Biliary complications (BCs) are one of the most common complications after liver transplantation (LT). BCs mainly include nonanastomotic stricture (NAS), anastomotic stricture (AS), biliary leak and biloma [1]. BCs mainly manifested bile leakage and biliary stricture, and they mainly occurred in the first 3 months after LT [1], [2]. Risk factors include the reconstruction technique, the type of LT procedure, recipient with a high model for end-stage liver disease (MELD) score and receiving living donor liver transplant (LDLT) [1], [3]. Due to improvements in surgical techniques and skills and optimization of patient management, the incidence of BCs has decreased from 24 to 41 % to 5–20 % in recent decades but remains unsatisfactory [1], [4], [5]. NAS and AS are the main types of BCs and are highly correlated with the immunosuppressive status of the recipient [6], [7]. However, the relationship between BCs incidence and tacrolimus concentration remains unclear.

Along with liver function, the trough concentration (C0) of tacrolimus is an important reference in the evaluation of immunosuppressive status [8]. Low concentrations lead to rejection, while high concentrations can lead to adverse effects like acute kidney injury (AKI) [9]. Tacrolimus minimization is beneficial to preventing renal dysfunction and malignancies and improving posttransplant hyperglycemia [10], [11]. However, to address BCs incidence, tacrolimus minimization may not be suitable, as the immune response is highly correlated with BCs [12]. There is no recommended range or tacrolimus management scheme for reducing BCs.

Cumulative exposure to tacrolimus (CET) is a novel parameter reflecting the actual immunosuppressive function, which could indicate the effect of tacrolimus in a time-dependent manner. Recent studies have recommended tacrolimus minimization assessed by CET to prevent renal impairment and tumorigenesis after LT [13], [14]. However, low exposure to tacrolimus results in higher rates of de novo donor-specific antibodies (dnDSAs) and a higher acute rejection risk [15], [16]. The favorable CET for BCs has not been elucidated. Variability is an index that reflects the degree of fluctuation of drug concentrations. The pharmacokinetics of tacrolimus are characterized by high variability among individuals and even in the same patient over time [17]. Studies have shown that high intrapatient variability is associated with a higher risk of graft loss and diminished survival [18], [19]. In summary, the physician’s comprehensive assessment of immunosuppressive status and its relationship with BCs might be improved by establishing not only the mean concentration but also indexes such as CET and the variability of tacrolimus. Whether adequate CET and low variability decrease the incidence of BCs needs to be revealed.

At present, BCs, especially NAS, which is the main type of BCs, are strongly related to immune factors [20], [21]. BCs typically occur within the first 6 months after LT [22], [23]. The fluctuations in concentration are more frequent within the first 3 months, and measurements are more frequently taken within this timeframe. Therefore, the present study aims to explore the association between tacrolimus concentration-related variables within 3 months after LT and the incidence of BCs (including all types), as well as survival.