Prognosis of acute-on-chronic liver failure patients treated with arti?cial liver support system

AIM: To establish a new model for predicting survival in acute-on-chronic liver failure (ACLF) patients treated with an artificial liver support system.METHODS: One hundred and eighty-one ACLF patients who were admitted to the hospital from January 1, 2012 to December 31, 2014 and were treated with an artificial liver support system were enrolled in this retrospective study, including a derivation cohort (n = 113) and a validation cohort (n = 68). Laboratory parameters at baseline were analyzed and correlated with clinical outcome. In addition to standard medical therapy, ACLF patients underwent plasma exchange (PE) or plasma bilirubin adsorption (PBA) combined with plasma exchange. For the derivation cohort, Kaplan-Meier methods were used to estimate survival curves, and Cox regression was used in survival analysis to generate a prognostic model. The performance of the new model was tested in the validation cohort using a receiver-operator curve.RESULTS: The mean overall survival for the derivation cohort was 441 d (95%CI: 379-504 d), and the 90- and 270-d survival probabilities were 70.3% and 58.3%, respectively. The mean survival times of patients treated with PBA plus PE and patients treated with PE were 531 d (95%CI: 455-605 d) and 343 d (95%CI: 254-432 d), respectively, which were significantly different (P = 0.012). When variables with bivariate significance were selected for inclusion into the multivariate Cox regression model, number of complications, age, scores of the model for end-stage liver disease (MELD) and type of artificial liver support system were defined as independent risk factors for survival in ACLF patients. This new prognostic model could accurately discriminate the outcome of patients with different scores in this cohort (P < 0.001). The model also had the ability to assign a predicted survival probability for individual patients. In the validation cohort, the new model remained better than the MELD.CONCLUSION: A novel model was constructed to predict prognosis and accurately discriminate survival in ACLF patients treated with an artificial liver support system.     

Comments on “Effect of type 2 diabetes mellitus in the prognosis of acute-on-chronic liver failure patients in China”

A study addressing the influence of type 2 diabetes on the prognosis of acute-on-chronic liver failure patients was reviewed. Some statistical deficiencies were found in the reviewed article, and the sample size was too small to support the study. In addition, age should have been considered as one of the prognostic factors.     

Defining acute-on-chronic liver failure: East,West or Middle ground?

Acute-on-chronic liver failure(ACLF),a newly recognized clinical entity seen in hospitalized patients with chronic liver disease including cirrhosis,is associated with high short- and medium term morbidity and mortality.Noneof the definitions of ACLF proposed so far have been universally accepted,the two most commonly used being those proposed by the Asia-Pacific Association for the Study of Liver(APASL) and the European Association for the Study of Liver- Chronic Liver Failure(EASL-CLIF) consortium.On paper both definitions and diagnostic criteria appear to be different from each other,reflecting the differences in cut-off values for individual parameters used in diagnosis,the acute insult or precipitating event and the underlying chronic liver disease.Data directly comparing these two criteria are limited,and available studies reveal different outcomes when the two are applied to the same set of patients.However a review of the literature suggests that both definitions do not seem to identify the same set of patients.The definition given by the APASL consortium is easier to apply in day-to-day practice but the EASLCLIF criteria appear to better predict mortality in ACLF.The World Gastroenterology Organization working party have proposed a working definition of ACLF which will identify patients from whom relevant data can be collected so that the similarities and the differences between the two regions,if any,can be clearly defined.     

Auxiliary liver transplantation: Regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure–a multicenter European study

Auxiliary liver transplantation (LT) is a special procedure of LT which could be proposed to patients with fulminant hepatic failure (FHF) and has for aim that complete regeneration of the native liver (NL) left in place will allow the graft recipient to resume normal liver function after allograft withdrawal. We report 30 cases of auxiliary LT performed for FHF in 12 European centers. Twenty-five of 30 patients were younger than 50 years. The cause of FHF was hepatitis A virus (HAV) in 4 patients, hepatitis B virus (HBV) in 7, paracetamol overdose in 5, ecstasy in 2, hepatotoxic drugs in 4, autoimmune hepatitis in 2, liver lesions of preeclampsia in 1 and unknown in 5. A postoperative, both clinical and histological follow-up of more than 3 weeks was obtained in 22 patients, enabling us to look for indicators predictive of NL regeneration and outcome. Histological changes observed in the NL included complete regeneration in 68%, incomplete regeneration with obvious fibrous sequelae in 14% and severe liver fibrosis or cirrhosis in 18%, of the 22 patients studied. The percentage and distribution of necrosis observed in tissue samples of the NL at the time of transplantation was not related to the final outcome. Complete NL regeneration was observed in 15 patients, out of whom 14 were younger than 40 years. Patients with complete regeneration were mainly affected by FHF due to HAV, HBV, or paracetamol overdose. After a follow-up of 18/11 (mean/median) months (range, 3 to 67 months), 19 of the 30 patients (63%) survived and 13 of them (68%), i.e., 43% of the 30 patients, had resumed normal NL function, with interrupted immunosuppression, the ultimate goal of emergency auxiliary LT. We conclude that, in patients with FHF, auxiliary LT is a procedure feasible in a number of centers and is associated with a complete regeneration capability of the NL in a majority of survivors, especially in those younger than 40 years. Confirmation of these encouraging preliminary results by large-scale prospective studies is required. (Hepatology 1996 May;23(5):1119-27)     

Diabetic foot ulcers—comparison of performance of ankle-brachial index and transcutaneous partial oxygen pressure in predicting outcome

Diabetic foot ulcer (DFU) is the commonest condition for hospital admission and usually the starting point of most diabetic related lower limb amputations. Considering the significant role played by vascularity in the outcome of ulcer healing, we undertook this study to find out the comparative utility of commonly used vascular assessment methods. This study was a single center prospective non-randomized observational study, conducted for a period of 6 months, in diabetic patients presenting with foot ulcers of Wagner Grade II and III. The aim of our study was to compare the performances of ankle-brachial index (ABI) and transcutaneous partial pressure of oxygen (tcPO₂) measurement in predicting wound healing in diabetic ulcers and to define the optimal cut-off value for Indian patients. Five hundred sixty-four patients were included in this study, with the mean age of 58 years. Eighty-seven patients (15%) had peripheral arterial occlusive disease. Four hundred seventy ulcers (83%) healed with the mean healing days of 42.6 days. Age, duration of diabetes, serum creatinine level, and presence of infection were the factors with negative impact in wound healing. In our study, ABI value of 0.6 was found to have 100% sensitivity and 70% specificity, and tcPO₂ value of 22.5 was found to have 75% sensitivity and 100% specificity in predicting wound healing. Both ABI and tcPO₂ are complementary, but tcPO₂ is a better predictor for amputation while ABI is a better predictor for ulcer healing. While assessing the ischemic status of foot ulcer, the cut-off values should be higher in diabetics than non-diabetics.     

Effects of urotensin-Ⅱ on cytokines in early acute liver failure in mice

AIM:To investigate urotensin-Ⅱ(UⅡ) and its effects on tumor necrosis factor(TNF)-α and interleukin(IL)-1β in early acute liver failure(ALF).METHODS:We investigated the time-dependent alteration in UⅡ levels and its effects on TNF-αand IL-1β in liver and blood in the early stage of lipopolysaccharide/D-galactosamine-induced ALF.RESULTS:After lipopolysaccharide/D-galactosamine challenge,UⅡ rose very rapidly and reached a maximal level 0.5 h,and the level remained significantly elevated after 2 h(P 0.05).Six hours after challenge,UⅡ began to degrade,but remained higher than at 0 h(P 0.05).Pretreatment with urantide,an inhibitor of the UⅡ receptor,suppressed the degree of UⅡ increase in liver and blood at 6 h after challenge(P 0.05 vs paired controls).In addition,liver and blood TNF-α increased from 1 to 6 h,and reached a peak at 1 and 2 h,respectively; however,IL-1β did not rise until 6 h after challenge.Urantide pretreatment inhibited the degree of TNF-α and IL-1β increase following downregulation of UⅡ post-challenge(all P 0.05).CONCLUSION:UⅡ plays a role in the pathogenesis and priming of ALF by triggering an inflammatory cascade and driving the early release of cytokines in mice.     

Elevated troponin I levels in acute liver failure: is myocardial injury an integral part of acute liver failure?

Although rare instances of cardiac injury or arrhythmias have been reported in acute liver failure (ALF), overall, the heart is considered to be spared in this condition. Troponin I, a sensitive and specific marker of myocardial injury, may be elevated in patients with sepsis and acute stroke without underlying acute coronary syndrome, indicating unrecognized cardiac injury in these settings. We sought to determine whether subclinical cardiac injury might also occur in acute liver failure. Serum troponin I levels were measured in 187 patients enrolled in the US Acute Liver Failure Study Group registry, and correlated with clinical variables and outcomes. Diagnoses were representative of the larger group of >1000 patients thus far enrolled and included 80 with acetaminophen-related injury, 26 with viral hepatitis, 19 with ischemic injury, and 62 others. Overall, 74% of patients had elevated troponin I levels (>0.1 ng/ml). Patients with elevated troponin I levels were more likely to have advanced hepatic coma (grades III or IV) or to die (for troponin I levels >0.1 ng/ml, odds ratio 3.88 and 4.69 for advanced coma or death, respectively). CONCLUSION: In acute liver failure, subclinical myocardial injury appears to occur more commonly than has been recognized, and its pathogenesis in the context of acute liver failure is unclear. Elevated troponin levels are associated with a significant increase in morbidity and mortality. Measurement of troponin I levels may be helpful in patients with acute liver failure, to detect unrecognized myocardial damage and as a marker of unfavorable outcome.     

Entecavir vs lamivudine therapy for na?ve patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure

AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.     

Does rhythm matter? The prognostic importance of atrial fibrillation in heart failure

BACKGROUND: Atrial fibrillation (AF) and congestive heart failure (HF) often coexist, but there is conflicting data regarding the association of AF with outcome in HF. To examine this further we have evaluated the prognostic effect of AF in two complementary CHF populations; a population based data set of 55,106 patients admitted to hospital with CHF, and a cohort of 197 patients recruited after a hospital admission with HF into a management clinical trial. METHODS: Firstly, data for all hospital admissions in New Zealand from 1988 to 1997 were obtained. Using coding data, 55,106 first admissions for HF were identified, the presence of AF was determined by secondary diagnosis coding, and all cause mortality was obtained. Secondly, patients enrolled in the Auckland Heart Failure Management Study were evaluated for the presence or absence of AF, and for all cause mortality at three years. RESULTS: Mortality at 30 days, 6 and 12 months was significantly lower for AF patients compared to sinus rhythm (SR) in the national admissions cohort. In the clinical trial cohort the presence of AF was also associated with lower three-year mortality, although this difference was not seen when the groups were stratified by Doppler mitral filling pattern (a restrictive filling pattern was associated with reduced longevity compared to SR, non-restrictive or AF). CONCLUSIONS: This data shows that the presence of AF in two general HF populations in New Zealand is not associated with an adverse prognosis. HF severity, and in particular a restrictive filling pattern, remain powerful predictors of mortality.     

Reduced intensity conditioning allogeneic stem cell transplantation for Hodgkin’s lymphoma: identification of prognostic factors predicting outcome

Background

The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkin’s lymphoma remains controversial.

Design and Methods

To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant.

Results

Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II–IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free.

Conclusions

This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICaIICalloSCT in Hodgkin’s lymphoma.     

Changes of gut flora and endotoxin in rats with D-galactosamine-induced acute liver failure

AIM:To investigate.the changes of gut microflora andendotoxin levels in rats with acute liver failure (ALF) inducedby D-galactosamine (GAIN).METHODS:Flora and endotoxin levels in the jejunum,ileumand colon in normal rats (group A) and rats with GaIN-induced ALF were determined at 24 h (group B) or 48 h(group C) after GaIN injection,as well as the endotoxin levelin portal venous blood (PVB) and right ventricle blood (RVB)were determined by chromogenic limulus amoebocyte assay.RESULTS:Intestinal (jejunum,ileum,colon) lactobacilluscount was statistically reduced in group B compared withthose in group A (3.4±0.3 vs 4.9±0.3,6.1±0.4 vs 8.0±0.3,8.1±0.2 vs 9.3±0.2,P<0.001,P<0.001 and P<0.001respectively) and recovered partially in the group C comparedwith those in the group B,whereas the count ofEnterobacteriaceae in the jejunum,ileum and colon ingroup B was increased markedly compared with thosein the group A (5.1±0.3 vs3.6±0.2,6.9±0.5 vs 5.3±0.3,8.7±0.2 vs 7.6±0.1,P<0.001,P<0.05 and P<0.05 respectively)and restored partially in the group C compared with thosein the group B.The endotoxin level in ileum was increasedin the group B compared with those in the group A(111.3±22.8 vs 51.5±8.9,P<0.05).In addition,theendotoxin level in PVB was obviously increased in groupB compared with that in the group A (76.8±9.1 vs40.6±7.3,P<0.01) and reduced to the baseline at 48 h (group C).CONCLUSION:Severely disturbed gut flora in rats withGaiN-induced acute liver failure plays an important role inthe elevation of endotoxin level in PVB.