Novel Prognostic Models for Predicting the 180-day Outcome for Patients with Hepatitis-B Virus-related Acute-on-chronic Liver Failure

Background and AimsIt remains difficult to forecast the 180-day prognosis of patients with hepatitis B virus-acute-on-chronic liver failure (HBV-ACLF) using existing prognostic models. The present study aimed to derive novel-innovative models to enhance the predictive effectiveness of the 180-day mortality in HBV-ACLF.MethodsThe present cohort study examined 171 HBV-ACLF patients (non-survivors, n=62; survivors, n=109). The 27 retrospectively collected parameters included the basic demographic characteristics, clinical comorbidities, and laboratory values. Backward stepwise logistic regression (LR) and the classification and regression tree (CART) analysis were used to derive two predictive models. Meanwhile, a nomogram was created based on the LR analysis. The accuracy of the LR and CART model was detected through the area under the receiver operating characteristic curve (AUROC), compared with model of end-stage liver disease (MELD) scores.ResultsAmong 171 HBV-ACLF patients, the mean age was 45.17 years-old, and 11.7% of the patients were female. The LR model was constructed with six independent factors, which included age, total bilirubin, prothrombin activity, lymphocytes, monocytes and hepatic encephalopathy. The following seven variables were the prognostic factors for HBV-ACLF in the CART model: age, total bilirubin, prothrombin time, lymphocytes, neutrophils, monocytes, and blood urea nitrogen. The AUROC for the CART model (0.878) was similar to that for the LR model (0.878, p=0.898), and this exceeded that for the MELD scores (0.728, p<0.0001).ConclusionsThe LR and CART model are both superior to the MELD scores in predicting the 180-day mortality of patients with HBV-ACLF. Both the LR and CART model can be used as medical decision-making tools by clinicians.     

Factors Associated with Survival of Patients With Severe Acute-On-Chronic Liver Failure Before and After Liver Transplantation

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A Comprehensive Method for Predicting Fatal Liver Failure of Patients With Liver Cancer Resection

There are many methods to assess liver function, but none of them has been verified as fully effective. The purpose of this study is to establish a comprehensive method evaluating perioperative liver reserve function (LRF) in patients with primary liver cancer (PLC).In this study, 310 PLC patients who underwent liver resection were included. The cohort was divided into a training set (n = 235) and a validation set (n = 75). The factors affecting postoperative liver dysfunction (POLD) during preoperative, intraoperative, and postoperative periods were confirmed by logistic regression analysis. The equation for calculating the preoperative liver functional evaluation index (PLFEI) was established; the cutoff value of PLFEI determined through analysis by receiver-operating characteristic curve was used to predict postoperative liver function.The data showed that body mass index, international normalized ratio, indocyanine green (ICG) retention rate at 15 minutes (ICGR15), ICG elimination rate, standard remnant liver volume (SRLV), operative bleeding volume (OBV), blood transfusion volume, and operative time were statistically different (all P < 0.05) between 2 groups of patients with and without POLD. The relationship among PLFEI, ICGR15, OBV, and SRLV is expressed as an equation of “PLFEI = 0.181 × ICGR15 + 0.001 × OBV − 0.008 × SRLV.” The cutoff value of PLFEI to predict POLD was −2.16 whose sensitivity and specificity were 90.3% and 73.5%, respectively. However, when predicting fatal liver failure (FLF), the cutoff value of PLFEI was switched to −1.97 whose sensitivity and specificity were 100% and 68.8%, respectively.PLFEI will be a more comprehensive, sensitive, and accurate index assessing perioperative LRF in liver cancer patients who receive liver resection. And keeping PLFEI <−1.97 is a safety margin for preventing FLF in PLC patients who underwent liver resection.     

Risk Prediction Model Based on Magnetic Resonance Elastography-Assessed Liver Stiffness for Predicting Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background/AimsPosthepatectomy liver failure (PHLF) is a major complication that increases mortality in patients with hepatocellular carcinoma after surgical resection. The aim of this retrospective study was to evaluate the utility of magnetic resonance elastography-assessed liver stiffness (MRE-LS) for the prediction of PHLF and to develop an MRE-LS-based risk prediction model.MethodsA total of 160 hepatocellular carcinoma patients who underwent surgical resection with available preoperative MRE-LS data were enrolled. Clinical and laboratory parameters were collected from medical records. Logistic regression analyses were conducted to identify the risk factors for PHLF and develop a risk prediction model.ResultsPHLF was present in 24 patients (15%). In the multivariate logistic analysis, high MRE-LS (kPa; odds ratio [OR] 1.49, 95% confidence interval [CI] 1.12 to 1.98, p=0.006), low serum albumin (≤3.8 g/dL; OR 15.89, 95% CI 2.41 to 104.82, p=0.004), major hepatic resection (OR 4.16, 95% CI 1.40 to 12.38, p=0.014), higher albumin-bilirubin score (>–0.55; OR 3.72, 95% CI 1.15 to 12.04, p=0.028), and higher serum α-fetoprotein (>100 ng/mL; OR 3.53, 95% CI 1.20 to 10.40, p=0.022) were identified as independent risk factors for PHLF. A risk prediction model for PHLF was established using the multivariate logistic regression equation. The area under the receiver operating characteristic curve (AUC) of the risk prediction model was 0.877 for predicting PHLF and 0.923 for predicting grade B and C PHLF. In leave-one-out cross-validation, the risk model showed good performance, with AUCs of 0.807 for all-grade PHLF and 0. 871 for grade B and C PHLF.ConclusionsOur novel MRE-LS-based risk model had excellent performance in predicting PHLF, especially grade B and C PHLF.     

Predicting the Onset of Hepatitis B Virus–Related Acute-on-Chronic Liver Failure

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Matrix Metalloproteinase (MMP)-3 Polymorphism in Patients with HBV Related Chronic Liver Disease

A common and important problem in patients with chronic hepatitis B is the progression of liver fibrosis. Matrix metalloproteinases (MMPs) play an important role in the progression of liver fibrosis. Our aim of this study was to examine the association of MMP-3 polymorphism with liver cirrhosis in Korean patients with chronic hepatitis B. Genomic DNA was extracted from 127 patients with chronic hepatitis B (CHB), 92 patients with hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC), and 146 healthy subjects. MMP-3 polymorphism was determined by polymerase-chain reaction-based assays, and the association with the progression of liver cirrhosis was investigated. With regard to MMP-3 polymorphism, there was no statistical difference in genotype distributions among the three groups. However, the peripheral platelet count of the 5A carriers was significantly lower than that of the 6A homozygotes in the HBV-LV group (85.0 ± 36.9 vs. 109.8 ± 47.0 × 10⁹/l; P = 0.02). With MMP-3 promoter polymorphism (rs3025058), a lower peripheral blood platelet count, which was related to advanced liver cirrhosis, was observed in 5A carriers. Therefore, more studies of MMP-3 gene polymorphism with larger populations should be conducted to further understand its role in the progression of liver cirrhosis.     

Augmenter of Liver Regeneration may be a Candidate for Prognosis of HBV Related Acute-on-Chronic Liver Failure as a Regenerative Marker

Background/Aims: To search for a new regenerative marker to estimate the prognosis of acute-on-chronic liver failure (ACLF). Methodology: The CCl4 induced liver regeneration models were prepared and observed the change of ALR, hepatocyte growth factor (HGF), proliferation cell nuclear antigen (PCNA) and pathology. Meanwhile the sera of patients with HBV related liver disease were collected to examine the changes of ALR level and the prognosis of patients with ACLF was followed up. Results: After CCl4 injection, serum ALR level rose firstly and then declined in the ensuing 12 hours to near-basal level (F=30.495, p<0.01). ALR level in the liver tissue showed an inverse pattern. The changes of PCNA, HGF and pathology showed a consistent trend with serum ALR level. Serum ALR level was higher in ACLF (n=20) and hepatocellular carcinoma (n=20) than in normal control (n=10) (2.68±1.95 vs. 0.74±0.31, p<0.01; 1.77±1.32 vs. 0.74±0.31, p=0.035). Serum ALR level of patients with ACLF was more significant in survival group (n=10) than in dead group (n=10) in early stage of disease (7.83±1.77 vs. 2.14±1.58, t=7.576, p<0.01). Conclusions: ALR level in serum may indicate hepatocyte proliferation or liver regeneration. High ALR level in serum in early stage of ACLF may mean a good prognosis.     

肝功能衰竭患者的胃肠道手术

肝功能衰竭患者非肝脏手术后的发病和死亡风险较非肝功能衰竭患者增高。肝硬化患者急诊手术后死亡率高于择期手术后。对接受非肝脏手术的肝功能衰竭患者行术前评估极为重要,可降低高术后并发症和死亡风险。     

Development and Validation of a Nomogram for 90-day Outcome in Patients with Hepatitis B Virus-related Acute-on-chronic Liver Failure

Background and AimsIt is challenging to predict the 90-day outcomes of patients infected with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) via prevailing predictive models. This study aimed to develop an innovative model to enhance the analytical efficacy of 90-day mortality in HBV-ACLF.MethodsIn this study, 149 HBV-ACLF patients were evaluated by constructing a death risk prediction nomogram. Bootstrap resampling and an independent validation cohort comprising 31 patients from June 2019 to February 2020 were assessed for model confirmation.ResultsThe nomogram was constructed by entering and identifying five factors (age, total bilirubin, prothrombin activity (PTA), lymphocyte (L)%, and monocyte (M)%. Healthy refinement was achieved from the nomogram analysis, where the area under the receiver operating characteristic curve was 0.864 for the training cohort and 0.874 was achieved for the validation cohort. There was admirable concordance between the predicted and true results in the equilibrium curve. The decision curve assessment revealed the useful clinical application of the nomogram.ConclusionsWe constructed an innovative nomogram and validated it for the prediction of 90-day HBV-ACLF patient outcomes. This model might help develop optimized treatment protocol recommendations for HBV-ACLF patients.     

Outcome Studies with Device Therapy in Patients with Heart Failure

Device Therapy for Heart Failure. Heart failure is a common debilitating condition for which pharmacologic therapy thus far has provided only partial relief. Despite, and sometimes because of, medical therapy, the overall prognosis remains poor, with high rates of sudden death and death from progressive heart failure. Device‐based therapies offer considerable promise for relief of symptoms and for improving prognosis. It is clear that implantable defibrillators should be considered for patients with heart failure who have been resuscitated from ventricular fibrillation or sustained ventricular tachycardia. Several large studies currently are investigating the effects of implantable defibrillators on total mortality in patients with major left ventricular systolic dysfunction but without other risk factors for sudden death. Cardiac resynchronization is a promising new therapy that may relieve the symptoms of heart failure in appropriately selected patients resistant to optimal pharmacologic therapy. Two large trials (CARE‐HF and COMPANION) currently are investigating the effects of cardiac resynchronization therapy (CRT) on morbidity and mortality. It is important that those involved in these trials enroll patients quickly and minimize device implantation into patients who have not been assigned this therapy (cross‐overs). Overenthusiasm for the benefits that doctors believe devices might bring could destroy the future basis for our clinical practice, denying future generations of patients and the doctors themselves access to what they believe to be effective treatments.     

应用MELD-Na模型评估失代偿期肝硬化患者的短期预后

目的评估终末期肝病血清钠(MELD-Na)、终末期肝病模型(MELD)及Child-Pugh评分系统对失代偿期肝硬化患者短期预后的预测价值。方法对具有完整记录和随访结果的96例失代偿期肝硬化患者的资料进行分析,分别计算每例患者的Chlid-Pugh、MELD及MELD-Na分值,使用受试者工作曲线(ROC)及曲线下面积(AUC)比较3种评分系统判断失代偿期肝硬化患者生存3个月的准确性。结果 96例患者3个月内有25例患者死亡。死亡组的Child-Pugh、MELD及MELD-Na评分均高于生存组(P0.01);MELD-Na和MELD评分在判断患者3个月生存时间的ROC曲线AUC均大于Child-Pugh(P0.001,P0.01),MELD-Na和MELD评分AUC差异均无统计学意义(P0.05)。结论 MELD-Na是判断失代偿期肝硬化患者短期预后的一个较好指标,其准确性优于Child-Pugh分级,但与MELD评分相比无明显差异。     

Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma

HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lym-phoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples “Federico II”. A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HB-sAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lami-vudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.     

Outcome of Orthotopic Liver Transplantation in Patients with Hepatitis C

Recurrence of chronic hepatitis C (HCV) after orthotopic liver transplantation (OLT) is universal. The published studies suggest that the short-term outcome is good in these patients, but the long-term prognosis remains unclear. The purpose of this study was to evaluate the outcome of patients with HCV undergoing OLT in a single center and to analyze the risk factors associated with poor outcome. In this retrospective study, we evaluated the outcome of 58 OLT patients with proven HCV who underwent OLT between February 1990 and April 1997 at our institution. The median follow-up time was 36.9 months. Recurrent posttransplant HCV hepatitis was confirmed by liver biochemistry, histology, and persistent HCV RNA in the serum. The patient and graft survival of patients with HCV was compared to that of 42 primary biliary cirrhosis (PBC) and 41 primary sclerosing cholangitis (PSC) patients transplanted during the same period. Following OLT, biochemical evidence of recurrent HCV hepatitis was absent in 46%. Forty percent of patients had recurrent HCV hepatitis and 14% had clinical evidence of recurrent HCV. Thirty-one patients were on cyclosporine, 22 patients on tacrolimus, and 5 patients had cyclosporine switched to tacrolimus or vice versa. The recurrence rate of HCV chronic hepatitis was similar in patients who had cyclosporine (35.5%) or tacrolimus (45.5%) based immunosuppression. Eleven patients (19%) died and five patients (8.6%) were retransplanted for chronic rejection (two), mismatch (one), or primary graft nonfunction (two). The cumulative patient survival rates of one, three, and five years were 94.8%, 84.1%, and 62.2%, respectively. The severity of liver disease progressed with time; 8% of patients developed cirrhosis within two years. The survival rate did not show any relation between HCV recurrence and the type of immunosuppression. In conclusion, although the survival of patients with HCV was not statistically significant compared to those with PBC or PSC, there was a trend towards a lower five-year survival in HCV.     

Serum Antithrombin III Level is Well Correlated with Multiple Indicators for Assessment of Liver Function and Diagnostic Accuracy for Predicting Postoperative Liver Failure in Hepatocellular Carcinoma Patients

Background/Aims: Evaluation of preoperative hepatic reserve is critical to avoid a fatal clinical course such as liver failure. We retrospectively evaluated 158 consecutive hepatocellular carcinoma (HCC) patients who underwent initial hepatectomy. The aim of this study was to determine the correlations of multiple indicators for assessment of liver function before hepatectomy. Furthermore, diagnostic probability for the pathological background and prediction of postoperative liver failure/dysfunction was compared between the antithrombin (AT) III level and indocyanine green retention rate at 15 minutes (ICGR15). Methodology: Between January 2001 and March 2008, 158 HCC patients who underwent initial hepatectomy were enrolled in this study. Spearman's correlation coefficients (r values) were obtained for 15 clinical laboratory tests including ATIII and ICGR15. Receiver operating characteristic (ROC) curve analysis was used for calculating the probability and predictive ability of the tests. Results: All 158 consecutive HCC patients were eligible for hepatectomy based on the Japanese guideline. ATIII is correlated with 13 of 14 other clinical tests, including albumin, bilirubin, prothrombin time, rapid turnover proteins, HGF, ICGR15 and others. The diagnostic probabilities to distinguish between normal liver and other pathological backgrounds of ATIII and ICGR15 were significantly different. The specificity of ATIII to predict postoperative liver failure/dysfunction was higher than that of ICGR15. Conclusions: The serum ATIII level before hepatectomy is valuable to estimate the pathological background and predict postoperative liver failure/ dysfunction. It should be possible to use ATIII as an additional indicator for liver function and substitute for ICGR15 in the future.     

T波电交替预测心力衰竭病人心源性猝死价值的新分歧

有半数的心力衰竭病AN致命性室性心律失常事件死于心源性猝死。T波电交替是公认的预测心源性猝死的重要指标。早在许多年前就发现T波电交替与心源性猝死有关,近年来新建了频域和时域测量方法。跨室壁复极离散度异常增大是T波电交替的机制。最近研究发布的用微伏级T波电交替进行心肌梗死后危险性分层的初步结果否定心肌梗死后左室射血分数〈30％的病人发生致死性快速室性心律失常的价值。但体内除颤器置入前T波电交替的对心源性猝死一级预防试验和非缺血性心肌病心力衰竭T波电交替的预测价值试验则强有力地支持T波电交替能预测心律失常。     

Peritoneal Dialysis Therapy for Patients with Liver and Renal Failure with Ascites

Two patients with severe liver disease complicated with ascites were recently treated at our institution. Both rapidly developed renal failure. In one patient, liver disease was the result of alcohol abuse, and in the other, was due to malnutrition associated with obesity and acute weight loss. The only reasonable therapeutic approach for these patients was believed to be a course of peritoneal dialysis, along with other supportive measures. In both cases, the management was successful. Furthermore, it was possible to discontinue dialysis at the time of discharge. We conclude that peritoneal dialysis can be a life-saving procedure in patients with severe liver disease and ascites complicated by renal failure.     

Thromboelastography Parameters in Patients with Acute on Chronic Liver Failure

Introduction and aim. Patients with acute on chronic liver failure (ACLF) have abnormal conventional coagulation tests- platelet count and international normalized ratio (INR). Thromboelastography (TEG) is a rapid, point-of-care assay, more comprehensive than platelet count and INR as it assesses for platelet adequacy(number and function), coagulation factors and clot retraction. The aim of the study was to evaluate the TEG parameters in patients with ACLF, chronic liver disease having acute decompensation (AD) and healthy subjects (HC).Material and methods. TEG parameters were assessed in patients with ACLF and AD within 24 h of admission. Consecutive patients were included in the study over 12 months. Healthy subjects were recruited as controls.Results. 179 patients were included- 68 ACLF, 53 AD and 58 HC. The mean values of INR in ACLF, AD and HC groups were 2.9 ± 1.4, 1.6 ± 0.4 and 1.1 ± 0.2; P < 0.001. Among TEG parameters - maximum amplitude (MA) was low in ACLF and AD patients as compared with HC (53.8 ± 15, 58.3 ± 13.9 mm and 67.2 ± 12.1 mm, respectively; P < 0.001). Lysis at 30 min (LY30) was high in ACLF patients, as compared to AD and HC (8.6 ± 14.1%, 5.0 ± 9.5% and 4.9 ± 9.8%, respectively; P = 0.060). There were no differences in r time, k time, and alpha angle between groups; normal in >90% patients. There was no difference in TEG parameters between different ACLF grades, whereas CCTs were more deranged with increasing grades of ACLF.Conclusion. Despite abnormal conventional coagulation tests, TEG parameters in ACLF patients are essentially normal, except reduced maximum amplitude. Future studies are needed to explore the utility of TEG in clinical management of ACLF patients.