Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis

AIM To evaluate the differences in acute kidney injury(AKI) between acute-on-chronic liver failure(ACLF) and decompensated cirrhosis(DC) patients. METHODS During the period from December 2015 to July 2017, 280 patients with hepatitis B virus(HBV)-related ACLF(HBV-ACLF) and 132 patients with HBV-related DC(HBV-DC) who were admitted to our center were recruited consecutively into an observational study. Urine specimens were collected from all subjects and the levels of five urinary tubular injury biomarkers were detected,including neutrophil gelatinase-associated lipocalin(NGAL), interleukin-18(IL-18), liver-type fatty acid binding protein(L-FABP), cystatin C(CysC), and kidney injury molecule-1(KIM-1). Simultaneously, the patient demographics, occurrence and progression of AKI, and response to terlipressin therapy were recorded. All patients were followed up for 3 mo or until death after enrollment. RESULTS AKI occurred in 71 and 28 of HBV-ACLF and HBV-DC patients, respectively(25.4% vs 21.2%, P = 0.358). Among all patients, the levels of four urinary biomarkers(NGAL, CysC, L-FABP, IL-18) were significantly elevated in patients with HBV-ACLF and AKI(ACLF-AKI), compared with that in patients with HBV-DC and AKI(DC-AKI) or those without AKI. There was a higher proportion of patients with AKI progression in ACLF-AKI patients than in DC-AKI patients(49.3% vs 17.9%, P = 0.013). Fortythree patients with ACLF-AKI and 19 patients with DC-AKI were treated with terlipressin. The response rate of ACLFAKI patients was significantly lower than that of patients with DC-AKI(32.6% vs 57.9%, P = 0.018). Furthermore, patients with ACLF-AKI had the lowest 90 d survival rates among all groups(P < 0.001).CONCLUSION AKI in ACLF patients is more likely associated with structural kidney injury, and is more progressive, with a poorer response to terlipressin treatment and a worse prognosis than that in DC patients.

Immune response pattern varies with the natural history of chronic hepatitis B

BACKGROUND Chronic hepatitis B is a highly heterogeneous disease that can be divided into four phases: Immune tolerant(IT), immune active(IA), inactive carrier(IC) and hepatitis B envelope antigen(HBeAg)-negative hepatitis(ENEG).AIM To investigate the immune status of natural killer(NK) and T cells in different phases of chronic hepatitis B.METHODS The frequency, phenotype and function of circulating NK cells, as well as nonantigen-specific and hepatitis B virus(HBV)-specific T cell responses were detected by flow cytometry in healthy and HBV-infected subjects.RESULTS The ability of NK cells to produce IFN-γ was markedly attenuated in HBVinfected patients overall but was less compromised in IC patients. Patients in the IT and IA phases also displayed significantly lower TNF-α production compared to healthy subjects. NK cells were phenotypically activated in the IA and ENEGphases, as evidenced by the upregulation of NKp44 in CD56^(bright) NK cells and CD69 in CD56^(dim) NK cells. Furthermore, global T-cells from the ENEG phase displayed a proinflammatory cytokine profile with upregulated IFN-γ and TNF-αexpression, while this profile was suppressed in IT and IA patients. Finally, core and S antigen-specific T cell responses were significantly stronger after in vitro expansion in the IC phase compared to other phases.CONCLUSION Our findings demonstrate the changes in immune response pattern during the natural history of HBV infection. Both NK and T cells are functionally impaired in the IT and IA phases. With the spontaneous clearance of HBeAg and hepatitis B surface antigen decline, NK cell cytokine production and HBV-specific T responses are partially restored in IC phase, and the ENEG phase is dominated by nonantigen-specific T cell responses.

Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B

Hepatitis E virus(HEV)infection is a major cause of morbidity in endemic areas.Its consequences among chronic hepatitis B(CHB)patients have been under-reported.The aim of this study was to assess the impact of superinfective HEV infection(acute and past)on virological and clinical features of patients with CHB infection.Clinical,biochemical,virological and immunological data of 153 CHB patients including 98 with hepatitis B virus(HBV)monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan,China.An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients.HBV-HEV superinfection patients showed significantly higher rate of complications(ascites,hepato-renal syndrome&encephalopathy)(all with P=0.04),cirrhosis(P<0.001)and acute-on-chronic liver failure(P<0.001)than HBV monoinfection patients.They also displayed elevated ALTs(P<0.001)and total serum bilirubin(P<0.001)with diminished albumin(P<0.001)and HBV viral load(P<0.001).Cytokines assay revealed increased expression of IL-6(P=0.02),IL-10(P=0.009)and TNF-α(P=0.003)in HBVHEV superinfection patients compared to HBV monoinfection patients.Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation,which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis.HEV was also associated with repressed HBV replication,but the underlying mechanism requires further investigation.

CAPRL Scoring System for Prediction of 30-day Mortality in 949 Patients with Coronavirus Disease 2019 in Wuhan,China:A Retrospective,Observational Study

Background:Coronavirus disease 2019(COVID-19)is a serious and even lethal respiratory illness.The mortality of critically ill patients with COVID-19,especially short term mortality,is considerable.It is crucial and urgent to develop risk models that can predict the mortality risks of patients with COVID-19 at an early stage,which is helpful to guide clinicians in making appropriate decisions and optimizing the allocation of hospital resoureces.Methods:In this retrospective observational study,we enrolled 949 adult patients with laboratory-confirmed COVID-19 admitted to Tongji Hospital in Wuhan between January 28 and February 12,2020.Demographic,clinical and laboratory data were collected and analyzed.A multivariable Cox proportional hazard regression analysis was performed to calculate hazard ratios and 95%confidence interval for assessing the risk factors for 30-day mortality.Results:The 30-day mortality was 11.8%(112 of 949 patients).Forty-nine point nine percent(474)patients had one or more comorbidities,with hypertension being the most common(359[37.8%]patients),followed by diabetes(169[17.8%]patients)and coronary heart disease(89[9.4%]patients).Age above 50 years,respiratory rate above 30 beats per minute,white blood cell count of more than 10×109/L,neutrophil count of more than 7×109/L,lymphocyte count of less than 0.8×109/L,platelet count of less than 100×109/L,lactate dehydrogenase of more than 400 U/L and high-sensitivity C-reactive protein of more than 50 mg/L were independent risk factors associated with 30-day mortality in patients with COVID-19.A predictive CAPRL score was proposed integrating independent risk factors.The 30-day mortality were 0%(0 of 156),1.8%(8 of 434),12.9%(26 of 201),43.0%(55 of 128),and 76.7%(23 of 30)for patients with 0,1,2,3,≥4 points,respectively.Conclusions:We designed an easy-to-use clinically predictive tool for assessing 30-day mortality risk of COVID-19.It can accurately stratify hospitalized patients with COVID-19 into relevant risk categories and could provide guidance to make further clinical decisions.