Special Report | The Mystery Behind the Proliferation of Liver Protection Drugs: Widespread Prescriptions Lack Evidence-Based Support (AI Translation)

特别报道｜保肝药泛滥之谜：大量处方并无循证依据

Summary:

Liver-protective drugs are widely used in China, often prescribed for various forms of liver damage, yet their clinical effectiveness remains a topic of ongoing debate and investigation [para. 1][para. 2][para. 3]. Typical scenarios involve patients with elevated liver enzymes due to drug-induced liver injury or traditional medicine usage, leading physicians to prescribe medications such as bicyclol and silymarin to normalize these markers, sometimes with apparent short-term benefits [para. 1].

Liver-protective drugs encompass a wide range of substances, generally derived from natural sources like animal bile, licorice, and milk thistle. The most commonly used include glycyrrhizin preparations, bicyclol, polyene phosphatidylcholine, silymarin, and glutathione. These drugs are said to reduce liver inflammation, aid detoxification, and promote liver cell regeneration [para. 3]. Despite some clinical observations that these medications can quickly lower ALT and AST levels, the liver has substantial self-repair capabilities, and there is insufficient high-quality evidence to confirm their long-term utility [para. 3][para. 4]. Globally, such drugs are not recommended by the World Health Organization (WHO) or incorporated into major hepatitis treatment guidelines due to a lack of rigorous supporting data [para. 5].

In China, the use of these drugs began in the 1980s but, due to a paucity of large, long-term, randomized controlled trials, their efficacy is not strongly endorsed in clinical guidelines for hepatitis B or fatty liver disease [para. 6]. Within the physician community, opinions are mixed: some see little value, while others think there may be some benefit; a minority are strong proponents [para. 7]. Notably, even when their role is contested, these drugs are commonly prescribed across multiple departments in Chinese hospitals [para. 7][para. 8].

Financially, the hepatoprotective drug market is substantial. Hospital sales reached nearly 10 billion yuan (approx. $1.4 billion) in 2023, mainly through urban public hospitals [para. 8]. From 2016 to 2023, prescriptions and spending on liver-protective drugs in Chinese outpatient settings grew steadily, with 8.64 million prescriptions to 3.19 million patients cumulatively, costing over 100 million yuan annually and imposing a rising burden on the national health insurance system [para. 9]. This is amplified by the relatively minor cost of highly effective treatments like entecavir for hepatitis B, now costing as little as 5 yuan per month, compared with hundreds of yuan monthly for liver-protective drugs whose benefits remain uncertain [para. 11][para. 12][para. 13].

The historical roots of reliance on these drugs stem from years when effective antivirals for hepatitis B were unavailable, leading to widespread use of symptomatic therapy and traditional Chinese remedies [para. 16]. Despite significant improvements in access to HBsAg-targeted antivirals since 2005 and major reductions in their prices, "side-dish" liver-protective drugs continue to account for high out-of-pocket expenditures, often exceeding that of main antiviral therapy [para. 18][para. 19][para. 20].

There are other conditions, such as fatty liver disease and drug-induced liver injury (DILI), where liver-protective drugs find widespread use. However, international and Chinese guidelines endorse lifestyle modification as the primary treatment for fatty liver, and the evidence for hepatoprotective drugs is weak, with no proven histological benefits [para. 39][para. 44]. For drug-induced liver injury, only a handful of drugs, such as magnesium isoglycyrrhizinate and bicyclol, are supported by guidelines for acute cases with markedly elevated enzymes, and their indication remains much narrower abroad [para. 56][para. 59][para. 61].

The overprescription of these drugs is driven by several factors: patient expectations, varying levels of professional competency among doctors, and at times, commercial incentives including kickbacks to physicians [para. 68][para. 77][para. 82]. Hospitals often depend on drug revenue for financial sustainability, further complicating rational drug use [para. 86][para. 90]. Attempts to improve the evidence base are hampered by the cost and complexity of conducting large-scale clinical trials, and most liver-protective drugs are not included in China's key drug monitoring list [para. 93][para. 97].

In sum, while liver-protective drugs have become a routine component of liver disease management in China, their overuse carries significant financial implications for both patients and the healthcare system, and their true medical value remains inadequately substantiated [para. 99][para. 101][para. 103]. Calls for tighter evidence standards and optimized prescribing practice are mounting to ensure safe, effective, and economic liver disease care [para. 101][para. 104].