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The Dual Role of Hypoxia-Inducible Factor-1α in Sepsis-Induced Immunomodulation and Organ Dysfunction: A Systematic Review and Meta-Analysis Hudari, Harun; Mega Permata; Ratna Maila Dewi Anggraini; Raden Ayu Linda Andriani
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1378

Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a leading cause of global mortality. Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of the cellular adaptive response to hypoxia but plays a complex, paradoxical role in sepsis. While essential for innate immune function, its sustained activation may amplify inflammation and drive organ damage. This meta-analysis was conducted to synthesize the evidence on the association of HIF-1α with key markers of immunomodulation and organ dysfunction in sepsis. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science was conducted for studies published between January 2014 and December 2024. We included observational studies that measured HIF-1α levels in adult sepsis patients and reported outcomes related to organ dysfunction (Sequential Organ Failure Assessment [SOFA] score) or mortality, and immunomodulation (Interleukin-6 [IL-6] levels). Seven studies meeting the inclusion criteria were included in the final analysis. Data were pooled using a random-effects model. Standardized Mean Difference (SMD) and Odds Ratios (OR) with 95% confidence intervals (CI) were calculated. Results: The seven included studies comprised 1,288 patients. The overall quality of the included studies was moderate to high as per the Newcastle-Ottawa Scale. The pooled analysis revealed that HIF-1α levels were significantly elevated in sepsis patients who died compared to those who survived (OR = 2.68, 95% CI: 1.55–4.64, p < 0.001), with moderate heterogeneity (I² = 45%). Furthermore, HIF-1α levels were strongly associated with greater organ dysfunction, as measured by the SOFA score (5 studies; SMD = 0.92, 95% CI: 0.51–1.33, p < 0.0001), with substantial heterogeneity (I² = 78%). HIF-1α levels also showed a significant positive correlation with the pro-inflammatory cytokine IL-6 (4 studies; SMD = 1.15, 95% CI: 0.65–1.65, p < 0.00001), with high heterogeneity (I² = 82%). Conclusion: This meta-analysis provides robust evidence that elevated HIF-1α levels are significantly associated with increased sepsis severity, characterized by greater organ dysfunction, a heightened pro-inflammatory state, and a higher risk of mortality. These findings underscore the maladaptive consequences of sustained HIF-1α activation in sepsis, positioning it as a critical prognostic biomarker and a complex, high-value target for future therapeutic modulation.

The Dual Role of Hypoxia-Inducible Factor-1α in Sepsis-Induced Immunomodulation and Organ Dysfunction: A Systematic Review and Meta-Analysis Hudari, Harun; Mega Permata; Ratna Maila Dewi Anggraini; Raden Ayu Linda Andriani
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 9 No. 9 (2025): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v9i9.1378

Background: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, remains a leading cause of global mortality. Hypoxia-inducible factor-1α (HIF-1α) is a master transcriptional regulator of the cellular adaptive response to hypoxia but plays a complex, paradoxical role in sepsis. While essential for innate immune function, its sustained activation may amplify inflammation and drive organ damage. This meta-analysis was conducted to synthesize the evidence on the association of HIF-1α with key markers of immunomodulation and organ dysfunction in sepsis. Methods: We performed a systematic review and meta-analysis following PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science was conducted for studies published between January 2014 and December 2024. We included observational studies that measured HIF-1α levels in adult sepsis patients and reported outcomes related to organ dysfunction (Sequential Organ Failure Assessment [SOFA] score) or mortality, and immunomodulation (Interleukin-6 [IL-6] levels). Seven studies meeting the inclusion criteria were included in the final analysis. Data were pooled using a random-effects model. Standardized Mean Difference (SMD) and Odds Ratios (OR) with 95% confidence intervals (CI) were calculated. Results: The seven included studies comprised 1,288 patients. The overall quality of the included studies was moderate to high as per the Newcastle-Ottawa Scale. The pooled analysis revealed that HIF-1α levels were significantly elevated in sepsis patients who died compared to those who survived (OR = 2.68, 95% CI: 1.55–4.64, p < 0.001), with moderate heterogeneity (I² = 45%). Furthermore, HIF-1α levels were strongly associated with greater organ dysfunction, as measured by the SOFA score (5 studies; SMD = 0.92, 95% CI: 0.51–1.33, p < 0.0001), with substantial heterogeneity (I² = 78%). HIF-1α levels also showed a significant positive correlation with the pro-inflammatory cytokine IL-6 (4 studies; SMD = 1.15, 95% CI: 0.65–1.65, p < 0.00001), with high heterogeneity (I² = 82%). Conclusion: This meta-analysis provides robust evidence that elevated HIF-1α levels are significantly associated with increased sepsis severity, characterized by greater organ dysfunction, a heightened pro-inflammatory state, and a higher risk of mortality. These findings underscore the maladaptive consequences of sustained HIF-1α activation in sepsis, positioning it as a critical prognostic biomarker and a complex, high-value target for future therapeutic modulation.

The Role of Tecovirimat in the Management of Monkeypox Prasetyo, Ari Dwi; Harun Hudari; Mega Permata; Nelda Aprilia Salin
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 7 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i7.1028

Monkeypox is a self-limited disease with symptoms that disappear within 14 to 21 days. Clinical management of monkeypox includes general supportive care and the use of antivirals that have activity against the monkeypox virus. This literature study aims to describe the role of tecovirimat in the management of monkeypox. Tecovirimat is an antiviral drug approved by the U.S. Food and Drug Administration (FDA) as part of the treatment management of smallpox in adults and children. Evidence of the efficacy of tecovirimat as mpox therapy was obtained from animal studies, where tecovirimat reduced mortality rates, reduced duration of illness and viral shedding. Tecovirimat inhibits the vp37 viral protein encoded by the F13 gene of the variola virus. This protein is highly conserved in orthopoxviruses, allowing tecovirimat to have in vitro activity against several orthopoxviruses, including vaccinia, variola, cowpox, and monkeypox viruses. In conclusion, tecovirimat is used in monkeypox sufferers with severe clinical conditions (sepsis, encephalitis, extensive lesions, bleeding manifestations), patients at risk of experiencing severe clinical conditions (immunocompromised, pregnant or breastfeeding, history of psoriasis, varicella zoster infection) and patients with one or more complications.

The Role of Tecovirimat in the Management of Monkeypox Prasetyo, Ari Dwi; Harun Hudari; Mega Permata; Nelda Aprilia Salin
Bioscientia Medicina : Journal of Biomedicine and Translational Research Vol. 8 No. 7 (2024): Bioscientia Medicina: Journal of Biomedicine & Translational Research
Publisher : HM Publisher

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.37275/bsm.v8i7.1028

Monkeypox is a self-limited disease with symptoms that disappear within 14 to 21 days. Clinical management of monkeypox includes general supportive care and the use of antivirals that have activity against the monkeypox virus. This literature study aims to describe the role of tecovirimat in the management of monkeypox. Tecovirimat is an antiviral drug approved by the U.S. Food and Drug Administration (FDA) as part of the treatment management of smallpox in adults and children. Evidence of the efficacy of tecovirimat as mpox therapy was obtained from animal studies, where tecovirimat reduced mortality rates, reduced duration of illness and viral shedding. Tecovirimat inhibits the vp37 viral protein encoded by the F13 gene of the variola virus. This protein is highly conserved in orthopoxviruses, allowing tecovirimat to have in vitro activity against several orthopoxviruses, including vaccinia, variola, cowpox, and monkeypox viruses. In conclusion, tecovirimat is used in monkeypox sufferers with severe clinical conditions (sepsis, encephalitis, extensive lesions, bleeding manifestations), patients at risk of experiencing severe clinical conditions (immunocompromised, pregnant or breastfeeding, history of psoriasis, varicella zoster infection) and patients with one or more complications.

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