Development and Validation of a Scoring System That Includes Corrected QT Interval for Risk Analysis of Patients With Cirrhosis and Gastrointestinal Bleeding.

BACKGROUND & AIMS: The electrocardiographic QT interval frequently is prolonged in patients with cirrhosis. Acute gastrointestinal bleeding further prolongs corrected QT (QTc) in patients with cirrhosis, which has been associated with an increased risk of death within 6 weeks. We aimed to confirm these findings and develop a mortality risk index that incorporates QTc. METHODS: We collected data from 274 patients with cirrhosis and acute gastrointestinal bleeding from any cause admitted to a hospital in Bologna, Italy, from January 2001 through December 2012 (training set). We used logistic regression analysis to identify patient factors associated with death within 6 weeks (6-week mortality). We validated our findings by using data from 200 patients with cirrhosis and gastrointestinal bleeding treated at 2 separate hospitals in Italy, from 2001 through 2016 and 2007 through 2012. Our primary aim was to confirm the prognostic effects of prolonged QTc in a large population of patients and develop a 6-week mortality risk score for acute gastrointestinal bleeding from any cause that incorporates the QTc interval. RESULTS: In the training set, QTc greater than 456 ms, the model for end-stage liver disease-sodium (MELD-Na) score, previous bleeding, and serum albumin concentration were associated independently with 6-week mortality. We combined these parameters to create a risk scoring system that we named MELD-Na acute gastrointestinal bleeding (MELDNa-AGIB). In the validation set, the MELDNa-AGIB identified patients who died within 6 weeks with an area under the receiver operating characteristic curve (AUROC) of 0.888; this value was higher than that of the MELD score (AUROC, 0.838; P = .031), MELD score with updated calibration (AUROC, 0.837; P = .029), Child-Turcotte-Pugh score (AUROC, 0.789; P = .004), D'Amico score (AUROC, 0.761; P = .003), and Augustin score (AUROC, 0.792; P = .001), with a net reclassification improvement better than the MELD-Na score (0.266; P = .045). In calibration, the MELDNa-AGIB produced a high score in the Hosmer-Lemeshow test (P = .947), which was superior to that of MELD-Na (P = .146). In the training set, only 6.3% of patients with MELDNa-AGIB scores of 4 or less died within 6 weeks. Among patients with a scores of 9, 16, and 25 or higher, 15.5%, 41.5%, and 81% or more patients died within 6 weeks, respectively. The probability of survival progressively and significantly decreased with increasing scores in the training and validation sets. CONCLUSIONS: We confirmed QTc as an independent predictor of 6-week mortality in a large population of patients with cirrhosis and acute gastrointestinal bleeding. The combination of QTc, MELD-Na, previous bleeding, and serum albumin (the MELDNa-AGIB score) accurately determines the risk of 6-week mortality, providing timely identification of patients at very high risk of death.

Biomarkers for the early diagnosis of bacterial infection and the surveillance of hepatocellular carcinoma in cirrhosis.

The early detection of bacterial infections and hepatocellular carcinoma (HCC) could ameliorate the prognosis of cirrhosis. C-reactive protein and procalcitonin are under investigation in the setting of cirrhosis as markers of sepsis. In the attempt to discriminate bacterial infection from systemic inflammation, the role of novel biomarkers such as lypopolysaccharide binding-protein, mid-regional fragment of pro-adrenomedullin and delta neutrophil index are currently in development. Concerning HCC, many studies attempted to evaluate biomarkers in the hope of ameliorating the accuracy of the surveillance based on ultrasound. The use of α-fetoprotein (AFP) has been extensively investigated, as well as other biomarkers expressed in the serum of HCC patients like lens culinaris agglutinin-reactive fraction of AFP, des-γ-carboxy prothrombin, glypican-3, α-l-fucosidase and their combined use.

A new prognostic model to predict dropout from the waiting list in cirrhotic candidates for liver transplantation with MELD score <18.

BACKGROUND & AIMS: The model for end-stage liver disease (MELD) is used for organ allocation in liver transplantation (LT), but its prognostic performance is less accurate in patients with low score. We assess the outcome of patients with MELD < 18 awaiting LT, finding prognostic variables to identify a high dropout risk. METHODS: Training set consisted of 277 patients and validation cohort of 292 patients. Competing risk regression analysis, taking into account LT, was used for univariate/multivariate analysis. RESULTS: Ascites, sodium, bilirubin, albumin and glomerular filtration rate were independently associated with a 12-month dropout risk in the training set. Combining these five prognostic parameters, we calculated a new score named liver-renal-risk (LIRER). In the validation set, the 12-month LIRER concordance index showed a discrimination power [0.798, 95% confidence interval (95% CI) 0.793-0.803] better than MELD (0.582, 95% CI 0.575-0.588), Child-Turcotte-Pugh (0.687, 95% CI 0.681-0.693), MELD-sodium (0.721, 95% CI 0.715-0.727) and MELD-ascites-sodium (0.729, 95% CI 0.724-0.735), with a remarkable calibration (Hosmer-Lemeshow test: P = 0.91; R(2) = 0.911). Considering all study patients, the risk of wait list dropout increased with the rise in LIRER. The survival benefit analysis comparing the wait list dropout risk with the mortality of the 216 transplanted patients with same LIRER showed an important benefit for LT in patients with LIRER > 15.9. CONCLUSIONS: In patients with low MELD (<18), combination of ascites, sodium, albumin, bilirubin and renal function in a new score (LIRER) discriminates patients at high risk of medium-term adverse outcome from those in whom LT may be safely deferred.

Hepatitis C virus reinfection after liver transplantation: is there a role for direct antiviral agents?

Recurrence of hepatitis C virus (HCV) infection following liver transplantation (LT) is almost universal and can accelerate graft cirrhosis in up to 30% of patients. The development of effective strategies to treat or prevent HCV recurrence after LT remains a major challenge, considering the shortage of donor organs and the accelerated progression of HCV in LT recipients. Standard antiviral therapy with pegylated-interferon plus ribavirin is the current treatment of choice for HCV LT recipients, even though the combination is not as effective as it is in immunocompetent patients. A sustained virological response in the setting of LT improves patient and graft survival, but this is only achieved in 30%-45% of patients and the treatment is poorly tolerated. To improve the efficacy of pre- and post-transplant antiviral therapy, a new class of potent direct-acting antiviral agents (DAAs) has been developed. The aim of this review is to summarize the use of DAAs in LT HCV patients. PubMed, Cochrane Library, MEDLINE, EMBASE, Web of Science and clinical trial databases were searched for this purpose. To date, only three clinical studies on the topic have been published and most of the available data are in abstract form. Although a moderately successful early virological response has been reported, DAA treatment regimens were associated with severe toxicity mitigating their potential usefulness. Moreover, the ongoing nature of data, the lack of randomized studies, the small number of enrolled patients and the heterogeneity of these studies make the results largely anecdotal and questionable. In conclusion, large well-designed clinical studies on DAAs in HCV LT patients are required before these drugs can be recommended after transplantation.