Clinicopathological Features of He Shou Wu-induced Liver Injury

This Ancient Anti-aging Therapy Is Not Liver-friendly

Yan Wang; Lan Wang; Romil Saxena; Aileen Wee; Ruiyuan Yang; Qiuju Tian; Jiping Zhang; Xinyan Zhao; Jidong Jia


Liver International. 2019;39(2):389-400. 

In This Article

Patients and Methods

Study Population

Medical records of patients who had been diagnosed with DILI and hospitalised at Beijing Friendship Hospital from August 2005 to August 2017 were retrospectively reviewed. DILI associated with He Shou Wu alone or herbal compounds containing He Shou Wu with Roussel Uclaf Causality Assessment Method (RUCAM) scores ≥3 were included.[20] Patients with concomitant liver diseases were excluded, including those with hepatotropic viral hepatitis (Hepatitis A, B, C, and E viruses), non-hepatotropic viral infections (cytomegalovirus and Epstein-Barr virus), liver injury induced by other drugs, primary biliary cholangitis, biliary obstruction, metabolic liver diseases, and ischemic hepatitis. No patient had history of excessive alcohol consumption (>40 g/d of alcohol for men and >20 g/d for women, lasting for 5 years).[21] Fatty liver disease was excluded by abdominal ultrasound in all patients within 1 month of presentation. Autoimmune liver disease was excluded based on medical history, status of serum autoantibodies, serum levels of immunoglobulin G (IgG) and immunoglobulin M, and clinical follow-up. This study complied with the Helsinki Declaration of 1975 revised in 1983 and was approved by Ethic review board of Beijing Friendship Hospital, Capital Medical University. The requirement of informed consent from patients was waived.

Data Collection

Detailed medical histories, time frame of exposure to He Shou Wu, and clinical and laboratory findings were obtained from medical records. For patients who had undergone liver biopsy, the histological sections were stained with H&E, Masson trichrome, reticulin, periodic acid-Schiff with diastase, Perls stain for iron, rhodanine stain for stainable copper. Additionally, immunohistochemical stains for cytokeratin 7 and cytokeratin 19 were performed. These sections were reviewed by two liver pathologists (RS, AW) and one hepatologist (XZ), who were blinded to the clinical information. RUCAM scores were calculated for each patient. A causal relationship between He Shou Wu and liver injury was categorised as highly probable (>8), probable (6–8), and possible (3–5). The pattern of injury was defined according to the R value [ratio of serum alanine aminotransferase (ALT)/upper limit of normal (ULN) to serum alkaline phosphatase (ALP)/ULN] as hepatocellular when R ≥ 5, mixed as 2 < R < 5, and cholestatic as R ≤ 2.[22] Disease severity was graded as mild, moderate, moderate-severe, severe, or fatal according to standard criteria.[23]

All patients had been followed up until normalisation of liver chemistries [ALT or aspartate aminotransferase (AST) < 1 × ULN and total bilirubin (TB) < 1.5 × ULN], chronic persistent abnormality of liver chemistries, or occurrence of endpoint events such as cirrhosis, liver transplantation, liver failure, or death. Liver chemistries, complete blood count, and coagulation profiles of each individual during follow-up (if any) were collected.

Statistical Analysis

Continuous variables are shown as median and quartiles and categorical variables data as percentages. Kruskal-Wallis and Chi-square (χ 2) tests, respectively, were performed to assess these types of variables. All tests were two-tailed and P < 0.05 was considered to denote significant differences. Data were analysed using SPSS software (version 22.0; SPSS, Chicago, IL, USA).