Violaine Ozenne

Accuracy and disagreement of computed tomography and magnetic resonance imaging for the diagnosis of small hepatocellular carcinoma and dysplastic nodules: Role of biopsy

Liver macronodules, ranging from benign to low‐grade or high‐grade dysplastic nodules (LGDNs/HGDNs) and hepatocellular carcinoma (HCC), may develop during chronic liver diseases (CLDs). Current guidelines were recently updated and the noninvasive criteria for the diagnosis of small HCC are based on a single typical radiological pattern and nonconclusive coincidental findings with two techniques. This study aimed to assess the accuracy and disagreements of noninvasive multiphasic examinations for the diagnosis of HCC and dysplastic nodules (DNs) and the role of biopsy. Seventy‐four consecutive patients with CLD with ultrasound‐detected 1‐2‐cm nodules underwent, within 1 month, multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and biopsy of the nodule. Median age was 60 years; 33 patients (45%) had hepatitis C virus, 20 (27%) had hepatitis B virus, and 13 (18%) patients had no cirrhosis. Biopsy revealed 47 HCCs, 6 HGDNs, 1 LGDNs, 1 cholangiocarcinoma, and 1 epithelioid hemangioendothelioma. There were no tumors in the other 18 patients. All patients (31 of 31; 100%) who had conclusive coincidental findings (i.e., arterial enhancement and washout) on both examinations had HCC or HGDN (sensitivity, 57%; specificity, 100%). All patients (51 of 51; 100%) who had conclusive findings on at least one of the two examinations had HCC or HGDN (sensitivity, 96%; specificity, 100%). There was a disagreement regarding imaging findings between CT and MRI in 21 of 74 (28%) patients and no washout on both examinations in 23 of 74 patients (31%). In these 44 patients, liver biopsy provided an initial accurate diagnosis. Conclusion: The noninvasive diagnosis of HCC or HGDN can be obtained if arterial enhancement and washout are found in a single dynamic imaging examination. These findings are frequently discordant on both CT and MRI, supporting the place of biopsy for the diagnosis of small HCCs. (HEPATOLOGY 2011)

Tolerance and outcome of patients with unresectable hepatocellular carcinoma treated with sorafenib.

Background Sorafenib is the standard treatment for patients with an advanced stage of hepatocellular carcinoma (HCC). The aims of this study were (i) to evaluate the tolerance and survival of sorafenib-treated patients, in a nonselected population, especially in Child–Pugh B patients; and (ii) to identify potential prognostic factors of survival. Patients and methods From April 2007 to December 2008, 50 patients received sorafenib for advanced HCC. Seventeen (34%) were Child–Pugh B patients. We recorded adverse events and the duration of treatment and survival. For 34 patients with histopathologically proven HCC, immunophenotypical analysis was carried out using antibodies against cluster differentiation 34, vascular endothelial growth factor, phosphorylated ERK, cytokeratin 19, and phosphorylated stat3. Results Patients with Child–Pugh B cirrhosis had a more advanced stage of the disease compared with Child–Pugh A patients. The occurrence of adverse events was similar in Child–Pugh A and Child–Pugh B patients. Duration of treatment until discontinuation for bad tolerance was lower in Child–Pugh B patients (1.8 vs. 5 months, P=0.02). Survival of Child–Pugh A patients was higher compared with Child–Pugh B patients (8.9 vs. 2 months, P=0.004). Barcelona Clinic Liver Cancer stage, Eastern Cooperative Oncology Group Performance Status, portal vein impairment, extra-hepatic spread, and α-foetoprotein were also prognostic factors. In multivariate analysis, the sole factor associated with survival was the Barcelona Clinic Liver Cancer stage. None of the immunohistological markers used was associated with tolerance and survival. Conclusion Occurrence of adverse events is similar in Child–Pugh A and Child–Pugh B patients. Nevertheless, the survival of Child–Pugh B patients is very low. Whether liver function or tumor spread is responsible for mortality is unclear. Opportunity of treatment for Child–Pugh B patients is questionable. The immunophenotype of tumoral tissue was not predictive of survival.

Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial

BACKGROUND & AIMS Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial. METHODS A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate. RESULTS Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (p<0.0001), pneumonia (p=0.0041), hyponatremia (p=0.031) and occurrence of renal failure (p<0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion. CONCLUSIONS In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.

Transarterial chemoembolisation: effect of selectivity on tolerance, tumour response and survival

AimsTo compare selective and non-selective TACE techniques in the treatment of HCC with a special emphasis on clinical and liver tolerance, tumour response and survival.Methods184 patients with advanced HCC were retrospectively included. Three different TACE techniques were compared: non selective lipiodol-chemotherapy + non selective embolisation (TACE-technique group 1), non selective lipiodol-chemotherapy + selective embolisation (group 2), and selective lipiodol-chemotherapy + selective embolisation (group 3).ResultsIn multivariate analysis TACE-technique group is an independently significant prognostic factor for poor clinical tolerance, poor liver tolerance and tumour response. The rate of patients with poor clinical tolerance was lower in group 3 (27.0%) than in groups 1 (64.1%, p < 10−3) or 2 (66.7%, p < 10−3). The rate of patients with poor liver tolerance was higher in group 2 (34.0%) than in groups 1 (17.6%, p = 0.050) or 3 (6.9%, p = 0.011). The rate of patients with tumour response was higher when embolisation was selective versus non-selective, i.e., group 2 + 3 (78.7%) versus group 1 (62.5%, p = 0.054). Overall survival was not significantly different between the three groups (p = 0.383).ConclusionBoth selective techniques resulted in better tumour response. As for improving tolerance, our study suggests that the main technical factor is the use of selective lipiodol-chemotherapy injection.

Prospective evaluation of the management of hepatocellular carcinoma in the elderly.

BACKGROUND An increasing proportion of patients with hepatocellular carcinoma are older than 75 years. Previous studies suggested that ageing does not adversely impact survival but they have the drawback of being retrospective and spanning a prolonged period of time. GOALS Evaluate management and prognosis of hepatocellular carcinoma in elderly. PATIENTS AND METHODS A multidisciplinary oncology meeting prospectively evaluated all patients with hepatocellular carcinoma. Management were standardised according to European and American guidelines. Forty patients older than 75 years were matched with younger patients for tumour extension and liver function. Both groups were compared for the type of treatment and survival. RESULTS Male/female ratio was 1.2 as compared to 7 in controls. Cirrhosis was related mostly to hepatitis C virus in elderly, and equally to hepatitis C or B virus and alcohol in controls. Curative treatments were recommended in 55% of elderly and 75% of controls. Treatment actually performed was curative in 25% in elderly as compared to 63% in controls. Median survival (30 months) was identical in both groups. CONCLUSION Despite more restricted access to curative treatments, survival of elderly patients with hepatocellular carcinoma is comparable to that of younger patients.

Levels and Initial Course of Serum Alanine Aminotransferase Can Predict Outcome of Patients With Budd–Chiari Syndrome

BACKGROUND & AIMS Patients with Budd-Chiari syndrome can present with acute, subacute, or chronic disease; the definitions and significance of these variants have been disputed. An increased level of serum alanine aminotransferase (ALT) is an objective marker for acute liver injury. We analyzed the significance of changes in ALT levels in Budd-Chiari syndrome patients. METHODS We performed a retrospective analysis of data from 96 consecutive Budd-Chiari syndrome patients. RESULTS A threshold peak ALT level that was 5-fold the upper limit of normal distinguished 2 groups of patients: patients with high levels of ALT (40% of patients) presented with more severe liver disease, less frequent liver fibrosis, and more frequent liver cell necrosis, compared with those with ALT levels below this threshold. Patients with levels of ALT that started out high but slowly declined (<50% of starting concentration within 3 days) had significantly lower odds of survival than those with a rapid decline and those with low levels of ALT (40 months transplantation-free survival, 31%, 63%, and 71%, respectively). When ALT level and the velocity of its decline are used as criterion, these data add significant prognostic information to Child-Pugh, to Clichy, and to Rotterdam Budd-Chiari syndrome scores. CONCLUSIONS Determination of ALT levels at patient presentation allows 2 variants of Budd-Chiari syndrome to be distinguished. High levels of ALT reflect acute, severe, but potentially reversible, ischemic liver cell necrosis. High levels of ALT that decrease slowly predict a poor outcome for patients and might justify rapid aggressive management.

Liver tumours in patients with Fanconi anaemia: a report of three cases.

Fanconi anaemia is an autosomal recessive disease, causing secondary aplastic anaemia and congenital abnormalities, associated with an increased risk of tumours. Liver cell adenoma and hepatocellular carcinoma have rarely been described. Clinical, radiological and histopathological features in three patients with Fanconi anaemia and liver tumours were analyzed. Only one patient had received androgens and none had chronic viral hepatitis. All had elevated serum ferritin with significant parenchymal iron overload. Alpha-fetoprotein levels were normal in all cases. Patient 1 had moderately differentiated hepatocellular carcinoma with venous invasion and satellite nodules. The patient underwent two consecutive resections. Patient 2 had hepatic nodules diagnosed at routine examination with radiological features of adenomas. The patient underwent resection, which showed liver cell adenoma with foci of carcinoma. Patient 3 had three nodules, with radiological and histological diagnosis of adenoma. In patients with Fanconi anaemia, androgen therapy and iron overload may contribute to the development of liver cell adenoma and hepatocellular carcinoma. Hepatocellular carcinoma may occur as a transformation of liver cell adenoma. With prolongation of survival, continued development of liver tumours can be expected. Routine detection should therefore be considered in these patients as curative resection can be performed.

Cirrhotic patients with portal hypertension-related bleeding and an indication for early-TIPS: A large multicentre audit with real-life results

BACKGROUND The Baveno VI consensus meeting concluded that an early TIPS must be considered in high-risk cirrhotic patients presenting with variceal bleeding (VB) (Child B + active bleeding at endoscopy or Child C10-13 patients). Whether this therapeutic approach is feasible in a real-life setting remains unclear. AIMS To determine (1) the proportion of patients eligible for early-TIPS among cirrhotic patients with VB, (2) the proportion of these patients who underwent early-TIPS placement and the main reasons for discarding TIPS, and (3) the outcomes of patients who experienced early-TIPS placement in a large, national, prospective, multicentre audit including academic and non-academic centres. MATERIALS AND METHODS All French centres recruiting gastrointestinal bleeding were invited to participate. All consecutive patients with cirrhosis and PHT-related bleeding were included. RESULTS 964 patients were included (58 centres: 26 academic, 32 non-academic; patient characteristics: male sex, 77%; age, 59.6 ± 12.1 years; aetiologies of cirrhosis (alcoholic,viral/other, 67%/15%/18%); source of bleeding (EV/GV/other, 80/11/9%); active bleeding at endoscopy 34%; Child A 21%/B 44%/C 35%. Overall, 35% of the patients were eligible for early-TIPS, but only 6.8%, displaying less severe cirrhosis underwent early-TIPS placement. The main reason for discarding TIPS was a lack of availability. The actuarial probability of survival at one year was significantly increased in early-TIPS patients (85.7±0.07% vs 58.9±0.03%, p=0.04). The severity of liver disease was the only parameter independently associated with improved one-year survival. CONCLUSION In this real-life study, one-third of the cirrhotic patients admitted for VB fulfilled the criteria for early-TIPS placement, whereas only 7% had access to TIPS. TIPS was restricted to patients displaying less severe cirrhosis. The severity of liver disease was the only parameter that influenced survival.

P1288 : Budd chiari syndrome (BCS) in France from a large national cohort

increased in recent years. This increase may be due to factors such as high HCV viral load in blood and semen, sex with risk of mucosal damage, a higher number of sexual partners, presence of concomitant ulcerative sexually transmitted diseases and the use of recreational drugs. The aim of our study was to investigate the dynamics of HCV transmission in an outbreak of acute hepatitis C in HIV-infected MSM in Barcelona. Methods: Between 2008 and 2013, 113 cases of acute hepatitis C in HIV-infected MSM were diagnosed in the Infectious Diseases Unit, Hospital Clinic, Barcelona. Phylogenetic analysis of the HCV NS5B gene was performed in a total of 70 patients. Viral RNA was extracted from serum samples collected from each patient at the time of diagnosis. Massive sequencing was performed using the Roche 454 GS Junior platform. To define possible transmission networks, phylogenetic trees and multidimensional scaling maps were constructed from genetic distance matrices (Da). Results: At the time of diagnosis of acute hepatitis C, 53 of the 70 (76%) patients included in the study were receiving antiretroviral therapy. HIV viral load was undetectable in 48 patients (69%) and the mean CD4 cell count was 923 cells /ul. HCV viral load was 6.37 log IU/mL (range 3.73–6.99). Thirty-five of 53 (66%) patients treated with pegIFN and ribavirin achieved a sustained virological response. The prevalence of HCV genotypes was: 4d 51% (n =36), 1a 40% (n =28), 1b 7% (n =5) and 3a 1% (n =1). Phylogenetic analysis showed the existence of at least 13 monophyletic groups: 5 of genotype 1a, 2 of genotype 1b and 6 genotype 4d. Molecular analysis showed that the genetic distances between genotype 4d viruses (Da 5.42) were significantly lower than those of the subtypes 1a (Da 18.50, p < 2.2×10−16) and 1b (Da 15.25, p < 1.1×10−6). This result may suggest the existence of a single source of infection for genotype 4d and different sources for subtypes 1a and 1b. Conclusions: HCV infection spreads rapidly among HIV-infected MSM through a local network in Barcelona. The implementation of public health campaigns and preventive measures, as well as treatment interventions with the new direct-acting antivirals will allow the development of strategies to reduce the HCV transmission of HCV within these high-risk groups.

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 ± 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.