Characterization of inflammatory response in hepatorenal syndrome: Relationship with kidney outcome and survival

Abstract

Background Several lines of evidence indicate that decompensated cirrhosis is characterized by the presence of systemic inflammation. Hepatorenal syndrome (HRS‐AKI) is a unique type of renal failure that occurs at late stages of cirrhosis. However, confirmation of the presence and significance of such inflammatory response in HRS‐AKI is lacking. Aim and Methods To characterize the systemic inflammatory response, as estimated by measuring a large number of cytokines, in 161 patients hospitalized for an acute decompensation of cirrhosis: 44 patients without acute kidney injury (AKI), 63 patients with hypovolaemia‐induced AKI and 58 patients with HRS‐AKI. Results HRS‐AKI was characterized by an altered cytokine profile compared to the other two groups, particularly IL‐6, IL‐8, TNF‐α, VCAM‐1, fractalkine and MIP‐1α. The inflammatory response was not related to presence of bacterial infection, concomitant acute‐on‐chronic liver failure or severity of renal dysfunction. Patients who responded to terlipressin and albumin had only a decrease in TNF‐α and RANTES after treatment without changes in other cytokines. Interestingly, patients with persistent HRS‐AKI had higher levels of IP‐10 and VCAM‐1 compared to those with resolution of HRS‐AKI. VCAM‐1 was also an independent predictor of 3‐month mortality. A systems biology analysis approach showed that the inflammatory status of HRS‐AKI was similar to that of chronic nonhepatic inflammatory conditions, such as lupus erythematosus or inflammatory bowel disease. Conclusion Hepatorenal syndrome is characterized by a marked systemic inflammatory state, reminiscent of that of nonhepatic inflammatory diseases, that correlates with patient outcomes.

Immune Regulatory Mediators in Plasma from Patients With Acute Decompensation Are Associated With 3-Month Mortality

“…Previous studies demonstrated an association between high circulatory inflammatory markers, eg, CRP, 18,19 and inflammatory cytokines at baseline 12,20,21 and increased mortality in AD/ACLF. In our cohort baseline clinical characteristics of the survivors and nonsurvivors were quite similar aside from serum creatinine and a non-significant increase in MELD score and infection rate, which may be due to the relatively small sample size.…”

Hepatorenal syndrome: pathophysiology, diagnosis, and management

“…28 More over, plasma concentrations of proinflammatory injury; CKD=chronic kidney disease; NAKI=non-acute kidney injury; NSAID=non-steroidal anti-inflammatory drug; RBC=red blood cell doi: 10.1136/bmj.m2687 | BMJ 2020;370:m2687 | the bmj cytokines (interleukin6, tumor necrosis factorα (TNFα), vascular cell adhesion protein1, and interleukin8) and urinary concentrations of mono cyte chemoattractant protein1 are increased in patients with AKIHRS compared with those with decompensated cirrhosis without AKI and patients with AKI secondary to prerenal azotemia. 29 Inflammation in cirrhosis is driven by two groups of molecules: pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). PAMPs represent bacterial products, such as lipopolysaccharide, flagellin, and nigericin, which result from translocation of gut bacteria or bacterial infections, whereas DAMPs represent intracellular components released from injured hepatocytes, including high mobility group protein B1, heat shock protein, adenosine triphosphate, double stranded genomic DNA, and others.…”

“…Downloaded from treatment, including model for end stage liver disease (MELD) score, 126 pretreatment serum creatinine concentration, 22 23 sepsis, 126 extrahepatic organ failure, 127 and systemic inflammation. 29 Lower serum creatinine concentrations at the start of treatment are associated with higher rates of HRS reversal, whereas only a negligible response is expected when creatinine exceeds 7 g/dL. 22 23 Thus, earlier diagnosis of AKIHRS with the elimination of creatinine concentration cutoff, will likely result in higher rates of response to treatment.…”

Role of Systemic Inflammatory Response in the Pathogenesis of Hepatorenal Syndrome

“…Останнім часом стає все більш очевидним, що цироз печінки є станом із вираженою системною запальною відповіддю (ССЗВ), яка збільшується із прогресуванням хвороби, від компенсованого до декомпенсованого цирозу, і сильно впливає на прогноз пацієнта [9]. У деяких клінічних дослідженнях оцінювали запалення при цирозі шляхом вимірювання кількості лейкоцитів або рівнів С-реактивного білка (CРБ) [10,11]; однак ці методи не є досить точними для оцінки запалення. Окрім того, дослідження на експериментальних тваринах також продемонстрували наявність ССЗВ, яка є більш помітною у тварин із асцитом, порівняно з іншими [12].…”