Hepatitis C viral load and mother-to-child transmission: A systematic review and meta-analysis.

BACKGROUND AND AIM: We aim to assess the association between maternal hepatitis C virus (HCV) viral load and human immunodeficiency virus (HIV) coinfection and the risk for mother-to-child transmission (MTCT) among pregnant women infected with HCV. METHODS: A literature search of the Medline, Embase, Central, Science Citation Index Expanded (SCIE), Conference Proceedings Citation Index-Science (CPCIS), Scopus, Literature Latino-Americana e do Caribe em Ciências da Saúde (LILACS), and WHO Global Index Medicus databases, from inception to June 21, 2022, was performed. Studies that reported the incidence HCV-MTCT were included. Pooled effect estimates were calculated using the random-effects model, and Holm-Bonferroni correction was performed for multiple pooled associations. RESULTS: The present meta-analysis included 26 studies involving 4934 newborns with maternal HCV infection. Pregnant women with HCV viremia exhibited increased risk for MTCT (odds ratio [OR] 8.25 [95% confidence interval (CI) 4.65-14.63]) compared with those negative for HCV-RNA. Multiple subgroup analysis revealed that the HCV viremia/HIV-positive group demonstrated the highest risk for HCV MTCT, followed by the HCV viremia mono-infected group, while HCV-RNA-negative women demonstrated the lowest risk for HCV MTCT. Among females with HCV viremia, elevated risk for MTCT was found among subjects with a viral load ≥ 6 log10 copies/mL compared with those with viral load < 6 log10 copies/mL (OR 4.58 [95% CI: 2.52-8.34]). CONCLUSION: The incidence of HCV MTCT was increased among pregnant women with detectable HCV viremia and was even higher in those with a viral load ≥ 6 log10 copies/mL. HIV coinfection further increased the risk for HCV MTCT.

HCV viraemia associates with NK cell activation and dysfunction in antiretroviral therapy-treated HIV/HCV-co-infected subjects.

The impact of hepatitis C virus (HCV) RNA levels on immune status in chronically HCV mono-infected when compared to HIV/HCV co-infected on antiretroviral therapy (ART) remains poorly understood. A total of 78 African American subjects HCV viraemic/naïve to HCV treatment (33 HCV genotype 1 mono-infected, 45 ART-treated HIV/HCV genotype 1 co-infected) were studied. Clinical and liver enzyme measurements were performed. Whole blood was analysed for immune subset changes by flow cytometry. Peripheral blood mononuclear cells (PBMC) were used for same-day constitutive and in vitro Interferon (IFN)-α-induced signal transducer and activator of transcription (STAT) phosphorylation, K562 target cell lysis and K562 target cell recognition-mediated IFN-γ production. Statistical analysis was performed using R (2.5.1) or JMP Pro 11. While both groups did not differ in the level of liver enzymes, HIV/HCV had higher T-cell activation/exhaustion, and constitutive STAT-1 phosphorylation compared to HCV. In contrast, CD4+ FoxP3+ CD25+ frequency, IFN-αR expression on NK cells, as well as constitutive and IFN-α-induced direct cytotoxicity were lower in HIV/HCV. Linear regression models further supported these results. Finally, increase in HCV viral load and CD4+ T-cell count had an opposite effect between the two groups on NK cell activity and T-cell activation, respectively. HCV viral load in ART-treated HIV/HCV co-infection was associated with greater immune activation/exhaustion and NK dysfunction than HCV viral load alone in HCV mono-infection. The more pronounced immune modulation noted in ART-treated HIV-co-infected/untreated HCV viraemic subjects may impact HCV disease progression and/or response to immunotherapy.

Does low-dose prolonged steroid therapy affect the natural history of chronic hepatitis C?

Chronic hepatitis C patients may require steroids due to other comorbidities. However, there is not enough information to consider steroids as beneficial or harmful drugs on natural history of chronic hepatitis C. The aim of the present study was to examine the effect of low-dose prolonged therapy with corticosteroids with or without azathioprine on these study patients. A retrospective-prospective observational study was established. Twenty-eight patients with chronic hepatitis C and treated with corticosteroids at low-dose (≤30 mg/day) with or without azathioprine for more than 6 months were included. AST, ALT, HCV RNA, and liver fibrosis were determined, and results were compared with a control group of non-treated chronic hepatitis C patients. The mean age was 47 ± 10 years. The male proportion was 43%. The mean dose of prednisone was 9 ± 5 mg/day (range: 2.5-30 mg/day). The mean treatment time was 76 ± 80 months (range: 7-349 months). Thirty six percent received concomitant azathioprine. Transaminases decreased significantly only within the first 3 months of treatment, with non-significant changes thereafter. Corticosteroids led to a non-significant increase in HCV RNA. Knodell Histology Activity Index decreased (from 8.5 ± 3.7 to 4.7 ± 1.7; P = 0.1). Fibrosis progression per year (final fibrosis stage-initial fibrosis stage/time between explorations, in years), was lower in treated cases than in control group (0.054 ± 0.25 units vs. 0.196 ± 0.6 units, P = 0.26). In conclusion, corticosteroid treatment caused a significant initial decrease in transaminases, non-significant changes in HCV RNA, and a trend to a slower fibrosis progression in comparison to a control group. Therefore, corticosteroids did not accelerate progression of chronic hepatitis C.

Point-of-care HCV RNA testing improves hepatitis C testing rates and allows rapid treatment initiation among people who inject drugs attending a medically supervised injecting facility.

BACKGROUND: To achieve hepatitis C virus (HCV) elimination targets, simplified care engaging people who inject drugs is required. We evaluated whether fingerstick HCV RNA point-of-care testing (PoCT) increased the proportion of clients attending a supervised injecting facility who were tested for hepatitis C. METHODS: Prospective single-arm study with recruitment between 9 November 2020 and 28 January 2021 and follow-up to 31 July 2021. Clients attending the supervised injecting facility were offered HCV RNA testing using the Xpert® HCV Viral Load Fingerstick (Cepheid, Sunnyvale, CA) PoCT. Participants with a positive HCV RNA test were prescribed direct acting antiviral (DAA) therapy. The primary endpoint was the proportion of clients who engaged in HCV RNA PoCT, compared to a historical comparator group when venepuncture-based hepatitis C testing was standard of care. RESULTS: Among 1618 clients who attended the supervised injecting facility during the study period, 228 (14%) engaged in PoCT. This was significantly higher than that observed in the historical comparator group (61/1,775, 3%; p < 0.001). Sixty-five (28%) participants were HCV RNA positive, with 40/65 (62%) receiving their result on the same day as testing. Sixty-one (94%) HCV RNA positive participants were commenced on DAA therapy; 14/61 (23%) started treatment on the same day as diagnosis. There was no difference in the proportion of HCV RNA positive participants commenced on treatment with DAA therapy when compared to the historical comparator group (61/65, 94% vs 22/26, 85%; p = 0.153). However, the median time to treatment initiation was significantly shorter in the PoCT cohort (2 days (IQR 1-20) vs 41 days (IQR 22-76), p < 0.001). Among participants who commenced treatment and had complete follow-up data available, 27/36 (75%) achieved hepatitis C cure. CONCLUSIONS: HCV RNA PoCT led to a significantly higher proportion of clients attending a supervised injecting facility engaging in hepatitis C testing, whilst also reducing the time to treatment initiation.

Evolutionary dynamics of hepatitis C virus NS3 protease domain during and following treatment with narlaprevir, a potent NS3 protease inhibitor.

Narlaprevir, a hepatitis C virus (HCV) NS3/4A serine protease inhibitor, has demonstrated robust antiviral activity in a placebo-controlled phase 1 study. To study evolutionary dynamics of resistant variants, the NS3 protease sequence was clonally analysed in thirty-two HCV genotype 1-infected patients following treatment with narlaprevir. Narlaprevir monotherapy was administered for one week (period 1) followed by narlaprevir/pegylated interferon-alpha-2b combination therapy with or without ritonavir (period 2) during two weeks, interrupted by a washout period of one month. Thereafter, all patients initiated pegylated interferon-alpha-2b/ribavirin combination therapy. Longitudinal clonal analysis was performed in those patients with NS3 mutations. After narlaprevir re-exposure, resistance-associated mutations at position V36, T54, R155 and A156 were detected in five patients in >95% of the clones. Narlaprevir retreatment resulted in a 2.58 and 5.06 log10 IU/mL viral load decline in patients with and without mutations, respectively (P=<0.01). After treatment, resistant variants were replaced with wild-type virus within 2-24 weeks in three patients. However, the R155K mutation was still observed 3.1 years after narlaprevir dosing in two patients in 5% and 45% of the viral population. Resistant variants could be detected early during treatment with narlaprevir. A slower viral load decline was observed in those patients with resistance-associated mutations detectable by direct population sequencing. These mutations disappeared within six months following treatment with the exception of R155K mutation, which persisted in two patients.

HCV Co-Infection and Its Genotypic Distribution in HIV-Infected Patients in Nepalese Population.

Hepatitis C Virus (HCV) co-infection and its genotypic distribution in people living with Human Immunodeficiency Virus (HIV) show global inconsistency. Therefore, the present study aimed to investigate the prevalence and genotypic distribution patterns of HCV, along with viral load, in people living with HIV. This cross-sectional study was conducted at SRL Diagnostics Nepal, Pvt. Ltd. in 203 HIV-seropositive patients attending the Tribhuvan University Teaching Hospital (TUTH), Maharajgunj, Kathmandu, Nepal from October 2021 to May 2022. The viral load and HCV genotypes were estimated from RNA extracted from the blood sample (plasma) of PLHIV by using a standard Q-PCR protocol. HCV infection was considered as a core variable, whereas covariates used for this study were duration of HIV infection, age, sex, and ART regimen. Out of total 203 PLHIV, the estimated prevalence of HCV co-infection was 115 (56.6%). Male gender was a unique characteristic associated with a high prevalence of HCV co-infection compared to females. The HCV viral load among PLHIV ranged from 34 to 3,000,000 IU/mL. Among HCV co-infected PLHIV, 56 (48.69%) had a low level of HCV viral load. Interestingly, only 3 (2.6%) patients had an HCV viral load higher than 3,000,000 IU/mL. Diverse HCV genotypes were found in the population, including genotypes 1, 1a, 3a, 5a, and 6. However, genotype 3 was the most prevalent HCV variant among HCV-co-infected PLHIV, with a distribution of 36 (61.1%) and viral load ranging from 34 to 3000 IU/mL. HCV co-infection is frequent in the Nepalese population of people living with HIV, particularly due to HCV genotypic variant 3. The findings of this study could be useful for the management and clearance of the HCV co-infection in PLHIV, aiming to provide a good quality of life.

Chemotherapy and targeted therapy for breast cancer patients with hepatitis C virus infection.

BACKGROUND: Hepatitis C virus infection (HCV) is a major health problem in Egypt. Breast cancer is the most common cancer among Egyptian women. Considering that both diseases are frequent in the Egyptian population, it is likely that many women are affected by both. PURPOSE: To evaluate patient safety and applicability of chemotherapy in chronic hepatitis C virus-infected patients with breast cancer. SUBJECTS AND METHODS: We performed retrospective survey of 58 Egyptian patients diagnosed with both diseases. We retrospectively investigated the baseline patient and tumor characteristics, the toxicities of chemotherapy, and the changes in HCV viral load before and after chemotherapy, in addition to treatment received for HCV infection. RESULTS: Forty-four (75.9%) out of the 58 patients received chemotherapy with or without trastuzumab and one patient received lapatinib. We reported 2 patients who had HCV viral reactivation. Treatment with trastuzumab or Lapatinib was not associated with elevation in liver enzymes or change in HCV RNA viral load. Treatment discontinuation occurred in 31.8% (14/44) of patients due to complications. Dose reductions and/or dose delays were common (27.2%). Elevated liver enzymes were developed in 20 out of 44 (45.5%) patients who received chemotherapy. Three patients received antiviral treatment concomitant with chemotherapy with no significant complications. CONCLUSIONS: Greater attention should be paid to the possibility of complications including HCV reactivation, fulminant hepatitis, and interrupted chemotherapy treatments in breast cancer patients with chronic HCV infection receiving immunosuppressive drugs. Close monitoring of patients with breast cancer and HCV infection should be done.

HCV viral load at baseline and at week 4 of telaprevir/boceprevir based triple therapies are associated with virological outcome in HIV/hepatitis C co-infected patients.

BACKGROUND: As first generation HCV-specific protease inhibitors, boceprevir (BOC) or telaprevir (TVR) can achieve 60% to 70% sustained virological response (SVR) for HCV infected patients with genotype 1 infections, they could remain temporary a therapeutic option in patients living in resources limited countries with limited access to the new anti-HCV direct acting antiviral (DAA) drugs, such as sofosbuvir. OBJECTIVES AND STUDY DESIGN: Here we evaluated in a routine practice setting, the treatment responses, tolerance and factors associated with SVR of a triple therapy with BOC or TVR, combined with pegylated interferon and ribavirin (PegIFN/RBV) in HIV/HCV co-infected patients, included in a large cohort of HIV/HCV coinfected patients (ANRS CO13-HEPAVIH). RESULTS: Among the 89 HIV/HCV coinfected patients treated, 65% of whom were previous non-responders to PegIFN/RBV therapy, 65%, 55% and 41% had at baseline genotype 1a, a high baseline HCV-RNA (≥800,000 IU/ml) and a cirrhosis, respectively. The SVR12 rate was 63% overall, 53% for BOC-based regimen and 66% for TVR-based regimen. In multivariate analysis, two factors were significantly associated with HCV SVR: HCV viral load <800,000 IU/mL at treatment initiation versus ≥800,000 IU/mL (OR 4.403, 95% CI 1.29-15.04; p=0.018) and virological response at W4 (HCV-RNA undetectable after 4 weeks of triple therapy) (OR 3.35, 95% CI 1.07-10.48; p=0.038). CONCLUSIONS: Overall SVR12 was 63% and our results suggest that HIV/HCV coinfected patients with low HCV viral load (<800,000 IU/mL) and undetectable HCV-RNA after 4 weeks of triple therapy with TVR or BOC-based regimen have a higher probability of treatment success.

Detection limit of architect hepatitis C core antigen assay in correlation with HCV RNA, and renewed confirmation algorithm for reactive anti-HCV samples.

BACKGROUND: hepatitis C infections are detected by anti-HCV screening tests. Reactive anti-HCV results give no information about the presence or absence of hepatitis C viruses, or of unspecific reactivity. To obtain information about the viral load, HCV RNA measurements, following a reactive anti-HCV result, are performed in well equipped and specialised laboratories. Anti-HCV immunoblots are the only means to exclude non specific reactivity. The measurement of HCV core antigen (HCV-Ag), as an alternative to HCV RNA, is discussed, as it can be analysed on the same instrument as anti-HCV. OBJECTIVES: The detection limit of HCV-Ag is crucial to use it in lieu of HCV RNA, in regard of the different genotypes. A renewed algorithm is proposed to exclude unspecific reactivity of anti-HCV. STUDY DESIGNS: Samples were tested on Architect i2000SR (Abbott) for anti-HCV and HCV-Ag. HCV RNA measurements were obtained by Cobas Ampliprep/Taqman (Roche) or m2000rt(®) (Abbott). RESULTS AND CONCLUSIONS: Comparison between HCV-Ag and HCV RNA from 126 samples of 101 patients with chronic hepatitis C gave linear regression R(2) 0.89, slope 0.885 and intercept -2.258, which were independent of the genotypes. The detection limit of HCV-Ag was between 2.4 and 4.5 Log(10)IU/mL. A renewed algorithm for confirmation of reactive anti-HCV results is proposed: active or resolved hepatitis C infections or false reactivity can be differentiated by sequenced reflex testing due to HCV-Ag, anti-HCV immunoblot and HCV RNA.