A practical approach to tuberculosis diagnosis and treatment in liver transplant recipients in a low-prevalence area.

Solid organ transplant candidates/recipients are at risk of mycobacterial infections. Although guidelines on the management of latent tuberculosis infection and active tuberculosis are available for solid organ transplant recipients, limited guidance focuses on end-stage liver disease or liver transplant recipients who require management in a referral center. Therapeutic challenges arise from direct antituberculosis drug-related hepatotoxicity, and substantial metabolic interactions between immunosuppressive and antituberculosis drugs. Another issue is the optimal timing of therapy with regards to the time of transplantation. This review focuses on the importance of tuberculosis screening with immunological tests, challenges in the diagnosis, management, and treatment of latent tuberculosis infection and active tuberculosis, as well as risk assessment for active tuberculosis in the critical peri-liver transplantation period. We detail therapeutic adjustments required for the management of antituberculosis drugs in latent tuberculosis infection and active tuberculosis, particularly when concomitantly using rifampicin and immunosuppressive drugs.

Safety of sofosbuvir-based regimens after liver transplantation: longitudinal assessment of renal function in the prospective ANRS CO23 CUPILT study.

BACKGROUND: In liver transplant recipients with hepatitis C virus recurrence, there is concern about renal safety of sofosbuvir-based regimens. Changes in serum creatinine or in the estimated glomerular filtration rate (eGFR) under treatment are used to look for possible renal toxicity. However, serum creatinine and eGFR are highly variable. AIM: To analyse renal function trajectory with numerous assays of serum creatinine over a long period of time. METHODS: In a multicentre cohort of 139 patients, the eGFR was obtained from serum creatinine using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. Slopes of eGFR were defined as a change in eGFR during a period divided by time. Pre-treatment, on-treatment and post-treatment periods were 9 months, 3-9 months and 4.5 months. Interactions between eGFR slopes and the pre-treatment eGFR, use of ribavirin or mycophenolate mofetil, and stage of fibrosis were addressed. On-treatment eGFR slopes were separated in tertiles. Pre- and post-treatment eGFR slopes were compared globally and according to tertiles. RESULTS: The post-treatment eGFR slope was significantly better than pre-treatment eGFR slope (+0.18 (IQR -0.76 to +1.32) vs -0.11 (IQR -1.01 to +0.73) mL/min/1.73 m2 /month, P = 0.03) independently of the pre-treatment eGFR (P = 0.99), ribavirin administration (P = 0.26), mycophenolate mofetil administration (P = 0.51) and stage of fibrosis (F3 and F4 vs lower stages, P = 0.18; F4 vs lower stages, P = 0.08; F4 Child-Pugh B and C vs lower stages, P = 0.38). Tertiles of on-treatment eGFR slopes were -1.71 (IQR -2.54 to -1.48), -0.78 (IQR -1.03 to -0.36) and +0.75 (IQR +0.28 to +1.47) mL/min/1.73 m2 /month. Pre- and post-treatment eGFR slopes were not significantly different according to tertiles (respectively, P = 0.34, 0.08, 0.73). CONCLUSION: The eGFR varies during treatment and gives a confusing picture of the renal safety of sofosbuvir-based regimens. In contrast, longitudinal assessment of the eGFR shows a rising trajectory over longer time, meaning that these therapies are safe for the kidneys in our cohort of liver transplant recipients.

Histological benefit of retreatment by pegylated interferon alfa-2b and ribavirin in patients with recurrent hepatitis C virus infection posttransplantation.

We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.

Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence.

BACKGROUND AND AIMS: A proportion of liver transplanted patients with recurrent chronic hepatitis have a sustained virological response to combination therapy with interferon plus ribavirin. However, the long term benefit of antiviral therapy with regard to hepatitis C virus (HCV) RNA clearance remains unknown in patients with HCV recurrence. This study examined the long term biochemical, virological, and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy. PATIENTS AND METHODS: Fifty four patients with recurrent hepatitis C were treated with antiviral therapy involving induction by combination therapy (interferon (IFN) plus ribavirin) for six months and maintenance ribavirin therapy for 12 months. Fourteen patients who had recurrent chronic hepatitis and sustained virological response to antiviral therapy were followed for three years after the end of antiviral therapy. Serum alanine aminotransferases were assessed every three months during the observation period. Serum hepatitis C RNA detected by polymerase chain reaction was evaluated every six months during follow up, and protocol biopsy procedures were performed routinely every year. Semiquantitative histopathological assessment of allograft hepatitis was performed using the Knodell score and HCV was also detected by polymerase chain reaction on frozen graft tissue samples. RESULTS: At the end of antiviral therapy, the sustained response rate was 26%. A complete response (normal serum alanine aminotransferase level and undetectable serum HCV RNA) was achieved in 13/14 (93%) patients three years after the end of treatment. A comparison of liver histology findings before and after a mean of three years after antiviral therapy showed a clear improvement in 12/14 (86%) patients. In 5/14 (36%) patients, the last biopsy showed normal or near normal histological findings. After three years of follow up, the total Knodell score was 3.2 (range 1-8) versus 8.3 (range 5-12) before treatment (p=0.001). Graft HCV RNA was detectable before treatment in all 14 patients and was undetectable at the end of follow up in 13/14 (93%) patients tested. CONCLUSION: In patients with biochemical and virological responses induced by ribavirin and interferon, a complete response was sustained in 93% for at least three years after cessation of therapy. This long term response was associated with absence of detectable intrahepatic hepatitis C RNA and marked histological improvement.

[Hepatitis G virus in blood donors]. / Virus de l'hépatite G chez les donneurs de sang.

PURPOSE: Anti-hepatitis C virus (HCV) antibodies (Abs) screening on blood donors has been introduced in France on March 1st, 1990. During the last years, a new agent named Hepatitis G Virus (HGV) has been described. We have tested different groups of blood donors with the aim of establishing the prevalence of the HGV. METHODS: Two hundred and forty-three donors negative for anti-HCV Abs, other viral markers and with normal Alanine Amino Transferase (ALT) as control [group 1], 91 with elevated ALT [group 2], 72 with Abs directed against the hepatitis B virus core (Anti-HBc) [group 3], 3 with elevated ALT and anti-HBc Abs [group 4] and 70 positive for anti-HCV Abs [group 5] were evaluated. HCV-RNA was tested by Polymerase Chain Reaction (PCR) (Amplicor, Roche) and HGV-RNA by in house PCR and Abbott Kit. Anti-HGV Abs were tested with Boehringer and/or Abbott tests. RESULTS: Among group 1, none subject is found HCV-RNA positive. Seven (2.9%) are HGV viremic and 19 positive for anti-HGV Abs (7.8%). Four (4.4%) and 5 (6.9%) donors were HGV-RNA positive and 15 (16.5%) and 16 (22.2%) anti-HGV Abs positive in group 2 and 3 respectively. In group 4, 2 donors are anti-HGV Abs positive. Furthermore, in group 5, 52 subjects (74.3%) are HCV-RNA positive and 9 HGV-RNA positive (12.9%). Six donors are viremic for the both viruses. Lastly, 26 donors have anti-HGV Abs (37.1%). None subject of the five groups has both HGV-RNA and anti-HGV Abs. CONCLUSION: The prevalence of HGV-RNA and anti-HGV is high among control donors. In donors with one or two hepatitis surrogate markers (ALT and/or anti-HBc Abs), the prevalence of HGV viremia and anti-HGV Abs is increased as well as among donors with HCV infection.

[Hemorrhagic complications of anti-vitamin K treatments]. / Complications hémorragiques des traitements antivitamine K.

Among iatrogenic complications of oral anticoagulation, hemorrhagic complications are the most frequent and potentially lethal. The major hemorrhagic risk is the intensity of anticoagulation. A decrease of this risk is obtained with tapering of INR. Age, sex, anticoagulant therapy, and other personal risk factors as duration of anticoagulation, are factors not admitted by all the authors. Our experience at Hôtel-Dieu University Hospital and the literature data provide evidence that patient follow-up in a specialized center should decrease the incidence of hemorrhagic complications.