AIM:To determine whether and how magnetic resonance imaging(MRI)-based total liver volume(TLV) and diffusion weighted imaging(DWI) could predict liver fibrosis.METHODS:Sixteen experimental mature mini-pigs(6 males,10 ...AIM:To determine whether and how magnetic resonance imaging(MRI)-based total liver volume(TLV) and diffusion weighted imaging(DWI) could predict liver fibrosis.METHODS:Sixteen experimental mature mini-pigs(6 males,10 females),weighing between 20.0 and 24.0 kg were prospectively used to model liver fibrosis induced by intraperitoneal injection of 40% CCl4 dissolved in fat emulsion twice a week for 16 wk,and by feeding 40% CCl4 mixed with maize flour twice daily for the subsequent 5 wk.All the survival animals underwent percutaneous liver biopsy and DWI using b = 300,500 and 800 s/mm2 followed by abdominal gadolinium-enhanced MRI at the 0,5th,9th,16th and 21st weekend after beginning of the modeling.TLV was obtained on enhanced MRI,and apparent diffusion coefficient(ADC) was obtained on DWI.Hepatic tissue specimens were stained with hematoxylin and Masson' s trichrome staining for staging liver fibrosis.Pathological specimens were scored using the human METAVIR classification system.Statistical analyses were performed to determine whether and how the TLV and ADC could be used to predict the stage of liver fibrosis.RESULTS:TLV increased from stage 0 to 2 and decreased from stage 3(r = 0.211;P < 0.001).There was a difference in TLV between stage 0-1 and 2-4(P = 0.03) whereas no difference between stage 0-2 and 3-4(P = 0.71).TLV could predict stage ≥ 2 [area under receiver operating characteristic curve(AUC) = 0.682].There was a decrease in ADC values with increasing stage of fibrosis for b = 300,500 and 800 s/mm2(r =-0.418,-0.535 and-0.622,respectively;all P < 0.001).Differences were found between stage 0-1 and 2-4 in ADC values for b = 300,500 and 800 s/mm2,and between stage 0-2 and 3-4 for b = 500 or 800 s/mm2(all P < 0.05).For predicting stage ≥ 2 and ≥ 3,AUC was 0.803 and 0.847 for b = 500 s/mm2,and 0.848 and 0.887 for b = 800 s/mm2,respectively.CONCLUSION:ADC for b = 500 or 800 s/mm2 could be better than TLV and ADC for b = 300 s/mm2 to pre-dict fibrosis stage ≥ 2 or ≥ 3.展开更多
BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,som...BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.展开更多
BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliativ...BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliative care(PC)is pronounced in patients grappling with ESLD and acute on chronic liver failure(ACLF).Unfortunately,the historical underutilization of PC in ESLD patients,despite their substantial needs and those of their family caregivers,underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.METHODS A systematic search in the Medline(PubMed)database was performed using a predetermined search command,encompassing studies published in English without any restrictions on the publication date.Subsequently,the retrieved studies were manually examined.Simple descriptive analyses were employed to summarize the results.RESULTS The search strategies yielded 721 references.Following the final analysis,32 fulllength references met the inclusion criteria and were consequently incorporated into the study.Meticulous data extraction from these 32 studies was undertaken,leading to the execution of a comprehensive narrative systematic review.The review found that PC provides significant benefits,reducing symptom burden,depressive symptoms,readmission rates,and hospital stays.Yet,barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization.Integrating PC early,upon the diagnosis of ESLD and ACLF,regardless of transplant eligibility and availability,improves the quality of life for these patients.CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF,where liver transplantation stands as the only curative treatment,albeit largely inaccessible,PC services have been overtly provided too late in the course of the illness.A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers,involving healthcare providers,patients,and caregivers.展开更多
AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full len...AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC >= 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.展开更多
End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver tran...End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.展开更多
Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and health...Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and healthcare resource utilisation.ACLF encompasses a dysregulated,systemic inflammatory response,which can precipitate extra hepatic organ failures.Common precipitants include infection,alcoholic hepatitis,and reactivation of viral hepatitis although frequently no cause is identified.Heterogenous definitions,diagnostic criteria,and treatment guidelines,have been proposed by international hepatology societies.This can result in delayed or missed diagnoses of ACLF,significant variability in clinical management,and under-estimation of disease burden.Liver transplantation may be considered but the mainstay of treatment is organ support,often in the intensive care unit.This review will provide clarity around where are the controversies and consensus in ACLF including:Epidemiology and resource utilisation,key clinical and diagnostic features,strategies for management,and research gaps.展开更多
End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and...End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.展开更多
Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortal...Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.展开更多
AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH).
BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate...BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not.Viscoelastic testing such as thromboelastography(TEG)correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion.Despite this,viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting.AIM To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure.METHODS PubMed and Google Scholar searches were performed using the key words“thromboelastography”,“TEG”or“viscoelastic”and“liver transplantation”,“cirrhosis”or“liver disease”and“transfusion”,“haemostasis”,“blood management”or“haemorrhage”.A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease.The study subjects,inclusion and exclusion criteria,methods,outcomes and length of follow up were examined.Data was extracted by two independent individuals using a standardized collection form.The risk of bias was assessed in the included studies.RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures(n=118),non-variceal haemorrhage(n=96),variceal haemorrhage(n=60)and liver transplantation(n=28).TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care.Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets.Two studies showed a significant reduction in cryoprecipitate transfusion.No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure.Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding.In those with variceal bleeding,there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10%(vs 26.7%in the standard of care arm P=0.012).Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm.One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6%(vs 74.5%in the control arm P<0.01).In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm(P=0.012).CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.展开更多
BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed to induce rapid liver hypertrophy and reduce posthepatectomy liver failure in patients wit...BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed to induce rapid liver hypertrophy and reduce posthepatectomy liver failure in patients with insufficient future liver remnant (FLR). ALPPS is still considered to be in an early developmental phase because surgical indications and techniques have not been standardized. This article aimed to review the current role and future developments of ALPPS. DATA SOURCES: Studies were identified by searching MED- LINE and PubMed for articles from January 2007 to October 2016 using the keywords "associating liver partition and portal vein ligation for staged hepatectomy" and "ALPPS" Addi- tional papers were identified by a manual search of references from key articles. RESULTS: ALPPS induces more hypertrophy of the FLR in less time than portal vein embolization or portal vein ligation. The benefits of ALPPS include rapid hypertrophy 47%-110% of the liver over a median of 6-16.4 days, and 95%-100% com- pletion rate of the second stage of ALPPS. The main criticisms of ALPPS are centered on its high morbidity and mortality rates. Morbidity rates after ALPPS have been reported to be 15.3%-100%, with ≥ the Clavien-Dindo grade III morbidity of 13.6%-44%. Mortality rates have been reported to be 0%-29%. The important questions to ask even if oncologic long-term results are acceptable are: whether the gain in quality and quantity of life can be off balance by the substantial risks of morbidity and mortality, and whether stimulation of rapid liver hypertrophy also accelerates rapid tumor progression and spread. Up till now, the documentations of the ALPPS procedure come mainly from case series, and most of these series include heterogeneous groups of malignancies. The numbers are also too small to separately evaluate survival for different tumor etiologies. CONCLUSIONS: Currently, knowledge on ALPPS is limited, and prospective randomized studies are lacking. From the reported preliminary results, safety of the ALPPS procedure remains questionable. ALPPS should only be used in experienced, high-volume hepatobiliary centers.展开更多
Therapeutic management of hepatocellular carcinoma(HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral s...Therapeutic management of hepatocellular carcinoma(HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer(BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.展开更多
Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is...Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant(FLR) to allow for resection directly. There are therefore strategies todecrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion(PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS(associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.展开更多
AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METH...AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.展开更多
End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive ...End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.展开更多
To investigate the relationship between 25-hydroxyvitamin D (25-OHD) deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease (CLD). METHODSA retrospective analysis of the results of 392 adult...To investigate the relationship between 25-hydroxyvitamin D (25-OHD) deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease (CLD). METHODSA retrospective analysis of the results of 392 adult patients with chronic liver disease who were assessed for liver transplantation between 2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD were analysed in patients assessed for liver transplantation between 2006 and 2010. Patients who presented with acute, fulminant or subacute disease, with a primary diagnosis of liver cancer, were assessed for re-transplantation or who did not have a 25-OHD measurement were excluded from the analysis. RESULTSOne hundred and sixty-five patients were included in this analysis. The mean age of all patients was 53 ± 8 years. Moderate to severe 25-OHD deficiency was identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients who were not encephalopathic (P ≤ 0.0001). Mild 25-OHD deficiency was not associated with HE. There was a significant correlation between the severity of 25-OHD deficiency and the severity of liver disease (r = 0.39, P ≤ 0.0001) and disease severity and the presence of HE (P ≤ 0.0001). Importantly, individuals with 25-OHD deficiency were more likely to have a diagnosis of overt HE (OHE) at a significantly lower model for end stage liver disease (MELD) score than individuals without OHE (P ≤ 0.0001). This significant difference was observed with MELD scores from 10 to 38. CONCLUSION25-OHD deficiency was observed in the majority of patients with CLD and for the first time was found to be significantly worse in patients with OHE.展开更多
Since the first successful liver transplantation was performed five decades ago,pediatric liver transplantation has become the gold standard treatment choice for pediatric liver disease,including metabolic diseases,li...Since the first successful liver transplantation was performed five decades ago,pediatric liver transplantation has become the gold standard treatment choice for pediatric liver disease,including metabolic diseases,liver tumors,and some acute liver failure.With improvements in immunosuppression,surgical techniques,and postoperative medical care,long-term outcomes of patients after liver transplantation have markedly improved,especially in pediatric patients.展开更多
BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate...BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate marker of malnutrition. L3SMIapplication is, however, limited by non-availability of computed tomographyscanning in remote areas, cost, need for extensive training, and the risk ofexposure to radiation. Therefore, an alternative dependable measure with wideravailability is needed. Malnutrition causes sarcopenia not only in skeletal musclesbut also in other muscular structures such as the psoas muscle, diaphragm andtongue. We therefore hypothesised that the tongue, being easily accessible forinspection and for measurement of thickness using ultrasonography, may be usedto document sarcopenia.AIMTo measure and compare tongue thickness in healthy individuals and in patientswith cirrhosis of the liver and to study its correlation with conventionalprognostic scores for patients with cirrhosis of the liver.METHODSTongue thickness was measured using ultrasonography. One hundred twentysubjects of either gender aged 18 to 65 years were studied, with 30 subjects in eachgroup. The tongue thickness was compared between groups based on “ChildTurcotte Pugh” (CTP) scores. The correlations between measured tonguethickness and “Model for end stage liver disease” (MELD) score and between age and measured tongue thickness were also assessed.RESULTSMean tongue thickness (mean ± SD) in patients with CTP class A, B and C was4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cmin normal healthy individuals. Significant differences were seen in tonguethickness between patients with CTP class C and those with CTP class A and B (P< 0.05). Patients with CTP class C also had a significantly reduced tonguethickness than normal individuals (P < 0.05). However, no significant differencewas seen in tongue thickness between patients with CTP class A and B andnormal individuals. A statistically significant, negative correlation was foundbetween MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlationwas observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI(mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patientswith CTP class C, and the difference was not significant. No significant correlationwas found between age of the patients and tongue thickness. Intra-classcorrelation coefficient was used to determine the reliability of the tonguethickness measurements. The intra-class correlation coefficient was 0.984 (95%CI:0.979-0.989) and was indicative of good reliability.CONCLUSIONTongue thickness measured by ultrasonography, correlates significantly with theseverity of liver disease, as assessed by CTP and MELD scores. The patients with aCTP score ≥ 10 have significantly reduced tongue thickness as compared tonormal individuals and those with less severe liver disease and CTP scores of 5-9.No significant difference in tongue thickness was found between healthyindividuals and CTP class A and B patients.展开更多
Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) has been recently demonstrated as a method to induce rapid and extensive hypertrophy within a short time and has been employed for a v...Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) has been recently demonstrated as a method to induce rapid and extensive hypertrophy within a short time and has been employed for a variety of primary and metastatic liver tumors. However, controversies remain due to its high morbidity and mortality. To enable safer surgery, liver surgeons have searched for better technical modifications, such as partial ALPPS, mini-ALPPS, minimally invasive ALPPS, and Terminal branches portal vein Embolization Liver Partition for Planned hepatectomy(TELPP). It seems that TELPP is very promising, because it has the main advantage of ALPPS-the rapid increase of future liver remnant volume, but the morbidity and mortality are much lower because only one surgical operation is required.展开更多
BACKGROUND Palliative care(PC)has been shown to be beneficial in end stage liver disease(ESLD),yet the hospitalization data for PC utilization is unknown.AIM To identify the trend of PC utilization for the special pop...BACKGROUND Palliative care(PC)has been shown to be beneficial in end stage liver disease(ESLD),yet the hospitalization data for PC utilization is unknown.AIM To identify the trend of PC utilization for the special population of alcoholassociated ESLD patients,factors affecting its use and ascertain its impact on healthcare utilization.METHODS We analyzed around 78 million discharges from the 2007-2014 national inpatient sample and 2010-2014 national readmission database including adult patients admitted for decompensated alcohol-associated cirrhosis.We identified patients with PC consultation as a secondary diagnosis.Odds ratios(OR)and means were adjusted for confounders using multivariate regression analysis models.RESULTS Out of the total 1421849 hospitalizations for decompensated liver cirrhosis,62782(4.4%)hospitalizations had a PC consult,which increased from 0.8%(1258)of all alcohol-associated ESLD hospitalizations in 2007 to 6.6%in 2014(P<0.01).Patient and hospital characteristics associated with increased odds of PC utilization were advanced age,lower income,Medicaid coverage,teaching institution,urban location,length of stay>3 d,prolonged ventilation,and administration of total parenteral nutrition(all P<0.01).Palliative encounters in alcohol-associated ESLD and acute-onchronic liver failure(ACLF)score were associated with increased odds of discharge to a rehabilitation facility,but significantly lower odds of 30-d readmissions(aOR:0.35,95%CI:0.31-0.41),lower total hospitalization charges and lower mean hospitalization days(all P<0.01).CONCLUSION Inpatient PC is sparingly used for patients with decompensated alcohol related liver disease,however it has increased over the past decade.PC consultation is associated with lower 30-d readmission rates on multivariate analysis,and lower hospitalization cost and length of stay in patients with ACLF score≥2.展开更多
基金Supported by National Natural Science Foundation of China,No. 81050033Key Projects in the Sichuan Province Science and Technology Pillar Program,No. 2011SZ0237the Science Fund for Distinguished Young Scholars of Sichuan Province,China,No. 2010JQ0039
文摘AIM:To determine whether and how magnetic resonance imaging(MRI)-based total liver volume(TLV) and diffusion weighted imaging(DWI) could predict liver fibrosis.METHODS:Sixteen experimental mature mini-pigs(6 males,10 females),weighing between 20.0 and 24.0 kg were prospectively used to model liver fibrosis induced by intraperitoneal injection of 40% CCl4 dissolved in fat emulsion twice a week for 16 wk,and by feeding 40% CCl4 mixed with maize flour twice daily for the subsequent 5 wk.All the survival animals underwent percutaneous liver biopsy and DWI using b = 300,500 and 800 s/mm2 followed by abdominal gadolinium-enhanced MRI at the 0,5th,9th,16th and 21st weekend after beginning of the modeling.TLV was obtained on enhanced MRI,and apparent diffusion coefficient(ADC) was obtained on DWI.Hepatic tissue specimens were stained with hematoxylin and Masson' s trichrome staining for staging liver fibrosis.Pathological specimens were scored using the human METAVIR classification system.Statistical analyses were performed to determine whether and how the TLV and ADC could be used to predict the stage of liver fibrosis.RESULTS:TLV increased from stage 0 to 2 and decreased from stage 3(r = 0.211;P < 0.001).There was a difference in TLV between stage 0-1 and 2-4(P = 0.03) whereas no difference between stage 0-2 and 3-4(P = 0.71).TLV could predict stage ≥ 2 [area under receiver operating characteristic curve(AUC) = 0.682].There was a decrease in ADC values with increasing stage of fibrosis for b = 300,500 and 800 s/mm2(r =-0.418,-0.535 and-0.622,respectively;all P < 0.001).Differences were found between stage 0-1 and 2-4 in ADC values for b = 300,500 and 800 s/mm2,and between stage 0-2 and 3-4 for b = 500 or 800 s/mm2(all P < 0.05).For predicting stage ≥ 2 and ≥ 3,AUC was 0.803 and 0.847 for b = 500 s/mm2,and 0.848 and 0.887 for b = 800 s/mm2,respectively.CONCLUSION:ADC for b = 500 or 800 s/mm2 could be better than TLV and ADC for b = 300 s/mm2 to pre-dict fibrosis stage ≥ 2 or ≥ 3.
基金Supported by the Science and Technology Planning Project of Guangdong Province,China,No.2019B0202280015010 Project of Sun Yatsen University,No.2018024Science and Technology Program of Guangzhou,China,No.202103000060.
文摘BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)is commonly utilized as a prognostic indicator in end-stage liver disease(ESLD),encompassing conditions like liver failure and decompensated cirrhosis.Nevertheless,some studies have contested the prognostic value of NLR in ESLD.AIM To investigate the ability of NLR to predict ESLD.METHODS Databases,such as Embase,PubMed,Web of Science,Cochrane Library,China National Knowledge Infrastructure,Weipu,and Wanfang,were comprehensively searched to identify studies published before October 2022 assessing the prognostic ability of NLR to predict mortality in patients with ESLD.Effect sizes were calculated using comprehensive meta-analysis software and SATAT 15.1.RESULTS A total of thirty studies involving patients with end-stage liver disease(ESLD)were included in the evaluation.Among the pooled results of eight studies,it was observed that the Neutrophil-to-Lymphocyte Ratio(NLR)was significantly higher in non-survivors compared to survivors(random-effects model:standardized mean difference=1.02,95%confidence interval=0.67-1.37).Additionally,twenty-seven studies examined the associations between NLR and mortality in ESLD patients,reporting either hazard ratios(HR)or odds ratios(OR).The combined findings indicated a link between NLR and ESLD mortality(randomeffects model;univariate HR=1.07,95%CI=1.05-1.09;multivariate HR=1.07,95%CI=1.07-1.09;univariate OR=1.29,95%CI=1.18-1.39;multivariate OR=1.29,95%CI=1.09-1.49).Furthermore,subgroup and meta-regression analyses revealed regional variations in the impact of NLR on ESLD mortality,with Asian studies demonstrating a more pronounced effect.CONCLUSION Increased NLR in patients with ESLD is associated with a higher risk of mortality,particularly in Asian patients.NLR is a useful prognostic biomarker in patients with ESLD.
文摘BACKGROUND End stage liver disease(ESLD)represents a growing health concern characterized by elevated morbidity and mortality,particularly among individual ineligible for liver transplantation.The demand for palliative care(PC)is pronounced in patients grappling with ESLD and acute on chronic liver failure(ACLF).Unfortunately,the historical underutilization of PC in ESLD patients,despite their substantial needs and those of their family caregivers,underscores the imperative of seamlessly integrating PC principles into routine healthcare practices across the entire disease spectrum.AIM To comprehensively investigate the evidence surrounding the benefits of incorporating PC into the comprehensive care plan for individuals confronting ESLD and/or ACLF.METHODS A systematic search in the Medline(PubMed)database was performed using a predetermined search command,encompassing studies published in English without any restrictions on the publication date.Subsequently,the retrieved studies were manually examined.Simple descriptive analyses were employed to summarize the results.RESULTS The search strategies yielded 721 references.Following the final analysis,32 fulllength references met the inclusion criteria and were consequently incorporated into the study.Meticulous data extraction from these 32 studies was undertaken,leading to the execution of a comprehensive narrative systematic review.The review found that PC provides significant benefits,reducing symptom burden,depressive symptoms,readmission rates,and hospital stays.Yet,barriers like the appeal of transplants and misconceptions about PC hinder optimal utilization.Integrating PC early,upon the diagnosis of ESLD and ACLF,regardless of transplant eligibility and availability,improves the quality of life for these patients.CONCLUSION Despite the substantial suffering and poor prognosis associated with ESLD and ACLF,where liver transplantation stands as the only curative treatment,albeit largely inaccessible,PC services have been overtly provided too late in the course of the illness.A comprehensive understanding of PC's pivotal role in treating ESLD and ACLF is crucial for overcoming these barriers,involving healthcare providers,patients,and caregivers.
基金Supported by National Science and Technology Key Project of China on"Major Infectious Diseases",No.2012ZX10002004-006,No.2012ZX10004904-003-001,No.2013ZX10002002-006-001Beijing Municipal Science and Technology Commission,No.Z131107002213019,No.Z131100004613030+2 种基金High Technical Personnel Training Program in Beijing Health System,No.2011-3-083,No.2013-3-071Special Scientific Research Fund for Beijing Health Development,No.2011-2018-04National Natural Science Foundation of China,No.30800979,No.30800517
文摘AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology. METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48). RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC >= 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%). CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
文摘End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.
文摘Acute-on-chronic liver failure(ACLF)is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease.Consequences include high short-term morbidity,mortality,and healthcare resource utilisation.ACLF encompasses a dysregulated,systemic inflammatory response,which can precipitate extra hepatic organ failures.Common precipitants include infection,alcoholic hepatitis,and reactivation of viral hepatitis although frequently no cause is identified.Heterogenous definitions,diagnostic criteria,and treatment guidelines,have been proposed by international hepatology societies.This can result in delayed or missed diagnoses of ACLF,significant variability in clinical management,and under-estimation of disease burden.Liver transplantation may be considered but the mainstay of treatment is organ support,often in the intensive care unit.This review will provide clarity around where are the controversies and consensus in ACLF including:Epidemiology and resource utilisation,key clinical and diagnostic features,strategies for management,and research gaps.
基金The European Association for the Study of the Liver(EASL) Sheila Sherlock Post-Doc Fellowship and by"Ordine dei Medici Chirurghi ed Odontoiatri di Bologna"(SL)
文摘End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.
文摘Diabetes mellitus(DM)negatively affects the development and progression of chronic liver diseases(CLD)of various etiologies.Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality,the occurrence of hepatic decompensation,and the development of hepatocellular carcinoma(HCC).Unfortunately,early diagnosis and optimal treatment of DM can be challenging,due to the lack of established clinical guidelines as well as the medical complexity of this patient population.We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population.We reviewed the epidemiological and pathophysiological associations between DM and CLD,the impact of insulin resistance on the progression and manifestations of CLD,the pathogenesis of hepatogenic diabetes,as well as the practical challenges in diagnosis and monitoring of DM in this patient population.We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes.Finally,we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.
基金Supported by National Institutes of Health,No.41301Veteran Administration Clinical Merit Review Grant,to Dr Dennis M JensenPhilippe Foundation Grant,to Dr.Marine Camus
文摘AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH).
文摘BACKGROUND Conventional coagulation tests are widely used in chronic liver disease to assess haemostasis and to guide blood product transfusion.This is despite the fact that conventional tests do not reliably separate those with a clinically significant coagulopathy from those who do not.Viscoelastic testing such as thromboelastography(TEG)correlate with bleeding risk and are more accurate in identifying those who will benefit from blood product transfusion.Despite this,viscoelastic tests have not been widely used in patients with chronic liver disease outside the transplant setting.AIM To assess the utility of Viscoelastic Testing guided transfusion in chronic liver disease patients presenting with bleeding or who require an invasive procedure.METHODS PubMed and Google Scholar searches were performed using the key words“thromboelastography”,“TEG”or“viscoelastic”and“liver transplantation”,“cirrhosis”or“liver disease”and“transfusion”,“haemostasis”,“blood management”or“haemorrhage”.A full text review was undertaken and data was extracted from randomised control trials that evaluated the outcomes of viscoelastic test guided transfusion in those with liver disease.The study subjects,inclusion and exclusion criteria,methods,outcomes and length of follow up were examined.Data was extracted by two independent individuals using a standardized collection form.The risk of bias was assessed in the included studies.RESULTS A total of five randomised control trials included in the analysis examined the use of TEG guided blood product transfusion in cirrhosis prior to invasive procedures(n=118),non-variceal haemorrhage(n=96),variceal haemorrhage(n=60)and liver transplantation(n=28).TEG guided transfusion was effective in all five studies with a statistically significant reduction in overall blood product transfusion compared to standard of care.Four of the five studies reported a significant reduction in transfusion of fresh frozen plasma and platelets.Two studies showed a significant reduction in cryoprecipitate transfusion.No increased risk of bleeding was reported in the three trials where TEG was used perioperatively or prior to an invasive procedure.Two trials in the setting of cirrhotic variceal and non-variceal bleeding showed no difference in control of initial bleeding.In those with variceal bleeding,there was a statistically significant reduction in rate of re-bleeding at 42 d in the TEG arm 10%(vs 26.7%in the standard of care arm P=0.012).Mortality data reported at various time points for all five trials from 6 wk up to 3 years was not statistically different between each arm.One trial in the setting of non-variceal bleeding demonstrated a significant reduction in adverse transfusion events in the TEG arm 30.6%(vs 74.5%in the control arm P<0.01).In this study there was no significant difference in total hospital stay although length of stay in intensive care unit was reduced by an average of 2 d in the TEG arm(P=0.012).CONCLUSION Viscoelastic testing has been shown to reduce blood product usage in chronic liver disease without compromising safety and may enable guidelines to be developed to ensure patients with liver disease are optimally managed.
文摘BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed to induce rapid liver hypertrophy and reduce posthepatectomy liver failure in patients with insufficient future liver remnant (FLR). ALPPS is still considered to be in an early developmental phase because surgical indications and techniques have not been standardized. This article aimed to review the current role and future developments of ALPPS. DATA SOURCES: Studies were identified by searching MED- LINE and PubMed for articles from January 2007 to October 2016 using the keywords "associating liver partition and portal vein ligation for staged hepatectomy" and "ALPPS" Addi- tional papers were identified by a manual search of references from key articles. RESULTS: ALPPS induces more hypertrophy of the FLR in less time than portal vein embolization or portal vein ligation. The benefits of ALPPS include rapid hypertrophy 47%-110% of the liver over a median of 6-16.4 days, and 95%-100% com- pletion rate of the second stage of ALPPS. The main criticisms of ALPPS are centered on its high morbidity and mortality rates. Morbidity rates after ALPPS have been reported to be 15.3%-100%, with ≥ the Clavien-Dindo grade III morbidity of 13.6%-44%. Mortality rates have been reported to be 0%-29%. The important questions to ask even if oncologic long-term results are acceptable are: whether the gain in quality and quantity of life can be off balance by the substantial risks of morbidity and mortality, and whether stimulation of rapid liver hypertrophy also accelerates rapid tumor progression and spread. Up till now, the documentations of the ALPPS procedure come mainly from case series, and most of these series include heterogeneous groups of malignancies. The numbers are also too small to separately evaluate survival for different tumor etiologies. CONCLUSIONS: Currently, knowledge on ALPPS is limited, and prospective randomized studies are lacking. From the reported preliminary results, safety of the ALPPS procedure remains questionable. ALPPS should only be used in experienced, high-volume hepatobiliary centers.
文摘Therapeutic management of hepatocellular carcinoma(HCC) is quite complex owing to the underlying cirrhosis and portal vein hypertension. Different scores or classification systems based on liver function and tumoral stages have been published in the recent years. If none of them is currently "universally" recognized, the Barcelona Clinic Liver Cancer(BCLC) staging system has become the reference classification system in Western countries. Based on a robust treatment algorithm associated with stage stratification, it relies on a high level of evidence. However, BCLC stage B and C HCC include a broad spectrum of tumors but are only matched with a single therapeutic option. Some experts have thus suggested to extend the indications for surgery or for transarterial chemoembolization. In clinical practice, many patients are already treated beyond the scope of recommendations. Additional alternative prognostic scores that could be applied to any therapeutic modality have been recently proposed. They could represent complementary tools to the BCLC staging system and improve the stratification of HCC patients enrolled in clinical trials, as illustrated by the NIACE score. Prospective studies are needed to compare these scores and refine their role in the decision making process.
文摘Colorectal cancer is the third most common cancer in the Western world. Approximately half of patients will develop liver metastases, which is the most common cause of death. The only potentially curative treatment is surgical resection. However, many patients retain a to small future liver remnant(FLR) to allow for resection directly. There are therefore strategies todecrease the tumor with neoadjuvant chemotherapy and to increase the FLR. An accepted strategy to increase the FLR is portal vein occlusion(PVO). A concern with this strategy is that a large proportion of patients will never be operated because of progression during the interval between PVO and resection. ALPPS(associating liver partition and portal vein ligation for staged hepatectomy) is a new procedure with a high resection rate. A concern with this approach is the rather high frequency of complications and high mortality, compared to PVO. In this review, it is shown that with ALPPS the resection rate was 97.1% for CRLM and the mortality rate for all diagnoses was 9.6%. The mortality rate was likely lower for patients with CRLM, but some data were lacking in the reports. Due to the novelty of ALPPS, the indications and technique are not yet established but there are arguments for ALPPS in the context of CRLM and a small FLR.
文摘AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.
文摘End stage liver diseases (ESLD) represent a major, neglected global public health crisis which requires an urgent action towards fnding a proper cure. Orthotro-pic liver transplantation has been the only definitive treatment modality for ESLD. However, shortage of donor organs, timely unavailability, post-surgery related complications and financial burden on the patients li-mits the number of patients receiving the transplants. Since last two decades cell-based therapies have revolu-tionized the feld of organ/tissue regeneration. However providing an alternative organ source to address the donor liver shortage still poses potential challenges. The developments made in this direction provide useful futuristic approaches, which could be translated into preclinical and clinical settings targeting appropriate applications in specific disease conditions. Earlier studies have demonstrated the applicability of this particular approach to generate functional organ in rodent system by connecting them with portal and hepatic circulatory networks. However, such strategy requires very high level of surgical expertise and also poses the technical and financial questions towards its future applicability. Hence, alternative sites for generating secondary organs are being tested in several types of disease conditions. Among different sites, omentum has been proved to be more appropriate site for implanting several kinds of functional tissue constructs without eliciting much immunological response. Hence, omentum may be con-sidered as better site for transplanting humanized bio-engineered ex vivo generated livers, thereby creating a secondary organ at intra-omental site. However, the expertise for generating such bioengineered organs are limited and only very few centres are involved for inve-stigating the potential use of such implants in clinical practice due to gap between the clinical transplant surgeons and basic scientists working on the concept evolution. Herein we discuss the recent advances and challenges to create functional secondary organs thr-ough intra-omental transplantation of ex vivo genera-ted bioengineered humanized livers and their further application in the management of ESLD as a supportive bridge for organ transplantation.
文摘To investigate the relationship between 25-hydroxyvitamin D (25-OHD) deficiency and hepatic encephalopathy (HE) in patients with chronic liver disease (CLD). METHODSA retrospective analysis of the results of 392 adult patients with chronic liver disease who were assessed for liver transplantation between 2006 and 2010 was undertaken. HE, severity of CLD, nutritional status and 25-OHD were analysed in patients assessed for liver transplantation between 2006 and 2010. Patients who presented with acute, fulminant or subacute disease, with a primary diagnosis of liver cancer, were assessed for re-transplantation or who did not have a 25-OHD measurement were excluded from the analysis. RESULTSOne hundred and sixty-five patients were included in this analysis. The mean age of all patients was 53 ± 8 years. Moderate to severe 25-OHD deficiency was identified in 49 patients of whom 36 had grade 2-3 HE compared with 13 patients who were not encephalopathic (P ≤ 0.0001). Mild 25-OHD deficiency was not associated with HE. There was a significant correlation between the severity of 25-OHD deficiency and the severity of liver disease (r = 0.39, P ≤ 0.0001) and disease severity and the presence of HE (P ≤ 0.0001). Importantly, individuals with 25-OHD deficiency were more likely to have a diagnosis of overt HE (OHE) at a significantly lower model for end stage liver disease (MELD) score than individuals without OHE (P ≤ 0.0001). This significant difference was observed with MELD scores from 10 to 38. CONCLUSION25-OHD deficiency was observed in the majority of patients with CLD and for the first time was found to be significantly worse in patients with OHE.
文摘Since the first successful liver transplantation was performed five decades ago,pediatric liver transplantation has become the gold standard treatment choice for pediatric liver disease,including metabolic diseases,liver tumors,and some acute liver failure.With improvements in immunosuppression,surgical techniques,and postoperative medical care,long-term outcomes of patients after liver transplantation have markedly improved,especially in pediatric patients.
文摘BACKGROUNDMalnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletalmuscle index (L3SMI) is presently accepted as the most objective and quantitativemeasure available for sarcopenia, a surrogate marker of malnutrition. L3SMIapplication is, however, limited by non-availability of computed tomographyscanning in remote areas, cost, need for extensive training, and the risk ofexposure to radiation. Therefore, an alternative dependable measure with wideravailability is needed. Malnutrition causes sarcopenia not only in skeletal musclesbut also in other muscular structures such as the psoas muscle, diaphragm andtongue. We therefore hypothesised that the tongue, being easily accessible forinspection and for measurement of thickness using ultrasonography, may be usedto document sarcopenia.AIMTo measure and compare tongue thickness in healthy individuals and in patientswith cirrhosis of the liver and to study its correlation with conventionalprognostic scores for patients with cirrhosis of the liver.METHODSTongue thickness was measured using ultrasonography. One hundred twentysubjects of either gender aged 18 to 65 years were studied, with 30 subjects in eachgroup. The tongue thickness was compared between groups based on “ChildTurcotte Pugh” (CTP) scores. The correlations between measured tonguethickness and “Model for end stage liver disease” (MELD) score and between age and measured tongue thickness were also assessed.RESULTSMean tongue thickness (mean ± SD) in patients with CTP class A, B and C was4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cmin normal healthy individuals. Significant differences were seen in tonguethickness between patients with CTP class C and those with CTP class A and B (P< 0.05). Patients with CTP class C also had a significantly reduced tonguethickness than normal individuals (P < 0.05). However, no significant differencewas seen in tongue thickness between patients with CTP class A and B andnormal individuals. A statistically significant, negative correlation was foundbetween MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlationwas observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI(mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patientswith CTP class C, and the difference was not significant. No significant correlationwas found between age of the patients and tongue thickness. Intra-classcorrelation coefficient was used to determine the reliability of the tonguethickness measurements. The intra-class correlation coefficient was 0.984 (95%CI:0.979-0.989) and was indicative of good reliability.CONCLUSIONTongue thickness measured by ultrasonography, correlates significantly with theseverity of liver disease, as assessed by CTP and MELD scores. The patients with aCTP score ≥ 10 have significantly reduced tongue thickness as compared tonormal individuals and those with less severe liver disease and CTP scores of 5-9.No significant difference in tongue thickness was found between healthyindividuals and CTP class A and B patients.
基金Supported by the National Natural Science Foundation of China,No.81570559 and No.81272673
文摘Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) has been recently demonstrated as a method to induce rapid and extensive hypertrophy within a short time and has been employed for a variety of primary and metastatic liver tumors. However, controversies remain due to its high morbidity and mortality. To enable safer surgery, liver surgeons have searched for better technical modifications, such as partial ALPPS, mini-ALPPS, minimally invasive ALPPS, and Terminal branches portal vein Embolization Liver Partition for Planned hepatectomy(TELPP). It seems that TELPP is very promising, because it has the main advantage of ALPPS-the rapid increase of future liver remnant volume, but the morbidity and mortality are much lower because only one surgical operation is required.
文摘BACKGROUND Palliative care(PC)has been shown to be beneficial in end stage liver disease(ESLD),yet the hospitalization data for PC utilization is unknown.AIM To identify the trend of PC utilization for the special population of alcoholassociated ESLD patients,factors affecting its use and ascertain its impact on healthcare utilization.METHODS We analyzed around 78 million discharges from the 2007-2014 national inpatient sample and 2010-2014 national readmission database including adult patients admitted for decompensated alcohol-associated cirrhosis.We identified patients with PC consultation as a secondary diagnosis.Odds ratios(OR)and means were adjusted for confounders using multivariate regression analysis models.RESULTS Out of the total 1421849 hospitalizations for decompensated liver cirrhosis,62782(4.4%)hospitalizations had a PC consult,which increased from 0.8%(1258)of all alcohol-associated ESLD hospitalizations in 2007 to 6.6%in 2014(P<0.01).Patient and hospital characteristics associated with increased odds of PC utilization were advanced age,lower income,Medicaid coverage,teaching institution,urban location,length of stay>3 d,prolonged ventilation,and administration of total parenteral nutrition(all P<0.01).Palliative encounters in alcohol-associated ESLD and acute-onchronic liver failure(ACLF)score were associated with increased odds of discharge to a rehabilitation facility,but significantly lower odds of 30-d readmissions(aOR:0.35,95%CI:0.31-0.41),lower total hospitalization charges and lower mean hospitalization days(all P<0.01).CONCLUSION Inpatient PC is sparingly used for patients with decompensated alcohol related liver disease,however it has increased over the past decade.PC consultation is associated with lower 30-d readmission rates on multivariate analysis,and lower hospitalization cost and length of stay in patients with ACLF score≥2.