Clinical risk factors for moderate and severe antituberculosis drug-induced liver injury

Serum visceral proteins such as albumin and prealbumin have traditionally been used as markers of the nutritional status of patients. Prealbumin is nowadays often preferred over albumin due to its shorter half live, reflecting more rapid changes of the nutritional state. However, recent focus has been on an appropriate nutrition-focused physical examination and on the patient’s history for diagnosing malnutrition, and the role of inflammation as a risk factor for malnutrition has been more and more recognized. Inflammatory signals are potent inhibitors of visceral protein synthesis, and the use of these proteins as biomarkers of the nutritional status has been debated since they are strongly influenced by inflammation and less so by protein energy stores. The current consensus is that laboratory markers could be used as a complement to a thorough physical examination. Other markers of the nutritional status such as urinary creatinine or 3-methylhistidine as indicators of muscle protein breakdown have not found widespread use. Serum IGF-1 is less influenced by inflammation and falls during malnutrition. However, its concentration changes are not sufficiently specific to be useful clinically as a marker of malnutrition, and serum IGF-1 has less been used in clinical trials. Nevertheless, biomarkers of malnutrition such as prealbumin may be of interest as easily measurable predictors of the prognosis for surgical outcomes and of mortality in severe illnesses.

Drug-induced liver injury (DILI) is the most frequent reason cited for the withdrawal of approved drugs from the market and accounts for up to 15% of the cases of acute liver failure. Investigators around the globe have begun to identify and study patients with DILI; several large registries and tissue banks are being established. In order to gain the maximum scientific benefit from these efforts, the definitions and terminology related to the clinical phenotypes of DILI must be harmonized. For this purpose, an international DILI Expert Working Group of clinicians and scientists reviewed current DILI terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute DILI. Consensus was established with respect to the threshold criteria for definition of a case as being DILI, the pattern of liver injury, causality assessment, severity, and chronicity. Consensus was also reached on approaches to characterizing DILI in the setting of chronic liver diseases, including autoimmune hepatitis (AIH).