Interleukin-mediated therapies in liver diseases and comorbidity effects

Table 1 Liver diseases and related comorbidity, risk factors and pathophysiological mechanisms

Liver diseases	Comorbidity/condition	Risk factors and pathophysiology
NAFLD	CKD	NAFLD (a liver manifestation of MetS) shares with CKD diverse cardiometabolic risk factors such as: hyperuricemia, dyslipidemia, abdominal-obesity, pro-inflammatory state, hypoadiponectin, and a prothrombotic-hypofibrinolytic event[6]
	AT (dysfunction), IR	AT dysfunction is an important factor involved in the occurrence of NAFLD and IR[9]
	NASH, MetS, CVD, T2DM, CKD, HCC	Morbidity and mortality in NASH patients the mostly exacerbated by the occurrence of CVD, T2DM or CKD. HCC can poorly lead to NASH progression in the affected individuals. MetS and CVD are mainly responsible for NAFLD mortality; whilst NAFLD comorbidity with CKD and diabete increases CVD mortality[10]
	Osteoporosis	NAFLD prevalence can reach 85% in patients with obesity. NAFLD and osteoporosis reported clinically and pathologically associated, mainly in elderly and senile patients[21]
	Psoriasis	Psoriasis patients experienced a high risk of NAFLD, as well as an increase in the levels of adipokines and hepatokines[23]
MAFLD	CKD	MAFLD reported significantly associated to CKD prevalence and incidence[7]
	SARS-CoV-2 (infection)	COVID-19 involved in glucose homeostasis alteration, inflammatory cytokines storm, and oxidative stress increase, which may worsen MAFLD state[18]
ALF/CLD	HE	ALF and CLD may trigger HE (a neurological alteration). Pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) release into brain, following microglial cells activation, characterizes neuroinflammation. That neuroinflammation may impair neurotransmission, which induces the both cognitive- and motor- dysfunction[20]

NAFLD: Nonalcoholic fatty liver disease; CKD: Chronic kidney disease; MetS: Metabolic syndrome; AT: Adipose tissue; IR: Insulin resistance; CVD: Cardiovascular disease; T2DM: Type 2 diabetes mellitus; HCC: Hepatocellular carcinoma; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus disease 2019; ALF: Acute liver failure; CLD: Chronic liver disease; HE: Hepatic encephalopathy; TNF: Tumor necrosis factors; IL: Interleukin.