Mono-infected Patients Research Articles

Dynamic personalized prediction of the individual liver-related risk after sustained viral response in HCV patients.

Sustained viral response (SVR) significantly improves the prognosis in patients with hepatitis C virus (HCV) chronic infection but does not totally alleviate the risk of liver-related complications (LRC). We aimed to evaluate whether the dynamics of multiple measurements of simple parameters after SVR enable the development of a personalized prediction of prognosis in HCV patients. HCV mono-infected patients who experienced SVR in two prospective cohorts (ANRS CO12 CirVir cohort: derivation set; ANRS CO22 HEPATHER cohort: validation set) were included. The study outcome was LRC, a composite criterion including decompensation of cirrhosis and/or hepatocellular carcinoma. Joint latent class modelling accounting for both biomarker trajectory and event occurrence during follow-up was developed in the derivation set to compute individual dynamic predictions, with further evaluation in the validation set. In the derivation set (n=695; 50 LRC during the median 3.8 [1.6-7.5] years follow-up), FIB4 was identified as a biomarker associated with LRC occurrence after SVR. Joint modelling used sex and the dynamics of FIB4 and diabetes status to develop a personalized prediction of LRC. In the validation set (n=7064; 273 LRC during the median 3.6 [2.5-4.9] years follow-up), individual dynamic predictions from the model accurately stratified the risk of LRC. Time-dependent Brier Score showed good calibration that improved with the accumulation of visits, justifying our modelling approach considering both baseline and follow-up measurements. Dynamic modelling using repeated measurements of simple parameters predicts the individual residual risk of LRC and improves personalized medicine after SVR in HCV patients.

Identification of N6-methylandenosine-related lncRNA for tuberculosis diagnosis in person living with human immunodeficiency virus

Development of a robust diagnostic test for patients co-infected with human immunodeficiency virus and tuberculosis (HIV/TB) is urgently needed. We believe N6-methyladenosine (m6A)- related long non-coding RNA (lncRNAs) from the host blood could be utilized to diagnose patients co-infected with HIV/TB. In this study, differentially expressed analysis, correlation analysis, univariate logistic regression, and logistic regression with least absolute shrinkage and selection operator (LASSO) were performed in RNA-Seq dataset containing of 14 HIV/TB co-infected subjects and 11 HIV mono-infected subjects. In total, five m6A related-lncRNAs with powerful diagnostic significance for HIV/TB co-infection were identified. We then built a deep learning model based on the five m6A related-lncRNAs for accurately discriminating the HIV/TB co-infected patients from HIV mono-infected patients with an accuracy of 92.0%, a sensitivity of 92.9%, a specificity of 90.9%, and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.935. Moreover, the diagnostic performance was validated in an external cohort containing 15 HIV/TB co-infected subjects and 16 HIV mono-infected subjects of whole blood. Overall, the findings showed that deep learning model based on five m6A-related lncRNAs had a worthy diagnostic performance for HIV/TB co-infection, and these diagnostic lncRNAs associated with m6A regulator genes could play a potential role in the pathogenesis of HIV/TB co-infection.

A Novel and Simplified Score for Determining Treatment Eligibility for Patients with Chronic Hepatitis B

Background: International guidelines for hepatitis B infection (HBV) recommend initiating antiviral treatment based on viral replication with inflammation or fibrosis. HBV viral loads and liver fibrosis measurements are not widely available in resource-limited countries. Aim: To develop a novel scoring system for the initiation of antiviral treatment in HBV-infected patients. Methods: We examined 602 and 420 treatment-naïve, HBV mono-infected patients for derivation and validation cohorts. We performed regression analysis to identify parameters associated with the initiation of antiviral treatment based on the European Association for the Study of the Liver (EASL) guidelines. The novel score was developed based on these parameters. Results: The novel score (HePAA) was based on HBeAg (hepatitis B e-antigen), the platelet count, alanine transaminase, and albumin. The HePAA score showed excellent performance, with AUROC values of 0.926 (95% CI, 0.901-0.950) for the derivation cohort and 0.872 (95% CI, 0.833-0.910) for the validation cohort. The optimal cutoff was ≥3 points (sensitivity, 84.9%; specificity, 92.6%). The HePAA score performed better than the World Health Organization (WHO) criteria and the Risk Estimation for HCC in Chronic Hepatitis B (REACH-B) score, and it performed similarly to the Treatment Eligibility in Africa for HBV (TREAT-B) score. Conclusions: The HePAA scoring system is simple and accurate for chronic hepatitis B treatment eligibility in resource-limited countries.

A79 THE RELATIONSHIP BETWEEN VISCERAL ADIPOSITY AND NONALCOHOLIC FATTY LIVER DISEASE DIAGNOSED BY CONTROLLED ATTENUATION PARAMETER IN PEOPLE WITH HIV: A PILOT STUDY

Abstract Background Aging people with HIV (PWH) on antiretroviral therapy face high rates of metabolic dysfunction and nonalcoholic fatty liver disease (NAFLD). Fat alterations are frequent in PWH and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is an important compartment of body fat tissue releasing bioactive molecules. As a hormonally active tissue, VAT critically contributes to obesity-related disorders and is associated with ectopic fat accumulation in the liver. Purpose We aimed to investigate NAFLD diagnosed by controlled attenuation parameter (CAP) as a marker of visceral adiposity in PWH. Method We conducted a prospective pilot study (ClinicalTrials.gov 2021-6656) of HIV mono-infected patients undergoing metabolic characterization and paired CAP by transient elastography with dual-energy X-ray absorptiometry (DEXA) scan. NAFLD was defined as CAP ≥285 dB/m, in absence of alcohol abuse. Excess visceral adiposity was defined as VAT>1.32 Kg. Pairwise correlation, area under the curve (AUC) and logistic regression analysis were employed to study the association between VAT and CAP. Result(s) 30 patients (90% male, mean age 48.5, mean BMI 29.9, mean waist circumference 100.9, 50% with NAFLD) were included. When compared to those without excess VAT, PWH with excess VAT were older (53+12 vs 43+13 years, p=0.035), had longer duration of HIV infection (20+13 vs. 9+9 years, p=0.021), had higher BMI (32+4 vs 27+4 Kg/m2, p=0.002) and waist circumference (107+11 vs. 93+12 cm, p=0.004). They also had more history of cardiovascular events (29% vs. 0, p=0.032) and higher lipid accumulation product, a marker of lipid accumulation based on waist circumference and triglycerides (112+53 vs. 38+27, p<0.001). CAP was higher in PWH with excess VAT (319+52 vs. 213+52 dB/m, p<0.001). CAP positively correlated with all visceral fat measurements by DEXA, including VAT (r=0.650, p<0.001), VAT/body weight ratio (r=0.565, p=0.001) and fat mass (r=0.390, p=0.033). Both BMI and waist circumference showed correlation with VAT and fat mass, but not with VAT/body weight ratio (see Figure). After adjusting for duration of HIV infection (aOR 1.01 per year, 95% CI 0.91-1.12; p=0.921), BMI (aOR 1.77, 95% CI 0.74-4.23; p=0.202) and waist circumference (aOR 0.91 per cm, 95% 0.68-1.21; p=0.509), CAP remained the only independent predictor of excess VAT (aOR 1.05 per dB/m, 95% CI 1.01-1.10; p=0.036). The AUC analysis determined CAP had excellent performance to diagnose excess VAT (AUC 0.92, 95% CI 0.81-1.00), higher than BMI (AUC 0.83, 95% CI 0.68-0.99) and waist circumference (AUC 0.81, 95% CI 0.65-0.97). The optimized CAP cut-off to diagnose excess VAT was 266 dB/m, with a sensitivity of 88.3% and a specificity of 84.6%. Image Conclusion(s) NAFLD diagnosed by CAP is associated with VAT in PWH independently of anthropometric measures of obesity. CAP could be used as a diagnostic marker of visceral adiposity in the practice of HIV medicine Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; CanHepC Disclosure of Interest W. Elgretli Grant / Research support from: CanHepC, N. Paisible: None Declared, C. Costiniuk: None Declared, J. Cox: None Declared, D. Kablawi: None Declared, M. Klein: None Declared, N. Kronfli: None Declared, J.-P. Routy: None Declared, J. Falutz: None Declared, B. Lebouche: None Declared, G. Guaraldi: None Declared, G. Sebastiani: None Declared

Delta virus predominates and potentially predicts liver cirrhosis among co-infected hepatitis b and hepatitis d virus patients in pakistan

Background: High prevalence of Hepatitis Delta virus (HDV) has been reported from some pockets in Pakistan. Typically, Hepatitis B (HBV) and HDV co-infection could cause severe hepatitis leading to cirrhosis at an early age. We aim to study the clinical outcomes of HBV/HDV co-infection compared to HBV mono-infection in a Punjabi, Pakistani population. Methods: The retrospective data on all HBV positive patients was extracted from Hepatitis Prevention and Treatment Program (HPTP) of Pakistan Kidney and Liver Institute in Punjab, Pakistan. Majority (32/50) of the HBV/HDV co-infection were identified from Rajanpur clinic of HPTP. Pre-treatment liver tests, HBV-DNA viral load, HDV-RNA viral load; AST to Platelet ratio (APRI) and Fibrosis-4 (Fib-4) were calculated from standard equations. Cirrhosis was based on APRI (≥1.5) or/and Fib4 (≥1.45). HBV-DNA level ≤ 2,000 IU and ≥20,000 IU were categorized as low and high viral load respectively. Results: 57 (53%) patients were HBV mono-infected and 50 (47%) were co-infected with HDV. Mean age was 36.2±12.99 in the entire cohort and was not different between the two groups. Older age correlated to a higher APRI and Fib-4 scores in both groups. The two groups were predominantly male, 75% in HBV and 76% HBV/HDV co-infected patients. Sharing of toothbrushes was reported to be significantly higher by HBV mono-infected patients; p 0.005. Other risk factors were equally prevalent. 78% of HBV mono-infected and 79% HBV/HDV co-infected patients had ≤ 20,000 IU/ml HBV-DNA. While 56% and 44% had ≤ 2,000 IU/ml HBV DNA levels respectively. APRI and Fib-4 scores were significantly higher in HBV/HDV coinfected; p 0.01. The cirrhosis was diagnosed in 29 patients in HBV/HDV co-infected group, while no patient had cirrhosis in HBV mono-infected group. Within HBV/HDV co-infected group, mean HDV-viral load was significantly higher compared to HBV viral load; p 0.05. Mean HBV-DNA and HDV RNA levels in non-cirrhotics were 326411 and 35358369; and in cirrhotics 3340429 and 31867418 IU/ ml, respectively. 4 patients had undetectable HBV viral load and one of them had cirrhosis. 10 patients were cirrhotics with ≤ 2,000 IU/ml of HBV-DNA. The mean HDV RNA level in these 10 patients was 63, 000000 IU/ml. Mean HDV viral load was one log higher in patients with ≤20,000 IU/ml HBV-DNA compared to those with ≥ 20,000 IU/ml HBV-DNA viral load. Conclusion: Overall mode of transmission of HBV and HBV/HDV infections are similar in Punjab. More patients had higher liver fibrosis scores in HDV/HBV co-infected groups. The significantly low level of HBV, in the co-infected population especially cirrhotic patients indicates that liver disease is driven by HDV rather than HBV infection among co-infected Pakistani patients and Peg-interferon alone might be the best treatment option for them.

Plasma IL-33 levels and immune activation in HIV-TB coinfection: a cross-sectional study in Yaoundé, Cameroon.

HIV-1 and Mtb are characterized by immune activation and unbalances production of cytokines, but the expression of IL33 in HIV/TB coinfection remain understudied. This study aimed to evaluate the level of IL-33 in plasma of HIV and M. tuberculosis (HIV/TB) coinfected patients compared to patients with respective mono infections in Yaoundé. a cross-sectional study was conducted among patients attending the pneumology service and HIV treatment center of the Yaoundé Jamot Hospital. Plasma samples of 157 HIV/TB coinfected patients (n =26, 50% males and 50% females, mean age 39), HIV-1 monoinfected patients (n = 41, 41% males and 59% females, mean age 35), TB monoinfected patients (n = 48, 56% males and 44% females, mean age 37) and healthy controls (n = 42, 29% males and 71% females, mean age 32) were examined by enzyme-linked immunoassay (ELISA) to detect the levels of IL-33 cytokine. plasma level of IL-33 were higher in HIV/TB coinfected (33.1±30.9 pg/ml) and TB monoinfected individuals (15.1±2.9 pg/ml) compared to healthy controls (14.0±3.4 pg/ml) and could not be detected in most of the HIV-1 monoinfected individuals (12.6±8.7 pg/ml). Interestingly, the increased plasma level of IL-33 in HIV/TB coinfected patients showed a statistically significant difference between healthy controls (33.1±30.9 pg/ml vs 14.0±3.4 pg/ml, P<0.0001) and HIV-1 monoinfected patients (33.1±30.9 pg/ml vs 12.6±8.7 pg/ml, P=0.0002). We further found that IL-33 was higher in patients with high viral load group (40.6±59.7 pg/ml vs 12.6±1.8 pg/ml), P= 0.47) whereas patients under highly active antiretroviral therapy (HAART) showed decreased level of IL-33 concentration as the number of years under ART increased. Our data showed a positive association between plasma IL-33 and viral load in the context of HIV/TB coinfection in our study population with a positive Pearson coefficient of r=0.21. this study indicates that plasma level of IL-33 differs among HIV/TB coinfected patients and respective monoinfections patients. The increased level of plasma IL-33 reveals that IL-33 measurement in HIV-1 monoinfected patients may represent an early predictor of development of tuberculosis.

Comparative outcomes of direct-acting antiviral treatment in patients with HIV-Hepatitis C co-infection: insights from a single center experience in Colombia.

Direct-acting antivirals (DAA) were introduced to Latin America with the aim of eliminating hepatitis C (HCV) in the region. There are scarce data on the outcomes of people living with HIV and HCV treated with these medications in Colombia. This study compares the outcomes of patients with HIV-HCV co-infection and HCV mono-infection treated with DAAs. Retrospective observational study including patients ≥18 years old with HCV infection treated with DAAs from August 2017 to December 2019 in a comprehensive center in Colombia. The main outcome was sustained virologic response (SVR). Secondary outcomes included reinfection, relapse and adverse events. We included 223 individuals with HCV treated with DAAs; 142 (63.6%) individuals were mono-infected and 81 (36.3%) co-infected. Genotypes 1b (49.7%) and 4 (33.9%) were the most common. Overall SVR after DAA treatment was 96.8%. Relapse rate was 2.24%, reinfection rate was 6.28% and adverse events occurred in 27.8% of cases. SVR was comparable in patients with co- and mono-infection (95% vs 97.8%, p=0.245). DAA were effective in mono-infected (HCV) and co-infected (HCV/HIV) patients and reinfection was high in this last group.

Seroprevalence and effect of HBV and HCV co-infections on the immuno-virologic responses of adult HIV-infected persons on anti-retroviral therapy.

Chronic hepatitis negatively affects persons living with HIV. While varying in their transmission efficiency, HIV, HBV, and HCV have shared routes of transmission. Available data suggest widely variable rates of HBV and HCV infections in HIV-infected populations across sub-Saharan Africa. With prolonged survival rates due to increased accessibility to antiretroviral drugs, HBV and HCV have the potential to complicate the prognosis of HIV co-infected patients by contributing significantly to continued morbidity and mortality. The study sought to determine the seroprevalence of HIV/HBV and HIV/HCV co-infections among HIV patients on antiretroviral therapy and to evaluate the effect of HIV/HBV and HIV/HCV co-infections on the immunologic and virologic responses of patients. A cross-sectional study in which samples were taken from 500 people living with HIV and attending ART clinic at the Fevers unit of the Korle Bu Teaching Hospital and tested for Hepatitis B Surface Antigen (HBsAg) and Hepatitis C virus antibody (HCV). CD4 cell counts and HIV-1 RNA levels were estimated as well. Data generated were analysed using IBM SPSS version 22. The seroprevalence of HIV/HBV and HIV/HCV co-infections among people living with HIV was 8.4% and 0.2% respectively. HIV/HBV coinfection included 15/42 (35.7%) males and 27/42 (64.3%) females out of which the majority (97.6%) were in the 21-60 years old bracket. HIV/HBV and HIV/HCV co-infections have varied effects on the immunological and virological response of HIV patients on ART. The mean CD cell count was 361.0 ± 284.0 in HIV/HBV co-infected patients and 473.8 ± 326.7 in HIV mono-infected patients. The mean HIV-1 RNA level was not significantly different (X2 [df] = .057 [1]; P = .811) among HIV/HBV co-infected patients (Log102.9±2.0 copies/mL), compared to that of HIV mono-infected patients (Log102.8±2.1 copies/mL) although HIV mono-infected patients had lower viral load levels. One-third (14/42) of HIV/HBV co-infected patients had virologic failure and the only HIV/HCV co-infected patient showed viral suppression. 336/500 (67.2%) patients had HIV-1 viral suppression (females [66.1%]; males [33.9%]) while 164/500 (32.8%) had virologic failure (females [67.7%]; males [32.3%]). The mean CD4 count of patients with viral suppression and patients with virologic failure was 541.2 cells/μL (95% CI 508.5-573.8) and 309.9 cell/μL (95% CI 261.9-357.9) respectively.The study concludes that, HIV/HBV and HIV/HCV coinfections do not significantly affect the immunologic and virologic responses of patients who have initiated highly active antiretroviral therapy, and treatment outcomes were better in females than in males. There was no HBV/HCV co-infection among patients.

Prevalence of hepatotoxicity among HIV-infected patients in Ethiopia: a systematic review and meta-analysis

BackgroundGlobally, the human immunodeficiency virus has been recognized as a major public health concern. The direct toxicity of antiretroviral medicines or their active metabolites causes liver cell destruction by different mechanisms, inducing immune-mediated inflammation, oxidative stress, and other mechanisms. On the other hand, the virus itself also produces hepatotoxicity. Therefore, this systematic review and meta-analysis aimed to assess the pooled prevalence of hepatotoxicity among HIV-infected patients in Ethiopia.MethodsPubMed, Science Direct, Cochrane Library, Web of Science, and ResearchGate databases were used to find relevant articles. As well, various professional associations were searched to retrieve grey literature. The Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of recruited studies. The data were extracted using Microsoft Excel, and the meta-analysis was carried out using STATA 14 software. I2 and Cochran’s Q test were employed to assess the presence of heterogeneity between studies. A random effect model was used. The funnel plot and Egger’s statistics were used to assess publication bias. Moreover, subgroup analysis and sensitivity analysis were also done.ResultsThe pooled prevalence of hepatotoxicity among HIV patients in Ethiopia was 25.45% (95% CI = 20.06–30.84%). There was high heterogeneity, with an I2 value of 93.7%. Subgroup analysis by HAART status showed a higher pooled prevalence of hepatotoxicity among HIV patients taking HAART (23.63%) than among HAART naive patients (7.29%). In subgroup analysis, the pooled prevalence of hepatotoxicity among HIV/Tb co-infected and HIV mono-infected patients was 26.3% and 17.94%, respectively.ConclusionThe current systematic review and meta-analysis showed a high prevalence of hepatotoxicity among HIV-infected patients. Therefore, regular monitoring of hepatotoxicity among HIV-infected patients is required in order to avoid liver damage and other complications.Systematic review registration PROSPERO (2022:CRD42022334704)

HTLV-1 Coinfection among Patients Attending a Large HIV Treatment Centre in Trinidad.

Studies have shown that HIV-1/HTLV-1 coinfected patients tend to have higher CD4+ counts than HIV singly infected patients. Two chart reviews were conducted at initial enrolment among patients attending a large HIV Clinic in Trinidad, one to determine the prevalence of HIV-1/HVLV-1 coinfection and another to compare the CD4+ counts and opportunistic infections among HIV-1/HTLV-1 coinfected patients compared to a randomly selected comparison group of HIV-1 singly infected patients. Sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002-December 2018, 8916 HIV-1 patients were enrolled at the clinic; 159 were HIV-1/HTLV-1 coinfected; the age range was 18-81 years; the median age was 40 years; 87 (54.7%) were females; and the median CD4+ count and median HIV-1 viral load at enrolment were 300 cells/mm3 and 128,543 copies/mL, respectively, with an HTLV-1 seroprevalence of 1.78%. Among the 477 HIV-1 singly infected patients, the age range was 18-71 years; the median age was 33 years; 248 (52.0%) were males; and the median CD4+ count and the median HIV viral load were 295 cells/mm3 and 23,369 copies/mL, respectively. Opportunistic infections (OIs) were diagnosed in 59 (37.1%) of the coinfected patients versus 48 (10.1%) among those HIV singly infected (p &lt; 0.001). HIV-1/HTLV-1 coinfected patients had higher HIV-1 viral loads (p &lt; 0.001) and more OIs, suggesting a worse prognosis though there were no statistically significant differences in CD4+ counts (p = 0.96) as compared to the HIV-1 mono-infected patients.

A Comprehensive Hepatitis C Treatment Program—An Observational Study of Collaboration Between Infectious Disease Specialists and General Internal Medicine Provider Serving a Majority Black Population

Background Hepatitis C (HCV) is a global health problem with a significant economic burden. The aim of this study was to explore the efficacy of oral direct acting antiviral HCV treatment in patients managed by infectious disease (ID) specialists and general internal medicine (GM) provider. Methods This is a retrospective cohort study on patients with HCV seen at the ID clinics at an academic medical center (January 2015–March 2021). Patients were managed either exclusively by ID specialists, comanaged by ID and GM practitioner (ID/GM), or independently managed by GM provider. Results A total of 532 patients (median age, 65 years (interquartile range, 58–68 years), 67.3% males, 87.2% Blacks) were seen for HCV treatment. There were 170 HIV-HCV coinfected patients and 362 HCV monoinfected patients. Almost 60% of the patients (n = 318) were seen by ID, 18.6% (n = 99) were comanaged by ID/GM, and 21.6% (n = 115) were seen by GM. Sustained virologic responses at 12 weeks after treatment completion were similar among the patients seen by different providers, 95.9% in ID versus 96.9% in ID/GM versus 100% in GM group (P = 0.33). In the multivariable regression model, sustained virologic response at 12 weeks had no significant association with the type of provider who treated the patients for HCV treatment (P = 0.78). Conclusions These findings support the high efficacy of HCV treatment, irrespective of whether the treatment was administered by ID or GM providers. More primary care providers trained in treating HCV can assist in the expansion of treatment initiatives aimed toward HCV elimination.

Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal

ABSTRACT Objectives Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. Methods In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. Results Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. Conclusion With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.

Co-infection of SARS-CoV-2 with other respiratory pathogens in patients with liver disease.

Respiratory illness caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was first documented in Wuhan, China, in December 2019, followed by its rapid spread across the globe. Accumulating evidence has demonstrated viral/bacterial co-infection in the respiratory tract could modulate disease severity and its outcome in COVID-19 infection. In this retrospective study, 300 chronic liver disease patients with radiologically confirmed lower respiratory tract infection were enrolled from September 2020 to December 2021. In all of them, along with SARS-CoV-2, other respiratory viral/bacterial pathogens were studied. In total, 23.7 % (n=71) patients were positive for SARS-CoV-2. Among the positive patients, 23.9 % (n=17) had co-infection with other respiratory pathogens, bacterial co-infections being dominant. The SARS-CoV-2 negative cohort had 39.7 % positivity (n=91) for other respiratory pathogens, the most common being those of the rhinovirus/enterovirus family. Ground glass opacity (GGO) with consolidation was found to be the most common radiological finding among SARS-CoV-2 positive co-infected patients, as compared to only GGO among SARS-CoV-2 mono-infected patients. Accurate diagnosis of co-infections, especially during pandemics including COVID-19, can ameliorate the treatment and management of suspected cases.

The Relationship between Visceral Adiposity and Nonalcoholic Fatty Liver Disease Diagnosed by Controlled Attenuation Parameter in People with HIV: A Pilot Study.

Fat alterations are frequent in people with HIV (PWH) and predict worse cardiometabolic outcomes. Visceral adipose tissue (VAT) is associated with ectopic fat accumulation in the liver. We aimed to investigate nonalcoholic fatty liver disease (NAFLD) diagnosed by controlled attenuation parameter (CAP) as a potential marker of visceral adiposity in PWH. We conducted a prospective pilot study of HIV mono-infected patients undergoing metabolic characterization and paired CAP measured by transient elastography with dual-energy X-ray absorptiometry (DEXA) scan. NAFLD was defined as CAP ≥ 285 dB/m, in absence of alcohol abuse. Excess visceral adiposity was defined as VAT &gt; 1.32 Kg. Pairwise correlation, area under the curve (AUC) and logistic regression analysis were employed to study the association between VAT and CAP. Thirty patients were included, of whom 50% had NAFLD. CAP was correlated with VAT (r = 0.650, p &lt; 0.001) measured by DEXA scan. After adjusting for duration of HIV infection, body mass index and waist circumference, CAP remained the only independent predictor of excess VAT (adjusted odds ratio 1.05, 95% confidence interval [CI] 1.01-1.10). The AUC analysis determined CAP had excellent performance to diagnose excess VAT (AUC 0.92, 95% CI 0.81-1.00), higher than BMI and waist circumference. The optimized CAP cut-off to diagnose excess VAT was 266 dB/m, with a sensitivity of 88.3% and a specificity of 84.6%. NAFLD diagnosed by CAP is associated with VAT in PWH independently of anthropometric measures of obesity. CAP may be a potential diagnostic marker of visceral adiposity in the practice of HIV medicine.

S1273 Prevalence of NAFLD and Fibrosis in Unselected Patients With HIV Monoinfection: A Systematic Review and Meta-Analysis

Introduction: Liver disease remains a leading cause of morbidity and mortality among patient with HIV infection. Nonalcoholic fatty liver disease (NAFLD) is an emerging concern for patients living with HIV. The aim of this review is to examine the current literature and provide an accurate estimate of the prevalence of NAFLD and fibrosis in patients with HIV monoinfection. Methods: This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). We performed a systematic search of Pubmed and Embase databases to identify studies reporting the prevalence of NAFLD and/or fibrosis in patients with HIV monoinfection. To be considered eligible for inclusion studies should met the following criteria: 1) exclude patients who had concurrent HCV or HBV infection, 2) exclude patients with heavy alcohol use (as defined by each study), 3) HIV patients must be unselected, 4) diagnosis of steatosis and fibrosis should be based on imaging and criteria should be reported. Our primary outcome of interest was the prevalence of NAFLD and fibrosis in unselected HIV monoinfected patients. To estimate the pooled prevalence of NAFLD and fibrosis we performed a random effects meta-analysis. Results: Our systematic search yielded 3078 studies of which 122 were eligible for full text review. A total of 20 studies met our eligibility criteria and were included in the meta-analysis (Table). The overall pooled prevalence of NAFLD among HIV monoinfected patients was 34.2% (95% CI: 29.7%-38.9%), but significantly varied based on the diagnostic method used (Figure). The prevalence of moderate to severe hepatic steatosis was 15.5% (95% CI: 8.9-23.5%). The overall pooled prevalence of fibrosis (defined as liver stiffness measurement >/ 7.1 kPa on transient elastography) was 12.3% (95% CI: 10.1%-14.7%). Conclusion: Our study presents the most uptodate information on the prevalence of NAFLD and fibrosis in patients with HIV monoinfection. Our results show that the prevalence of NAFLD and fibrosis remain concerningly high among HIV monoinfected individuals. Several factors, including traditional NAFLD risk factors and HIV related factors, such as lipodystrophy and antiretroviral therapy, are probably contributing to these findings. Future studies should better characterize these factors, while screening for NAFLD and fibrosis should be considered in HIV monoinfected individuals. Table 1. - Studies characteristics Study Published Study Period Country Study Type Population Patients Diagnostic Method Almeida et al. 2021 2015-2019 Brazil Cross Sectional Adult 412 TE with CAP Pezzini et al. 2020 2016-2017 Brazil Cross Sectional Adult 98 TE with CAP Cervo et al. 2020 2013-2018 Canada-Italy Cross Sectional Adult 1511 TE with CAP Liu et al. 2020 2019-2020 China Cross Sectional Adult 361 TE with CAP Kirkegaard-Klitbo et al. 2020 2015-2016 Denmark Longitudinal Prospective Observational Adult 453 CT Lallukka-Brück et al. 2020 2019 Finland Longitudinal Prospective Observational Adult 41 H-MRS Lemoine et al. 2017 2011-2012 France Cross Sectional Adult 405 TE with CAP Bischoff et al. 2021 2013-2018 Germany Longitudinal Prospective Observational Adult 301 TE with CAP Lui et al. 2016 Not Reported Hong Kong Cross Sectional Adult 80 H-MRS Guaraldi et al. 2011 2007-2008 Italy Cross Sectional Adult 103 U/S Guaraldi et al. 2008 2006-2007 Italy Cross Sectional Adult 225 CT Milic et al. 2020 2018-2019 Italy Cross Sectional Adult 707 TE with CAP Nishijima et al. 2014 2004-2013 Japan Cross Sectional >17 435 U/S Vujanovic et al. 2019 2016-2018 Serbia Cross Sectional 22-50 88 U/S Jongraksak et al. 2021 2017-2018 Thailand Cross Sectional Adult 150 TE with CAP Aepfelbacher et al. 2019 2016-2018 USA Cross Sectional Adult 46 TE with CAP Crum-Cianflone et al. 2009 2006-2007 USA Cross Sectional Adult 216 U/S Price et al. 2019 2010-2013 USA Cross Sectional 40-70 340 CT Sim et al. 2021 Not Reported USA Cross Sectional 18-60 125 CT Lombardi et al. 2016 2015-2016 Greece Cross Sectional Adult 125 U/S Abbreviations: TE with CAP: Transient elastography with controlled attenuation parameter, CT: Computed Tomography, U/S: Ultrasound, H-MRS: Proton Magnetic Resonance Spectroscopy. Figure 1.: Prevalence of any grade hepatic steatosis.

Risk factors associated with response to highly active antiretroviral therapy after 24 months of administration to HIV, HIV/HBV and HCV patients in Kumba Health District, South West Region of Cameroon

Hepatitis B (HBV) and C (HCV) are two other forms of infections for which co-infection in HIV has been associated with alteration of the immune response, increased risk of progression to liver diseases, and increased risk of hepatotoxicity associated with antiretroviral therapy. This study aimed to establish the prevalence of hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCVAb) among HIV patients, evaluate response to treatment between the different categories and identify the possible risk factors associated with this burden of hepatitis B/C among HIV patients and the resulting responses to HAART in Kumba Health, in the South West Region of Cameroon. Method: We performed a systematic screening using Rapid Diagnostic Test, for HBsAg and HCVAb among 299 HIV patients enrolled at the treatment centers in Kumba Health District (District hospital Kumba, Kumba Town Sub-Divisional hospital, and the Apostolic hospital Banga Bakundu), with all positives for HBV or HCV confirmed by the ELISA and results analyzed using SPSS version 20. Out of the 299 participants, 52 HIV patients, 36 HIV/HBV, and 12 HIV/HCV patients were involved in the prospective cohort study for 24 months which permitted monitored the immune response (CD4 counts and viral load test), as well as variation of biochemical parameters (ALAT/ASAT, albumin, bilirubine, creatinine) and weights of the studied participants. Result: Out of the 100 HIV patients involved in the prospective cohort, 36 and 12 were hepatitis B and C virus-positive respectively. Following the analysis of the viral load and CD4 cell counts, there were differences in response to HAART after 24 months between the mono-infected and co-infected patients, taking into consideration the, CD4 cell counts (HIV: 930.846 cells/mm3, HIV/HBV: 595.139 cells/mm3 and HIV/HCV: 678.500cells/mm3), and viral load (HIV: 1777.85copies/ml, HIV/HBV: 2232.61copies/ml and HIV/HCV: 750.83copies/ml). There were variations in biomarkers of the liver (ALAT/ASAT, bilirubin, and albumine) and renal function (creatinine) for both patients. There were also variations of the different biomarkers linked to the infection status of the different participants. Conclusion: There were positive variations in viral load and CD4 cell counts among the studied participants, with a more rapid response to the mono-infected HIV patients compared to the co-infected patients. Similar strength was observed in the variation of the different biomarkers and such variation indicates that co-infection of HIV patients with either hepatitis B or C virus can affect rapid response to HAART and the variations in the level of Biochemical markers among the different categories are linked to the alteration of the functions of the respective organs and so this result could be used for health decisions regarding co-infections.

Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis.

Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters mitochondria in experimental models. Our goal was to investigate whether HBV might alter liver mitochondria also in humans, and the resulting mitochondrial stress might account for the progression of fibrosis in chronic hepatitis B (CHB). The study included 146 treatment-naïve CHB mono-infected patients. Patients with CHB and advanced fibrosis (AF) or cirrhosis (F3-F4) were compared to patients with no/mild-moderate fibrosis (F0-F2). Patients with CHB were further compared to patients with chronic hepatitis C (CHC; n = 33), nonalcoholic steatohepatatis (NASH; n = 12), and healthy controls ( n = 24). We detected oxidative damage to mitochondrial DNA (mtDNA), including mtDNA strand beaks, and identified multiple mtDNA deletions in patients with F3-F4 as compared to patients with F0-F2. Alterations in mitochondrial function, mitochondrial unfolded protein response, biogenesis, mitophagy, and liver inflammation were observed in patients with AF or cirrhosis associated with CHB, CHC, and NASH. In vitro , significant increases of the mitochondrial formation of superoxide and peroxynitrite as well as mtDNA damage, nitration of the mitochondrial respiratory chain complexes, and impairment of complex I occurred in HepG2 cells replicating HBV or transiently expressing hepatitits B virus X protein. mtDNA damage and complex I impairment were prevented with the superoxide-scavenging Mito-Tempo or with inducible nitric oxide synthase (iNOS)-specific inhibitor 1400 W. Our results emphasized the importance of mitochondrial OS, mtDNA damage, and associated alterations in mitochondrial function and dynamics in AF or cirrhosis in CHB and NASH. Mitochondria might be a target in drug development to stop fibrosis progression.

Nationwide retrospective study of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue.

BACKGROUNDHepatitis B virus (HBV) nucleos(t)ide analog (NA) therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen (HBsAg) loss. There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine (LAM) to tenofovir disoproxil fumarate (TDF).AIMTo assess impact of NA on virological response and fibrosis regression using liver stiffness measurement (LSM) (i.e., FibroScan®).METHODSRetrospective, observational cohort study from the Canadian HBV Network. Data collected included demographics, NA, HBV DNA, alanine aminotransferase (ALT), and LSM. Patients were HBV monoinfected patients, treatment naïve, and received 1 NA with minimum 1 year follow-up.RESULTSIn 465 (median 49 years, 37% female, 35% hepatitis B e antigen+ at baseline, 84% Asian, 6% White, and 9% Black). Percentage of 64 (n = 299) received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years, respectively. The mean baseline LSM was 11.2 kPa (TDF) vs 8.3 kPa (LAM) (P = 0.003). At 5-year follow-up, the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM (P = 0.83). There was a significant difference in fibrosis regression between groups (i.e., mean -4.2 kPa change in TDF and -1.6 kPa in LAM, P < 0.05). The last available data on treatment showed that all had normal ALT, but more TDF patients were virologically suppressed (< 10 IU/mL) (n = 170/190, 89%) vs LAM-treated (n = 35/58, 60%) (P < 0.05). None cleared HBsAg.CONCLUSIONIn this real-world North American study, approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.

Characterization of the Intestinal Fungal Microbiome in HIV and HCV Mono-Infected or Co-Infected Patients.

Intestinal mycobiome dysbiosis plays an important role in the advancement of HIV- and HCV-infected patients. Co-infection with HCV is an important risk factor for exacerbating immune activation in HIV-infected patients, and gut fungal microbial dysbiosis plays an important role. However, no systematic study has been conducted on the intestinal fungal microbiome of HIV/HCV co-infected patients to date. Patients infected with HIV and HCV, either alone or in combination, and healthy volunteers were included. Stool samples were collected for fungal ITS sequencing and for further mycobiome statistical analysis. We found that the abundance of fungal species significantly decreased in the HIV/HCV co-infection group compared to in the healthy control group, while no significant differences were found in the mono-infection groups. Low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group were discovered to have a more chaotic fungal community. Furthermore, the opportunistic pathogenic fungal profiles and fungal inter-correlations in the co-infection group became less characteristic but more complicated than those in the mono-infection groups. Intestinal fungal dysregulation occurs in HIV- and HCV-infected patients, and this dysregulation is further complicated in HIV/HCV co-infected patients.

Effects of co-infection with Clonorchis sinensis on the sex hormones levels in male patients with chronic hepatitis B.

ObjectiveWe evaluated the levels of sex hormones in male hepatitis B patients co‐infected with Clonorchis sinensis (C. sinensis).MethodsA total of 136 male individuals were enrolled in this study, including 27 healthy controls, 28 patients with C. sinensis mono‐infection, 19 patients with only chronic hepatitis B, 18 patients with post‐hepatitis B liver cirrhosis, 26 chronic hepatitis B patients co‐infected with C. sinensis, and 18 post‐hepatitis B liver cirrhosis patients coinfected with C. sinensis. Serum levels of progesterone (P), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), and follicle stimulating hormone (FSH) in these groups were measured.ResultsThe results showed that compared with the LC group, the LC+ C. sinensis co‐infected group had an increase in E2 but decrease in T and FSH. The levels of E2 in CHB+ C. sinensis co‐infected patients were significantly higher than those in CHB mono‐infected patients, but the significantly lower levels of T were observed. Compared with HCs group, the LC group showed significant increase in all terms of sex hormones, except PRL. By contrast, the CHB mono‐infected group presented an apparent decrease in E2, T, and PRL than the HCs group. However, there were no significant differences in sex hormone levels between the C. sinensis mono‐infected patients and HCs.ConclusionThis study suggests that C. sinensis co‐infection aggravates the sex hormone disturbance in HBV patients at both chronic hepatitis and cirrhosis stages, providing evidences for potential strategies in disease prevention and treatment.