinoma. Many years of research have resulted in remarkable advances in the elucidation of the biology of these viruses, resulting in the development of highly effective therapies for these conditions that are reducing the terrible human toll taken by these diseases. The high worldwide prevalence of these infections, vast numbers of as yet undiagnosed patients, continued transmission of the causative viruses, and disparities in access to health care dispel any notion that these diseases will be eliminated in the near future. However, the tools are now available to enable us to envision a future in which these infections will affect far fewer people and eventually be eradicated (Table 1). Despite its higher worldwide prevalence, the actual eradication of HBV is probably a more realistic goal than that of HCV because of the availability of effective immunization. The development of an effective vaccine for hepatitis B, first a plasma-derived product more than three decades ago followed by a recombinant vaccine more than three decades ago, can justly be regarded as one of the great medical advances of the 20th Century. Infant immunization is highly effective in conferring long-lasting protection against infection, and is more than 95% effective in preventing acquisition of infection even from highly viremic mothers, with concomitant third trimester antiviral therapy in mothers boosting protection against transmission to nearly 100%.Immunization programs have resulted in a reduction in the global prevalence of infection, and in countries with effective immunization programs a reduction in hepatocellular carcinoma incidence at young ages has been demonstrated. 3 If socioeconomic conditions and health care systems permitted universal immunization in infants, as currently recommended, the near or complete eradication of HBV infection should theoretically be attainable in the next two generations. Failure to attain this goal, which is likely, will entail needless tragedies.Effective treatment of existing HBV infection reduces inflammation and fibrosis and is critical to the reduction of morbidity and mortality from cirrhosis and liver cancer in affected individuals, 4-6 and reduces or eliminates the risk of transmission ( Table 2). The hepatitis B virus is unlike HCV in that infection results in an intranuclear, minichromosomal form of the viral genome. The fundamental limitation of current HBV therapy is that it confers profound suppression of viral replication but seldom eliminates the carrier state. The episomal, intranuclear covalently closed circular DNA (cccDNA) of th...

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Treatment options beyond IFNα and NUCs for chronic HBV infection: expectations for tomorrow

Cited by 12 publications

References 63 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

Interferon-stimulated gene 15 in hepatitis B-related liver diseases

The extinction of chronic viral hepatitis?

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