The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

Relevance of liver surface nodularity for preoperative risk assessment in patients with resectable hepatocellular carcinoma.

BACKGROUND: Quantification of liver surface nodularity (LSN) on routine preoperative CT images allows detection of cirrhosis and clinically significant portal hypertension. This study aimed to assess the relevance of LSN in preoperative assessment of operative risks for patients with resectable hepatocellular carcinoma (HCC). METHODS: All patients undergoing hepatectomy for HCC between 2012 and 2017 were analysed retrospectively. LSN was assessed at the liver-fat interface on the left liver lobe on preoperative CT images. The feasibility of LSN quantification was assessed. The association between LSN and outcomes (severe complications and posthepatectomy liver failure (PHLF)) was evaluated by multivariable analysis and after propensity score matching. RESULTS: Among 210 patients, LSN measurement was successful in 187 (89·0 per cent). Among these, the median LSN score was 2·42 (i.q.r. 2·21-2·66) and 52·9 per cent had severe fibrosis, including 33·7 per cent with cirrhosis. LSN score increased with hepatic venous pressure gradient (P = 0·048), severity of steatosis (P = 0·011) and fibrosis grade (P = 0·001). LSN score was independently associated with severe complications (odds ratio (OR) 5·25; P = 0·006) and PHLF (OR 6·78; P = 0·003). After matching with respect to model for end-stage liver disease, aspartate aminotransferase-to-platelet ratio index and fibrosis-4 score, patients with a LSN score of 2·63 or higher retained an increased risk of PHLF (OR 5·81; P = 0·018). In the subgroup of patients without severe fibrosis, LSN was accurate in predicting severe complications (P = 0·005). Patients with (P = 0·039) or without (P = 0·018) severe fibrosis with increased LSN score had a higher comprehensive complication index score. Among patients with cirrhosis who had clinically significant portal hypertension, a LSN value below 2·63 ruled out the risk of PHLF. CONCLUSION: LSN measurement represents a practical tool that may allow improvement in the preoperative evaluation and management of patients with HCC.

ANTECEDENTES: La cuantificación de la nodularidad de la superficie hepática (liver surface nodularity, LSN) en las imágenes de la tomografía computarizada (TC) de rutina preoperatoria permite detectar la cirrosis y la hipertensión portal clínicamente significativa (clinically significant portal hypertension, CSPH). Este estudio tuvo como objetivo evaluar la relevancia de la LSN en la evaluación preoperatoria del riesgo quirúrgico en pacientes con carcinoma hepatocelular resecable (hepatocellular carcinoma, HCC). MÉTODOS: Todos los pacientes sometidos a hepatectomía por HCC entre 2012 y 2017 fueron analizados de forma retrospectiva. La LSN se evaluó en la interfase hígado-grasa en el lóbulo hepático izquierdo en la TC preoperatoria. Se evaluó la viabilidad de la cuantificación de la LSN. La asociación entre la LSN y los resultados (complicaciones graves e insuficiencia hepática poshepatectomía (post-hepatectomy liver failure, PHLF) se analizó en un análisis multivariable y después del método de emparejamiento por puntaje de propensión. RESULTADOS: Del total de 210 pacientes, la medición de la LSN fue exitosa en 187 (89,0%). En estos pacientes, la mediana de LSN fue de 2,42 (rango intercuartílico 2,21-2,66) y el 53,0% tenía fibrosis severa, incluyendo un 33,7% con cirrosis. La LSN aumentó con el gradiente de presión venosa hepática (P = 0,048), la gravedad de la esteatosis (P = 0,011) y el grado de fibrosis (P = 0,001). La LSN se asoció de forma independiente con complicaciones graves (razón de oportunidades, odds ratio, OR = 5,25; P = 0,006) y PHLF (OR = 6,78; P = 0,003). Después de emparejar para el modelo de enfermedad hepática terminal, el índice de relación aspartato amino transferase-plaquetas y el grado de fibrosis-4, los pacientes con LSN ≥ 2,63 mantuvieron un mayor riesgo de PHLF (OR = 5,81; P = 0,018). Dentro del subgrupo de pacientes sin fibrosis severa, la LSN fue precisa en predecir complicaciones graves (P = 0,005). Los pacientes con (P = 0,039) y sin (P = 0,018) fibrosis severa con aumento de la LSN tuvieron un índice de complicación global más alto. De los pacientes cirróticos con CSPH, un valor de LSN de 2,63 descartó el riesgo de PHLF. CONCLUSIÓN: La LSN representa una herramienta práctica, que puede permitir mejorar la evaluación preoperatoria y el manejo de pacientes con HCC.

[Splanchnic vein thrombosis]. / Thromboses veineuses splanchniques.

Splanchnic vein thrombosis includes Budd-Chiari syndrome and portal vein thrombosis. These diseases share common features: (i) they are rare diseases and (ii) they can lead to portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, the most common being myeloproliferative neoplasms. A rapid and comprehensive workup for thrombosis risk factors is necessary in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis, and is associated with a worse course of cirrhosis. Indications for anticoagulation in patients with cirrhosis are increasing. Transjugular intrahepatic portosystemic shunt is a second-line procedure in this setting. Because of the rarity of these diseases, high-level evidence studies are rare. However, collaborative studies have provided a better understanding of their natural history and allowed to improve the management of these patients. This review focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, patients with portal vein thrombosis without underlying liver disease, and patients with cirrhosis and portal vein thrombosis.

Pregnancy in women with portal vein thrombosis: results of a multicentric European study on maternal and fetal management and outcome.

BACKGROUND & AIMS: Women of childbearing age account for approximately 25% of patients with non-cirrhotic portal vein thrombosis (PVT). We aimed at assessing maternal and fetal outcome in pregnant women with known PVT. METHODS: We performed a retrospective analysis of the files of women with chronic PVT in three European referral centers between 1986 and 2010. RESULTS: Forty-five pregnancies, 28 (62%) treated with low molecular weight heparin, occurred in 24 women. Nine (20%) were lost before gestation week 20. Preterm birth occurred in 38% of deliveries: there were 3 births at week 24-25, 7 at week 32-36, and 26 after week 37. A term birth with a healthy infant occurred in 58% of pregnancies. Cesarean section was used in 53% of deliveries. Two women developed HELLP syndrome. A favorable outcome happened in 64% of pregnancies. Pregnancies with an unfavorable outcome were associated with a higher platelet count at diagnosis. Bleeding from esophageal varices occurred in 3 patients during pregnancy, all without adequate primary prophylaxis. Genital or parietal bleeding occurred postpartum in 4 patients, only one being on anticoagulation therapy. Thrombotic events occurred in 2 patients, none related to lower limbs or mesenteric veins. There were no maternal deaths. CONCLUSIONS: In pregnant PVT patients treated with anticoagulation on an individual basis, the rate of miscarriage and preterm birth appears to be increased. However, fetal and maternal outcomes are favorable for most pregnancies reaching gestation week 20. High platelet counts appear to increase the risk for unfavorable outcome. Pregnancy should not be contraindicated in stable PVT patients.

Hepatocellular carcinoma in Budd-Chiari syndrome: characteristics and risk factors.

BACKGROUND AND AIMS: To analyse the characteristics of and the factors associated with the development of hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). PATIENTS AND METHODS: 97 consecutive patients with BCS and a follow-up > or = 1 year were evaluated retrospectively. Liver nodules were evaluated using serum alpha-fetoprotein (AFP) level and imaging features (CT/MRI). Biopsy of nodules was obtained when one of the following criteria was met: number < or = 3, diameter > or = 3 cm, heterogeneity, washout on portal venous phase, increase in size on surveillance, or increase in AFP level. RESULTS: Patients were mainly Caucasian (69%) and female (66%). Mean age at the diagnosis of BCS was 35.8 (SE 1.2 years), and median follow-up 5 years (1-20 years). The inferior vena cava (IVC) was obstructed in 13 patients. Liver nodules were found in 43 patients, 11 of whom had HCC. Cumulative incidence of HCC during follow-up was 4%. Liver parenchyma adjacent to HCC showed cirrhosis in nine patients. HCC was associated with male sex (72.7% v 29.0%, p = 0.007); factor V Leiden (54.5% v 17.5%, p = 0.01); and IVC obstruction (81.8% v 4.6%, p < 0.001). Increased levels of serum AFP were highly accurate in distinguishing HCC from benign nodules: PPV = 100% and NPV = 91% for a cut-off level of 15 ng/ml. CONCLUSION: The incidence of HCC in this large cohort of BCS patients was similar to that reported for other chronic liver diseases. IVC obstruction was a major predictor for HCC development. Serum AFP appears to have a higher utility for HCC screening in patients with BCS than with other liver diseases.

Non-invasive evaluation of portal hypertension using shear-wave elastography: analysis of two algorithms combining liver and spleen stiffness in 191 patients with cirrhosis.

BACKGROUND: Two algorithms based on sequential measurements of liver and spleen stiffness using two-dimensional shearwave elastography (2D-SWE) have been recently proposed to estimate clinically significant portal hypertension (hepatic venous pressure gradient [HVPG] ≥10 mm Hg) in patients with cirrhosis, with excellent diagnostic accuracy. AIM: To validate externally these algorithms in a large cohort of patients with cirrhosis. METHODS: One hundred and ninety-one patients with stable cirrhosis (Child-Pugh class A 39%, B 29% and C 31%) who underwent liver and spleen stiffness measurements using 2D-SWE at the time of HVPG measurement were included. Diagnostic accuracy of the 2 algorithms was assessed by calculating sensitivity, specificity, positive and negative predictive values. RESULTS: The first algorithm, using liver stiffness <16.0 kilopascals (kPa) and then spleen stiffness <26.6 kPa, was used to rule-out HVPG ≥10 mm Hg. In our population, its sensitivity and negative predictive value were 95% and 63% respectively. The second algorithm, using liver stiffness >38.0 kPa, or liver stiffness ≤38.0 kPa but spleen stiffness >27.9 kPa, was used to rule-in HVPG ≥10 mm Hg. In our population, its specificity and positive predictive value were 52% and 83% respectively. Restricting the analyses to the 74 patients without any history of decompensation of cirrhosis or to the 65 patients with highly reliable liver stiffness measurement did not improve the results. CONCLUSION: In our population, diagnostic accuracies of non-invasive algorithms based on sequential measurements of liver and spleen stiffness using 2D-SWE were acceptable, but not good enough to replace HVPG measurement or to base clinical decisions.

Microvesicles in hepatic and peripheral vein can predict nonresponse to corticosteroid therapy in severe alcoholic hepatitis.

BACKGROUND: Severe alcoholic hepatitis patients have high mortality and limited response to corticosteroids. Microvesicles reflect cellular stress and disease conditions. AIMS: To investigate whether microvesicles are associated with severity, response to steroid therapy and inflammation in severe alcoholic hepatitis. METHODS: Microvesicles originating from different cells were studied pre-therapy in 101 patients; (71 responder to corticosteroid therapy and 30 nonresponders) and 20 healthy controls. Microvesicles and cells were determined in peripheral and hepatic vein samples using flow cytometry and correlated with outcomes. Inflammatory signalling pathways and functional alterations of immune cells after stimulation with microvesicles were also investigated. RESULTS: Microvesicles mean levels were higher in nonresponders for T cells (CD3+ CD4+ ; 10.1 MV/µL vs 5.4; P = 0.06), macrophages (CD68+ CD11b+ ; 136.5 vs 121.9 MV/µL; P = 0.01), haematopoietic stem-cells (CD45+ CD34+ ; 116.8 vs 13.4 MV/µL; P = 0.0001) and hepatocytes (ASGPR+ ; 470 vs 361 MV/µL; P = 0.01); the latter two predicting steroid nonresponse in 94% patients at baseline in peripheral plasma. Microvesicle levels correlated with histological and liver disease severity indices. Whereas, in non-responders hepatic vein CD34+ cells were lower (P = 0.02), the CD34+ microvesicles there from were higher (P = 0.04), thus suggesting impaired regeneration. Also, microvesicles of 0.2-0.4 µm size were higher in nonresponders (P < 0.03) at baseline. Microvesicles from patients trigger more (P = 0.04) ROS generation, TNF-α production (P = 0.04) and up-regulate pro-inflammatory cytokine related genes in neutrophils in vitro. CONCLUSIONS: Pre-therapy peripheral plasma levels of CD34+ and ASGPR+ microvesicles are reliable non-invasive markers of steroid nonresponse and mortality in patients with severe alcoholic hepatitis.

Lack of clinical or haemodynamic rebound after abrupt interruption of beta-blockers in patients with cirrhosis.

BACKGROUND: Beta-blockers may have to be interrupted in patients with cirrhosis. The concept of a rebound after interruption of beta-blockers is based on an animal study and on isolated case reports of variceal bleeding. AIM: To determine if a rebound occurs in patients with cirrhosis following abrupt interruption of beta-blockers. METHODS: We prospectively included all consecutive patients with cirrhosis undergoing right heart and hepatic vein catheterisation. Four groups were defined: 'no beta-blockers' including patients not receiving beta-blockers; '≤1 day', '2-3 days' and '≥4 days' classified according to the time patients had interrupted beta-blockers before catheterisation. Results were expressed as median (interquartile range). RESULTS: A total of 150 patients were included. Among the 25 patients in the groups '2-3 days' and '≥4 days', median duration of beta-blockers interruption was 4 (3-6) days. No gastrointestinal bleeding occurred during that period, nor during the following month. Hepatic venous pressure gradient was not different among patients in usually treated with beta-blockers. After adjustment, beta-blockers interruption was not associated with hepatic venous pressure gradient. Cardiac index was higher in the '≥4 days' group [4.6 L/min/m(2) (3.5-5.1)] than in the '≤1 day' group [3.4 (2.6-4.0); P = 0.001] or in the '2-3 days' group [3.1 (2.7-3.7); P = 0.007], but not different from the 'no beta-blockers' group. CONCLUSIONS: Abrupt interruption of beta-blockers is associated neither with an apparent increase in the risk of variceal bleeding nor with a haemodynamic rebound. Thus, interruption of beta-blockers in patients with cirrhosis may not require particular dosing or surveillance.

[Diagnosis of spontaneous ascites infection in patients with cirrhosis: reagent strips]. / Diagnostic des infections spontanées du liquide d'ascite chez le cirrhotique par bandelette urinaire.

AIM: To evaluate the sensitivity, specificity, and predictive values of dipstick testing (DT) for detecting spontaneous bacterial peritonitis (SBP), defined by an ascites neutrophil polymorphonuclear cell count > or = 250/mm3, in patients with cirrhosis. METHODS: The study includes all patients with cirrhosis and ascites admitted to our general hospital on the southern outskirts of the Paris metropolitan area (France) from June 2003 to May 2004 (n = 47:27 men and 20 women). Diagnostic abdominal paracentesis was performed on admission, and a Multistix SG (Bayer Pharma) reagent strip was immersed in one ascitic sample from each patient. Readings after 120 s were either negative (DT-) or positive (DT+, with 4 levels of positivity: trace, +, ++, or +++). In case of cytologically-proven SBP, patients were treated with cefotaxime, and subsequent paracentesis with DT and cytologic testing took place every 48 hours, until recovery. RESULTS: Six of the 47 patients had proven SBP, all with clinical signs of SBP (fever and/or abdominal pain); five of these patients were DT+ and one was DT-. In the five patients initially DT+, the DT became negative at the same time as the cytologic criteria for SBP disappeared. Forty-one patients did not meet the cytologic criteria for SBP: 34 were DT- and 7 were DT+ (traces: 4, ++: 2, +++:1); two of these had clinical signs suggestive of SBP. CONCLUSION: Although the sensitivity (83%), specificity (83%) and negative predictive value (97%) of DTwere satisfactory, its positive predictive value (42%) was low. Dipstick testing of ascitic fluid is easy to perform and inexpensive and may be recommended for diagnosis and follow-up of SBP, especially in emergency settings.

Chronic hepatitis C: viral clearance several months after discontinuation of therapy in two non-responders.

When hepatitis C virus (HCV) infection becomes chronic, spontaneous viral eradication is a rare event. We report two patients with chronic hepatitis C, non-responders to standard interferon alone. They were treated with Pegylated interferon plus ribavirin. At the end of therapy, HCV RNA was still detectable. Several months after stopping treatment, aminotransferase level normalized and HCV RNA became undetectable. No case of sustained viral response happening several months after therapy has been yet described. During long-term follow-up of non-responders, when a persistent normalization of aminotransferase level is observed after stopping treatment, viral clearance could be suspected.