Efficacy and Safety of Glucocorticosteroid Treatment in the Patients With Chronic Recurrent DILI
Condition: Drug-induced Liver Injury,Chronic
MeSH terms: Chemical and Drug Induced Liver Injury; Chemical and Drug Induced Liver Injury, Chronic
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study is to observe the efficacy and safety of glucocorticosteroid treatment in the
      patients with chronic recurrent drug-induced liver injury (DILI).
    

Detailed description: 
      Drug-induced liver injury (DILI) refers to liver diseases caused by drugs and toxic
      substances. DILI is a clinical event that can be associated with severe outcomes such as
      acute liver failure. Up to now, approximately 1000 drugs, herbal products, vitamins and
      illicit compounds are associated with liver injury. Recently, the incidence of DILI is
      rising. In our hospital, hospitalized patients with DILI was increased from 1.39% in 2002 to
      2.31% in 2006, and further up to 3.17% in 2011, which indicated 2.3-folds increase over last
      ten years.15% to 20% patients with acute DILI are prone to chronic liver disease. For
      patients with chronic recurrent DILI, routine liver protective treatment was difficult to
      rescue abnormal liver functions. Moreover, increasing health care costs seriously affect the
      patient's quality of life. Glucocorticosteroids can inhibit the non-specific inflammation and
      permeability of the capillary bile duct, limit the activation of T lymphocytes, and
      selectively inhibit B lymphocytes to produce antibodies, thus preventing or delaying the
      immune-induced liver injury. Glucocorticoid treatment of severe DILI has accepted some
      recognition, but the effect of repeated episodes of chronic DILI, due to a lack of randomized
      controlled studies, is still unclear. Therefore, we shall design two groups on the basis of
      the ratio of 1:1, namely, glucocorticoid treatment group and standard treatment alone group.
      Participants in glucocorticoid treatment group will receive methylprednisolone,48mg/d for the
      1st week, 32mg/d for the 2nd week, 24mg/d for the next two weeks, followed by 16mg/d for 32
      weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal.
      Participants in glucocorticoid treatment group also receive standard treatment including
      reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA)
      in the first 12 weeks. Participants in standard treatment group will only receive treatment
      by routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine,
      alprostadil, or ursodeoxycholic acid (UDCA) in the first 12 weeks.The efficacy and safety of
      glucocorticoid treatment in the patients with chronic recurrent DILI will be observed during
      the treatment and follow-up period.
    

Intervention name(s): Methylprednisolone; Standard Treatment
Intervention type(s): Drug; Drug
Intervention description(s): Participants will receive methylprednisolone,48mg/d for the 1st week,32mg/d for the 2nd week,24mg/d for the next two weeks, followed by 16mg/d for 32 weeks and reduction in doses of methylprednisolone by 4 mg per 4 weeks until drug withdrawal.Participants will also receive standard treatment including reduced glutathione, glycyrrhizin, ademetionine, alprostadil, or ursodeoxycholic acid (UDCA) in the first 12 weeks.The total treatment duration will be 48 weeks. Follow-up duration is 24 weeks.; Participants will only receive standard treatment,namely,routine liver protection drugs including reduced glutathione, glycyrrhizin, ademetionine, alprostadil,or ursodeoxycholic acid (UDCA) from week 0 through week 12 study visit. Participants will then be followed until week 72.
Other intervention name(s): MEDROL,NDC0009-0056-02; Routine liver protection drugs
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug-induced Liver Injury; Recurrence; Methylprednisolone