Systematic screening for advanced liver fibrosis in patients with coronary artery disease: The CORONASH study.

Although coronary artery disease (CAD) and advanced liver fibrosis (AdLF) are commonly associated in patients with non-alcoholic fatty liver disease (NAFLD), the prevalence of AdLF and the diagnostic performance of non-invasive fibrosis tests (NITs) in CAD patients remains unknown. We aimed to prospectively screen for AdLF in patients with documented CAD using NITs and Fibroscan. High and intermediate zones of NITs were combined to define AdLF. AdLF was suspected whenever APRI ≥ 0.5, Forns index ≥ 4.2, NAFLD fibrosis score (NFS) ≥ -1.455/0.12 for age

Multicenter study on recent portal venous system thrombosis associated with cytomegalovirus disease.

BACKGROUND & AIMS: Recent non-malignant non-cirrhotic portal venous system thrombosis (PVT) is a rare condition. Among risk factors for PVT, cytomegalovirus (CMV) disease is usually listed based on a small number of reported cases. The aim of this study was to determine the characteristics and outcomes of PVT associated with CMV disease. METHODS: We conducted a French multicenter retrospective study comparing patients with recent PVT and CMV disease ("CMV positive"; n = 23) to patients with recent PVT for whom CMV testing was negative ("CMV negative"; n = 53) or unavailable ("CMV unknown"; n = 297). RESULTS: Compared to patients from the "CMV negative" and "CMV unknown" groups, patients from the "CMV positive" group were younger, more frequently had fever, and had higher heart rate, lymphocyte count and serum ALT levels (p ≤0.01 for all). The prevalence of immunosuppression did not differ between the 3 groups (4%, 4% and 6%, respectively). Extension of PVT was similar between the 3 groups. Thirteen out of 23 "CMV positive" patients had another risk factor for thrombosis. Besides CMV disease, the number of risk factors for thrombosis was similar between the 3 groups. Heterozygosity for the prothrombin G20210A gene variant was more frequent in "CMV positive" patients (22%) than in the "CMV negative" (4%, p = 0.01) and "CMV unknown" (8%, p = 0.03) groups. Recanalization rate was not influenced by CMV status. CONCLUSIONS: In patients with recent PVT, features of mononucleosis syndrome should raise suspicion of CMV disease. CMV disease does not influence thrombosis extension nor recanalization. More than half of "CMV positive" patients have another risk factor for thrombosis, with a particular link to the prothrombin G20210A gene variant. LAY SUMMARY: Patients with cytomegalovirus (CMV)-associated portal venous system thrombosis have similar thrombosis extension and evolution as patients without CMV disease. However, patients with CMV-associated portal venous system thrombosis more frequently have the prothrombin G20210A gene variant, suggesting that these entities act synergistically to promote thrombosis.

A pragmatic non-invasive assessment of liver fibrosis in patients with psoriasis, rheumatoid arthritis or Crohn's disease receiving methotrexate therapy.

BACKGROUND AND AIMS: The reported hepatotoxicity of methotrexate underlines the need for a repeated non-invasive and reliable evaluation of liver fibrosis. We estimated, using a non-invasive strategy, the prevalence of significant liver fibrosis in patients treated by methotrexate and the predictors of significant fibrosis (fibrosis≥F2). METHODS: Fibrosis was prospectively evaluated using 9 non-invasive tests in consecutive patients with psoriasis, rheumatoid arthritis, or Crohn's disease. Significant fibrosis was assessed without liver biopsy by defining a "specific method" (result given by the majority of the tests) and a "sensitive method" (at least one test indicating a stage≥F2). RESULTS: One hundred and thirty-one patients (66 Psoriasis, 40 rheumatoid arthritis, and 25 Crohn's disease) were enrolled, including 83 receiving methotrexate. Seven tests were performed on average per patient, with a complete concordance in 75% of cases. Fibroscan® was interpretable in only 61% of patients. The best performances (AUROC>0.9) for predicting significant fibrosis were obtained by tests dedicated to steatohepatitis (FibroMeter NAFLD, NFS and FPI). The prevalence of fibrosis≥F2 according to the "specific" or the "sensitive" assessment of fibrosis was 10% and 28%, respectively. Methotrexate exposure did not influence the fibrosis stage. Factors independently associated with significant fibrosis according our "sensitive method" were age, male gender, and metabolic syndrome. CONCLUSION: We provided a non-invasive approach for identifying liver fibrosis≥F2 by using 8 biochemical tests and Fibroscan®. In this population, the risk of significant fibrosis was related to age, male gender, and presence of metabolic syndrome, but was not influenced by methotrexate.

The epidemiology of Budd-Chiari syndrome in France.

INTRODUCTION: Epidemiological data is lacking on primary Budd-Chiari syndrome (BCS) in France. METHODS: Two approaches were used: (1) A nationwide survey in specialized liver units for French adults. (2) A query of the French database of discharge diagnoses screening to identify incident cases in adults. BCS associated with cancer, alcoholic/viral cirrhosis, or occurring after liver transplantation were classified as secondary. RESULTS: Approach (1) 178 primary BCS were identified (prevalence 4.04 per million inhabitants (pmi)), of which 30 were incident (incidence 0.68 pmi). Mean age was 40 ±â€¯14 yrs. Risk factors included myeloproliferative neoplasms (MPN) (48%), oral contraceptives (35%) and factor V Leiden (16%). None were identified in 21% of patients, ≥2 risk factors in 25%. BMI was higher in the group without any risk factor (25.7 kg/m2 vs 23.7 kg/m2, p < 0.001). Approach (2) 110 incident primary BCS were admitted to French hospitals (incidence 2.17 pmi). MPN was less common (30%) and inflammatory local factors predominated (39%). CONCLUSION: The entity of primary BCS as recorded in French liver units is 3 times less common than the entity recorded as nonmalignant hepatic vein obstruction in the hospital discharge database. The former entity is mostly related to MPN whereas the latter with abdominal inflammatory diseases.

Role of the transjugular intrahepatic portosystemic shunt in the management of severe complications of portal hypertension in idiopathic noncirrhotic portal hypertension.

UNLABELLED: Idiopathic noncirrhotic portal hypertension is a heterogeneous group of diseases characterized by portal hypertension in the absence of cirrhosis. The efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in this population are unknown. The charts of patients with idiopathic noncirrhotic portal hypertension undergoing TIPS in seven centers between 2000 and 2014 were retrospectively reviewed. Forty-one patients were included. Indications for TIPS were recurrent variceal bleeding (n = 25) and refractory ascites (n = 16). Patients were categorized according to the presence (n = 27) or absence (n = 14) of significant extrahepatic comorbidities. Associated conditions were hematologic, prothrombotic, neoplastic, immune, and exposure to toxins. During follow-up (mean 27 ± 29 months), variceal rebleeding occurred in 7/25 (28%), including three with early thrombosis of the stent. Post-TIPS overt hepatic encephalopathy was present in 14 patients (34%). Eleven patients died, five due the liver disease or complications of the procedure and six because of the associated comorbidities. The procedure was complicated by hemoperitoneum in four patients (10%), which was fatal in one case. Serum creatinine (P = 0.005), ascites as indication for TIPS (P = 0.04), and the presence of significant comorbidities (P = 0.01) at the time of the procedure were associated with death. Mortality was higher in patients with significant comorbidities and creatinine ≥100 µmol/L (P < 0.001). CONCLUSION: In patients with idiopathic noncirrhotic portal hypertension who have normal kidney function or do not have severe extrahepatic conditions, TIPS is an excellent option to treat severe complications of portal hypertension. (Hepatology 2016;64:224-231).

Prognostic value of C-reactive protein levels in patients with cirrhosis.

I dentifying cirrhosis with a poor short-term prognosis remains crucial for improving the allocation of liver grafts. The purpose of this study was to assess the prognostic value of a model combining the variation of C-reactive protein (CRP) levels within 15 days, the Model for End-Stage Liver Disease (MELD) score, and the presence of comorbidities in patients with decompensated cirrhosis with a Child-Pugh score > B7 and to test the relevance of this model in patients with compensated cirrhosis. We collected data for cirrhotic patients without hepatocellular carcinoma, extrahepatic malignancy, human immunodeficiency virus infection, organ transplantation, seen between January 2010 and December 2011. Multivariate analyses of predictors of 3-month mortality used Cox models adjusted with the age-adjusted Charlson comorbidity index. The prognostic performance [area under receiver operating characteristic curves (AUROCs)] of the 3-variable model was compared to that of the MELD score. The 241 patients who met the inclusion criteria included 109 patients with a Child-Pugh score > B7 who were hospitalized for decompensation. In these patients with severe cases, the 3-month mortality was independently predicted by the MELD score [hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.05-1.14; P < 0.001] and a CRP level > 32 mg/L at the baseline and on day 15 (HR, 2.21; 95% CI, 1.03-4.76; P = 0.042). This model was better than MELD alone (AUROC, 0.789 versus 0.734; P = 0.043). In the whole population with cirrhosis, the 3-month mortality was also predicted by high MELD scores (HR, 1.11; 95% CI, 1.07-1.16; P < 0.001) and a CRP level > 10 mg/L at the baseline and on day 15 (HR, 2.89; 95% CI, 1.29-6.48; P < 0.001), but the AUROCs of the 3-variable model and the MELD score alone were no longer significantly different (0.89 versus 0.88, not significant). In conclusion, prognostic models incorporating variations in CRP predict 3-month mortality in patients with cirrhosis. Such models are particularly relevant for patients with decompensated cirrhosis but provide a limited increase in prediction in comparison with the MELD score in the whole population with cirrhosis.

C-reactive protein predicts short-term mortality in patients with cirrhosis.

BACKGROUND & AIMS: We aimed at improving prediction of short-term mortality in cirrhotic inpatients by evaluating C-reactive protein (CRP) as a surrogate marker of systemic inflammatory response syndrome (SIRS). METHODS: One-hundred and forty-eight consecutive cirrhotic patients with Child-Pugh score ≥ B8 and without hepatocellular carcinoma were prospectively included and followed for 182 days. The primary end point was 6-month survival. RESULTS: Main baseline characteristics were as follows: alcoholic liver disease in 88.5%; bacterial infection in 37%; hepatorenal syndrome in 7% of cases. CRP range was 1-240 mg/L (median 26 mg/L); 42 patients (28.4%) had SIRS as defined by ACCP/SCCM-criteria. CRP levels were higher in patients with SIRS (50 vs. 21 mg/L; p<0.0001), infection (46 vs. 27 mg/L; p<0.0001), and alcoholic hepatitis (44 vs. 32 mg/L, p=0.049). Forty-two patients died within the first 6 months of follow-up. Short-term mortality was associated with extrahepatic co-morbidities (p=0.002), high MELD score (p<0.001; AUROC=0.67), renal failure (p=0.008), elevated blood lactates (p<0.001), and high baseline CRP levels (p=0.003; AUROC=0.63; best cut-off value at 29 mg/L). Among patients with baseline CRP ≥ 29 mg/L, 32 still had CRP ≥ 29 mg/L at day 15 (group A). Group A was associated with 6-month mortality in the overall population (p<0.001) and also through sensitivity analyses restricted to patients without infection or alcoholic hepatitis. Multivariate analysis (Cox) adjusted for age identified three predictors of mortality: high MELD score (HR=1.08; 95% CI: 1.03-1.12; p<0.001), extrahepatic co-morbidities (HR=2.51; 95% CI: 1.31-4.84; p=0.006), and CRP level (group A) (HR=2.73; 95% CI: 1.41-5.26; p=0.003). The performance of the three variables taken together for predicting death was 0.80 (AUROC). CONCLUSIONS: In Child-Pugh score ≥ B8 cirrhotic patients, persistent CRP levels ≥ 29 mg/L predicted short-term mortality independently of age, MELD, and co-morbidities, and better than infection or clinically-assessed SIRS.