PFIC null genotype linked to 2.79-fold higher odds of liver transplantation

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PloS one Published June 2, 2026 Medically reviewed June 2, 2026 Study authors: Sakka Rania, Abroug Hela, Youssef Sabrine Ben, Mekki Mongi, M'rad Ridha PubMed ↗ DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider PFIC null genotype as a potential risk factor for liver transplantation, but confirm with further trials.

This meta-analysis of observational studies examined the association between PFIC null genotype and liver transplantation (LT) events in 420 patients with progressive familial intrahepatic cholestasis (PFIC). The primary outcome was LT event, and the analysis compared patients with null genotype versus non-null genotype.

The pooled analysis showed a close relationship between PFIC null genotype and LT event, with an odds ratio of 2.79 (95% CI: 1.63 to 4.77; p < 0.001). This indicates a positive association, meaning patients with null genotype had higher odds of requiring liver transplantation.

The authors acknowledge that further trials are needed to confirm these results and to guide decisions regarding personalized and early preventive liver transplantation. The evidence is observational, so causal conclusions cannot be drawn. Adverse events and other clinical outcomes beyond LT were not reported.

For clinicians, this finding suggests that PFIC null genotype may be a marker for increased risk of needing liver transplantation, but the association should be interpreted cautiously until confirmed by prospective studies.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedJan 2026

PMID42224341

View Original Abstract ↓

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) refers to a group of inherited cholestatic liver diseases that affect children, often leading to liver failure and requiring liver transplantation (LT). Many studies have established correlations between the effect of the causal gene variant types and the severity of the PFIC phenotype, the treatment considered, or its outcomes in patients. Nevertheless, no selection criteria for LT based on genotypes have been adopted for patients affected by this group of diseases. Therefore, we conducted a meta-analysis to investigate the association between the main PFIC subtype genotypes and the treatment with LT. METHODS: Online databases were searched for articles on PFIC1-4 and LT. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The genotypes of patients were extracted from the included studies and categorized into a group of cases, harboring null genotypes, and a group of controls, harboring non-null genotypes. The relationship between the genotype type and LT outcome was expressed as an OR by assessing the LT event among the case group and the control group. RESULTS: Eighteen studies involving 420 PFIC patients were included. A random-effects model was used to assess the OR. Overall, we observed a close relationship between the PFIC null genotype and the LT event; OR=2.79 (95% CI:1.63 to 4.77; p < 0.001). Subgroup analysis according to the PFIC subtype showed the same effect. CONCLUSIONS: Our results provide evidence of a potential association between null genotypes in PFIC diseases and the indication of LT as a treatment. Further trials are needed to confirm our results and guide decisions regarding personalized and early preventive LT. RESEARCH PROTOCOL REGISTRATION: https://doi.org/10.17605/OSF.IO/MNQWB.