Predictors associated with treatment initiation and switch in a real-world chronic hepatitis B population from five European countries.

In Europe, healthcare systems differ between countries and different factors may influence Chronic hepatitis B (CHB) treatment choices in different counties. This analysis from a prospective, longitudinal, non-interventional study in five EU countries aimed to explore determinants associated with treatment initiation or switch in patients with CHB. A total of 1267 adult patients with compensated CHB in Germany, France, Poland, Romania and Turkey were prospectively followed for up to 2 years (March 2008-December 2010). Determinants of treatment initiation or switch were analysed using multivariate Cox proportional hazards regression. Median time since CHB diagnosis was 2.6 (0-37.7) years. Among 646 treatment-naïve patients, the probability of treatment initiation during follow-up was higher: in Germany (P = 0.0006), Poland (P < 0.0001) and Romania (P = 0.0004) compared with Turkey; in patients with alanine transaminase (ALT) 1-2 × upper limit of normal (ULN) (P = 0.0580) or >2 × ULN (P = 0.0523) compared with ALT ≤ 1 × ULN; and in patients with hepatitis B virus (HBV) DNA ≥ 2000 IU/mL (P < 0.0001) compared with HBV DNA <2000 IU/mL or undetectable. Among 567 treated patients, 87 switched treatment during follow-up. The probability of treatment switch was higher: in France (P = 0.0029), Germany (P = 0.0078) and Poland (P = 0.0329) compared with Turkey; and in patients with HBV DNA <2000 (P < 0.0001) or ≥ 2000 IU/mL (P < 0.0001), compared with undetectable. Viral load and ALT level were identified as the major drivers of treatment initiation. HBV DNA level was also a significant determinant of treatment switch. Results were statistically different across EU countries.

Fibrosis progression under maintenance interferon in hepatitis C is better detected by blood test than liver morphometry.

We evaluated whether quantitative measurements of liver fibrosis with recently developed diagnostics outperform histological staging in detecting natural or interferon-induced changes. We compared Metavir staging, morphometry (area and fractal dimension) and six blood tests in 157 patients with chronic hepatitis C from two trials testing maintenance interferon for 96 weeks. Paired liver biopsies and blood tests were available for 101 patients, and there was a significant improvement in Metavir activity and a significant increase in blood tests reflecting fibrosis quantity in patients treated with interferon when compared with controls - all per cent changes in histological fibrosis measures were significantly increased in F1 vs F2-4 stages only in the interferon group. For the whole population studied between weeks 0 and 96, there was significant progression only in the area of fibrosis (AOF) (P = 0.026), FibroMeter (P = 0.020) and CirrhoMeter (P = 0.003). With regards to dynamic reproducibility, agreement was good (r(ic) ≥ 0.72) only for Metavir fibrosis score, FibroMeter and CirrhoMeter. The per cent change in AOF was significantly higher than that of fractal dimension (P = 0.003) or Metavir fibrosis score (P = 0.015). CirrhoMeter was the only blood test with a change significantly higher than that of AOF (P = 0.039). AOF and two blood tests, reflecting fibrosis quantity, have high sensitivity and/or reproducibility permitting the detection of a small progression in liver fibrosis over two years. A blood test reflecting fibrosis quantity is more sensitive and reproducible than morphometry. The study also shows that maintenance interferon does not improve fibrosis, whatever its stage.

[Influence of treatment on long-term evolution of chronic hepatitis B]. / Influence du traitement sur l'évolution à long terme de l'hépatite chronique B.

The treatment of chronic hepatitis B is essentially based on the use of nucleoside or nucleotide analogues, which lead to viral suppression in the majority of cases. Viral suppression is associated with normal ALT values and progressive histological improvement of not only necroinflammatory lesions but also fibrosis. Regression of cirrhosis can be observed in severe cases. With the use of second-generation nucleoside or nucleotide analogues, the risk of mutation resistance is rare or inexistent. Finally, negativation and seroconversion of the HBs antigen can be observed in the medium-term. This seroconversion is usually associated with a decreased risk of complications and morbidity-mortality improvement.

Biological autoimmunity screening in hepatitis C patients by anti-HepG2 lysate and anti-heat shock protein 70.1 autoantibodies.

Viruses require viral and cellular chaperones during their life cycle and interactions of these molecules with the immune system are probable during the infection. Thus, an anti-chaperone antibody response has been firstly investigated in hepatitis C patients in this paper. A HepG2-lysate antigen (90, 79, 72, 70, 62, 54 and 48 kDa) was assayed in sera from 59 (19F/40M) chronic hepatitis C patients without cirrhosis before therapy. Forty of them were positive for anti-HepG2 lysate antigen antibodies and this test may evaluate biological autoimmunity. Hsp70.1, Hsp90 and calreticulin levels were significantly higher in this antigen than in a control HepG2 antigen. Secondly, Hsp70.1 was identified as Hsp 70 kDa protein-1 by proteomic analysis and studied as a possible antibody target. Fourteen out of 59 patients were positive for anti-Hsp70.1 antibodies that were inversely correlated with alanine aminotransferase levels, the Metavir activity index and viraemia. Finally, for comparative purposes, 50 sera from systemic lupus erythematosus (SLE) patients have been tested: eight and 41 of them were positive for anti-Hsp70.1 and anti-HepG2 lysate antigen antibodies, respectively. Therefore, anti-Hsp70.1 autoantibodies may be produced and can partially lead to biological autoimmunity in chronic hepatitis C patients.

[The patient with uncontrolled chronic hepatitis B]. / Le patient atteint d'hépatite chronique B non contrôlé

The treatment of chronic hepatitis B is now based on the using of pegylated interferon or nucleoside or nucleotide analogs. In the majority of cases, these drugs can control viral replication with an hepatitis B virus (HBV) DNA negativation after approximately 6 months of therapy. In case of primary non response, it is necessary to modify antiviral therapy and if resistance appears to combine a nucleoside and a nucleotide analog. In patients treated by nucleoside analog, if HBV DNA is not negative or do not dramatically decreases at the week 24, it is also necessary to add a nucleotide analog. However, for adefovir therapy, it is usually preferable to wait at week 48. In summary, a regular following every 3 months of HBV DNA detection by a sensitive method (Real Time PCR) allows to evaluate the therapeutic efficacy and to prevent the risk of biochemical and clinical rebound due to appearance of resistance mutations.

[Hepatitis C, cirrhosis and hepatocellular carcinoma]. / Hépatite C, cirrhose et carcinome hépatocellulaire.

The screening for the detection of hepatocellular carcinoma is based on ultrasound sonography which should be realised in patients with post-hepatitis C cirrhosis with a delay between 3 and 6 months according to the most identified risk factors, in particular age and sex male. In the case of discovery of hypoechogen nodule < or = 1cm, a follow-up is mandatory because it is usually untypical by ultrasound sonography and to propose a liver biopsy in the case of an increasing in size is shown. The ultrasound guided cutting biopsy can precise the histological characteristics of the nodule, the grade, and indicate prognostic factors. The liver biopsy is also mandatory in the case of a nodule > 2 cm and when the ultrasound sonography is not contributive, especially when the nodule is between 1 and 2 cm in size.

The negative impact of HBV/HCV coinfection on cirrhosis and its consequences.

BACKGROUND: Hepatitis B virus (HBV)/hepatitis C virus (HCV) confection has been rarely studied in nonasian series. AIM: To compare the characteristics of HBV/HCV coinfected patients to those of HBV- or HCV-monoinfected patients in the ANRS CO22 HEPATHER cohort study. PATIENTS AND METHODS: Of the 20 936 included patients, 95 had HBV/HCV coinfection (hepatitis B surface antigen, anti-HCV antibody and HCV RNA positive) and were matched with 375 HBV- and 380 HCV-monoinfected patients on age, gender and time since HBV or HCV diagnosis. RESULTS: F3-F4 fibrosis was more frequent in coinfected patients (58%) than in HBV- (32%, P < .0001), but similar in HCV-monoinfected patients (52%, P = .3142). Decompensated cirrhosis was more frequent in coinfected patients (11%) than in HBV- (2%, P = .0002) or HCV- (4%, P = .0275) monoinfected patients. Past excessive alcohol use was more frequent in coinfected patients (26%) than in HBV (12%, P = .0011), but similar in HCV monoinfected patients (32%, P = .2868). Coinfected patients had a higher proportion with arterial hypertension (42%) than HBV- (26%) or HCV-monoinfected patients (25%) (P < .003). Multivariable analysis confirmed the association between F3-F4 fibrosis and HCV infection in HBV-infected patients (OR = 3.84, 95% CI 1.99-7.43) and the association between decompensated cirrhosis and coinfection in HBV infected (OR = 5.58, 95% CI 1.42-22.0) or HCV infected patients (OR = 3.02, 95% CI 1.22-7.44). CONCLUSIONS: HCV coinfection harmfully affects liver fibrosis in HBV patients, while decompensated cirrhosis is increased in coinfected patients compared with HBV- or HCV-monoinfected patients. HCV treatment is as safe and effective in coinfected as monoinfected patients and should be considered following the same rules as HCV monoinfected patients.

Effectiveness of interferon plus ribavirin combination in the treatment of naive patients with hepatitis C virus type 5. A French multicentre retrospective study.

AIM: To assess the rate of sustained virological response in naïve hepatitis C virus-type 5 patients treated by standard interferon or pegylated-interferon [corrected] (peg-interferon) and ribavirin combination for 48 weeks. PATIENTS AND METHODS: A total of 87 hepatitis C virus patients were included from 12 centres in France; 28 patients received interferon plus ribavirin and 59 were treated with peg-interferon plus ribavirin. RESULTS: Baseline characteristics were: mean age 58 +/- 11 years, sex ratio 1, 66% had metavir fibrosis score >or=F2, 21% were cirrhotics and 53% had pretherapeutic viral load >or=800,000 IU/mL. Sustained virological response was achieved in 64% and 58% of hepatitis C virus-5 patients treated with interferon and peg-interferon, respectively (NS). In adherent patients, sustained virological response was obtained in 75% of patients. Sustained virological response in hepatitis C virus-5 patients (60%) was significantly higher than sustained virological response in hepatitis C virus-1 patients (37%) (P = 0.0499) and not significantly different from sustained virological response in hepatitis C virus-2-3 patients (63%) (P = 0.8098). CONCLUSIONS: Combination therapy is effective in 60% of hepatitis C virus-5-infected patients. Sustained virological response seems better in hepatitis C virus-5 patients than in hepatitis C virus-1 patients, and is similar to that of hepatitis C virus-2-3 patients. More studies are needed to determine optimal duration of treatment in hepatitis C virus-5 patients.

Dynamics of viral quasispecies during interferon therapy in non responder chronic hepatitis C patients.

BACKGROUND: the reference method to study the HCV complexity was cloning and sequence analysis of a sufficient number of clones. The evolution of the viral complexity in chronic non responder patients during treatment with standard doses of interferon was not very well investigate because this method was expensive and labour intensive when large series of patients were concerned. Meanwhile, with the alternative Single-Strand Conformation Polymorphism (SSCP) method, a rough estimation of the quasispecies present in a given sample could be obtained. OBJECTIVES: the aim of the study was to analyse the evolution of HCV heterogeneity, investigated by SSCP analysis targeted to the HVR-1, in 30 nonresponders chronic hepatitis C patients treated by Interferon-alpha 3MUI. RESULTS: genotype 1 was the main HCV type found in this population (77% of non responder patients). Before treatment, the SSCP assay revealed a high complexity pattern: the median of SSCP band number was 9. During IFN-alpha treatment, SSCP band number didn't change. However a significant decrease of the viral load was observed (P<0.01). Patients with variations in their SSCP patterns after therapy significantly decreased HCV RNA levels (P<0.002). In one third of patients the SSCP profile didn't change at all. CONCLUSIONS: we observed that viral heterogeneity didn't change in non responder chronic hepatitis C patients during IFN-alpha treatment. Nevertheless patients with a low number of pre-treatment quasispecies exhibited an improvement of the response (P<0.02). These phenomena were probably due to a selection of resistant variants present prior onset of therapy.

EBV-B cells as antigen presenting cells in characterization of the self/donor context of allorecognition by T lymphocytes.

Alloreactivity is caused by T cell recognition of foreign histocompatibility antigens according to two models: (i) indirect recognition, in which processed allogeneic antigens are presented by self-major histocompatibility complexes like any other foreign antigen, and (ii) direct recognition, where the foreign MHC itself is recognized breaking the T cell recognition rule of self-restriction. This paper uses these two cases of alloantigen presentation as illustrative examples to investigate (i) the capacity of Epstein-Barr virus-transformed B cells (EBV-B cells) to process alloantigens, and (ii) in vitro assays with EBV-B cell lysate as a source of alloantigen, in order to characterize alloreactive T cell populations. A microculture system was established using donor EBV-B cell lysate as a source of the allogeneic antigen and donor or recipient EBV-B cells as antigen presenting cells to investigate whether alloantigen is recognized by effector T cells from the recipient. T lymphocytes produced after expansion in the presence of interleukin-2 from four samples of liver biopsies (three patients) and four samples of bronchoalveolar lavages (four patients) were used as effector cells. Upon human leucocyte antigen class II typing, these expressed the patient phenotype. When the T lymphocytes were from liver grafts, the recognition involved donor antigens presented by donor EBV-B cells (direct recognition). On the other hand, when the T lymphocytes were cultured from lung grafts, they mainly recognized antigens of donor EBV-B cell lysates in a self-restricted context (indirect recognition). These data suggest that EBV-B cells can provide allogeneic determinants recognized by T cells in donor or self-contexts, i.e. through either direct or indirect recognition.

Quantitative detection of hepatitis B virus DNA in serum using chemiluminescence: comparison with radioactive solution hybridization assay.

A quantitative, non-radioactive hybrid capture HBV DNA assay (Digene Diagnostics), which uses an efficient solution hybridization procedure coupled to a sensitive chemiluminescent signal amplification system, was compared with the quantitative, radioactive solution hybridization assay (Genostics, Abbott Laboratories), in hepatitis B virus carriers, particularly in those undergoing antiviral therapy. The qualitative reproducibility of the chemiluminescent method, tested on 30 sera, was acceptable, with a reproducibility rate of 93.3%. A comparison of this hybrid capture HBV DNA assay with the radioactive test on 113 sera obtained from 48 patients (39 HBsAg-positive patients) gave a sensitivity of 87.2%, a specificity of 100% and an agreement between the two tests of 89.4% (101 sera including 82 HBV DNA positive and 19 negative samples). Changes in HBV DNA levels measured by the two assays showed a good correlation with each other during interferon therapy. However, the hybrid capture values were higher than the radioactive assay values, with the ratio of the two values being variable in the same patient during the course of treatment. The Genostics assay therefore seems to be a more accurate procedure for evaluating changes in viral replication, particularly at high HBV DNA levels. However, the hybrid capture method is faster and has the advantage of being a non-radioactive procedure. This chemiluminescent assay is easy to perform as a routine diagnostic procedure and may be a useful alternative to the radioactive solution hybridization method.

Combination treatment for chronic hepatitis C: what is the role of ribavirin?

Ribavirin in combination with interferon-alpha2b is the new standard for chronic hepatitis C (CHC) treatment. Although usually considered as an antiviral compound, this guanosine analogue shows some additional effects on the immune system that could largely contribute to its clinical efficacy in CHC. Numerous in vitro experiments demonstrate that ribavirin has a selective down-regulatory effect on TH2 cytokine release with, in some cases, a concomitant TH1 cytokine up-regulation. In vivo, combination treatment of CHC patients was shown to induce a predominant TH1 response in isolated PBMCs, but also a reduction of peripheral TH2 response. Considering that: 1) a strong CD(4)+ helper T-cell response is associated with viral clearance in acutely infected patients; 2) a weak T-cell response to the viral antigens is common in chronic infected patients; 3) responding patients to combination treatment (but not non-responding patients) altered their cytokine profile under treatment, either to express IFN-gamma or to reduce pro-inflammatory mediators; it is highly presumed that ribavirine participates to restore an efficient T-cell response and to reduce the non-specific inflammatory cytolytic activity during CHC combination treatment.

Interferon for acute hepatitis C.

BACKGROUND: Acute hepatitis C virus (HCV) infection progresses to chronicity in the majority of patients. In order to prevent the progression to chronic disease, several studies have assessed interferon in patients with acute hepatitis C. OBJECTIVES: The aim of this review was to assess the efficacy of interferon in acute HCV infection. SEARCH STRATEGY: We searched MEDLINE, the Cochrane Controlled Trials Register, and the abstracts of the American Association for the Study of Liver Diseases (June 2001). We also contacted pharmaceutical companies to obtain unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo or no treatment, and published as an article, abstract, or letter were selected. No language limitations were used. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The following endpoints were analysed: normalization of alanine aminotransferase (ALT) activity at the end of treatment (biochemical ETR); sustained ALT normalization at the end follow-up (biochemical SR); disappearance of serum HCV RNA by polymerase chain reaction assay at the end of treatment (virologic ETR) and at the end of follow-up (virologic SR). Histologic data and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Six randomised trials involving 206 patients with acute hepatitis C met the inclusion criteria. Four trials assessing interferon alfa-2b in 141 patients, all with transfusion-acquired acute hepatitis C, were included. They demonstrated no significant heterogeneity in the outcomes assessed. When compared with no treatment, interferon alfa-2b was associated with an increase in the rates of virologic ETR and SR by 45% (95% CI 31-59%, P < 0.00001) and 29% (95% CI 14-44%, P = 0.0002), respectively. The virologic ETR was 42% (95% CI: 30-56%) in the interferon alfa-2b group versus 4% (95% CI 0-13%, P < 0.00001) in the control group. At the end of follow-up, a virologic SR was seen in 32% (95% CI 21-46%) of interferon-treated patients versus only 4% (95% CI 0-13%, P = 0.00007) of controls. The tolerability of therapy, or the impact of interferon alfa-2b on hepatic histology, was not reported. Two trials assessed interferon beta in a total 65 patients. The efficacy of interferon beta could not be assessed, however, due to heterogeneity of these trials. REVIEWER'S CONCLUSIONS: Interferon alfa is effective in improving biochemical outcomes and achieving sustained virologic clearance in patients with transfusion-acquired acute hepatitis C. The effect on long-term clinical outcomes could not be assessed due to limitations in the current data.

Interferon for interferon naive patients with chronic hepatitis C.

BACKGROUND: A previous meta-analysis of interferon therapy in naive patients with chronic hepatitis C has documented its efficacy in achieving virologic clearance, and improving liver biochemistry and histology; however, since its publication additional trials have been reported. OBJECTIVES: To evaluate the response to interferon in interferon naive patients with chronic hepatitis C. The effect of treatment dose and duration, and the response in patients with cirrhosis and those with normal aminotransferases was also investigated. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Cochrane Library Issue 1, 1999), MEDLINE (January 1966 to December 1999), and reference lists were searched, and pharmaceutical companies were contacted for unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo, no treatment, or different regimens of interferon were selected. Abstracts were excluded. DATA COLLECTION AND ANALYSIS: The primary outcome measure was sustained disappearance of serum HCV RNA (virologic sustained response (SR)). Biochemical and end of treatment responses, liver histology, and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Fifty-four trials enrolling 6545 patients were included. Compared with no treatment, interferon 3 MU thrice weekly for 12 months increased the probability of a virologic SR (Peto odds ratio (OR) 4.60; 95% confidence interval (CI) 1.53 to 13.85). At this dosage and duration of therapy, the rate of virologic SR was 17% (95% CI 10 to 28%) in interferon-treated patients versus 3% (95% CI 1 to 10%) in controls. A dose of 6 MU was more effective than 3 MU thrice weekly (OR for 12 months treatment, 2.21; 95% CI 1.10 to 4.45), as were durations of 12 months or greater versus six months (OR 1.87; 95% CI 1.30 to 2.67). Adverse events were more common with higher doses and prolonged durations of treatment. Compared with no therapy, interferon increased the probability of histologic improvement (OR 9.22; 95% CI 5.69 to 14.94). The response to interferon in cirrhotic patients (virologic SR, 17%; 95% CI 11 to 26%) was similar to that in non-cirrhotic patients. However, interferon was no more effective than control in patients with normal aminotransferases. REVIEWER'S CONCLUSIONS: Interferon is effective in achieving viral clearance and improving liver biochemistry and histology in interferon naive patients with chronic hepatitis C. Higher doses and prolonged durations are more effective, but associated with more frequent adverse events. Interferon is associated with similar benefits in patients with cirrhosis, but the efficacy in patients with normal aminotransferases is unproven.

[Comparative efficacy of endoscopic sclerosis of esophageal varices by intravariceal injection of polidocanol and perivariceal injection of quinine-urea]. / Efficacité comparée de la sclérose endoscopique des varices oesophagiennes par injection intra-variqueuse de polidocanol et péri-variqueuse de quinine-urée.

Concerned by mortality due to recurrent bleeding and associated risk factors in cirrhotic patients, we attempted to compare the efficiency of perivascular sclerotherapy using quinine urea with that of intravascular polidocanol and to determine the predictive factors of clinical outcome. Of 74 patients admitted for bleeding esophageal varices, 31 were treated with perivascular sclerotherapy (group I), and 43 with intravascular sclerotherapy (group II). Three months later, only 63 p. 100 of patients in group I had not rebled, compared to 90 p. 100 of patients in group II (p less than 0.001). After 6 months, no significative difference was found between the two groups. The one year survival rate was 44 p. 100 in group I and 79 p. 100 in group II (p less than 0.002). Encephalopathy and ascites were found to be predictive factors of mortality, whereas neither clinical or biologic factors were found to be predictive for recurrent bleeding. These results suggest that in esophageal sclerotherapy, the intravascular route with polidocanol provides earlier results and a better one year survival rate, compared with the perivascular route. However, survival rates depend on encephalopathy and ascites criteria.

[Trace elements (zinc, copper, manganese) in alcoholic cirrhosis: effect of chronic alcoholism]. / Oligo-éléments (zinc, cuivre, manganèse) dans la cirrhose alcoolique: influence de l'alcoolisme chronique.

The authors studied the influence of alcohol intake and liver disease in the disturbances of trace elements detected in patients with alcoholic cirrhosis. A determination of zinc, copper and manganese was carried out in the serum, the 24 h urine and a liver sample in 15 patients with alcoholic cirrhosis, 11 chronic alcoholics and 17 control subjects. In the serum of cirrhotic patients, zinc was significantly decreased, copper and manganese significantly increased. In the liver, zinc was decreased and copper increased, but the difference did not read significantly. The elimination of zinc in urine was increased and that of manganese decreased. In the chronic alcoholic patients only the serum zinc was decreased. Chronic alcoholism seemed to be therefore one of the factors responsible for low serum zinc in patients with alcoholic liver disease.

[Is the intestinal lavage with a solution of mannitol effective in the prevention of post-hemorrhagic hepatic encephalopathy in patients with liver cirrhosis? Results of a randomized prospective study]. / Le lavage intestinal par une solution au mannitol est-il efficace dans la prévention de l'encéphalopathie hépatique post-hémorragique chez le malade atteint de cirrhose?

OBJECTIVES: The aim of this study was to evaluate the usefulness of whole gut irrigation with a mannitol solution in the prevention of hepatic encephalopathy in patients with cirrhosis and bleeding oesophageal or gastric varices. METHODS: The randomized prospective study included 40 patients with a mean age of 59.6 +/- 9.6 years. Bleeding was controlled by a Blakemore or Linton haemostatic tube, in all cases. The patients were divided into a "mannitol" group (n = 20) treated by whole gut irrigation with a 5 L solution containing 40 g/L of mannitol, and a "control" group (n = 20). The two groups did not differ for age, sex, aetiology of cirrhosis or gastrointestinal bleeding, Child-Pugh classification, delay of minimum fare or the number of transfused blood units. The onset of hepatic encephalopathy was investigated within the first 48 hours after the beginning of gastrointestinal bleeding. The grade of hepatic encephalopathy was established using an index with 4 criteria (mental status, asterixis, number connection test, arterial ammonia concentrations), each with 5 grades of severity. RESULTS: There were no adverse side-effects in the mannitol group. The incidence of hepatic encephalopathy (5 vs 30%) and the length of hospitalization (8.2 +/- 2.3 vs 13.6 +/- 3.1 days) were significantly decreased in the mannitol group (P < 0.05). Mortality was not different between the 2 groups (P = 0.4). CONCLUSION: Whole gut mannitol irrigation appears to be an effective, simple, inexpensive, well tolerated technique in the prevention of hepatic encephalopathy after variceal bleeding in patients with cirrhosis.

[Extrahepatic digestive surgery in cirrhotic patients: mortality, morbidity and preoperative prognostic factors]. / La chirurgie digestive extra-hépatique chez le cirrhotique: mortalité, morbidité, facteurs pronostiques pré-opératoires.

The purpose of this work was to study postoperative mortality and morbidity with respect to preoperative prognostic factors in 67 patients with alcoholic or posthepatitis cirrhosis. Surgical procedures involved the biliary tract (n = 20), stomach (n = 16), colon or rectum (n = 12), and hernia (n = 7). Thirteen preoperative clinical and biological variables were subjected to mono- and multivariate statistical analysis. The mortality rate was 23 p. 100. There was no statistical difference between the three main surgical procedures. No patients died after herniorrhaphy. The rate of morbidity was 37 p. 100. The most common complications were sepsis, organ failure, and ascites. Three preoperative variables were found to be different between survivors and non survivors: ascites, prothrombin time and the Child-Pugh score. Multidimensional analysis demonstrated that the only variable to have an independent unfavorable prognostic value was albuminemia. These results suggest that postoperative mortality following extrahepatic abdominal surgery in cirrhotic patients is: 1) especially high after digestive procedures, 2) increased by ascites, low prothrombin time and high Child-Pugh score. Only hypoalbuminemia had a significant independent explanatory value regarding prognosis.

c-Ha-ras polymorphism in patients with hepatocellular carcinoma. Comparison of healthy subjects and alcoholic patients with cirrhosis.

It has been observed that certain rare alleles of the c-Ha-ras gene occur more frequently in patients with certain malignant tumors than in healthy individuals, suggesting that these alleles may serve as markers for particular types of cancer. In this study, we compared the restriction fragment length polymorphism at the c-Ha-ras gene locus in 40 patients with cirrhosis and hepatocellular carcinoma with that in 39 patients with cirrhosis and in 42 normal subjects, all of Caucasian origin. Southern blotting of leukocyte DNA from the above patients, after digestion with either BamH1 or AvaII, revealed the presence of allele fragments of different sizes, corresponding to 4 common alleles and 3 rare alleles. The occurrence of the 3 rare alleles was not significantly different in the 3 populations studied. On the other hand, 2 of the common alleles, a3 (P < 0.01) and a4 (P < 0.03), were found at a significantly higher frequency in patients with cancer than in the 2 other groups. These results suggest that, in hepatocellular carcinoma, there is no increase in the frequency of occurrence of the rare alleles of the c-Ha-ras, but that the distribution of the common alleles may be modified.