Prognostic value of liver outcome score and hemoglobin in autoimmune liver disease overlap syndromes

Abstract

This letter addresses the study by Jayabalan et al, which underscores the liver outcome score (LOS) and hemoglobin (Hb) as key prognostic markers for patients with autoimmune liver disease overlap syndromes (AILDOS), with particular relevance to the autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) subgroup. The findings indicate that an LOS threshold of 6 achieves high sensitivity and specificity in predicting liver-related mortality among AIH-PBC patients. Moreover, low Hb levels emerge as a significant mortality predictor across all AILDOS cases. These results contribute valuable perspectives on risk stratification in AILDOS, highlighting the promise of non-invasive prognostic tools. Future studies with larger cohorts are needed to substantiate LOS and Hb as robust markers for clinical application.

Key Words: Autoimmune liver disease overlap syndromes; Anemia; Autoimmune hepatitis; Clinical decision-making; Hemoglobin; Liver outcome score; Predictive accuracy; Risk stratification

Core Tip: The liver outcome score (LOS) and hemoglobin (Hb) levels are important prognostic markers in autoimmune liver disease overlap syndromes (AILDOS), especially within the autoimmune hepatitis-primary sclerosing cholangitis subgroup. LOS demonstrates a high degree of predictive accuracy for liver-related mortality, positioning it as a valuable tool for risk stratification where traditional scoring systems may be insufficient. Additionally, consistently low Hb levels correlate with increased mortality across AILDOS cases, highlighting the prognostic impact of anemia in these patients. These findings indicate that non-invasive markers like LOS and Hb could improve clinical decision-making for managing complex liver diseases. Further research with larger cohorts is needed to validate LOS and Hb as effective prognostic tools in AILDOS management.

TO THE EDITOR

I found the recent article by Jayabalan et al[1], titled “Predictors of Survival in Autoimmune Liver Disease Overlap Syndromes”, published in the World Journal of Hepatology, particularly compelling. This study offers valuable insights into the prognostic landscape for patients with autoimmune liver disease overlap syndromes (AILDOS), with a focus on liver-related mortality and predictive scores, including the liver outcome score (LOS). The authors’ work is commendable, addressing a critical gap in our understanding of AILDOS, especially given the rarity and complexity of these syndromes, which include conditions such as autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) and autoimmune hepatitis-primary sclerosing cholangitis (AIH-PSC).

Prognostic significance of LOS and survival variability in AILDOS subgroups

This study makes a significant contribution by identifying LOS as a key predictor of liver-related mortality, particularly in the AIH-PBC subgroup. In a cohort of 22 AILDOS patients, Jayabalan et al[1] found that an LOS threshold of 6 achieved 100% sensitivity and 77.8% specificity for predicting liver-related mortality in AIH-PBC patients. This level of predictive accuracy suggests that LOS could be highly effective for risk stratification in this patient group, where traditional markers such as MELD and MELD-Na scores often fall short[2]. Notably, while these conventional scores offered limited prognostic value, LOS demonstrated a Harrell’s C-statistic of 0.867 for AIH-PBC patients, underscoring its robust performance in identifying high-risk individuals.

In assessing survival outcomes, the authors reported that 57% of AILDOS patients were free from liver-related mortality after five years. The survival disparity between AIH-PBC and AIH-PSC patients was particularly striking; AIH-PBC patients demonstrated a significantly higher survival rate (74%) compared to AIH-PSC patients (27%). This difference highlights the variability in prognosis across overlap syndromes, likely influenced by the distinct pathophysiological mechanisms underlying AIH-PBC and AIH-PSC. AIH-PBC, generally associated with milder cholestasis than AIH-PSC, may inherently offer a more favorable survival outlook.

Biomarkers and their roles in anemia and fibrosis in AILDOS

In patients with AILDOS, chronic inflammation is a key driver of anemia. It promotes the release of cytokines such as interleukin-6, which in turn stimulates hepatic production of hepcidin. Elevated hepcidin levels disrupt iron homeostasis by inhibiting its absorption and release, ultimately leading to iron-deficiency anemia—a mechanism well-documented in various chronic diseases[3,4]. Impaired liver function in AILDOS patients may further dysregulate hepcidin production. Studies have demonstrated that chronic liver disease is often associated with elevated hepcidin levels, which not only restrict intestinal iron uptake but also suppress macrophage-mediated release of stored iron, thereby compounding anemia[5,6].

The spleen also plays a pivotal role in anemia pathogenesis by clearing aged red blood cells and platelets. Portal hypertension frequently results in splenomegaly, which can lead to excessive destruction of red blood cells and platelets, aggravating anemia and potentially correlating with worsening liver function[1,7].

Research by Jayabalan et al[1] underscores anemia, particularly low Hb levels, as a robust predictor of liver-related mortality in AILDOS patients. This form of anemia reflects the complex interplay of multiple factors, including hepcidin dysregulation, hypersplenism, and chronic blood loss. Even after accounting for confounding variables, low Hb remains an independent and critical predictor of mortality[8].

Given the profound impact of anemia on morbidity and quality of life, its inclusion alongside LOS as a prognostic marker could significantly enhance clinical decision-making in AILDOS management[1,9]. Additionally, incorporating biomarkers such as ferritin and transferrin into anemia evaluation may provide a more holistic understanding of its pathophysiological role in AILDOS, facilitating more precise therapeutic strategies[5].

Ferritin, a critical marker of iron storage in the body, is strongly correlated with the severity of liver inflammation and fibrosis. Research indicates that iron overload triggers oxidative stress, which activates hepatic stellate cells and accelerates the progression of fibrosis[10,11].

Similarly, low albumin levels are indicative of impaired liver function and are associated with poor clinical outcomes. Beyond serving as a marker of nutritional status, albumin plays an essential role in maintaining plasma oncotic pressure and providing antioxidative protection.

Incorporating these biomarkers into clinical assessments offers a more holistic understanding of the condition in patients with AILDOS, thereby enhancing clinical management and improving prognostic evaluations.

Challenges and future directions in understanding AILDOS prognostic markers and mechanisms

In this study, we systematically assessed the prognostic value of the LOS and Hb levels in patients with AILDOS, with a particular emphasis on the AIH-PBC subgroup. The findings revealed that LOS is a reliable predictor of liver-related mortality in AILDOS patients. Specifically, when the LOS threshold was set at 6, it achieved 100% sensitivity and 77.8% specificity in the AIH-PBC subgroup. Additionally, low Hb levels were identified as significant predictors of mortality in AILDOS patients. Notably, while LOS has been extensively validated in chronic hepatitis C patients, this study underscores its valuable application in the AILDOS context.

Despite these promising results, the study has certain limitations. It was a single-center retrospective analysis with a relatively small sample size, particularly in the AIH-PSC group, which included only eight patients, thereby restricting the generalizability of the findings. Moreover, combining AIH-PBC and AIH-PSC patients for analysis may have introduced confounding factors, potentially masking the effects of distinct pathophysiological mechanisms on prognosis.

Future studies should aim to validate the prognostic utility of LOS and Hb levels through larger-scale prospective investigations, ensuring more detailed subgroup analyses. Additionally, integrating other biochemical markers, such as ferritin and albumin, could offer a more comprehensive evaluation of liver inflammation and fibrosis progression in AILDOS patients, thereby providing a more robust foundation for personalized treatment strategies[12,13].

CONCLUSION

The findings of this study highlight the potential of non-invasive prognostic indicators in managing complex liver diseases and provide valuable insights to guide clinical decision-making. Jayabalan et al[1] have made a significant contribution to the field by identifying LOS and low Hb as critical predictors of liver-related mortality in AILDOS, particularly within the AIH-PBC subgroup. Their research underscores the importance of developing non-invasive and reliable prognostic models for effective management of complex liver conditions. These results lay a strong foundation for future studies to build upon and advance this promising area of research.