Mono-infected Patients Research Articles

Seroprevalence, risk factors and impact of dengue fever/hepatitis B coinfection on liver function parameters in Cameroonian patients.

IntroductionDengue and hepatitis B are viral infections endemic to tropical areas with liver consequences. However, coinfection cases have been poorly documented worldwide and especially on the African continent. This study aimed at analysing the seroepidemiology of dengue-hepatitis B co-infection in patients recruited at the Regional Hospital of Ngaoundere (Cameroon).Material and methodsA cross-sectional study was conducted among 225 patients, aged 15-55 years, enrolled at the Laboratory service of Ngaoundere Regional Hospital from 25 September to 10 December 2021. HBsAg and dengue infection were diagnosed using the serological rapid tests. Part of the blood samples was used to quantify lipid profile and liver function parameters.ResultsOf the 225 patients recruited, 22.22% (50) tested positive for hepatitis B and 18.18% (38/202) were positive for dengue fever, with a dengue-hepatitis B coinfection rate of 4.95% (10/202). Coinfected patients were not significantly associated with liver injury compared to monoinfected patients. However, they displayed a higher risk of presenting abnormal γ-glutamyltransferase (γ-GT) (RR = 1.74, 90% vs. 51.51%) and alanine aminotransferase (ALT) values (RR = 1.52, 60% vs. 39.39%) compared to the monoinfected group. Also, there was no difference in total and direct bilirubin between patient groups. The mean triglyceride and low-density lipoprotein (LDL) cholesterol levels and coronary heart index values were higher in the coinfected group than in the monoinfected group, but without significance.ConclusionsTaken altogether, these findings suggest that the presence of hepatitis B in dengue patients may slightly affect the liver’s metabolic functions. Clinical surveillance of this coinfection is therefore required to avoid further liver complications.

Comparative analysis of HBV basic core promoter/pre-core gene mutations and viral quasispecies diversity in HIV/HBV co-infected and HBV mono-infected patients.

Human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection accelerates the progression of HBV-related liver diseases. HBV basic core promoter (BCP)/pre-core (preC) gene mutations may be one of the most important risk factors. In this study, atotal of 230 patients were recruited, and 199 patients whose HBV BCP/preC gene were successfully amplified and sequenced, including 99 HIV/HBV co-infected and 100 HBV mono-infected patients. Next-generation sequencing was used for detection of BCP/preC mutations which were then compared in patients with different HBV genotypes and different HBeAg statuses, and 1% and 20% cutoff values were defined to evaluate the mutations. HBV quasispecies diversity was also compared in HIV/HBV co-infected and HBV mono-infected patients. Among the patients infected with HBV genotype C and HBeAg-negative status, the frequency of A1762T/G1764A double mutations was significantly lower in HIV/HBV co-infected patients than in HBV mono-infected patients (53.3% vs. 100.0%, P = 0.008) regardless of the 1% or 20% cutoff value level. However, A1762T/G1764A double mutations did not differ in the other groups (P >0.05). Viral quasispecies diversity was lower in HIV/HBV co-infected patients than in HBV mono-infected patients (P Keywords: human immunodeficiency virus, hepatitis B virus; mutations; viral quasispecies; next-generation sequencing.

Association of C-reactive protein polymorphisms with serum-CRP concentration and viral load among dengue-chikungunya mono/co-infected patients

India being endemic to Dengue (DENV) and chikungunya (CHIKV) infections faces high patient-mortality and morbidity with overlapping clinical features. C-reactive protein (CRP) acts as early defence system in response to these infections. This study investigated role of CRP single-nucleotide polymorphism (SNP) genotypes and protein levels towards DENV/CHIKV mono and co-infection among eastern Indian patients. 128 DENV-CHIKV co-infected, 206 DENV and 167 CHIKV mono-infected patients were subjected to genotyping of two CRP SNPs by PCR-RFLP along with 102 healthy individuals. CRP levels were determined by immunoturbidimetry. Statistical correlation of CRP genotypes with CRP concentration, DENV-CHIKV mono/co-infection and viral load was performed. Patients with rs3093059-CT and rs3091244-TT were more susceptible to DENV-CHIKV co-infection, whereas, rs3091244-CT might have imparted protection against CHIKV mono-infection. DENV-HVL was more prevalent within rs3093059-TT and rs3091244-CT co-infected patients, whereas, CHIKV-HVL among rs3091244-CC. Acute phase co-infected patients had significantly higher CRP level compared to mono-infections. Both mono and co-infected patients with aches/pain exhibited 2-3-fold higher CRP levels compared to those without. rs3093059-CT and rs3091244-CT co-infected patients had higher CRP concentration compared to rs3093059-TT and rs3091244-CC, respectively. Co-infected patients with WHO-defined warning signs had higher anti-dengue IgG/IgM ratio and serum CRP level compared to those without warning signs. Thus, patient's CRP genotype might play significant role in determining serum-CRP concentration, viral load and DENV-CHIKV mono/co-infection.

912. Expansion of Hepatitis C Treatment with New Medicaid Subscription Model in Louisiana

BackgroundIt is estimated that nearly 80,000 people with hepatitis C are living in Louisiana, many with Medicaid coverage. Previously, only Medicaid patients free from drugs and alcohol with a fibrosis score of F3 or F4 were eligible for treatment, resulting in few patients receiving treatment. Beginning in July 2019, generic sofosbuvir/velpatasvir was made available through the Medicaid program in a subscription model, allowing unlimited hepatitis C treatment in Louisiana’s Medicaid program for 5 years at a set price to the program. This has dramatically expanded access to Hepatitis C treatment for people with Medicaid in Louisiana. MethodsPatients with Hepatitis C seen in the Infectious Diseases Center at University Medical Center in New Orleans, in 2020 by the 5 main hepatitis C providers were included. Demographics and laboratory data were collected to determine outcomes. ResultsMost patients with a hepatitis C (HCV) viral load and insurance data had Medicaid (80%, N=275). Twenty-two (8%) were HIV co-infected. Most were men (75%) and African-American (77%). Among the mono-infected patients with Medicaid and an HCV viral load, 216 (85%) had an undetectable viral load by the beginning of June 2021. Of the remaining 37 patients, 30 patients were prescribed treatment; but did not take it (n=4), didn’t follow-up (n=23), or followed-up but never got labs (n=3). One was treated but had a treatment failure (n=1). Six of the 37 were not prescribed medications due to a short life expectancy or significant drug interactions. The percentage of patients with an undetectable viral load was similar by gender and race, however younger age groups had lower viral suppression. In those aged less than 35, only 47% had an undetectable viral load and among those aged 36 to 44, it was 66%. Using the previous criteria of requiring a fibrosis score of F3 or F4, only 20% (n=44) would have been eligible for medicine to treat hepatitis C. ConclusionThe new hepatitis C treatment subscription model with resultant removal of previous barriers has dramatically expanded treatment for people with Medicaid in Louisiana. More than five times the number of Medicaid patients received treatment in 2020 in our academic medical clinic.Disclosures Yussef Bennani, MD, MPH, Gilead Sciences (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator)

Analysis of Immune Markers and Hematological Features in Plasmodium/Dengue Virus Co-infected Patients in Ouagadougou, Burkina Faso

Malaria and dengue are two important vector‑borne infections that are common in tropical countries. In these areas, simultaneous occurrence of malaria and dengue in an individual cannot be excluded, although published reports of co‑infections are scarce till date. The Aims of this study were to identify dengue and malaria co-infection cases as well as to ascertain the severity of dengue and malaria in co‑infection based on some hematological parameters. A cross-sectional study was conducted from June to November 2019 and 385 subjects with an undifferentiated febrile illness patients were recruited at outpatient clinics and blood sample were collected. All samples were tested for dengue NS1 antigen and for dengue IgM/IgG. Malaria diagnosis was based on the identification of Plasmodium parasites on a thin and thick blood films microscopy. Among the 385 patients included in the study, 23.9% were tested positive for malaria, 32.5% were positive for dengue, and 7.01% showed concurrent infection of both malaria and dengue. Malaria and dengue co-infected patients presented lower leukocytes level (5.024±0.559) than malaria monoinfected patients (7.304± 0.388; p=0.002). A significant reduction in platelet counts was observed in co-infected patients (164.0±10.91 vs 229.1±14.32; p=0.005). Conversely, hemoglobin level was statistically lower in malaria monoinfected patients than dengue monoinfected patients (p=0.014). Thus this study demonstrates that the diagnosis of dengue and malaria should be carried out routinely for better management of fever.

Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy.

Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.

Brief Report: Increased Inflammation and Liver Disease in HIV/HBV-Coinfected Individuals.

HIV and hepatitis B virus (HBV) coinfection can accelerate morbidity and mortality, especially in sub-Saharan Africa where both infections are common. Although inflammation contributes to disease progression, more information is needed to better understand the pathology. This study compared markers of cirrhosis and inflammation in HIV/HBV-coinfected individuals compared with monoinfected and uninfected patients. The HIV/HBV-coinfected subjects from the Ugandan arm of the prospective African Cohort Study were selected for evaluation and matched by age and gender with HIV-monoinfected, HBV-monoinfected, and uninfected controls. Plasma samples were used to quantify markers of immune activation and inflammation. The FIB-4 (a simple index to predict significant liver fibrosis) score was used to estimate liver fibrosis. Demographic and laboratory characteristics were compared across the groups. Together, 31 HIV/HBV-coinfected participants were identified and compared with 62 HIV-monoinfected, 7 HBV-monoinfected, and 62 uninfected controls. The HIV/HBV-coinfected group had generally higher levels of inflammation. Most notably, matrix metalloproteinase-2, matrix metalloproteinase-9, and fibroblast growth factor-19 levels were dysregulated among the HIV/HBV-coinfected individuals. Furthermore, the FIB-4 score was higher in the HIV/HBV-coinfected group compared with the HIV-monoinfected group and revealed that 11% of HIV/HBV-coinfected individuals had evidence of undiagnosed advanced liver disease. Differences in levels of inflammation exist between individuals with HIV/HBV coinfection compared with monoinfected and uninfected controls. A distinct signature of inflammation was associated with HIV/HBV coinfection that could reflect the mechanism of liver fibrosis and increased risk for disease progression. Finally, there may be an underappreciated amount of undiagnosed advanced liver disease in sub-Saharan Africa.

CCR5+ T-Cells Homed to the Liver Exhibit Inflammatory and Profibrogenic Signatures in Chronic HIV/HCV-Coinfected Patients.

Liver fibrosis is accelerated in patients coinfected with hepatitis C virus and human immunodeficiency virus (HIV), compared with HCV monoinfected patients, although the underlying mechanisms are unknown. We hypothesize that T cells expressing the HIV co-receptor, chemokine receptor 5 (CCR5), preferentially migrate to the inflamed liver and contribute to enhanced fibrogenesis. We compared the peripheral and intrahepatic CCR5 expression on CD4+ and CD8+ T cells in 21 HIV/HCV-coinfected patients with 14 chronic HCV monoinfected patients. Using 12-color flow cytometry, phenotypic and functional characterization of CCR5+ and negative cells pre- and post-stimulation with HCV genotype specific overlapping pooled peptides was conducted. Patients with HIV/HCV coinfection had significantly more CD4+CCR5+ and CD8+CCR5+ T cells in the liver as compared with peripheral blood (p = 0.0001 for both). Compared with patients with HCV monoinfection, patients with HIV/HCV coinfection also had fewer peripheral CD4+CCR5+ and CD8+CCR5+ T cells (p = 0.02, p = 0.001 respectively), but more intrahepatic CD4+CCR5+ and CD8+CCR5+ cells (p = 0.0001 for both). Phenotypic analysis of CCR5+ sorted cells demonstrated an increased expression of markers of exhaustion, senescence, immune activation and liver homing (PD1, CD57, CD38, HLADR, and CXCR3). Post-stimulation with HCV peptides, CCR5+ T cells secreted more proinflammatory and profibrogenic cytokines and chemokines rather than antiviral cytokines. Phenotypic and functional analyses of CCR5+ T cells in HIV/HCV-coinfected patients revealed a pathogenic role for CCR5+ T cells in hepatic fibrogenesis. These cells are functionally proinflammatory, pro-fibrogenic and preferentially accumulate in liver, accelerating fibrosis. These findings suggest that targeting CCR5 may be a therapeutic strategy for be ameliorating liver fibrosis.

Effects of direct-acting antiviral treatment on reducing mortality among Medicare beneficiaries with HIV and HCV coinfection

ABSTRACT Hepatitis C virus (HCV) infection is common among people living with HIV. HIV and HCV coinfected patients have higher overall mortality rates compared with HIV mono-infected patients. With its high cure rate of HCV infection, direct-acting antiviral (DAA) treatment provides an opportunity to improve the survival of the HIV/HCV coinfected population. The objective of this study is to investigate the association between DAA treatment and all-cause mortality among HIV/HCV coinfected people. The study included 7103 Medicare beneficiaries in the United States who were infected with both HIV and HCV between 2014 and 2017. Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) of death for patients with and without DAA treatment while controlling for patient characteristics. During the study period, 1675 patients initiated DAA treatment (23.6%). The adjusted hazard ratio (aHR) of all-cause mortality between patients with and without DAA treatment was 0.37 (95% CI, 0.29–0.48), regardless of cirrhosis status. DAA treatment was associated with a smaller reduction in all-cause mortality for females (aHR, 0.50 [95% CI, 0.30–0.85]) compared with males (aHR, 0.34 [95% CI, 0.25–0.46]). DAA treatment was associated with improved survival among all HIV/HCV coinfected patients regardless of sex or HCV disease progression.

Late presentation for HCV care: Time to target people with diabetes and/or hazardous alcohol use (ANRS CO22 HEPATHER cohort).

Late presentation for care of hepatitis C virus (HCV) infection - defined as having severe liver fibrosis when first consulting a specialist for HCV care - increases morbidity and mortality. Identifying the socio-behavioural correlates of late presentation is essential to improve HCV strategies to optimize HCV cascade of care. We investigated clinical and socio-behavioural correlates of late presentation for care in HCV mono-infected individuals. This study included chronic HCV mono-infected patients participating in the French national cohort ANRS CO22 HEPATHER, starting in 2012. The correlates of late presentation were estimated using a Heckman probit selection model, which takes into account the possible selection bias because of missing data in the outcome. Among the 9174 study patients, 1236 had available data on liver fibrosis stage at first presentation for HCV care. Of these, 591 (47.8%) were late presenters. In a multivariable analysis adjusted for age, sex and HCV genotype, having diabetes (adjusted coefficient [95% confidence interval]: 0.55 [0.30; 0.80]), current hazardous alcohol use (0.36 [0.03; 0.69]) and current abstinence but past hazardous alcohol use (0.42 [0.19; 0.64]) (vs. current abstinence and no past hazardous use) were all independently associated with late presentation for HCV care. As late presentation severely affects HCV cascade of care, our findings bring important new evidence about the need to promptly identify and target people with diabetes and/or past or current hazardous alcohol use for HCV screening and treatment within the wider context of the WHO goal to eliminate HCV by 2030.

Direct-acting antiviral regimens in Egyptian patients with chronic hepatitis C virus infection: A real-world single-center experience

Background and study aims:Chronic hepatitis C virus (HCV) infection has always been identified as a major health threat and a potential cause of liver cirrhosis, portal hypertension, and other associated problems. The introduction of direct-acting antiviral agents (DAAs) has represented a paradigm shift in HCV management. In this study, we aim to observe the rate of sustained virologic response (SVR12) in a large scale of patients at a single center as well as record the post-treatment changes in the hematologic, hepatic, and renal biochemical profiles. Patients and methodsIn total, 1933 chronic HCV genotype 4 mono-infected non-HCC patients who completed the treatment with six different DAA regimens in the Faculty of Medicine, Ain Shams University Research Institute (MASRI), were retrospectively enrolled in this study. The rate of sustained virologic response after 12 weeks off-therapy (SVR12) was assessed. The baseline characteristics to predict the SVR12 were then analyzed. The post-treatment changes in many profiles were recorded and analyzed. ResultsThe overall SVR12 rate was 96.2% (after excluding 84 cases who were lost to follow-up). It was achieved in 346/375 patients (92.3%), 466/477 patients (97.7%), 60/62 patients (96.8%), 11/11 patients (100%), 532/545 patients (97.6%), and 445/463 patients (96.1%) who received sofosbuvir/daclatasvir (SOF/DCV), sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV), sofosbuvir/ledipasvir (SOF/LDV), sofosbuvir/ledipasvir/ribavirin (SOF/LDV/RBV), sofosbuvir/simeprevir (SOF/SMV), and ombitasvir/paritaprevir/ritonavir/ribavirin (OBV/PTV/r + RBV), respectively. In total, 73 patients (3.8%) failed to achieve SVR12. The baseline aspartate aminotransferase (AST), cirrhotic status, and treatment regimen were determined to have a significant impact on SVR12. In the overall treated population, the levels of serum AST, alanine aminotransferase, albumin, creatinine, bilirubin, and hemoglobin and platelet count improved significantly after treatment. Furthermore, sustained virologic response was strongly related to cirrhosis and its degree. ConclusionThe interferon-free DAA regimens offered high SVR12 rates in Egyptian patients with chronic HCV infection. They were associated with a significant improvement in the hematologic, hepatic, and renal biochemical profiles. The baseline AST, liver cirrhosis, and treatment regimen might have an impact on achieving SVR.

HDV Seroprevalence in HBsAg-Positive Patients in China Occurs in Hotspots and Is Not Associated with HCV Mono-Infection.

HDV infection causes severe liver disease, the global health burden of which may be underestimated due to limited epidemiological data. HDV depends on HBV for infection, but recent studies indicated that dissemination can also be supported by other helper viruses such as HCV. We used a rapid point-of-care test and an ELISA to retrospectively test for antibodies against the Hepatitis Delta antigen (anti-HDV-Ab) in 4103 HBsAg-positive and 1661 HBsAg-negative, anti-HCV-positive sera from China and Germany. We found that the HDV seroprevalence in HBsAg-positive patients in China is limited to geographic hotspots (Inner Mongolia: 35/251, 13.9%; Xinjiang: 7/180, 3.9%) and high-risk intravenous drug users (HBV mono-infected: 23/247, 9.3%; HBV-HCV co-infected: 34/107, 31.8%), while none of the 2634 HBsAg carriers from other metropolitan regions were anti-HDV-Ab-positive. In Germany, we recorded an HDV seroprevalence of 5.3% in a university hospital environment. In a cohort of HBsAg-negative, anti-HCV-positive patients that were not exposed to HBV before (anti-HBc-negative), HDV was not associated with HCV mono-infection (Chinese high-risk cohort: 0/365, 0.0%; German mixed cohort: 0/263, 0.0%). However, 21/1033 (2.0%) high-risk HCV patients in China with markers of a previously cleared HBV infection (anti-HBc-positive) were positive for anti-HDV-Ab, with two of them being positive for both HDV and HCV RNA but negative for HBV DNA. The absence of anti-HDV-Ab in HCV mono-infected patients shows that HCV cannot promote HDV transmission in humans.

Stratifying the risk of NAFLD in patients with HIV under combination antiretroviral therapy (cART).

BackgroundDe novo steatosis is the main criteria for non-alcoholic fatty liver disease (NAFLD), which is becoming a clinically relevant comorbidity in HIV-infected patients. This may be due to the HIV virus itself, as well as long-term toxicities deriving from antiretroviral therapy. Therefore, HIV infected patients require prevention and monitoring regarding NAFLD.MethodsThis study investigated the differential role of body mass index (BMI) and combination antiretroviral treatment (cART) drugs on NAFLD progression. This single center prospective longitudinal observational study enrolled HIV monoinfected individuals between August 2013 to December 2018 with yearly visits. Each visit included liver stiffness and steatosis [defined as controlled attenuation parameter (CAP)>237 dB/m] assessment by annually transient elastography using an M- or XL-probe of FibroScan, and calculation of the novel FibroScan-AST (FAST) score. Risk factors for denovo/progressed steatosis and tripling of FAST-score increase were investigated using Cox regression model with time-dependent covariates.Findings319 monoinfected HIV positive patients with at least two visits were included into the study, of which 301 patients had at least two valid CAP measurements. 51·5%(155) patients did not have steatosis at first assessment, of which 45%(69) developed steatosis during follow-up. A BMI>23 kg/m2 (OR: 4·238, 95% CI: 2·078–8·938; p < 0·0001), tenofovir-alafenamid (TAF) (OR: 5·073, 95% CI: 2·362–10·899); p < 0·0001) and integrase strand transfer inhibitors (INSTI) (OR: 2·354, 95% CI: 1·370–4·048; p = 0·002), as well as type 2 diabetes mellitus (OR: 7·605, 95% CI: 2·315–24·981; p < 0·0001) were independent predictors of de novo steatosis in multivariable analysis. Tenofovir disoproxilfumarate (TDF) was associated with a lower risk for weight gain and steatosis progression/onset using CAP value (HR: 0·28, 95% CI: 0·12–0·64; p = 0·003) and FAST scores (HR: 0·31, 95% CI: 0·101–0·945; p = 0·04).InterpretationSteatosis can develop despite non-obese BMI in patients with HIV monoinfection under cART, especially in male patients with BMI over 23 kg/m2. While TAF and INSTI increase the risk of progression of steatosis, TDF was found to be independently associated with a lower risk of a clinically significant weight gain and thereby, might slow down development and progression of steatosis.FundingThere was no additional funding received for this project. All funders mentioned in the ‘declaration of interests’ section had no influence on study design, data collection and analysis, decision to publish, or preparation of the manuscript.

A meta-analysis on the prevalence and characteristics of severe malaria in patients with Plasmodium spp. and HIV co-infection

Co-infection with malaria and human immunodeficiency virus (HIV) increases the severity and mortality rates of both diseases. A better understanding of the effects of co-infections could help in the diagnosis, prompt treatment, prevention, and control of malarial parasites among HIV-infected patients. In this systematic review and meta-analysis, we estimated the prevalence and characteristics of severe malaria (SM) caused by co-infection with HIV. We included relevant studies that were conducted between the years 1991 and 2018 and reporting on SM. We pooled the prevalence of SM in patients with co-infection, pooled odds ratios of SM in patients with co-infection and Plasmodium mono-infection, and differences in laboratory parameters such as parasite density and leucocyte counts, between co-infected and Plasmodium mono-infected patients. The meta-analysis included 29 studies (1126 SM cases). The pooled prevalence of SM in co-infected patients using the data of 23 studies (SM = 795 cases, all co-infection cases = 2534 cases) was 43.0% (95% confidence interval [CI] 31.0–56.0%; I2, 98.0%). Overall, the odds of SM from 18 studies were pooled. The odds of SM were significantly higher in co-infected patients than in Plasmodium mono-infected patients (OR 2.41; 95% CI 1.43–4.08; I2 = 85%; P = 0.001) and also significantly higher in children (OR 9.69; 95% CI 5.14–18.3; I2, 0%; P < 0.0001; two studies) than in adults (OR 2.68; 95% CI 1.52–4.73; I2, 79.0%; P = 0.0007; 12 studies). Co-infected patients with SM had a higher parasite density than those with Plasmodium mono-infection when the data of seven studies were analysed (SMD, 1.25; 95% CI 0.14–2.36; I2, 98.0%; P = 0.03) and higher leukocyte counts when the data of four studies were analysed (MD, 1570 cells/µL; 95% CI 850–2300 cells/µL; I2, 21.0%; P < 0.0001). Thus, the prevalence of SM among patients co-infected with Plasmodium spp. and HIV is high. Because co-infections could lead to SM, patients with Plasmodium spp. and HIV co-infection should be identified and treated to reduce the prevalence of SM and the number of deaths.

Hepatitis C continuum of care: Experience of integrative hepatitis C treatment within a human immunodeficiency virus clinic in Indonesia.

Direct-acting antiviral drugs (DAAs) have changed the paradigm of hepatitis C therapy for both HCV/HIV co-infected and HCV mono-infected patients. We aimed to describe the HCV continuum of care of HIV-infected patients treated in an HIV clinic after a free DAA program in Indonesia and identify factors correlated with sofosbuvir-daclatasvir (SOF-DCV) treatment failure. We did a retrospective cohort study of adult HIV/HCV co-infected patients under routine HIV-care from November 2019 to April 2020 in the HIV integrated clinic of Cipto Mangunkusumo Hospital, Jakarta, Indonesia. We evaluated some factors correlated with sofosbuvir-daclatasvir treatment failure: gender, diabetes mellitus, previous IFN failure, cirrhosis, concomitant ribavirin use, high baseline HCV-RNA, and low CD4 cell count. Overall, 640 anti-HCV positive patients were included in the study. Most of them were male (88.3%) and former intravenous drug users (76.6%) with a mean age of 40.95 (SD 4.60) years old. Numbers and percentages for the stages of the HCV continuum of care were as follows: HCV-RNA tested (411; 64.2%), pre-therapeutic evaluation done (271; 42.3%), HCV treatment initiated (210; 32.8%), HCV treatment completed (207; 32.2%), but only 178 of these patients had follow-up HCV-RNA tests to allow SVR assessment; and finally SVR12 achieved (178; 27.8%). For the 184 who completed SOF-DCV treatment, SVR12 was achieved by 95.7%. In multivariate analysis, diabetes mellitus remained a significant factor correlated with SOF-DCV treatment failure (adjusted RR 17.0, 95%CI: 3.28-88.23, p = 0.001). This study found that in the HCV continuum of care for HIV/HCV co-infected patients, gaps still exist at all stages. As the most commonly used DAA combination, sofosbuvir daclatasvir treatment proved to be effective and well-tolerated in HIV/HCV co-infected patients. Diabetes mellitus was significant factor correlated with not achieving SVR12 in this population.

The Effect of HBV/HCV in Response to HAART in HIV Patients after 12 Months in Kumba Health District in the South West Region of Cameroon.

Hepatitis B (HBV) and C (HCV) are two among the numerous forms of infections whose clinical degeneration, morbidity–mortality and low immune responsiveness in people living with human immunodeficiency virus (HIV) are highly evident. Co-infection of HIV with HBV and HCV has been associated with reduced survival, increased risk of progression to liver diseases and increased risk of hepatotoxicity associated with antiretroviral therapy (ARV). We carried out biochemical, immunological, virological and clinical analysis of hepatitis B and C positive HIV patients as well as some HIV positive individuals receiving antiretroviral therapy in Kumba Health District to evaluate the immune response to the ARV therapy and identified risk factors associated with the treatment outcomes. A total of 52 HIV patients, 36 HIV/HBV and 12 HIV/HCV patients were involved in this study. We performed CD4 counts, viral load test, analyzed ALAT/ASAT, albumin, bilirubin, and creatinine and measured the weights of HIV patients, HIV/HBV and HIV/HCV enrolled for not more than one year in Kumba Health District. The results were analyzed to evaluate the immune response and possible risk factors associated with the treatment outcomes. The mean increase in weight in participants of all groups over 12 months (17.12 kg) was greater than the mean increase in CD4 (8.92 cell/mm3). However, the mean decrease in viral loads over a 12 months was also very high (1035.17 copies/mL). There was a significant change in the mean values from baseline for all the three variables (p < 0.0001). HIV disease outcomes following HAART (high active antiretroviral therapy) do not appear to be adversely affected by HBV or HCV co-infection, except for slightly poorer CD4 count responses in HIV/HCV co-infected patients. Concerning the renal and liver functions, all the biomarkers witnessed a decrease in patients of all groups in response to HAART over time, with a more rapid decrease in mono-infected patients as compared with those co-infected with HBV but the case was contrary for those co-infected with HCV. Co-infection with HBV or HCV was relatively common among HIV infected participants in Kumba Health District. There were differences in response to HAART between the mono-infected compared with the co-infected, taking into consideration the weight, CD4 count, and viral load. In addition, there was also a variation in the different biomarkers of liver and renal function between mono-infected and co-infected patients.

Dynamics of hepatitis C epidemic among people living with HIV in Estonia based on Estonian HIV cohort study

BackgroundEstonia has a typical Eastern European HIV epidemic where the most frequent co-infection is chronic hepatitis C (HCV). We aimed to describe the changes in HCV prevalence, the distribution of HCV genotypes (GT), and HCV treatment in Estonian people living with HIV over 15 years.MethodsWe used data of subjects included to the Estonian HIV Cohort Study (E-HIV) before 31st of December 2015. We compared two time periods—first, 1st of January 2000 to 31st of December 2008 when the HIV epidemic was mostly spreading among people who inject drugs (PWID) and second, 1st of January 2009 to 31st of December 2015 when HIV started to emerge to the general population.ResultsOf 4422 HIV positives 3708 (84%) had information about their HCV serostatus; 2706 (61%) were HCV seropositive, of latter 1625 (60%) were HCV RNA positive, 239 (9%) had their HCV GT determined, and 141 (5%) received treatment for HCV. The dominating subtypes were 1b (42%) and 3a (37%) followed by 1a (16%), and the few cases of 2 (1.5%). HCV prevalence was 1.5 times (95% CI 1.4–1.6) higher in subjects diagnosed with HIV in first as compared to those diagnosed in second period (84% vs 56%, respectively). There were more men and the median age at HIV diagnosis was lower in HIV/HCV co-infected than in HIV mono-infected patients (70% vs 47% and 24 years vs. 30 years, respectively; both p < 0.001).ConclusionThere is a decrease in HCV prevalence but it remains high among HIV positive PWID, suggesting that there is need for improvement of harm reduction programs among PWID.

Long-term outcome of liver complications in patients with chronic HBV/HCV co-infection after antiviral therapy: a real-world nationwide study on Taiwanese Chronic Hepatitis C Cohort (T-COACH).

The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44years. Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65year-old, BMI ≥ 27kg/m2, FIB-4 ≥ 3.25, eGFR < 60ml/min/1.73m2, and non-HCV SVR, but not HBV co-infection. Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups.

Late presentation of chronic hepatitis C patients in the era of direct-acting antivirals-Data from the German Hepatitis C-Registry.

Late presentation for care in chronic viral hepatitis has been estimated to occur in approximately 25% of patients initiating treatment with direct acting antivirals. We evaluated the extent of late presentation since the implementation of direct acting antivirals and established differences between HCV monoinfected and HIV/HCV coinfected patients. The German Hepatitis C Registry is a multicenter non-interventional registry study. We analysed patients enrolled between 02/2014 and 12/2018. Advanced liver disease was defined as an aspartate aminotransferase to platelet-ratio-index score ≥ 1.5, a FibroScan ≥ 9.5 kPa or a METAVIR stage ≥ F3. HCV monoinfected and HIV/HCV coinfected patients were analysed separately and baseline characteristics of both subgroups were compared. 8003 treatment naive patients were analysed. Overall, 2197/8003 (28%) patients presented late for care (HCV monoinfection: 2067/7452 (28%); HIV/HCV coinfection: 130/551 (24%)). Late presentation decreased comparing the year 2014 to the years 2015 (p≤0.001), 2017 (p≤0.001) and 2018 (p≤0.001) and was significantly lower in 2018 in HIV/HCV coinfected patients compared to HCV monoinfected patients (HIV/HCV: 15/89 (17%) vs. 415/1566 (27%); p=0.047). We observed a significant decrease of late presentation from 2014 to 2018. Despite the decrease during the observation period, approximately one in four patients continued to be affected in 2018, with a lower proportion of late presentation being seen in patients coinfected with HIV/HCV. This trend might indicate effects of a closer linkage to care and a more frequent detection of acute HCV infections of HIV+ patients.

Risk of hepatocellular carcinoma in hepatitis B and D virus co-infected patients: A systematic review and meta-analysis of longitudinal studies.

Hepatitis D virus (HDV) infection causes a severe chronic viral hepatitis with accelerated development of liver cirrhosis and decompensation, but whether it further increases the risk of hepatocellular carcinoma (HCC) is unclear. We performed a comprehensive systematic review of the published literature and meta-analysis to assess the risk of HCC in HDV and hepatitis B virus (HBV) co-infected, compared to HBV mono-infected patients. The study was conducted per a priori defined protocol, including only longitudinal studies, thus excluding cross-sectional studies. Random-effects models were used to determine aggregate effect sizes (ES) with 95% confidence intervals (CI). Meta-regression was used to examine the associations among study level characteristics. Twelve cohort studies comprising a total of 6099 HBV/HDV co-infected and 57,620 chronic HBV mono-infected patients were analysed. The overall pooled ES showed that HBV/HDV co-infected patients were at 2-fold increased risk of HCC compared to HBV mono-infected patients (ES=2.12, 95% CI 1.14-3.95, I2 =72%, N=12). A six-fold significant increased risk of HCC was noted among HIV/HBV/HDV triple-infected, compared to HIV/HBV co-infected patients. The magnitude of ES did not differ significantly after adjustment for study design and quality, publication year and follow-up duration in univariable meta-regression analysis. This systematic review and meta-analysis shows that infection with HDV is associated with a 2-fold higher risk of HCC development compared to HBV mono-infection. HCC surveillance strategies taking this increased risk into account, and new treatment options against HDV, are warranted.