The trial showed that low-dose interleukin-2 was not associated with adverse effects and led to Treg recovery and concomitant clinical improvement in patients with HCV-induced vasculitis, an autoimmune condition. (Funded by the French Agency for Research on AIDS and Viral Hepatitis [ANRS] and others; ClinicalTrials.gov number, NCT00574652.).

The impact of hepatitis B (HBV) and C (HCV) on patient survival after kidney transplantation is controversial. The aims of this study were (1) to assess the independent prognostic values of HBsAg and anti-HCV in a large renal transplant population, (2) to compare infected patients with noninfected patients matched for factors possibly associated with graft and patient survival, and (3) to assess the prognostic value of biopsy-proven cirrhosis. Eight hundred thirty-four transplanted patients were included: 128 with positive HBsAg (group I), 216 with positive anti-HCV (group II), and 490 without serological markers of HBV and HCV (group III). Fifteen percent and 29% of patients were HBsAg-positive and anti-HCV-positive, respectively. Tenyear survivals of group I (55 ؎ 6%) and group II (65 ؎ 5%) were significantly lower than survival of group III (80 ؎ 3%, P F .001). At 10 years, among overall patients with HCV screening (n ‫؍‬ 834), four variables had independent prognostic values in patient survival: age at transplantation (P F .0001), year of transplantation (P ‫؍‬ .02), biopsyproven cirrhosis (P ‫؍‬ .03), and presence of HCV antibodies (P ‫؍‬ .02). In the case control study, comparison of infected patients with their matched control patients showed that age at transplantation (P F .05), HBsAg (P ‫؍‬ .005), and anti-HCV (P ‫؍‬ .005) were independent prognostic factors. HCV, biopsy-proven cirrhosis, and age are independent prognostic factors of 10-year survival in patients with kidney grafts. The case-control study showed that anti-HCV and HBsAg were independently associated with patient and graft survivals. In infected patients, a routine liver histological analysis would improve selection of patients for renal transplantation.(HEPATOLOGY 1999;29:257-263.) Improvement in renal transplantation in the past 25 years has been the result of better immunosuppression, organ preservation, and patient selection. 1,2 In patients receiving a kidney transplant, chronic liver disease remains a major problem and leads to enhanced morbidity and mortality. 3 In these cases, HBV and HCV infection are the main causes of liver injury. [4][5][6] In transplanted patients, immunosuppressive therapy increases viral replication, and disappearance of anti-HCV antibodies is observed in 20% of cases. [5][6][7][8] Paradoxically, no consensus is available concerning the prognostic influence of HBV and HCV infections on graft and patient survival.Although liver injury progression seems to be greater in transplanted patients than in immunocompetent patients, the influence of HBV on patient and graft survival remains controversial. 4,9-14 These contradictory results may be attributed to the wide heterogeneity of characteristics of patients at the time of transplantation.In kidney transplanted patients, prevalence of HCV infection ranged from 20% to 30%. [15][16][17][18] Now, since the advent of routine HBV vaccination, most hepatic diseases in kidney transplantation are mainly a result of HCV virus infection. 19,20 The most frequent risk facto...

Background:The FibroTest and ActiTest are noninvasive biochemical markers of liver injury that are intended for use as alternatives to liver biopsy in patients with chronic hepatitis C. The aims of this study were to assess the quality of biopsy and the prevalence of discordances between biopsy and markers, to identify factors associated with discordances, and to attribute these discordances to either markers or biopsy failure. Methods: Fibrosis stage and activity grade were prospectively assessed on the same day by a liver biopsy and by markers. On the basis of risk factors for failure and independent endpoints, discordance was classified as being attributable to biopsy or to markers. Results: Only 74 of 537 patients (14%) had a biopsy size >25 mm. Discordance was observed in 154 of 537 patients (29%), including 16% for fibrosis staging and 17% for activity grading. Steatosis, an inflammatory profile, and biopsy size were associated with discordance. Discordance was attributable to failure of markers in 13 patients (2.4%) and to biopsy failure in 97 (18%; P <0.001 vs Fibrotest and Actitest), and was nonattributable in 44 patients (8.2%). The most frequent failures attributable to markers were false negatives (1.3%) attributable to inflammation. The most frequent failures attributable to biopsy were false negatives of activity grading (10.1%) and of fibrosis staging (4.5%), both associated with smaller biopsy size and steatosis. False

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10−4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10−3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

Hepatitis B virus (HBV) resistance to lamivudine has not been extensively documented in human immunodeficiency virus (HIV)-infected patients. We studied the long-term incidence of HBV resistance to lamivudine in HIV-positive patients. Sixty-six HIV-HBV-coinfected patients were studied while receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy. All these patients had a detectable serum HBV DNA at the beginning of lamivudine therapy. Serum HBV DNA was quantified by molecular hybridization. Sequence analysis of the HBV polymerase was performed in patients who became resistant to lamivudine. After 2 months of lamivudine, HBV DNA became undetectable in 57 patients (86.4%, 95% CI: 75.7%-93.6%). After 2 years of lamivudine, 47% ؎ 18.6% of the patients, had sustained HBV-DNA suppression. In deeply immunosupressed HIV-HBV-coinfected patients, histological and biological activities are lower than in HIVnegative patients. 2,5 However, the natural history of liver fibrosis of coinfected patients has not been studied. Furthermore, the underlying liver disease of HIV-HBV-coinfected patients with immune restoration related to potent antiretroviral therapy is currently unknown.In HIV-HBV-coinfected patients, inhibition of HBV replication had been obtained in less than 8% of the cases with interferon alfa. 6,7 Lamivudine, an oral nucleoside analogue, is effective against both HIV and HBV replication. Lamivudine has promptly inhibited HBV replication in more than 80% of cases in both HIV-and non-HIV-infected patients. 8-10 However, HBV resistance to lamivudine caused by HBV-DNA polymerase gene mutations has been reported in both liver transplanted and immunocompetent patients. 8,[11][12][13][14][15][16][17] Incidence of HBV resistance to lamivudine is of 14% to 27% after 1 year of treatment in non-HIV-infected patients. 8,11 HBV resistance to lamivudine in HIV-infected patients has not been studied. We retrospectively analyzed a cohort of HIV-HBV-coinfected patients receiving lamivudine as a part of their antiretroviral therapy to study the long-term incidence of HBV resistance to lamivudine and to assess risk factors associated with this resistance. PATIENTS AND METHODSPatients. Studied patients belong to a cohort of 226 consecutive HBsAg carriers HIV-infected patients followed-up at our infectious diseases department since 1986. Patients were included if they fulfilled all the following criteria: (1) were receiving lamivudine (150 mg twice daily) as a part of antiretroviral therapy; (2) had a detectable serum HBV DNA by molecular hybridization at the beginning of lamivudine therapy. HBV-precore mutant infected patients (positive serum anti-HBe antibodies [HBeAb], negative HBeAg, and detectable serum HBV DNA) were also included; and (3) had serum HBV DNA and HBV-serological markers determinations at the second month of lamivudine therapy and at least twice during lamivudine therapy. Patients with hepatitis C or delta virus coinfections and those who had received a potent anti-HBV drug (ganciclovir, fosca...

Hepatitis C virus (HCV)-related liver fibrosis progression is accelerated in human immunodeficiency virus (HIV)-

In chronic hepatitis B (CHB), the persistence of hepatitis B surface antigen (HBs Ag) is sometimes associated with antibodies (Ab) to HBs (anti-HBs). To assess the hypothesis of the selection of HBs Ag immune escape variants in CHB patients, the variability of the HBV S gene was determined for patients persistently carrying both HBs Ag and anti-HBs antibodies and patients solely positive for HBs Ag. We selected 14 patients who presented both markers (group I) in several consecutive samples and 12 patients positive for HBs Ag only (group II). The HBs Ag-encoding gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed. The number of residue changes within the S protein was 2.7 times more frequent for group I than for group II patients and occurred mostly in the "a" determinant of the major hydrophilic region (MHR), with 9.52 versus 2.43 changes per 100 residues (P ‫؍‬ 0.009), respectively. Ten patients (71%) from group I, but only three (25%) from group II, presented at least two residue changes in the MHR. The most frequent changes in group I patients were located at positions s145, s129, s126, s144, and s123, as described for immune escape variants. In CHB patients, the coexistence of HBs Ag and anti-HBs Ab is associated with an increase of "a" determinant variability, suggesting a selection of HBV immune escape mutants during chronic carriage. The consequences of this selection process with regard to vaccine efficacy, diagnosis, and clinical evolution remain partially unknown.

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