Visceral fat and clinical outcome in patients receiving first-line chemotherapy with bevacizumab for metastatic colorectal cancer.

BACKGROUND: Visceral fat produces angiogenic factors such as vascular endothelial growth factor that promote tumoral growth. However, its influence on outcome for patients with advanced cancer treated with anti-angiogenic agents is controversial. AIMS: The aim of this study was to determine whether visceral fat volume, visceral fat area and body mass index are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic colorectal cancer. METHODS: This multicenter prospective study included 103 patients with metastatic colorectal cancer who received first-line bevacizumab-based chemotherapy. Computed tomography was used to measure visceral fat volume and visceral fat area. Endpoints were tumoral response at 2 months, progression free survival and overall survival. RESULTS: Visceral fat volume and visceral fat area, but not body mass index, were significantly associated with better outcome. Using sex-specific median values progression free survival was significantly longer in patients with high visceral fat volume (13.2 versus 9.4 months; p = 0.0043). In the same way, high visceral fat volume and visceral fat area were associated with a significantly better overall survival: 31.3 versus 20.5 months (p = 0.0072) and 29.3 versus 20.5 months (p = 0.0078), respectively. By multivariate analysis, visceral fat volume was associated with longer progression free survival and overall survival. CONCLUSION: This study demonstrates that a high visceral fat volume is associated with better outcome in patients receiving first-line bevacizumab-based chemotherapy for metastatic colorectal cancer.

Vibration-controlled transient elastography for noninvasive evaluation of liver steatosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) refers to a large spectrum of liver disorders and is the most common cause of metabolic liver disease. The current gold standard for diagnosing NAFLD is liver biopsy, which can lead to severe complications. PURPOSE: Among the noninvasive diagnostic options, we chose to use a FibroScan and developed an algorithm applying the Voigt rheological model to assess the viscoelastic properties of the liver and evaluate its performance for the diagnosis of steatosis. METHODS: Twenty-two healthy volunteers and 20 patients with steatosis were included. For each subject, we used a modified FibroScan, whose data had been processed by our algorithm to separate the two viscoelastic components, stiffness µ, and viscosity η. The liver elasticity µFibroscan measured by the FibroScan was also recorded. Mann-Whitney tests and receiver operating characteristics (ROCs) curve analyses were performed to compare the parameters between the two groups, and Pearson's correlation coefficients were used to assess the correlations between the parameters. RESULTS: We found a good correlation between η and µFibroscan (r = 0.75), and poor correlations between µ and both η and µFibroscan (r = 0.33 and r = 0.03, respectively). We also showed that η and µFibroscan were higher in patients with steatosis compared to healthy volunteers, with area under the ROCs (AUROC) curve at 0.814 and 0.891, respectively. Conversely, µ was not different between the two groups (AUROC = 0.557). CONCLUSIONS: Our novel method successfully separated the two viscoelastic properties of the liver, of which the parameter η is a sensitive indicator for steatosis.

Development of a New Index to Assess Small Bowel Inflammation Severity in Crohn's Disease Using Magnetic Resonance Enterography.

Background: The severity of small bowel (SB) inflammation in Crohn's disease (CD) patients is a key component of the therapeutic choice. We aimed to develop a SB-CD Magnetic Resonance Enterography (MRE) index of Inflammation Severity (CDMRIS). Methods: Each gastroenterologist/radiologist pair in 13 centers selected MREs from 6 patients with SB-CD stratified on their perceived MRE inflammation severity. The 78 blinded MREs were allocated through balanced incomplete block design per severity stratum to these 13 pairs for rating the presence/severity of 13 preselected items for each SB 20-cm diseased segment. Global inflammation severity was evaluated using a 100-cm visual analog scale. Reproducibility of recorded items was evaluated. The CDMRIS was determined through linear mixed modeling as a combination of the numbers of segments with lesions highly correlated to global inflammation severity. Results: Four hundred and forty-two readings were available. Global inflammation severity mean ± SD was 21.0 ± 16.2. The independent predictors explaining 54% of the global inflammation severity variance were the numbers of segments with T1 mild-moderate and severe intensity of enhancement, deep ulceration without fistula, comb sign, fistula, and abscess. Unbiased correlation between CDMRIS and global inflammation severity was 0.76. Conclusions: The CDMRIS is now available to evaluate the severity of SB-CD inflammation. External validation and sensitivity-to-change are mandatory next steps.

Natural history of liver adenomatosis: A long-term observational study.

BACKGROUND & AIMS: Liver adenomatosis (LA) is characterized by the presence of at least 10 hepatocellular adenomas (HCAs), but the natural history of this rare liver disorder remains unclear. Thus, we aimed to reappraise the natural history and the risk of complications in a cohort of patients with at least 10 HCAs. METHODS: We analyzed the natural history of 40 patients with LA, excluding glycogen storage disorders, in a monocentric cohort. Pathological examination was performed, with immunostaining and molecular biology carried out on surgical specimens or liver biopsies. RESULTS: Forty patients (36 female) were included with a median follow-up of 10.6 (1.9-26.1) years. Six (15%) patients had familial LA, all with germline HNF1A mutations. Median age at diagnosis was 39 (9-55) years. Thirty-three (94%) women had a history of oral contraception, and 29 (81%) women had a pregnancy before LA diagnosis. Overall, thirty-seven (93%) patients underwent surgery at diagnosis. Classification of HCAs showed 46% of patients with HNF1A-mutated HCA, 31% with inflammatory HCA, 3% with sonic hedgehog HCA, 8% with unclassified HCA. Only 15% of the patients demonstrated a "mixed LA" with different HCA subtypes. Hepatic complications were identified in 7 patients: 1 patient (3%) died from recurrent hepatocellular carcinoma after liver transplantation; 6 (15%) had hemorrhages, of which 5 occurred at diagnosis, with 1 fatal case during pregnancy, and 2 occurred in male patients with familial LA. Four patients (10%) had repeated liver resections. Finally, 4 (10%) patients developed extrahepatic malignancies during follow-up. CONCLUSIONS: The diversity in HCA subtypes, as well as the occurrence of bleeding and malignant transformation during long-term follow-up, underline the heterogeneous nature of LA, justifying close and specific management. In patients with germline HNF1A mutation, familial LA occurred equally frequently in males and females, with a higher rate of bleeding in male patients. LAY SUMMARY: Liver adenomatosis is a rare disease characterized by the presence of 10 or more hepatocellular adenomas that may rarely be of genetic origin. Patients with liver adenomatosis have multiple adenomas of different subtypes, with a risk of bleeding and malignant transformation that justify a specific management and follow-up.

Acute fatty liver of pregnancy simulating liver tumor.

Acute fatty liver of pregnancy (AFLP) is a rare liver disease unique to pregnancy that can lead to acute liver failure. Clinicians must have a high index of suspicion for AFLP because only early diagnosis and prompt delivery improve maternal and fetal prognosis.

Severe chronic hepatitis secondary to prolonged use of ecstasy and cocaine.

BACKGROUND AND AIMS: Severe acute hepatotoxicity is a well known complication following the ingestion of ecstasy (3,4-methylenedioxymethamphetamine [MDMA] ecstasy). Hepatic dysfunction has also been reported after acute cocaine intoxication. However, chronic hepatitis after prolonged use of ecstasy and/or cocaine has rarely been reported. METHODS: We report the case of a 27-year-old woman hospitalized with edema, ascites and severe liver failure (prothrombin rate 33%), following the use of ecstasy and cocaine over the previous 9 months. Clinical, biological, radiological and pathology findings were recorded at admission and over 8 years' follow-up. RESULTS: Liver biopsy showed architectural distortion caused by bridging fibrosis, proliferation of cholangioles, and lesions of active interface hepatitis. Other causes of acute and chronic liver disease were excluded. Magnetic resonance imaging showed marked liver fibrosis. After withdrawal of both substances clinical examination and liver function tests progressively normalized. Long-term monitoring with magnetic resonance imaging showed progressive regression of fibrosis. CONCLUSION: Use of ecstasy and cocaine may cause chronic hepatitis leading to marked liver fibrosis, which may regress after withdrawal of both substances.

[Recurrent acute fatty liver of pregnancy]. / Stéatose hépatique aiguë gravidique récidivante.

Acute fatty liver of pregnancy (AFLP) is a rare liver disease unique to pregnancy potentially fatal for both mother and child. Only a few cases of recurrence have been published. We report a new case. A 27-year-old primiparous patient presented a first episode of AFLP in 1991 at 37 week's gestation. Diagnosis was suspected because of vomiting, thrombocytopenia, and liver function tests abnormalities. It was confirmed by liver ultrasonography and abdominal computed tomography. Clinical and biological improvement was observed after caesarean delivery. Six years later, the woman began a second pregnancy. Liver function tests and complete blood count were regularly checked. At 30 weeks' gestation, recurrent AFLP occurred and caesarean section was performed. Again, diagnosis was confirmed by both ultrasonography and abdominal computed tomography. In 2006, the mother and the two girls, 15 and 8-year-old respectively, were in good health. The study of the HADHA gene, coding alpha subunit long chain 3-hydroxyacyl coenzyme A dehydrogenase (LCHAD) in the patient failed to find mutations, particularly the common mutation c.1528G>C (Glu474-Gln, p.E474Q). In conclusion, after an episode of AFLP, women should be clearly warned of the risk of recurrence and regularly monitored during the next pregnancy, even if the search of HADHA gene mutation is negative.

[Paroxysmal nocturnal hemoglobinuria revealed by hepatic vein thrombosis (Budd-Chiari syndrome) during Infliximab therapy]. / Thrombose des veines hépatiques au cours d'un traitement par infliximab (Remicade) révélant une hémoglobinurie paroxystique nocturne.

We report the case of a 41-Year-old man presenting with hepatic vein thrombosis (Budd-Chiari syndrome) during Infliximab therapy for ankylosing spondylitis. The systematic work-up revealed paroxysmal nocturnal hemoglobinuria. One Year later the patient was receiving anticoagulation therapy and was in good condition. The role of Infliximab in the development of thrombosis in this patient with rare underlying thrombophilia is discussed.

Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.

BACKGROUND & AIMS: Germline mutations in hepatocyte nuclear factor 1alpha (TCF1/HNF-1alpha) are associated with maturity-onset diabetes of the young type 3 (MODY3), and somatic biallelic inactivations of the gene are found in hepatocellular adenomas and liver adenomatosis. This study investigated cosegregation of HNF-1alpha germline mutations with diabetes and liver adenomatosis in 2 families. METHODS: Two unrelated patients with liver adenomatosis and harboring HNF-1alpha germline and somatic mutations were studied. Subsequently, we screened 9 relatives in the 2 independent families for diabetes, hepatocellular adenomas, and HNF-1alpha germline mutations. RESULTS: In family A, a father and his son presented with an intraperitoneal hemorrhagic rupture of a liver adenomatosis without diabetes. A heterozygous R229X germline mutation was identified in HNF-1alpha in the father and his son and also in his second 27-year-old son without hepatocellular adenomas. In family B, a diagnosis of liver adenomatosis was made fortuitously in a 14-year-old girl. A heterozygous G55fsX57 germline mutation in HNF-1alpha was identified in this patient, her diabetic father, and her 2 sisters. Systematic exploration showed liver adenomatosis in the 2 sisters. Somatic inactivation of the second HNF-1alpha allele was found in liver tumors in both families. CONCLUSIONS: This study describes familial liver adenomatosis and shows the association with germline HNF-1alpha mutations in adults and children. It also highlights the importance of screening for hepatocellular adenomas, diabetes, and HNF-1alpha germline mutations in relatives of patients with liver adenomatosis. Finally, prevalence of liver adenomatosis remains to be evaluated in MODY3 subjects.