International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Hepatitis B virus and hepatitis delta virus subtypes circulating in Algeria and seroprevalence of HDV infection.

BACKGROUND: Little is known about molecular characteristics of HBV strains circulating in Algeria and there are few data regarding HDV infection. OBJECTIVES: The aim of this study is to describe the genetic diversity of HBV and HDV strains existing in Algeria and to determine the seroprevalence of HDV infection. STUDY DESIGN: Plasma samples from 134 patients were analyzed by enzyme immunoassay method for HBV and HDV serological markers. Genotyping of HBV and HDV strains were performed using direct sequencing followed by phylogenetic analyses of the PreS1 and R0 region of the HBV and HDV genome respectively. RESULTS: The PreS1 gene was successfully amplified in 119 patients (82 males and 37 females). Phylogenetic analysis of HBV strains revealed the presence of genotypes D (86.5%) and A2 (11.76%). The subgenotypes D are distributed as follows: HBV/D7 (43.5%), HBV/D3 (24.75%), HBV/D1 (16.8%) and HBV/D2 (14.85%). A recombinant between genotypes A, E and D was found. The seroprevalence of HDV infection among HBV carriers was less than 5.35%. Only one isolate of HDV genotype 1 was identified. CONCLUSIONS: Our data indicate the predominance of HBV subgenotype D7 and a low prevalence of HDV infection.

Alternative splicing of hepatitis B virus: A novel virus/host interaction altering liver immunity.

BACKGROUND & AIMS: Hepatitis B virus (HBV) RNA can undergo alternative splicing, but the relevance of this post-transcriptional regulation remains elusive. The mechanism of HBV alternative splicing regulation and its impact on liver pathogenesis were investigated. METHODS: HBV RNA-interacting proteins were identified by RNA pull-down, combined with mass spectrometry analysis. HBV splicing regulation was investigated in chemically and surgically induced liver damage, in whole HBV genome transgenic mice and in hepatoma cells. Viral and endogenous gene expression were quantified by quantitative reverse transcription polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay. Resident liver immune cells were studied by fluorescence-activated cell sorting. RESULTS: HBV pregenomic RNA-interacting proteins were identified and 15% were directly related to the splicing machinery. Expression of these splicing factors was modulated in HBV transgenic mice with liver injuries and contributed to an increase of the HBV spliced RNA encoding for HBV splicing-generated protein (HBSP). HBSP transgenic mice with chemically induced liver fibrosis exhibited attenuated hepatic damage. The protective effect of HBSP resulted from a decrease of inflammatory monocyte/macrophage recruitment through downregulation of C-C motif chemokine ligand 2 (CCL2) expression in hepatocytes. In human hepatoma cells, the ability of HBSP to control CCL2 expression was confirmed and maintained in a whole HBV context. Finally, viral spliced RNA detection related to a decrease of CCL2 expression in the livers of HBV chronic carriers underscored this mechanism. CONCLUSION: The microenvironment, modified by liver injury, increased HBSP RNA expression through splicing factor regulation, which in turn controlled hepatocyte chemokine synthesis. This feedback mechanism provides a novel insight into liver immunopathogenesis during HBV infection. Lay summary: Hepatitis B virus persists for decades in the liver of chronically infected patients. Immune escape is one of the main mechanisms developed by this virus to survive. Our study highlights how the crosstalk between virus and liver infected cells may contribute to this immune escape.

Widespread geographical disparities in chronic hepatitis B virus infection in Algeria.

Algeria is the largest country of Africa, with a population of 40 million inhabitants living in disparate environments from the Sahara to the large cities of the Mediterranean coast. The molecular epidemiology of hepatitis B virus (HBV) variants has been partially described, but variations in the seroprevalence of HBV surface antigen (HBsAg) throughout the Algerian territories are still poorly described. We analyzed demographic features of new cases of chronic infection collected in 41 administrative regions (covering 92% of the population) in 2013. The mean age of the 1876 HBsAg(+) patients was 36.8 ± 14.2 years, with a slight excess of males (54%). The seroprevalence of HBV early antigen (HBeAg) was 9.3%, and the mean virus load was 3.2 ± 1.8 log IU/ml. A subset of 15.2% of patients was already cirrhotic at disease discovery. An important heterogeneity was observed throughout the country, with nine regions displaying a significant excess of cases. These regions formed four distinct foci located in distant parts of the country: Adrar-Bechar (southwest), El-Oued-Tebessa (east), M'Sila-Sétif (north central) and Oran-Aïn Temouchent (northwest). An excess of cases was found as well in the national capital Algiers. Patients from southern regions with an excess of cases (Bechar, Adrar, El Oued) were significantly younger (32.0 ± 10.7 years), as were patients from the regions of Bejaia and Bouira (32.1 ± 10.6). The southwestern regions were also marked by a significant imbalance of the sex ratio (58 vs 39% of female cases, P = 4.5 E-5). The highest HBeAg seroprevalence was observed in Setif (26.4 vs. 7.6%, OR = 4.3, 95% CI 2.6-6.5, P = 1.1 × 10-11) in accordance with the higher virus loads observed in the patients (3.9 ± 2.3 vs. 3.1 ± 1.6, P = 0.0002). In conclusion, we observed heterogeneity in HBsAg seroprevalence, demographic traits, and disease evolution in Algeria. Further studies are now warranted to shed light on these differences, which are presumably due to variability in transmission routes or in the infectivity of viral isolates.

Budd-Chiari syndrome: an update on imaging features.

Budd-Chiari syndrome (BCS) is a rare cause of portal hypertension and liver failure. This condition is characterized by an impaired hepatic venous drainage. The diagnosis of BCS is based on imaging, which helps initiate treatment. Imaging findings can be categorized into direct and indirect signs. Direct signs are the hallmarks of BCS and consist of visualization of obstructive lesions of the hepatic veins or the upper portion of the inferior vena cava. Indirect signs, which are secondary to venous obstruction, correspond to intra- and extrahepatic collateral circulation, perfusion abnormalities, dysmorphy and signs of portal hypertension.

Eastern region represents a worrying cluster of active hepatitis C in Algeria in 2012.

Algeria is the largest country of Africa, peopled with populations living a range of traditional/rural and modern/urban lifestyles. The variations of prevalence of chronic active hepatitis care poorly known on the Algerian territory. We conducted a retrospective survey on all patients (n = 998) referred to our institution in 2012 and confirmed by us for an active hepatitis C. Half of the hepatitis C virus (HCV) isolates were genotyped. Forty Algerian regions out of the 48 were represented in our study. Three geographical clusters (Aïn-Temouchent/SidiBelAbbes, Algiers, and a large Eastern region) with an excess of active hepatitis C were observed. Patients coming from the Eastern cluster (Batna, Khenchela, Oum el Bouaghi, and Tebessa) were strongly over-represented (49% of cases, OR = 14.5, P < 0.0001). The hallmarks of Eastern region were an excess of women (65% vs. 46% in the remaining population, P < 0.0001) and the almost exclusive presence of HCV genotype 1 (93% vs. 63%, P = 0.0001). The core of the epidemics was apparently located in Khenchela (odds ratio = 24.6, P < 0.0001). This situation is plausibly connected with nosocomial transmission or traditional practices as scarification (Hijama), piercing or tattooing, very lively in this region. Distinct hepatitis C epidemics are currently affecting Algerian population. The most worrying situation is observed in rural regions located east of Algeria. J. Med. Virol. 88:1394-1403, 2016. © 2016 Wiley Periodicals, Inc.

Aetiological factors of Budd-Chiari syndrome in Algeria.

AIM: To study the clinical presentation of Budd-Chiari syndrome (BCS) and identify the aetiologies of this disease in Algeria. METHODS: Patients with BCS, hospitalised in our unit from January 2004 until June 2010 were included and the aetiological factors were assessed. Patients presenting a BCS in the setting of advanced-stage cirrhosis or a liver transplantation were excluded from the study. The diagnosis was established when an obstruction of hepatic venous outflow (thrombosis, stenosis or compression) was demonstrated. We diagnosed myeloproliferative disease (MPD) by bone marrow biopsy and V617F JAK2 mutation. Anti-phospholipid syndrome (APLS) was detected by the presence of anticardiolipin antibodies, anti-ß2 glycoprotein antibodies and Lupus anticoagulant. We also detected paroxysmal nocturnal haemoglobinuria (PNH) by flow cytometry. Celiac disease and Behçet disease were systematically investigated in our patients. Hereditary anticoagulant protein deficiencies were also assessed. We tested our patients for the G20210A mutation at Beaujon Hospital. Imaging procedures were performed to determine a local cause of BCS, such as a hydatid cyst or a liver tumour. RESULTS: One hundred and fifteen patients were included. Mean follow up: 32.12 mo. Mean age: 34.41 years, M/F = 0.64. Chronic presentation was frequent: 63.5%. The revealing symptoms for the BCS were ascites (74.8%) and abdominal pain (42.6%). The most common site of thrombosis was the hepatic veins (72.2%). Involvement of the inferior vena cava alone was observed in 3 patients. According to the radiological investigations, BCS was primary in 94.7% of the cases (n = 109) and secondary in 5.2% (n = 6). An aetiology was identified in 77.4% of the patients (n = 89); it was multifactorial in 27% (n = 31). The predominant aetiology of BCS in our patients was a myeloproliferative disease, observed in 34.6% of cases. APLS was found in 21.7% and celiac disease in 11.4%. Other acquired conditions were: PNH (n = 4), systemic disease (n = 6) and inflammatory bowel disease (n = 5). Anticoagulant protein deficiency was diagnosed in 28% of the patients (n = 18), dominated by protein C deficiency (n = 13). Secondary BCS was caused by a compressing hydatic cyst (n = 5) and hepatocellular carcinoma (n = 1). CONCLUSION: The main aetiologic factor of BCS in Algeria is MPD. The frequency of celiac disease justifies its consideration when BCS is diagnosed in our region.

Budd-Chiari syndrome: a prospective analysis of hepatic vein obstruction on ultrasonography, multidetector-row computed tomography and MR imaging.

PURPOSE: The goal of this study was to prospectively describe the imaging presentation of hepatic vein (HV) obstruction in patients with Budd-Chiari syndrome (BCS) on duplex and color Doppler ultrasonography (DCD-US), multidetector-row computed tomography (MDCT) and magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 176 patients with primary BCS (mean age, 33 years; 101 women) were prospectively included. BCS diagnosis was made by direct visualization of HV and/or upper portion of the inferior vena cava (IVC) obstruction on DCD-US and/or MDCT and/or MRI. Location (right, middle, and left HV), type (thrombus, stenosis, or both), and age (recent vs. long-standing) of HV obstruction were described on each imaging examination. RESULTS: HV obstruction was a constant (100%) finding and associated with IVC abnormalities in 51/176 (28.98%) patients. Obstruction of the three HVs was present in 158/176 (89.77%) patients. The prevalences of right, middle, and left HV thrombus were 151/169 (89.35%), 146/169 (86.39%), and 111/169 (65.68%), respectively. Long-standing HV thrombus was observed in more than 92% of patients on the three imaging methods. Agreement between DCD-US, MDCT, and MRI was perfect in the identification of long-standing HV thrombus (κ = 0.9); this agreement was slight to moderate in revealing the type of HV abnormality (i.e., fibrotic cord and non-visible HV). CONCLUSION: Our results indicate that BCS is a chronic and insidious disease, more often discovered at an advanced stage. These results should warrant further evaluation of screening strategies in patients with risk factors for BCS to identify the disease at an early stage.

First multicenter study for risk factors for hepatocellular carcinoma development in North Africa.

AIM: To assess the role of the major risk factors for hepatocellular carcinoma (HCC) development in the western part of North Africa. METHODS: A multicenter case control study was conducted in Tunisia, Morocco and Algeria in collaboration with Pasteur Institutes in these countries. A total of 164 patients with HCC and 250 control subjects without hepatic diseases were included. Prevalences of HBsAg, anti-hepatitis C virus (HCV) and diabetes were assessed. HCV and HBV genotyping were performed for anti-HCV and HBsAg positive patients. RESULTS: The mean age of patients was 62 ± 10 years old for a 1.5 M:F sex ratio. Sixty percent of HCC patients were positive for anti-HCV and 17.9% for HBsAg. Diabetes was detected in 18% of cases. Odd ratio (OR) and 95% confidence intervals (CI) were 32.0 (15.8 - 65.0), 7.2 (3.2 - 16.1) and 8.0 (3.1 - 20.0) for anti-HCV, HBsAg and diabetes respectively. Multivariate analysis indicated that the three studied factors were independent. 1b HCV genotype and D HBV genotype were predominant in HCC patients. HCV was the only risk factor significantly associated with an excess of cirrhosis (90% vs 68% for all other risk factors collectively, P = 0.00168). Excessive alcohol consumption was reliably established for 19 (17.6%) cases among the 108 HCC patients for whom data is available. CONCLUSION: HCV and HBV infections and diabetes are the main determinants of HCC development in North Africa. An active surveillance and secondary prevention programs for patients with chronic hepatitis and nutrition-associated metabolic liver diseases are the most important steps to reduce the risk of HCC in the region.