Efficacy and safety of chloroquine plus prednisone for the treatment of autoimmune hepatitis in a randomized trial

Abstract

Background and Aim Standard treatment for autoimmune hepatitis (AIH) consists of predniso(lo)ne and azathioprine. However, alternative therapy is required for non‐ or partial responders and in cases of side effects. The aim of this study was to evaluate the treatment outcomes associated with chloroquine plus prednisone in AIH patients. Methods Fifty‐seven patients were recruited to receive either azathioprine or chloroquine, both with prednisone, in a randomized trial. The primary end‐point was complete remission, based on normalization of aminotransferase levels in the first 6 months of treatment plus maintenance for at least 18 months, with minimal or no inflammatory activity in the liver biopsy. Secondary end‐points were partial and nonresponse, severe side effects, and treatment withdrawal. Results There were no differences between groups regarding clinical, serological, histological, and treatment characteristics at baseline. There were no significant differences in the biochemical response rate (67.7 vs 53.8%, P = 0.41) or the complete remission rate (32.26 vs 15.38%, P = 0.217). However, despite the long study period, the sample size was smaller than that required for a noninferiority study. The mean prednisone dose was similar in both groups. There was a nonsignificantly higher rate of adverse effects and a tendency toward improvement in glycemic and cholesterol profiles in the chloroquine group (P = 0.09 and P = 0.07, respectively). Conclusions The combination of chloroquine and prednisone exhibited potentially beneficial effects in AIH patients (https://ClinicalTrials.gov: NCT02463331).

Systematic Review of Psychiatric Adverse Effects Induced by Chloroquine and Hydroxychloroquine: Case Reports and Population Studies

“…In a sample of AIH patients (88.5% female, mean age = 37.54), Falcão et al 26 evaluated treatment outcomes associated with CQ plus prednisone and azathioprine plus prednisone. In this small sample size (overall N = 57; CQ + prednisone = 26), no patient developed psychosis after CQ ingestion, and 1 patient developed neuropathy as a consequence of the medication.…”

“…Most populational studies do not specify the dose in which individuals ingested CQ, especially survey-based and retrospective studies. The studies that addressed how much CQ was ingested reported a mean of 443 mg, ranging from 250 to 2700 mg. 7,11,16,19,26,39,80 Ursing et al 20 and Saint-Gerons et al 40 reported a more detailed dose, in which patients took 10 mg/kg on days 0 and 1 and 2 doses of 5 mg/kg on day 2, and 10 mg/kg on day 1 and 7.5 mg/kg on days 2 and 3, respectively.…”

Particularities of Autoimmune Hepatitis in Latin America

“…To reduce relapse rates after treatment withdrawal, a randomized, double‐blind, 3‐year study with 250 mg/day chloroquine diphosphate versus placebo showed significant differences between the two groups. In this study, the features associated with reduced risk for AIH relapse were the anti‐SLA/LP seronegativity and chloroquine use . In another study to evaluate the role of chloroquine in association with prednisone (Pred) to induce a complete treatment response, the results showed its potential effects in the initial therapeutic regimen for the induction of remission …”

Zinc(II)—The Overlooked Éminence Grise of Chloroquine’s Fight against COVID-19?

“…Chloroquine and its derivatives have not only an enormous impact on the treatment of coronaviruses [ 53 , 55 , 59 , 64 ] (see the previous section), but are also effective against several others viruses in vitro, including: (i) human immunodeficiency virus (HIV) [ 95 , 96 , 97 , 98 , 99 , 100 , 101 ], (ii) hepatitis A (HAV) [ 102 ], B (HBV) [ 103 ], C (HCV) [ 104 ] viruses and autoimmune hepatitis [ 105 ], (iii) poliovirus [ 106 ], (iv) influenza A [ 107 , 108 ], B [ 109 ] and H5N1 [ 110 ] viruses, (v) Zika virus (ZIKV) [ 111 , 112 , 113 ], (vi) Ebola virus (EBOV) [ 114 ], (vii) Crimean–Congo hemorrhagic fever virus (CCHFV) [ 115 ], (viii) rabies virus [ 116 ], (ix) Chikungunya virus (CHIKV) [ 117 , 118 ], (x) Dengue virus (DENV) [ 119 , 120 , 121 ], (xi) Hendra, Nipah viruses [ 122 ], and (xii) herpes simplex virus (HSV) [ 123 ]. In this section, we briefly discuss the possible “non-Zn(II)-based” modes of action (if known) of chloroquine and hydroxychloroquine.…”