The natural history of occult hepatitis B virus infection (OBI) and the mechanism involved in HBV reactivation are only partially understood. As regards people living with HIV (PLWH), HBV ...reactivation is estimated to occur with an incidence ratio of 0.019 cases per 100 person-year. Here we report the case of OBI reactivation in a HIV/HCV co-infected patient followed for 25 years at our Infectious Diseases Unit, but, unfortunately, lost to follow-up about 19 months after Direct-acting antivirals (DAAs) treatment. At re-engagement, blood tests showed high replication of plasmatic HIV-RNA along with severe immunosuppression and normal levels of liver enzymes. However, 3 months after ART reintroduction, an immune reconstitution inflammatory syndrome (IRIS) was diagnosed with high detectable HBV-DNA load and transaminase elevation. Our case report shows how the balance between the virus and the host immune system is quite a dynamic process that might significantly impact the course of the disease. The aim of this case report is to bring to the attention of physicians that, although OBI reactivation is a rather rare occurrence, even amongst PLWH, its potential consequences compel to a high alertness on the matter. Therefore, especially in patients with an impaired immune system and on a tenofovir or lamivudine-sparing regimen, HBV serological and virological markers should always be strictly monitored, even in the absence of a hepatitis flare.
Approved direct antiviral agent (DAA) combinations are associated with high rates of sustained virological response (SVR) and the absence of a detectable hepatitis C viral load 12-24 weeks after ...treatment discontinuation. However, a low percentage of individuals fail DAA therapy. Here, we report the case of a HIV/HBV/HCV co-infected patient who failed to respond to DAA pangenotypic combination therapy. The sequencing of NS5a, NS5b, NS3 and core regions evidenced a recombinant intergenotypic strain 4/1b with a recombination crossover point located inside the NS3 region. The identification of this natural recombinant virus underlines the concept that HCV recombination, even if it occurs rarely, may play a key role in the virus fitness and evolution.
Background and Aims
To date, the literature shows that HCV eradication with DAA leads to remission from HCV-related cryoglobulinemic syndrome (CS). The goal of our study is to evaluate the effect of ...DAA treatment on cryoglobulinemic kidney disease.
Method
Since 2015, 58 patients (pts) have been treated in our Centre; among them we have selected 12 pts with active kidney disease at the time of treatment. Clinical manifestations, renal function and immunological tests were monitored during follow-up (range 6-48 months).
Results
General characteristics of the population are shown in Table 1.
At the time of treatment 6 pts had nephritic syndrome (sdr), 1 had nephrotic sdr and 5 pts had mixed nephritic-nephrotic sdr.
It should be noted that 8/12 pts had been treated with Rituximab (RTX) in the 6 months preceding the DAA; despite that they had active disease at baseline.
Ten out of 12 pts went into complete remission after HCV-eradication, 1 went into partial remission. One pt, never treated, did not respond clinically to HCV eradication and therefore underwent RTX therapy.
Other 2 pt with a recent diagnosis of cryoglobulinemic syndrome came to our attention with a clinical picture of nephritic sdr: they’d never been treated with immunosuppressive therapy and get remission only whit HCV eradication.
One pt, although complete CS remission, started hemodialysis for ESRD secondary to ADPKD.
During follow-up 3 pts underwent CS relapse: 2 pts, one with lymphoma, were retreated with RTX after 12 and 48 months respectively; 1 pt, with type I cryoglobulinemia and clinical manifestation of vasculitis, died of acute disease reactivation in Cameroon after 9 months from the end of DAA.
By evaluating the overall population there is a rapid and prolonged clinical response to DAA therapy, in particular a complete resolution of skin ulcers (Tab 2).
Cryocrit decreases and C3 and C4 increase early and persistently after treatment; vice versa the rheumatoid factor does not undergo significant variations.
Proteinuria is reduced at the end of the treatment (EOT) and shows a decreasing trend also afterwards; urinary sediment is drastically reduced at EOT and further decreases during follow-up up to the presence of only isolated urinary anomalies in almost all patients (Tab 3).
Conclusion
The eradication of HCV, and therefore the removal of the immunological stimulus underlying the cryogloblinemic syndrome, appears to be crucial in the control of cryoglobulinemic glomerulonephritis, also after failure of RTX treatment.
However, relapses at variable interval from DAA therapy do not allow us to lose these patients to follow-up even after several years from disease remission.
Penitentiaries have a higher burden of communicable diseases compared to the general population. Prisoners should be tested for hepatitis C virus (HCV) and have direct access to treatment. We ...analysed the HCV cascade of care in two penitentiaries in Brescia, Northern Italy. At admission, prisoners are offered a voluntary screening for HCV, while patients with known infections are tested with an HCVRNA measurement. We performed an observational retrospective study including all the subjects admitted to the penitentiaries from 1 January 2015 to 31 October 2021. We conducted a descriptive analysis. During the study period, 5378 admissions were registered, and 2932 (54.5%) screenings were performed. Hepatitis C virus antibody positivity was found in 269 tests (9.2%). Hepatitis C virus RNA was detectable in 169 people. During the study period, 77 treatments with direct-acting antivirals (DAAs) were administered. Follow-up was available in 45 patients, and sustained virological response (SVR) was documented in 44 of them. Retention in care occurred in less than half of the prisoners after release. Our data demonstrate poor screening adherence that could benefit from educational programs. Treatment rates could be improved with test-and-treat programs. More efforts are needed to eliminate HCV as a public threat by 2030. Dedicated local networks, including infectious diseases (ID) departments, substance abuse services and prisons, could mitigate these issues.
Highlights • Tenofovir (TDF) is increasingly used to treat CHB patients worldwide. • We describe two cases of TDF-induced Fanconi syndrome in CHB patients. • Fanconi syndrome reverted after TDF ...withdrawal while HBV was suppressed by ETV. • Glomerular and tubular function should be carefully monitored in patients under TDF. • Several factors, including age and ADV exposure, may increase the risk of this complication.
Background & Aims Twenty-four weeks of treatment with peginterferon and ribavirin for chronic hepatitis C virus (HCV) genotype 2 or 3 infection produces a sustained virologic response (SVR) in ...70%–80% of patients. We performed a randomized, double-blind, phase 2b study to assess whether adding daclatasvir, a nonstructural protein 5A (NS5A) inhibitor that is active against these genotypes, improves efficacy and shortens therapy. Methods Patients with HCV genotype 2 or 3 infection (n = 151), enrolled at research centers in North America, Europe, or Australia, were assigned randomly to groups given 12 or 16 weeks of daclatasvir (60 mg once daily), or 24 weeks of placebo, each combined with peginterferon alfa-2a and ribavirin. Treatment was extended to 24 weeks for recipients of daclatasvir who did not meet the criteria for early virologic response. The primary end point was SVR at 24 weeks after treatment (SVR24). Results Baseline characteristics were similar among patients within each HCV genotype group. However, the 80 patients with HCV genotype 3, compared with the 71 patients with HCV genotype 2, were younger (mean age, 45 vs 53 y, respectively), and a larger proportion had cirrhosis (23% vs 1%, respectively). Among patients with HCV genotype 2 infection, an SVR24 was achieved by 83%, 83%, and 63% of those in the daclatasvir 12-week group, the daclatasvir 16-week group, or the placebo group, respectively; among patients with HCV genotype 3 infection, an SVR24 was achieved by 69%, 67%, and 59% of patients in these groups, respectively. Differences between genotypes largely were attributable to the higher frequency of post-treatment relapse among patients infected with HCV genotype 3. In both daclatasvir arms for both HCV genotypes, the lower bound of the 80% confidence interval of the difference in SVR24 rates between the daclatasvir and placebo arms was above –20%, establishing noninferiority. Safety findings were similar among groups, and were typical of those expected from peginterferon alfa and ribavirin therapy. Conclusions Twelve or 16 weeks of treatment with daclatasvir, in combination with peginterferon alfa-2a and ribavirin, is a well tolerated and effective therapy for patients with HCV genotype 2 or 3 infections. Daclatasvir-containing regimens could reduce the duration of therapy for these patients. Clinicaltrials.gov number: NCT01257204.
Background and Aims
Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, ...multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF‐associated glomerular and/or tubular dysfunction.
Methods
A total of 103 TDF‐treated patients were included as follows: age 64 years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV‐R) and 71% previously treated with adefovir. Twenty‐nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFRMDRD) was <60 mL/min, 37 (36%) because blood phosphate (P) levels were <2.5 mg/dL and 37 (36%) for both reasons. Kidney, liver and virological parameters were recorded every 4 months thereafter.
Results
During 46 (4‐115) months of ETV treatment, all patients’ renal parameters significantly improved as follows: creatinine from 1.30 to 1.10 mg/dL (P < 0.0001), eGFRMDRD from 54 to 65 mL/min (P = 0.002), P from 2.2 to 2.6 mg/dL (P < 0.0001) and maximal tubule phosphate reabsorption (TmPO4/eGFR) from 0.47 to 0.62 mmol/L (P < 0.0001). Thirteen patients (52%) improved their eGFRMDRD class, P levels were normalised in 13 (35%), and eight (22%) showed improvements in both parameters. Viral suppression was maintained in all but five patients (5%), all of whom had been LMV‐R. The 5‐year cumulative probability of ETV‐R was 0% in LMV‐naïve patients, and 11% in LMV‐R patients (P = 0.018).
Conclusions
Entecavir is an effective and safe rescue strategy for CHB patients who develop renal dysfunction during long‐term TDF treatment.
Sofosbuvir (SOF)-based regimens have been associated with renal function worsening in HCV patients with estimated glomerular filtration rate (eGFR) ≤ 45 ml/min, but further investigations are ...lacking.
To assess renal safety in a large cohort of DAA-treated HCV patients with any chronic kidney disease (CKD).
All HCV patients treated with DAA in Lombardy (December 2014–November 2017) with available kidney function tests during and off-treatment were included.
Among 3264 patients 65% males, 67% cirrhotics, eGFR 88 (9–264) ml/min, CKD stage was 3 in 9.5% and 4/5 in 0.7%. 79% and 73% patients received SOF and RBV, respectively. During DAA, eGFR declined in CKD-1 (p < 0.0001) and CKD-2 (p = 0.0002) patients, with corresponding rates of CKD stage reduction of 25% and 8%. Conversely, eGFR improved in lower CKD stages (p < 0.0001 in CKD-3a, p = 0.0007 in CKD-3b, p = 0.024 in CKD-4/5), with 33–45% rates of CKD improvement. Changes in eGFR and CKD distribution persisted at SVR. Baseline independent predictors of CKD worsening at EOT and SVR were age (p < 0.0001), higher baseline CKD stages (p < 0.0001) and AH (p = 0.010 and p < 0.0001, respectively).
During DAA, eGFR significantly declined in patients with preserved renal function and improved in those with lower CKD stages, without reverting upon drug discontinuation.
PDF