Letter: Insulin-Like Growth Factor-1 in Cirrhosis Is Linked to Hepatic Dysfunction and Fibrogenesis and Predicts Liver-Related Mortality

We read the article published in your esteemed journal titled, “Insulin-like growth factor-1 in cirrhosis is linked to hepatic dysfunction and fibrogenesis and predicts liver-related mortality” by Hartl et al. with great interest. We appreciate the authors for investigating the prognostic role of insulin-like growth factor-1 (IGF-1) in advanced chronic liver disease (ACLD) patients [1]. While the study provides valuable insights, we believe certain limitations warrant further discussion.

Firstly, the small sample size of 269 patients does not reflect the global heterogeneity of cirrhosis patients, which potentially limits the generalizability of the findings. Studies with larger sample sizes, ideally ranging from 500 to 1000 patients, would offer more statistically robust conclusions. This is particularly important given the various etiologies of cirrhosis, such as metabolic dysfunction-associated steatohepatitis (MASH), alcohol-related liver disease, and viral hepatitis, which affect IGF-1 levels differently [2]. Expanding the cohort to include a more diverse population could improve the validity of the findings.

Secondly, the potential confounding variables such as obesity and diabetes are not addressed by the authors, which could distort the interpretation of IGF-1 as a measure of the severity of liver diseases. For instance, Aleidi et al. found that type 2 diabetes is associated with significantly lower IGF-1 levels, irrespective of liver function. By not controlling for these metabolic factors, the study may misattribute changes in IGF-1 levels to liver dysfunction alone. Future studies should include these factors in multivariate models to provide a clearer understanding of IGF-1's role in cirrhosis [3].

Lastly, the median follow-up period of 604 days may be insufficient to capture the full progression of cirrhosis and its complications, such as hepatocellular carcinoma and liver-related mortality. Studies like Saeki et al. have demonstrated the importance of long-term follow-up, using a median duration of 57.1 months to assess the prognostic value of IGF-1 [4]. Given the slow progression of cirrhosis, a follow-up period of at least 5 years would provide a more comprehensive evaluation of IGF-1's predictive power and help capture critical outcomes such as development of hepatocellular carcinoma, survival rates, and complications like hepatic encephalopathy.

Future studies should address these limitations by incorporating a larger sample size, extending follow-up periods, and accounting for potential confounding factors such as diabetes and obesity. Doing so will not only strengthen the study's findings but also provide deeper insights into the long-term outcomes of cirrhosis management and the prognostic value of IGF-1 across diverse populations. Ultimately, this will contribute to improved patient outcomes and more refined therapeutic approaches.