Clinicopathological features of Bu Gu Zhi‐induced liver injury, a long‐term follow‐up cohort study

Abstract

Background & Aims Bu Gu Zhi (BGZ) is a Chinese herb consumed mainly for osteoporosis treatment. Only small case series of BGZ‐induced liver injury (BGZILI) have been reported. We describe the clinicopathological features and clinical course of BGZILI. Methods Patients diagnosed with drug‐induced liver injury (DILI) at Beijing Friendship Hospital from 2005 to 2017 were reviewed. Clinical and follow‐up data were analysed. Results Of the 547 DILI patients, 40 cases (7.3%) were attributed to BGZILI. About 34/40 (85.0%) patients were females with a median age of 63 (range, 54‐70) years. The median latency period was 45 (range, 29‐90) days. Patients commonly presented with loss of appetite (57.5%), dark urine (57.5%) and fatigue (55.0%). The median level of alanine aminotransferase and aspartate aminotransferase at BGZILI onset was 673.5 and 423.0 U/L respectively. Total bilirubin (TB) and direct bilirubin (DB) were 59.0 and 39.4 µmol/L respectively. The biochemical liver injury pattern was hepatocellular (92.5%), cholestatic (5.0%) and mixed (2.5%). They were categorized into ‘mild’ (N = 23, 57.5%), ‘moderate’ (6, 15.0%) or ‘severe’ (11, 27.5%) according to severity assessment by DILI network. The main histological injury pattern in 9/40 patients with liver biopsy was acute hepatitis with/without cholestasis. Median duration of follow‐up was 26.3 months with recovery in 37 patients within 6 months. No patients died or required transplantation. Conclusions BGZ‐induced liver injury manifested more often as a hepatocellular injury pattern with mild to moderate hepatocellular damage. Most patients recovered after cessation of BGZ within 6 months, and none developed end‐stage liver disease or died.

Identification of naturally occurring inhibitors in Xian-Ling-Gu-Bao capsule against the glucuronidation of estrogens

“…Psoralea corylifolia L., an important herb of XLGB, has been widely used for the treatment of bone fracture and osteoporosis ( Li et al, 2017 ). However, several clinical cases of acute liver injury after oral administration of Psoralea corylifolia L. have been reported ( Teschke and Bahre, 2009 ; Wang et al, 2020 ). This hepatotoxicity may involve in the destruction of the biosynthesis and transportation of bile acid, whereas bakuchiol was identified as the important component for cholestatic hepatotoxicity ( Li et al, 2017 ).…”

Yin/Yang associated differential responses to Psoralea corylifolia Linn. in rat models: an integrated metabolomics and transcriptomics study

“…Although some studies have con rmed that BGZ and some of its components have hepatotoxicity (Li et al, 2017; Wang et al, 2020;Zhang et al, 2022), these studies only focused on the drug itself and did not consider the host factors that induced DILI. Accordingly, by integrating the basic disease characteristics of the population treated with BGZ, our previous study found that most BGZ-induced DILI patients had osteoporosis, psoriasis, osteoarthritis, and other basic diseases related to immune activation (Ge et al, 2021), and such diseases were found to be closely related to the imbalance of kidney-yang de ciency syndrome (Yang syn ) and kidney-yin de ciency syndrome (Yin syn ) according to TCM diagnosis (Dermatology Branch of China Association of Chinese Medicine.…”

“…(Zhang et al, 2020) and Psoralea corylifolia Linn. (BGZ) (Wang et al, 2020), which have been used for thousands of years in China. This increase is causing great confusion for doctors and patients.…”

“…In addition, BGZ and its related compounds are also commonly used in health food and dietary supplements. However, in recent years, BGZ and its related compound preparations Zhuanggu Guanjie Pill and Xianling Gubao Capsules were reported to induce DILI in China (Deng et al, 1996Liu et al, 2019;Wang et al, 2020). The BGZ-induced liver injury also occurred in South Korea (Nam et al, 2005).…”

Transcriptomics and metabolomics reveal the role of CYP1A2 in psoralen/isopsoralen‐induced metabolic activation and hepatotoxicity

“…Psoraleae Fructus ( PF ), a commonly used Chinese herbal medicine derived from the dried mature fruits of Psoralea corylifolia L. (Fam. Leguminaceae), has been warned of hepatotoxic risks (Li et al, 2019; Wang et al, 2020). Psoralen and isopsoralen (Figure 1a,b), belonging to linear and angular furanocoumarins in PF , are important bioactive components with anti‐osteoporotic, anti‐tumor, anti‐bacterial, antiinflammatory, estrogen‐like neuroprotective effects (Han et al, 2021; Li, Yu, et al, 2018; Li et al, 2017; Ren et al, 2020).…”