Neonatal-Perinatal MedicineNeonatal-Perinatal Medicine

To the Editor: Traditional Chinese herbs have widespread use outside of China by both emigrants and an increasing number of Western patients. Typically, 3 to 15 different drugs are combined in a prescription based on the patient's individual symptoms. While Chinese herbal remedies appear to be relatively safe, they are not free of risks, and a number of severe adverse events, including death, have been reported.¹ Although hepatotoxic effects associated with Chinese drugs have been described,^{2 - 3} it is unclear how often such adverse effects occur.

We investigated the frequency of clinically relevant elevations of liver enzymes in 1507 consecutive patients treated with traditional Chinese herbs at the Hospital for Traditional Chinese Medicine in southeast Germany. Seventy-two percent of patients were female, the mean (SD) age was 52 (14) years, two thirds experienced chronic pain, and the mean (SD) hospital stay was 27 [5] days. Blood samples were obtained at admission and during the last 3 days before discharge. The enzymes measured routinely were aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase. A liver enzyme elevation was defined as any elevation over the normal range in patients with normal values at admission, or any elevation over admission values in patients with elevated values at admission. The main outcome measure was the proportion of patients with a more than 2-fold elevation (compared with upper limit of normal values or elevated admission values) of ALT.

Table 1 summarizes the number of patients with elevated values for the 3 enzymes monitored. A more than 2-fold elevation of ALT values was observed in 14 (0.9%) of the 1507 patients consuming Chinese herbs. Two of the 14 patients also had temporary clinical symptoms (nausea and vomiting in 1 patient, itching in the second patient). Based on assessments by 2 independent physicians reviewing the records, a causal relationship of elevated ALT levels with Chinese drug therapy seemed possible in 13 patients and likely in 1. All patients were also receiving non–Chinese drug treatment, and, for some of the drugs used (for example, minocycline, mesalazine, and diclofenac), liver enzyme elevations are listed as possible adverse effects.⁴ Thirteen patients had started these treatments with non–Chinese drugs before their hospital stays, and the dosages had been kept constant or diminished.

Follow-up values of ALT obtained within 8 weeks of hospital discharge were normal in 11 patients (6 of them had continued to take traditional Chinese drugs) and nearly normal in the remaining 3. In 5 patients there were indications of previous liver function abnormalities. The 14 patients with increased ALT levels had received a total of 115 different traditional Chinese drugs. When the frequency of drugs used in these cases was compared with the frequency in patients who had normal liver enzyme values, an increased risk was observed for formulas containing Glycyrrhizae radix and Atractylodis macrocephalae rhizoma.

In the population and setting studied, clinically relevant liver enzyme elevations occurred in about 1 in 100 patients treated with traditional Chinese drugs who also were receiving non–Chinese drug treatments. Based on these findings, we recommend that liver function be monitored in patients receiving traditional Chinese drugs, especially in patients with possible previous liver disease or risk of decreased liver function.