Dataset Information

Complement C3 Facilitates Stratification of Stages of Chronic Hepatitis B and Signifies Development of Acute-on-Chronic Liver Failure in Acute Decompensated Cirrhosis

ABSTRACT:

Introduction

Patients with chronic hepatitis B (CHB) have a dynamic disease process and risk of end-stage liver disease. It is critical to unambiguously differentiate the stages of the disease and focus on therapy prior to onset of an irreversible clinical endpoint.

Methods

We retrospectively analyzed a wide range of CHB patients at different stages. The predictive power of serum complement component 3 (C3) levels for the development of acute-on-chronic liver failure (ACLF) in patients with decompensated cirrhosis was established and validated.

Results

The decrease in serum C3 levels paralleled the severity of diseases related to hepatitis B virus. Patients with decompensated cirrhosis who developed ACLF had significantly lower serum C3 levels than others on admission (0.50 vs. 0.80 g/L, P < 0.001). Data analysis also revealed that low serum C3 was a significant risk factor for developing ACLF (hazard ratio = 0.32, P < 0.01). The area under the receiver operating characteristic curve (auROC) for serum C3 levels that predicted the development of ACLF in patients with decompensated cirrhosis was 0.90, which had sensitivity and specificity of 88.2% and 88.7%, respectively. A similar result was observed in the validation set (auROC = 0.86 for predicting development of ACLF in patients with decompensated cirrhosis).

Conclusions

Serum C3 levels are valuable in assessing the severity of CHB-related stages. Low C3 levels signifies the development of ACLF in patients with decompensated cirrhosis.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12325-022-02416-7. Plain Language Summary Generally, acute-on-chronic liver failure is a rapidly worsening liver failure syndrome. This disease is intractable and with high mortality. Acute decompensation of the liver is defined as the occurrence of complications of liver disease (i.e., ascites, hepatic encephalopathy, gastrointestinal bleeding, and bacterial infection). Clinically, acute decompensation in hepatitis B virus-related cirrhosis (a result of chronic liver injury by virus) often develops into acute-on-chronic liver failure. In addition, the complement component 3 is a serum protein, which participates in the immune response against virus infection and has been reported to be associated with liver failure. We tried to explore the feature of serum complement component 3 to differentiate the stages of the disease and assess its predictive value for acute-on-chronic liver failure. So, we analyzed the complement component 3 data from a broad range of hepatitis B virus-cirrhosis patients. Through analysis, we found that complement component 3 levels are valuable in assessing the severity of chronic hepatitis B-related stages. Low complement component 3 levels can also signify the development of acute-on-chronic liver failure in patients with decompensated cirrhosis.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12325-022-02416-7.

SUBMITTER: Chen C

PROVIDER: S-EPMC9848025 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Project description:Background and Aims: Patients with acute decompensated (AD) cirrhosis are frequently readmitted to the hospital. An accurate predictive model for identifying high-risk patients may facilitate the development of effective interventions to reduce readmission rates. Methods: This cohort study of patients with AD cirrhosis was conducted at six tertiary hospitals in China between September 2012 and December 2016 (with 705 patients in the derivation cohort) and between January 2017 and April 2020 (with 251 patients in the temporal validation cohort). Least absolute shrinkage and selection operator Cox regression was used to identify the prognostic factors and construct a nomogram. The discriminative ability, calibration, and clinical net benefit were evaluated based on the C-index, area under the curve, calibration curve, and decision curve analysis. Kaplan-Meier curves were constructed for stratified risk groups, and log-rank tests were used to determine significant differences between the curves. Results: Among 956 patients, readmission rates were 24.58, 42.99, and 51.78%, at 30, 60, and 90 days, respectively. Bacterial infection was the main reason for index hospitalization and readmission. Independent factors in the nomogram included gastrointestinal bleeding [hazard rate (HR): 2.787; 95% confidence interval (CI): 2.221-3.499], serum sodium (HR: 0.955; 95% CI: 0.933-0.978), total bilirubin (HR: 1.004; 95% CI: 1.003-1.005), and international normalized ratio (HR: 1.398; 95% CI: 1.126-1.734). For the convenience of clinicians, we provided a web-based calculator tool (https://cqykdx1111.shinyapps.io/dynnomapp/). The nomogram exhibited good discrimination ability, both in the derivation and validation cohorts. The predicted and observed readmission probabilities were calibrated with reliable agreement. The nomogram demonstrated superior net benefits over other score models. The high-risk group (nomogram score >56.8) was significantly likely to have higher rates of readmission than the low-risk group (nomogram score ≤ 56.8; p < 0.0001). Conclusions: The nomogram is useful for assessing the probability of short-term readmission in patients with AD cirrhosis and to guide clinicians to develop individualized treatments based on risk stratification.

Project description:Background & aimsBacterial infections, in particular a spontaneous bacterial peritonitis (SBP), are a major threat in patients with liver cirrhosis. Recently, it has been shown that the impact on mortality might be underestimated by established risk-scores. Onset of infection was suggested to define a distinct stage of cirrhosis. However, it remains unclear whether all stages of decompensated cirrhosis are equally affected. Moreover, if there is such a distinct stage, it must be determined whether it is reversible after the infection has resolved. In this study we aimed to further analyze the impact of a current as well as a resolved SBP in different stages of decompensated liver cirrhosis.MethodsA number of 579 patients with liver cirrhosis and ascites were included. MELD-score was used to determine the stage of liver disease. Low (<15), intermediate (15-25) and high (>25) MELD-groups were compared. Patients were followed up for 90 days. Primary endpoint was overall mortality. Statistical analyses were performed using the log-rank test, Cox regression and competing risk analysis.ResultsMortality was significantly higher in patients with nosocomial-acquired SBP (nSBP) compared to patients without SBP (p<0.001;HR = 2.05). However, the most prominent difference in mortality was documented in the intermediate MELD-group (nSBP: p = 0.02;HR = 2.10). Importantly, mortality in nSBP patients remained increased even after the initial nSBP episode had resolved (p<0.01;HR = 1.90). Again, this was only significant in those with intermediate MELD-scores (p = 0.02;HR = 2.28). While a current as well as a resolved nSBP were significantly linked to a higher mortality, neither of them did increase the likelihood for liver transplantation.ConclusionsDevelopment of nSBP is independently associated with increased mortality supporting the concept of a distinct status of cirrhosis. Importantly, the prognosis remains unfavorable even after resolution of nSBP. This could be particularly relevant for patients with intermediate MELD-scores, who have limited chances for a donor liver.

Project description:INTRODUCTION:Muscle mass has been shown to be a prognostic marker in patients with liver cirrhosis. Transversal psoas muscle thickness normalized by height (TPMT/height) obtained by routine computed tomography is a simple surrogate parameter for sarcopenia. TPMT/height, however, is not sex specific, which might play a role in risk stratification. Its association with acute-on-chronic liver failure (ACLF) has not been established yet. ACLF is associated with systemic inflammatory dysregulation. This study aimed at evaluating the role of sarcopenia in ACLF development of patients with decompensated cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS) using sex-specific TPMT/height. METHODS:One hundred eighty-six patients from the prospective Non-invasive Evaluation Program for TIPS and Follow Up Network cohort (observational, real-world TIPS cohort with structured follow-up) were analyzed. TPMT/height was measured from routine computed tomography. The sex-specific cutoff was determined to classify patients as sarcopenic and nonsarcopenic for 1-year mortality after TIPS. Clinical outcome was compared. Primary end points were ACLF and 1-year mortality after TIPS. Secondary end points were development of decompensations (hepatic encephalopathy and ascites) after TIPS. RESULTS:The sex-specific cutoff increases the diagnostic accuracy with regard to primary and secondary end points compared with the unisex cutoff. Sex-specific sarcopenia classification is an independent predictor of 1-year mortality and ACLF development in patients with cirrhosis receiving TIPS. Patients in the sarcopenia group showed significantly higher rates of mortality, ascites, overt hepatic encephalopathy, and ACLF after TIPS compared with the nonsarcopenia group. The Chronic Liver Failure Consortium Acute Decompensation score as a marker of systemic inflammation was significantly higher in sarcopenic patients. CONCLUSIONS:This study demonstrates for the first time that sarcopenia is related to ACLF development and systemic inflammation. The prognostic value of TPMT/height can be improved by using sex-specific cutoffs. ClinicalTrials.gov identifier: NCT03584204.

Dataset Information

Complement C3 Facilitates Stratification of Stages of Chronic Hepatitis B and Signifies Development of Acute-on-Chronic Liver Failure in Acute Decompensated Cirrhosis

Introduction

Methods

Results

Conclusions

Supplementary Information

Supplementary Information

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