The Clinical Characteristics And Treatment Of Drug-induced Liver Injury

Background:Drug-induced liver injury (DILI) is a frequent cause of liver diseases and remains one of the most challenging disorders faced by clinicians and researchers. Recently herbs is increasingly being recognized as a significant cause of DILI. However, the data on herb-induced liver injury (HILI) are remarkably limited. Objective:To analyze the etiology, clinical features, diagnostic methods, treatment, and prognosis of DILI, especially HILI in China. Methods:All patients hospitalized with DILI between January 2009 and January 2014 were retrospectively studied. Patients hospitalized with DILI between June 2014 and December 2011 were enrolled to prospectively study the HILI diagnosis system based on the "the chain of integrated evidence" and the effects of high dosage of Radix Paeoniae Rubra (RPR) for treatment of severe DILI with intractable jaundice. Results:① In overall 2035 DILI cases, Chinese herbal medicine (CHM) was used for 595 patients (29.2%), whereas Western medicine (WM) or the combination of WM and CHM was applied in 875 cases (43.0%) and the remaining patients (27.8%), respectively.13.3% developed into chronicity, 3.1% died and 0.5% underwent liver transplantation. A four-parameter model for the prognosis of DILI, including alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TBiL), and international normalized ratio (INR), was established and achieved both a sensitivity and specificity over 0.90.② In 595 HILI cases,47 (7.9%) patients were diagnosed as acute liver failure,45 (7.6%) presented with cirrhosis,78 (13.1%) developed into chronic DILI, only 2 (0.3%) underwent liver transplantation, and the mortality rate was 3.2%. The major clinical injury pattern of HILI was hepatocellular (85.9%), and the median time from TCM initiation to symptom onset was 30 (15,75) days. Compared to WM, the cases caused by CHM showed lower levels of ALP and INR (312±214 U/L vs 192±123 U/L,1.36± 0.65 vs 1.22±0.51, P< 0.001); however, no differences in outcomes were found (P> 0.05).207 kinds of Chinese patent medicine, such as Ku-kang capsule, Yang-xue-sheng-fa capsule, and Dan-lu-tong-du tablet, were involved in HILL The major herbs associated with HILI were Polygonum multiflorum. ③ Of 158 hospitalized patients with the application of Polygonum multiflorum and its preparation before the onset of DILI,58.2% applied Polygonum multiflorum and its preparation combined with WM or CHM without Polygonum multiflorum. In 66 patients with DILI caused by Polygonum multiflorum and its preparation, 77.3% were induced by compound and 22.7% by single Polygonum multiflorum; 6.1% were caused by crude Polygonum multiflorum and 92.4% by processed Polygonum multiflorum; 4 patients presented with liver failure,4 developed into cirrhosis, and only 1 died.④ A total of 37.7% of the children had medical histories of respiratory infection. Antibiotics (26.1%) were the most common WM causing DILI in children, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum.⑤ According to the HILI diagnosis system based on the "the chain of integrated evidence",22 cases with HILI diagnosed by American College of Gastroenterology (ACG) caused by Polygonum multiflorum were further subdivided into:14 cases were definitely diagnosed with HILI,7 with suspected HILI, and 1 was excluded.⑥ High dosage of RPR cured all 6 DILI cases with severe DILI with intractable jaundice, better than glucocorticoid (2 of cases were cured,1 was invalid, and 2 died, P= 0.036). High dosage of RPR could significantly decreased the levels of ALT and TBiL (79 ±46 U/L vs 27±13 U/L, P= 0.048; 345.5±162.1μmol/L vs 15.0 ±1.6 μmol/L, P= 0.004). Conclusion:Herbs could result in liver injury and attention should be paid to study on HILI. The clinical diagnosis of HILI need to be cautious and is recommended based on the "the chain of integrated evidence". High dosage of RPR may be an alternative and efficient choice of treatment for severe DILI patients with intractable jaundice.