Preventive use of hepatoprotectors yields limited efficacy on the liver toxicity of anti‐tuberculosis agents in a large cohort of <scp>C</scp>hinese patients

Wu, Shanshan; Xia, Yuqing; Lv, Xiaozhen; Tang, Shaowen; Yang, Zhirong; Zhang, Yuan; Hu, Daiyu; Liu, Feiying; Yuan, Yanli; Tu, Dehua; Sun, Feng; Zhou, Lin; Zhan, Siyan

doi:10.1111/jgh.12717

Cited by 18 publications

(22 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Once DILI was developed, changes of anti-TB treatment could be considered according to the physician's clinical decision, including drug interruption, discontinuation or change the regimen15. Any could extend the treatment duration, induce the drug resistance, poor adherence, or treatment failure after all.…”

Section: Discussionmentioning

confidence: 99%

Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity

Heo

Kim

et al. 2017

Tuberc Respir Dis

View full text Add to dashboard Cite

BackgroundThe first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by anti-TB drugs.MethodsThis is a prospective, randomized, double-blind and placebo-controlled study. Patients were eligible if they were 20 years of age or order and started the first-line anti-tuberculosis drugs. Eligible patients were randomized for receiving silymarin or a placebo for the first 4 weeks. The primary outcome was the proportion of patients who showed elevated serum liver enzymes more than 3 times the upper normal limit (UNL) or total bilirubin (TBil) > 2× UNL within the first 8 weeks of anti-TB treatment.ResultsWe enrolled a total of 121 patients who silymarin or a placebo to start their anti-TB treatment, for the first 8 weeks. The proportions of elevated serum liver enzymes more than 3 times of UNL at week 2, week 4, and week 8 did not show any significant difference between the silymarin and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and 8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >2× ULN at week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043).ConclusionOur findings did not show silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity

Heo

Kim

et al. 2017

Tuberc Respir Dis

View full text Add to dashboard Cite

show abstract

“…[23][24][25] In China, the reported incidence of ATLI varies from 2.6% to 7.5%. 21,26 In a population-based prospective study by Shang et al, 106 of 4304 tuberculosis patients receiving Figure 2 Evaluation of drug-induced serious hepatotoxicity plot. Each point in the figure represents a unique subject's peak serum alanine aminotransferase (ALT) and peak serum total bilirubin (TBiL) values.…”

Section: Discussionmentioning

confidence: 99%

“…Until now, there has been no scientific evidence to support the hypothesis that hepatoprotectants can lower the risk of hepatotoxicity imposed by anti-tuberculosis drugs. 26 Hepatoprotectants are not free under the current National Tuberculosis Control Program in China. Overprescription of these medications to patients, regardless of the risk, can increase patients' financial burden.…”

Section: Discussionmentioning

confidence: 99%

Preventive use of a hepatoprotectant against anti‐tuberculosis drug‐induced liver injury: A randomized controlled trial

Zhang

Pan²,

Peng

et al. 2016

J of Gastro and Hepatol

View full text Add to dashboard Cite

Background and Aim: Hepatoprotectants are routinely prescribed in China to prevent anti-tuberculosis drug-induced liver injury (ATLI). However, their biological mechanismshave not yet been clearly demonstrated. This study aims to evaluate the preventive effects of Silybum marianum against drug-induced liver injury among tuberculosis patients and to provide clinical guidelines for tuberculosis management in China. Methods: A randomized controlled trial was performed in Jiangsu, China. Tuberculosis patients were randomly allocated to the experimental group (anti-tuberculosis therapy plus S. marianum capsule) or the control group (anti-tuberculosis therapy plus vitamin C tablet). The primary outcomes were the occurrence of probable and possible ATLI, the peak aspartate aminotransferase/alanine aminotransferase ratio and the maximum altered alkaline phosphatase or gamma-glutamyl transferase.Results: The final analysis comprised 183 cases in the experiment group and 187 cases in the control group. The risk of developing probable ATLI was not significantly different between the two groups. During the follow-up period, 43.72% of cases in the experiment group and 35.83% of cases in the control group were determined to have possible ATLI (relative risk = 1.23, 95% confidence interval: 0.94-1.54). When using a more strict definition of possible ATLI, the adjusted relative risk (95% confidence interval) was 1.76 (1.14-2.56). The risks of adverse drug reactions, prolonged treatment length, taking second-line tuberculosis drugs, and the clearance of tuberculosis bacteria were similar between the two groups. Conclusions: No significant preventive effect of silymarin was found for either lowering the risk of liver injury or boosting the positive outcomes. Worse, we even found a potential risk of liver damage caused by the hepatoprotectant.

show abstract

“…Therefore, currently this guideline does not recommend the combination of two or more types of AIHPAs to treat DILI. Also, to date there is no evidence supporting the value and necessity of prophylactic use of AIHPAs for reducing the risk of DILI in clinical contexts with potentially increased risk of DILI, such as during anti-tuberculosis or anti-tumor therapy [123]. However, in these clinical contexts, especially within the first three months of anti-tuberculosis therapy, it is very important to do enhanced monitoring of liver-related biochemical tests to detect liver injury earlier and give rational intervention.…”

Section: Treatment Of Dilimentioning

confidence: 99%

CSH guidelines for the diagnosis and treatment of drug-induced liver injury

et al. 2017

View full text Add to dashboard Cite

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

show abstract

Preventive use of hepatoprotectors yields limited efficacy on the liver toxicity of anti‐tuberculosis agents in a large cohort of Chinese patients

Abstract: No preventive effect of hepatoprotectors was observed in patients receiving anti-TB treatment.

Cited by 18 publications

References 17 publications

Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity

Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity

Preventive use of a hepatoprotectant against anti‐tuberculosis drug‐induced liver injury: A randomized controlled trial

CSH guidelines for the diagnosis and treatment of drug-induced liver injury

Contact Info

Product

Resources

About