Entecavir therapy for adefovir-resistant hepatitis B virus infection in kidney and liver allograft recipients

The aim of our study was to assess the efficacy and safety of entecavir in kidney- and liver-transplant recipients with chronic hepatitis B virus (HBV) infection. Ten male transplant patients with chronic HBV infection (eight kidney- and two liver-transplant patients), who have become adefovir (n=9) or lamivudine-resistant (n=1) were given entecavir at 0.5 to 1 mg/d. All patients were HBs Ag positive: six were HBe Ag(-)/HBe Ab(+), and four were HBe Ag(+)/HBe Ab(-). After a median follow-up of 16.5 months, entecavir therapy was associated with a significant decrease in HBV DNA viral load, that is, 3.86 (2.71-6.46) log10 copies/mL at baseline down to 2.94 (2.15-4) log10 copies/mL at last follow-up (P=0.004). Rate of HBV DNA clearance was 50% in both HBeAg(+) and HBeAg(-) patients. There were no significant changes in renal function or hematological parameters. This study demonstrates that entecavir therapy is safe and efficient in HBV(+) organ-transplant patients.     

JC virus DNA in the peripheral blood of renal transplant patients: a 1-year prospective follow-up in France

There is little information on JC virus (JCV) infection in renal transplant patients. A long-term prospective follow-up study was conducted to assess the incidence of JCV DNA in the blood of 103 adult renal transplant patients enrolled prospectively between 1 January and 31 December 2006. Patients were monitored until April 2008. JCV DNA was quantified by a real-time polymerase chain reaction in whole blood samples collected regularly for at least 1 year post-transplant. JCV was detected in seven patients (6.8%) (31/1,487 whole blood samples) at a median time of 139 days post-transplant. The median JC virus load of the first positive DNA blood sample was 3.4 log(10) copies/ml (1.9-5.7 log(10) copies/ml). Induction therapy were either anti-CD25 monoclonal antibodies (n = 5) or antithymocyte globulins (n = 2). Post-transplant immunosuppressive treatment included steroids with tacrolimus/mycophenolate mofetil (MMF) (n = 2), or ciclosporin/MMF (n = 1), or belatacept/MMF (n = 4). Two patients were also treated with rituximab. All seven patients infected with JCV had other viral infections(s): BK virus (3), Epstein-Barr virus (2), Cytomegalovirus (1) or both BK virus and Epstein-Barr virus (1). Three patients had BKV-associated nephropathy and decoy cells shedding. JCV infection was not associated with acute rejection episodes or nephropathy, regardless of the virus load. No patient developed progressive multifocal leukoencephalopathy during follow-up. Thus the incidence of JCV infection in renal transplant patients was low and not associated with any specific clinical manifestations. JCV replication must still be diagnosed and differentiated from BK virus infection because of its non-aggressive course.     

Relevance of individual characteristics for thermoregulation during exercise in a hot-dry environment

The aim of this study was to investigate the relevance of individual characteristics for thermoregulation during prolonged cycling in the heat. For this purpose, 28 subjects cycled for 60 min at 60% VO_2peak in a hot-dry environment (36 ± 1°C; 25 ± 2% relative humidity, airflow 2.5 m/s). Subjects had a wide range of body mass (99–43 kg), body surface area (2.2–1.4 m²), body fatness (28–5%) and aerobic fitness level (VO_2peak = 5.0–2.1 L/min). At rest and during exercise, rectal and mean skin temperatures were measured to calculate the increase in body temperature (ΔT _body) during the trial. Net metabolic heat production (M _NET) and potential heat loss (by means of evaporation, radiation and convection) were calculated. Although subjects exercised at the same relative intensity, ΔT _body presented high between-subjects variability (range from 0.44 to 1.65°C). ΔT _body correlated negatively with body mass (r = −0.49; P < 0.01), body surface area (r = −0.47; P < 0.01) and T_body at rest (r = −0.37; P < 0.05), but it did not significantly correlate with body fatness (r = 0.12; P > 0.05). ΔT _body positively correlated with the body surface area/mass ratio (r = 0.46; P < 0.01) and the difference between M _NET and potential heat loss (r = 0.56; P < 0.01). In conclusion, a large body size (mass and body surface area) is beneficial to reduce ΔT _body during cycling exercise in the heat. However, subjects with higher absolute heat production (more aerobically fit) accumulate more heat because heat production may exceed potential heat loss (uncompensability).     

Prevalence of cryoglobulinemia and autoimmunity markers in renal-transplant patients

AIMS: To examine the prevalence of cryoglobulinemia (Cryo) and autoimmune markers in renal-transplant recipients in a stable condition, and to determine its risk factors and impact upon allograft function. PATIENTS AND METHODS: In May, 2006, 117 kidney-transplant (KT) recipients, aged 31 a 76 years, were tested for cryoglobulinemia, hepatitis B and C, complement C3, C4, CH50, antinuclear (ANAs), anticytoplasmic nuclear (ANCAs) and anticardiolipid antibodies, rheumatoid factor (RF), and lymphocyte subpopulations. Renal, liver, and hematological tests were also performed. Immunosuppressive regimens were based on calcineurin inhibitors (82%). RESULTS: Cryo was positive in 47 patients (Cryo(+): 40.2%), of whom 13 were HCV+ (27.7%), with characteristics of Type II in 21.2% and Type III in 78.8%. Cryo was positive in 13/16 (81.2%) of HCV+/RNA+ patients vs. 34/101 (33.6%, p = 0.0003) of HCV-negative patients. Cryo(+) RT patients had been recipients of a graft for longer (142 months) than Cryo(-) patients, i.e., 95 months (p = 0.02). Creatinine clearances were similar in the two groups (56 vs. 50 ml/mn, p = 0.5), as were microalbuminuria and albuminemia. There was no difference between Cryo(-) and Cryo(+) patients in terms of age, sex, HLA mismatch, daily steroid doses, liver and hematological tests, ANAs, anticardiolipid antibodies, serum complement, and lymphocyte subpopulations. RF occurred in all Cryo(+) patients and in 82.8% of Cryo(-) patients, with higher titers in the Cryo(+) group (23 vs. 9 UI/ml, p = 0.012). ANCA occurred in nine Cryo(-) but in no Cryo(+) patients (p = 0.013). Finally, a multivariate analysis was not able to determine any predictive factor associated with cryoglobulinemia. CONCLUSION: Cryoglobulinemia is frequent after KT, and is associated with HCV markers, RF, and absence of ANCA.     

Alteration of direct and indirect effects of cytomegalovirus

For recipients of a solid organ transplant, cytomegalovirus infection causes many pathological conditions including direct and indirect effects, most notably owing to the potency of the immunosuppressive medications used. Effects attributed to cytomegalovirus infection include graft rejection, decreased graft and patient survival rates, predisposition to other opportunistic infections, virally mediated malignancies, and various injuries specific to the transplanted organs (eg, accelerated coronary atherosclerosis following heart transplant, bronchiolitis obliterans syndrome in lung transplants, and vanishing bile-duct syndrome in liver allografts). Other indirect effects include posttransplant lymphoproliferative disorders, posttransplant new onset diabetes, and recurrence of hepatitis C virus infection. Direct effects are related to viral burden, whereas indirect effects may be observed even in the presence of low levels of cytomegalovirus replication. Being a function of the interaction between the virus and the host's immune and inflammatory responses, the underlying indirect effects of viral infection are not completely understood. Whereas it has been shown that cytomegalovirus prophylaxis can decrease the direct and indirect effects of the virus, recent data indicate that pre-emptive therapy has no long-term impact upon the indirect effects. Prevention of cytomegalovirus-related indirect effects might be achieved only with prophylaxis.     

Perihepatitis and perinephric abscess due to Mycoplasma hominis in a kidney transplant patient

Mycoplasma hominis has been incriminated in several genital and extragenital infections. Here, we report the first case of perihepatitis associated with a perinephric abscess in a woman who had received a kidney transplant. Four months after the transplant, the patient was admitted for perirenal allograft pain, fever, and elevated inflammatory parameters and liver enzyme levels. A renal ultrasonography found a collection of fluid. Results of blood and urine analyses were within normal limits. Fluid aspiration of the peritoneal cavity was performed, and the results of cultures for bacteria and fungi were negative. The patient was treated by surgical lavage of the peritoneal cavity. Her fever resolved 5 days later. Two months after surgical lavage of the peritoneal cavity, her liver enzyme levels returned to the normal range. Three months after surgical lavage, cultures of the perinephric fluid showed Mycoplasma hominis. We conclude that in patients who present with perinephric fluid suspected of being infected, bacteriologic analysis of the fluid (from surgical lavage of the peritoneal cavity) should be performed. Antibiotics active against intracellular bacteria should be administered.     

Remdesivir for COVID‐19 pneumonia in patients with severe chronic kidney disease: A Case series and review of the literature

Remdesivir was the first antiviral agent to receive FDA authorization for severe COVID‐19 management, which restricts its use with severe renal impairment due to concerns that active metabolites might accumulate, causing renal toxicities. With limited treatment options, available evidence on such patient groups is important to assess for future safety.     

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Background & Aims

Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH).

Methods

A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded.

Results

The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4–53.8). Median follow-up was 87.0 months (IQR, 43.5–168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4–6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2–5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5–5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4–6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2–3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0–3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2–3.5; p = 0.006) complications.

Conclusion

Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.