Philippe Sogni

Aortic hyporeactivity to norepinephrine induced by lipopolysaccharide in cirrhotic rats: Beneficial effects of a non‐steroidal anti‐inflammatory drug coupled with a nitric oxide donor

Background and Aims: Cirrhosis is associated with a hyperdynamic syndrome and arterial vasodilation that is related to nitric oxide (NO) synthase 3 overactivity. Septic shock is frequently associated with cirrhosis and with a vascular induction of NO synthase 2. The aims of this study were to compare the effects of lipopolysaccharide (LPS) in normal and cirrhotic rats, and to test the effects of a‐non‐steroidal anti‐inflammatory drug (NSAID) coupled with a (NO) donor.

Hepatitis E–associated subacute liver failure: a rare indication for liver transplantation

blood pressure (digital photopletysmography [Finapres, Ohmeda, Tewksbury, MA]) and heart rate (surface electrocardiography) were monitored continuously. At 40 cpm on insufflation, the patient became profoundly hypotensive in association with a persistent bradycardia of ,30 bpm requiring atropine. The procedure reproduced syncopal symptoms. Because of the persistent bradycardia during symptom reproduction this woman had a pacemaker inserted. Six months after dual chamber physiological pacemaker implantation (Kappa 700, Medtronic, Minneapolis, MN) she has had no further episodes of syncope. This patient had symptom reproduction with a hypotensive response and a profound bradycardia during colonoscopy; in addition, there has been clear benefit from pacing intervention, suggesting a diagnosis of cardioinhibitory situational vasovagal syncope. We were able to detect these subtle changes because we used a real-time beat by beat method of recording blood pressure, combined with continuous measurement of heart rate. To our knowledge this is the first reported case of defecation syncope where hemodynamic changes have been documented in real time, where an abnormality of autonomic function has been demonstrated, and where treatment (in this case, permanent pacemaker implantation) has proved curative.

Prise en charge des complications de la cirrhose chez les patients VIH co-infectés par une hépatite virale B ou C

Cirrhosis is a serious complication of viral hepatitis, and its incidence is increasing in HIV patients coinfected with HCV or HBV as they live longer, thanks to effective antiretroviral treatment (Haart). HIV coinfection accelerates the progression of fibrosis in hepatitis. To implement preventive measures, prompt diagnosis of cirrhosis is important, either by liver biopsy or the noninvasive tests for fibrosis now under wide study (FibroTest, FibroScan, etc.). Afterwards, assessment of the severity of cirrhosis and screening for complications are both necessary: testing for liver failure (Child-Pugh and MELD scores), portal hypertension (upper gastrointestinal endoscopy), and hepatocellular carcinoma (ultrasound and alpha fetoprotein assay). Careful consideration of drug prescriptions and possible interactions is essential. Specific treatment for hepatitis B or C virus is possible at this stage of cirrhosis, although more difficult, especially for HCV (results influenced by genotype, additional risk of complications by lactic acidosis or hepatic decompensation). Management of the complications of portal hypertension must be planned, as for those without HIV infection. Treatment of hepatocellular carcinoma is still disappointing, and liver transplantation, although possible in these patients, must be evaluated.Points essentiels • La cirrhose est une complication grave dont l’incidence augmente chez les patients co-infectes VIH-VHC ou VHB en raison des progres dans les traitements anti-VIH (Haart). L’existence d’une co-infection par le VIH accelere en outre la progression de la fibrose de l’hepatite. • Le diagnostic de cirrhose est important afin de mettre en place des mesures preventives, par la realisation d’une biopsie hepatique ou de tests non invasifs de fibrose maintenant largement etudies (FibroTest, FibroScan, etc.). • La gravite de la cirrhose doit alors etre appreciee avec depistage des complications : evaluation de l’insuffisance hepatocellulaire (scores de Child-Pugh, MELD), de l’hypertension portale (endoscopie digestive haute) et du carcinome hepatocellulaire (echographie et dosage de l’α-fœtoproteine). Des precautions en termes de prescriptions medicamenteuses associees doivent etre respectees. • Les traitements specifiques des hepatites virales B ou C sont possibles a ce stade de cirrhose, bien que plus difficiles a mettre en œuvre notamment pour le VHC (resultats influences par le genotype, risque supplementaire de complications de type acidose lactique ou de decompensation hepatique). • La prise en charge des complications de l’hypertension portale doit s’envisager comme chez le non-infecte par le VIH. Le traitement du carcinome hepatocellulaire reste decevant et la transplantation hepatique, bien que realisable chez ces patients, reste a evaluer.

Hepatitis delta virus super-infection in a co-infected patient with the human immunodeficiency virus type 1 and a surface antigen-negative hepatitis B virus variant

Human immunodeficiency virus infection has a major impact on the natural history of chronic hepatitis B and favours the emergence of viral mutants. We describe an acute hepatitis D virus superinfection in an HIV-1-infected patient under HAART treatment who was previously a chronic carrier of a surface negative HBV variant resistant to lamivudine.

Utilisation des antirétroviraux chez le patient cirrhotique infecté par le VIH

Points essentiels • Depuis l’avenement des traitements antiretroviraux actifs, l’avenir des patients infectes par le VIH est transforme. Mais l’evolution des hepatites virales B ou C (20 a 25 % des patients VIH sont co-infectes) en est d’autant plus severe, les patients co-infectes ayant une sensibilite augmentee a la toxicite hepatique des antiretroviraux. • La relation entre concentrations plasmatiques elevees des antiretroviraux et toxicite a ete bien demontree pour certains inhibiteurs de protease (IP) et inhibiteurs non nucleosidiques de transcriptase inverse (NNRTI), qui ont un metabolisme hepatique predominant (CYP4503A4). Quant aux inhibiteurs nucleosidiques de transcriptase inverse (NRTI), ils ne sont pas metabolises de facon preponderante par le foie mais peuvent neanmoins etre toxiques pour le foie par le biais d’une atteinte mitochondriale. • La toxicite hepatique observee chez un malade traite par antiretroviraux, precoce ou retardee, peut etre de mecanisme cytolytique, cholestatique ou mixte, direct ou indirect. • Avant d’initier le traitement antiretroviral, la fibrose hepatique doit etre evaluee (ponction-biopsie, test biologique de fibrose, score de Child-Pugh). Il est conseille d’eviter les medicaments les plus hepatotoxiques, notamment didanosine, didanosine + stavudine, nevirapine, ritonavir a pleine dose. • Meme s’il est possible de debuter a dose usuelle un traitement antiretroviral chez un patient cirrhotique (la marge therapeutique des antiretroviraux est large), la realisation d’un dosage precoce s’avere neanmoins indispensable, notamment pour les IP et NNRTI, afin de pouvoir adapter les doses en cas de surdosage et eviter les effets indesirables. Une surveillance etroite est dans tous les cas fondamentale.