Caution With the Use of Lopinavir/Ritonavir in Severely Ill Patients for the Treatment of SARS-CoV-2: A Report of Severe Jaundice

Abstract

INTRODUCTION: We investigated the potential hepatotoxicity of lopinavir/ritonavir recently used in the treatment of Severe Acute Respiratory Syndrome Coronavirus. METHODS: This is a retrospective cohort of critical patients in a teaching hospital: 12 treated with lopinavir/ritonavir and 30 in the standard-of-care group. RESULTS: Elevation occurred more frequently in patients treated with lopinavir/ritonavir (33% vs 6.7%). DISCUSSION: Caution is advised regarding the use of lopinavir/ritonavir in the most severe cases of Severe Acute Respiratory Syndrome Coronavirus.

Efficacy of Lopinavir–Ritonavir Combination Therapy for the Treatment of Hospitalized COVID-19 Patients: A Meta-Analysis

“…Characteristics of included studies are tabulated in Table 1 . Four studies [ 89–91 , 95 ] only included patients hospitalized in intensive care units (ICUs), while Yao et al [ 100 ] excluded ICU-hospitalized patients. Cao et al [ 34 ] and Lecronier et al [ 91 ] only included patients with severe disease, while four studies [ 86 , 88 , 92 , 98 ] excluded severe patients.…”

“…The risk of bias in included observational studies was assessed using ROBINS-I ( Figure 2 B). Ten studies [ 36 , 87 , 88 , 93–95 , 97 , 98 , 100 , 103 ] were rated as having a serious risk of bias, while ten studies [ 37 , 38 , 89–92 , 96 , 99 , 101 , 102 ] were rated as having a critical risk of bias. Five studies [ 36 , 38 , 89 , 90 , 103 ] were rated as having a serious risk of bias due to confounding factors, while one study [ 37 ] was rated as having a critical risk of bias due to either a lack of reporting for important patient characteristics (e.g., disease severity) or an imbalance in the reported patient characteristics.…”

“…Ten studies [ 36 , 87 , 88 , 93–95 , 97 , 98 , 100 , 103 ] were rated as having a serious risk of bias, while ten studies [ 37 , 38 , 89–92 , 96 , 99 , 101 , 102 ] were rated as having a critical risk of bias. Five studies [ 36 , 38 , 89 , 90 , 103 ] were rated as having a serious risk of bias due to confounding factors, while one study [ 37 ] was rated as having a critical risk of bias due to either a lack of reporting for important patient characteristics (e.g., disease severity) or an imbalance in the reported patient characteristics. In terms of risk of bias due to selection of participants, three studies [ 38 , 92 , 103 ] were rated as having a serious risk of bias due to suspected selection bias, such as only including discharged patients in retrospective analyses.…”

“…Nine studies [ 17 , 33 , 34 , 38 , 89–91 , 94 , 103 ] (3 RCTs and 6 observational studies) with 8240 patients assessed the effect of LPV/r on incidences of mechanical ventilation in hospitalized COVID-19 patients. The pooled OR was 1.04 (95% CI: 0.55–1.97) with no significant heterogeneity (I 2 = 32%; P Q = 0.16; Figure 6 ).…”

“…The NNH was 4.6 patients. The most commonly reported adverse events in the LPV/r group were gastrointestinal side effects such as diarrhea, nausea, vomiting, stomach pain and loss of appetite [ 34 , 87 , 89 , 99 , 101–103 ] and liver-related toxicities such as elevated liver enzymes and elevated bilirubin [ 89 , 101 , 103 ].…”