Tenofovir Treatment Research Articles

Prevalence, risk factors and the impact of tenofovir treatment in SARS-CoV-2 infection and COVID-19 disease among people living with HIV: A cross-sectional population-based study

ObjectivesThe prevalence and risk factors of SARS-CoV-2 infection among unvaccinated people living with HIV (PWH) are not well understood, and the protective role of tenofovir remains controversial. This study aimed to assess the SARS-CoV-2 prevalence and associated risk factors among unvaccinated PWH, and to evaluate the impact of tenofovir. MethodsWe conducted as a cross-sectional study between November 2020 and May 2021. Plasma samples from 4,400 of 5,476 PWH were tested for total antibodies, IgG, IgM, and IgA. ResultsAmong the participants (median age 48 years, 84% male), 92% had undetectable HIV viral loads and 5% had syphilis. The prevalence of SARS-CoV-2 infection was 18% (95% CI 17-19), with 1,180 individuals showing antibodies (IgG 13%, IgA 10%, IgM 11%). Of those seropositive for SARS-CoV-2, 67.5% were asymptomatic, 29% had mild disease, and 3.5% had severe/critical conditions. Risk factors included younger age, being female, men who have sex with men (MSM) status, non-European origin, and a history of syphilis. Neither antiretrovirals nor tenofovir provided protection against SARS-CoV-2 infection or COVID-19 disease. ConclusionOngoing surveillance and tailored interventions are crucial for at-risk PWH amid evolving SARS-CoV-2 variants. Tenofovir did not prevent SARS-CoV-2 infection or COVID-19.

Baseline Viral Load and On-treatment Hepatocellular Carcinoma Risk in Chronic Hepatitis B: A Multinational Cohort Study

Hepatocellular carcinoma (HCC) risk persists in chronic hepatitis B (CHB) patients despite antiviral therapy. The relationship between pre-treatment baseline hepatitis B virus (HBV) viral load and HCC risk during antiviral treatment remains uncertain. This multinational cohort study aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in 20,826 noncirrhotic, hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with baseline HBV DNA levels ≥2,000 IU/mL (3.30 log10 IU/mL) who initiated entecavir or tenofovir treatment. The primary outcome was on-treatment HCC incidence, stratified by baseline HBV viral load as a categorical variable. In total, 663 patients developed HCC over a median follow-up of 4.1 years, with an incidence rate of 0.81 per 100 person-years (95% confidence interval [CI], 0.75-0.87). Baseline HBV viral load was significantly associated with HCC risk in a non-linear parabolic pattern, independent of other factors. Patients with baseline viral load between 6.00 and 7.00 log10 IU/mL had the highest on-treatment HCC risk (adjusted hazard ratio, 4.28; 95% CI, 2.15-8.52; P < .0001) compared to those with baseline viral load ≥8.00 log10 IU/mL, who exhibited the lowest HCC risk. Baseline viral load showed a significant, non-linear, parabolic association with HCC risk during antiviral treatment in noncirrhotic CHB patients. Early initiation of antiviral treatment based on HBV viral load may help prevent irreversible HCC risk accumulation in CHB patients.

Prevalence of residual replication in HIV-1 patients on Tenofovir, Lamuvidine and Dolutegravir (TLD) treatment followed at Al-Nadjma Multipurpose Center from 2021 to 2023

Objective: The objective of this study is to determine the prevalence of residual replication in HIV-1-infected patients receiving TLD from 2021 to 2023 followed at the Polyvalent Al-Nadjma center. Material and method: This was a retrospective and prospective study with an analytical aim which took place at the Polyvalent Al-Nadjma center from April 2022 to December 2023 in the city of N’Djamena. The study began with the interview of 135 patients, 108 of whom signed informed consent to participate in this study. Patients infected with HIV 1 on ART based on the combination of Tenofovir, Lamivudine and Dolutegravir (TLD) for at least 2 years with a load of 999 copies/mL were included. A total of 108 plasmas were collected and analyzed by the RT-PCR technique. The data from the interviews as well as the RT-PCR results were analyzed with R Studio software. Results: the results of this study revealed a female predominance with 70% (76/108) with a M/F sex ratio of 0.42. The average age of the patients was 40.58 ± 9.58 years. The prevalence of persistent residual replication was 22.22% (n = 24/108), 54.60% (n = 59/108) of patients had virological success, and 19.44% (n = 21/108) of patients had a viral load greater than or equal to 1000 copies/mL and 3.70% (n = 4/108) had an invalid plasma viral load. Conclusion: The aim of this work was to determine the prevalence of residual replication in patients infected with HIV-1 under Tenofovir, Lamuvidine and Dolutegravir (TLD) followed at the Al-Nadjima/APMS multipurpose center in N’Djamena, Chad. The prevalence of residual replication in this study was 22.22%. This study demonstrated that individuals with a persistent viral load below 1000 copies/mL were at increased risk of therapeutic and virological failure due to the lack of consensus and failure to control the phenomenon of residual replication in patients infected with HIV-1 under TLD

Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients.

A single-nation study reported that pretreatment HBV viral load is associated with on-treatment risk of HCC in patients who are HBeAg-positive without cirrhosis and with chronic hepatitis B initiating antiviral treatment. We aimed to validate the association between baseline HBV viral load and on-treatment HCC risk in a larger, multinational cohort. Using a multinational cohort from Korea, Hong Kong, and Taiwan involving 7545 adult patients with HBeAg-positive, without cirrhosis and with chronic hepatitis B who started entecavir or tenofovir treatment with baseline HBV viral load ≥5.00 log 10 IU/mL, HCC risk was estimated by baseline viral load. HBV viral load was analyzed as a categorical variable. During continuous antiviral treatment (median, 4.28y), HCC developed in 200 patients (incidence rate, 0.61 per 100 person-years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a nonlinear pattern. HCC risk was lowest with the highest baseline viral load (≥8.00 log 10 IU/mL; incidence rate, 0.10 per 100 person-years), but increased sharply as baseline viral load decreased. The adjusted HCC risk was 8.05 times higher (95% CI, 3.34-19.35) with baseline viral load ≥6.00 and <7.00 log 10 IU/mL (incidence rate, 1.38 per 100 person-years) compared with high (≥8.00 log 10 IU/mL) baseline viral load ( p <0.001). In a multinational cohort of adult patients with HBeAg-positive without cirrhosis and with chronic hepatitis B, baseline HBV viral load was significantly associated with HCC risk despite antiviral treatment. Patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC development.

Association of HBsAg levels with differential gene expression in NK, CD8 T, and memory B cells in treated patients with chronic HBV

HBsAg secretion may impact immune responses to chronic HBV infection. Thus, therapeutic approaches to suppress HBsAg production are being investigated. Our study aims to examine the immunomodulatory effects of high and low levels of circulating HBsAg and thereby improve our understanding of anti-HBV immunity. An optimized 10x Genomics single-cell RNA sequencing workflow was applied to blood samples and liver fine-needle aspirates from 18 patients undergoing tenofovir/entecavir (NUC) treatment for chronic HBV infection. They were categorized based on their HBsAg levels: high (920-12,447 IU/ml) or low (1-100 IU/ml). Cluster frequencies, differential gene expression, and phenotypes were analyzed. In the blood of HBV-infected patients on NUC, the proportion of KLRC2+ "adaptive" natural killer (NK) cells was significantly lower in the HBsAg-high group and, remarkably, both KLRC2+ NK and KLRG1+ CD8 T cells display enrichment of lymphocyte activation-associated gene sets in the HBsAg-low group. High levels of HBsAg were associated with mild immune activation in the liver. However, no suppression of liver-resident CXCR6+ NCAM1+ NK or CXCR6+ CD69+ CD8 T cells was detected, while memory B cells showed signs of activation in both the blood and liver. Among NUC-treated patients, we observed a minimal impact of HBsAg on leukocyte populations in the blood and liver. However, for the first time, we found that HBsAg has distinct effects, restricted to NK-, CD8 T-, and memory B-cell subsets, in the blood and liver. Our findings are highly relevant for current clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. This study provides unique insight into the impact of HBsAg on gene expression levels of immune cell subsets in the blood and liver, particularly in the context of NUC-treated chronic HBV infection. It holds significant relevance for current and future clinical studies evaluating treatment strategies aimed at suppressing HBsAg production and reinvigorating immunity to HBV. Our findings raise questions about the effectiveness of such treatment strategies and challenge the previously hypothesized immunomodulatory effects of HBsAg on immune responses against HBV.

Higher HBeAg-reversion virological relapse and lower sustained remission after treatment cessation in tenofovir-treated HBeAg-positive patients.

A complete investigation of the clinical outcomes after treatment cessation in HBeAg-positive patients with HBeAg loss is limited. We retrospectively recruited 242 HBeAg-positive patients with HBeAg loss after a median duration of 37.2 months with tenofovir (TDF, n = 77) or entecavir (ETV, n = 165) treatment. There were 77 (31.8%) patients with sustained virological remission (SVR), 85 (35.1%) with HBeAg-reversion virological relapse, 80 (33.1%) with HBeAg-negative virological relapse after treatment cessation, and 23 (9.5%) with HBsAg loss. Clinical data at baseline, on-treatment and during off-treatment follow-up were analyzed. The 3-year cumulative incidences of overall, HBeAg-reversion and HBeAg-negative virological relapse were 70.2%, 54%, and 53.5%, respectively. The common factors associated with HBeAg-reversion and HBeAg-negative virological relapse were tenofovir treatment (hazard ratio [HR] = 5.411, p < 0.001; HR = 2.066, p = 0.006, respectively) and HBsAg at end of treatment (EOT) (HR = 1.461, p = 0.001; HR = 1.303, p = 0.019, respectively). The 5-year cumulative incidence of HBsAg loss in SVR patients was 13.7% and EOT HBsAg was the only associated factor (HR = 0.524, p = 0.024). Compared to that of ETV-treated patients, TDF-treated patients had a significantly higher 3-year cumulative incidence of virological relapse (87.3% vs. 62.8%, p < 0.001), earlier HBeAg-reversion virological relapse (2.9 vs. 7.8 months, p < 0.001), a higher rate of HBeAg-reversion virological relapse (53.2% vs. 26.7%) and a lower SVR rate (15.6% vs. 39.4%) (p < 0.001). In summary, the clinical outcomes after treatment cessation in HBeAg-positive patients with HBeAg loss were composed of HBeAg-reversion virological relapse, HBeAg-negative virological relapse and SVR. TDF was significantly associated with off-treatment virological relapse. EOT HBsAg plays an important role in HBsAg loss among SVR patients and posttreatment virological relapse.

ANTIVIRAL RESPONSE OF DRUGS USED AGAINST HBV PATIENTS OF KHYBER PAKHTUNKHWA, PAKISTAN

Hepatitis B virus is an ample cause of end-stage liver diseases and hepatocellular carcinoma. Effective treatment in high-risk countries such as Pakistan can help delay or prevent these consequences.The existing study aims to evaluate the response rates of antiviral drugs tenofovir and entecavir (6-48 months) based on different clinical parameters. Sera collected from HBV patients (43) subjected to DNA extraction, followed by real-time PCR detection. Furthermore, ICT was performed to detect HBs-Ag and ELISA for HBe-Ag. Response rate after 6 months of tenofovir treatments showed 100% normal creatinine and ultrasound and ALT (50%) and while in the case of entecavir, each ALT and ultrasound normalization (66.7%), showed creatinine (100%). The fatty liver was reported 50% and 33.3% after tenofovir and entecavir treatment, respectively. The response after 12 months of treatment with tenofovir showed normalization of ALT and ultrasound (84.6%), bilirubin and creatinine normalization (92.3%), and fatty liver (15.4%). Whereas bilirubin and creatinine levels showed (100%) normal, ALT and ultrasound normalization (80%) with 20% of patients having congenital left lobe of the liver after entecavir. Patients profiles after 24 months of tenofovir treatment showed normal ALT and ultrasound (85.7%), bilirubin (100%), and renal impairment observed in patients (14.3%). The 24 months entecavir treatment showed significant improvement in various clinical parameters normalization with 100% such as ALT, bilirubin, and creatinine in all patients. The efficacy of entecavir showed a significant response as compared to Tenofovir. Furthermore, nucleoside/nucleotide analogues enhanced its efficacy with longer treatment duration.

Long-term comparisons of the durability of 6 months versus 12 months antiviral therapy for hepatitis B after chemotherapy cessation

BackgroundProphylaxis antiviral therapy is recommended for patients with hepatitis B receiving chemotherapy but the ideal treatment duration after chemotherapy cessation needs more evidence for clarification. AimsThis study aimed to compare the relapse rate of short finite intervals of 6 months and 12 months of -nucleos(t)ide analogue (NA) therapy in patients stratified by low hepatitis B virus (HBV)-DNA of < 2000 IU/ml or high HBV DNA of ≥ 2000 IU/ml. MethodsPatients started tenofovir or entecavir treatment 1 week before chemotherapy and were assigned to different treatment duration groups randomly after stratified by HBV DNA pretreatment: (1) HBV DNA of < 2000 IU/ml at 6-month or 12-month duration; (2)HBV DNA of ≥ 2000 IU/ml at 6-month or 12-month duration. Virological relapse (VR) was defined as HBV DNA of > 2000 IU/ml, and clinical relapse (CR) was defined as HBV DNA of > 2000 IU/ml and alanine aminotransferase of > 80 IU/L during the follow-up period. The primary endpoint was to compare the durability between groups 1 year after antiviral therapy cessation. The secondary endpoint was VR and CR rate at long-term follow-up after antiviral therapy cessation. ResultsThis study enrolled 61 patients, and 5 patients were lost to follow-up or tumor recurrence. VR and CR rates were 46.4% and 14.3% at 1-year and 55.3% and 16.1%, at long-term follow-up, respectively. VR and CR rates demonstrated no difference between the groups. Pretreatment HBV DNA at ≥ 2000 IU/ml and end-of-treatment hepatitis B surface antigen (HBsAg) at ≥ 500 IU/ml were the predictor of VR (hazard ratio [HR]: 2.98; p = 0.010 and HR: 2.38; p = 0.037). ConclusionsProlongation from 6 months to 12 months of NA consolidation after chemotherapy cessation did not affect the VR or CR of HBV. High pretreatment HBV DNA and end-of-treatment HBsAg levels could predict VR after antiviral therapy cessation for chemotherapy.

Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay.

In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA.

Evaluation of the HBV liver reservoir with fine needle aspirates

Background & AimsFinite duration of treatment associated with HBsAg loss is the current goal for improved therapeutic approaches against chronic HBV infection, as it indicates elimination or durable inactivation of intrahepatic covalently closed circular DNA (cccDNA). To assist drug development, the definition of early predictive markers of HBsAg loss by assessing their value in reflecting intrahepatic cccDNA levels and transcriptional activity is essential. Fine needle aspirates (FNAs) have recently emerged as a less invasive alternative to core liver biopsy (CLB) and showed to be useful for investigating intrahepatic immune responses. The aim of this study was to optimise and validate the use of FNA vs. CLB to evaluate the intrahepatic viral reservoir. MethodsPaired FNA/CLB samples were obtained from patients with HBeAg+ chronic hepatitis (n = 4), HBeAg− chronic hepatitis (n = 4), and HBeAg− chronic infection (n = 1). One HBeAg+ patient was undergoing tenofovir treatment. HBV 3.5-kb RNA and cccDNA were quantified by droplet digital PCR. ResultscccDNA was quantifiable in all but one FNA/CLB pair, showing the highest levels in untreated HBeAg+ patients, except for the tenofovir-treated patient. Similarly, 3.5-kb RNA was detectable in all but one FNA sample and showed higher levels in HBeAg+ patients. When comparing cccDNA and 3.5-kb RNA quantification in FNA vs. CLB samples, no statistically significant differences were identified. ConclusionsThese results demonstrate the possibility to quantify cccDNA and assess its transcriptional activity in patients with chronic hepatitis B by combining FNA and droplet digital PCR. This supports the use of FNA in clinical trials to evaluate the intrahepatic viral reservoir during the development of new antivirals and immunomodulatory agents. Impact and implicationsChronic hepatitis B infection is characterised by a complex interplay between immune responses and viral replication in the liver, which determines the long-term outcome of the disease. In this study, we show that fine needle aspiration of the liver, a less-invasive alternative to core biopsies, allows the assessment of the hepatic viral reservoir.

SAT-163 - Incomplete response with/without genotypic resistance to prior antivirals is not associated with a higher risk of hepatocellular carcinoma during tenofovir treatment for chronic hepatitis B

SAT-163 - Incomplete response with/without genotypic resistance to prior antivirals is not associated with a higher risk of hepatocellular carcinoma during tenofovir treatment for chronic hepatitis B

The expression of interleukin-1β in patients with chronic hepatitis B treated with pegylated-interferon-alpha combined with tenofovir disoproxil fumarate and monotherapy

BackgroundAnti-hepatitis B virus (HBV) treatment uses tenofovir disoproxil fumarate (TDF) along with Pegylated-interferon-alpha (Peg-IFN-α), which is more effective than TDF/Peg-IFN-α monotherapy. We have previously shown that interleukin-1beta (IL-1β) is related to the effectiveness of IFN-α treatment in chronic hepatitis B (CHB) patients. The aim was to investigate the expression of IL-1β in CHB patients treated with Peg-IFN-α combination with TDF and TDF/Peg-IFN-α monotherapy.MethodsHuh7 cells infected with HBV were stimulated by Peg-IFN-α and/or Tenofovir (TFV) for 24h. A single-center cohort study of prospective recruitment of CHB patients: untreated CHB (Group A), TDF combined with Peg-IFN-α therapy (Group B), Peg-IFN-α monotherapy (Group C), TDF monotherapy (Group D). Normal donors served as controls. The clinical datas and blood of patients were collected at 0, 12, and 24 weeks. According to the early response criteria, Group B and C were divided into two subgroups: the early response group (ERG) and the non-early response group (NERG). Stimulation of HBV-infected hepatoma cells with IL-1β to validate the antiviral activity of IL-1β. To test the blood sample, cell culture supernatant, and cell lysates and to assess the expression of IL-1β and HBV replication levels in various treatment protocols, Enzyme-Linked Immunosorbent Assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used. SPSS 26.0 and GraphPad Prism 8.0.2 software were used for statistical analysis. P values < 0.05 was considered to be statistically significant.ResultsIn vitro experiments, Peg-IFN-α plus TFV treatment group expressed higher IL-1β and inhibited HBV more effectively than monotherapy. Finally, 162 cases were enrolled for observation (Group A (n = 45), Group B (n = 46), Group C (n = 39), and Group D (n = 32)), and normal donors (n = 20) were enrolled for control. The early virological response rates of Group B, C, and D were 58.7%, 51.3%, and 31.2%. At 24 weeks, IL-1β in Group B(P = 0.007) and C(P = 0.034) showed higher than at 0 week. In Group B, the IL-1β showed an upward trend at 12w and 24w in the ERG. IL-1β significantly reduced HBV replication levels in hepatoma cells.ConclusionThe increased expression of IL-1β may enhance the efficacy of TDF combined with Peg-IFN-α therapy in achieving an early response for CHB patients.

Hepatitis B virus down-regulates the expression of inhibin and promotes the proliferation and survival of hepatocellular carcinoma cells

Objective: To investigate the effect and role of the hepatitis B virus (HBV) on the expression of inhibin (PHB) in the proliferation and survival of hepatocellular carcinoma (HCC) cells. Methods: The expression of PHB in 13 pairs of HBV-infected livers, normal livers and HepG2.2.15 and HepG2 cells was detected by real-time fluorescent quantitative PCR and Western blot. Liver tissues were collected from seven patients with chronic hepatitis B before and after antiviral (tenofovir) treatment, and the expression of PHB was detected by RT-PCR and Western blot. HepG2.2.15 cells were transfected with Pcmv6-AC-GFP-PHB, and control vectors were collected. DNA content was analyzed by flow cytometry. The proliferation level of each cell group was detected using the EdU cell proliferation assay. HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB and the control vector were cultured in serum-free medium for 6 days. Apoptosis was measured at the indicated time points using fluorescence-activated cell sorting (FACS)-based Annexin-V/PI double staining. Results: Compared with normal liver tissue, the expression of PHB in HBV-infected liver tissue was down-regulated (P < 0.01). Compared with HepG2 cells, the expression of PHB in HepG2.2.15 cells was significantly decreased (P < 0.01). The expression level of PHB in liver tissue after antiviral treatment (tenofovir) was significantly higher than that before treatment (P < 0.01). Compared with the control vector, the proliferation rate of HepG2.2.15 cells transfected with Pcmv6-AC-GFP-PHB was significantly lower than that of the control vector, and the apoptosis rate of HepG2.2.15 cells transfected with the Pcmv6-AC-GFP-PHB vector was significantly higher than the control vector (P < 0.01). Conclusion: HBV down-regulates the expression of inhibin to promote the proliferation and survival of hepatocellular carcinoma cells.

The Different Prognoses of Hepatocellular Carcinoma with Previous Tenofovir versus Entecavir Treatment for Chronic Hepatitis B Virus: Analysis Based on 15 Propensity Score-Matched Studies

Background: Currently, enough studies with aggregated study-level data have demonstrated that there was no clinically meaningful difference in the risk of hepatocellular carcinoma (HCC) between patients who received entecavir and patients who received tenofovir treatment for chronic hepatitis B virus (CHBV). However, many studies found many differences in prognosis of these HCC patients. This meta-analysis of high-quality propensity score-matched (PSM) studies was designed to provide robust estimates for comparative HCC prognosis between groups receiving tenofovir or entecavir. Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to July 10, 2022, for relevant studies that compare the different prognoses of HCC between tenofovir and entecavir treatment. The primary outcomes were the difference of overall death or liver transplantation between tenofovir and entecavir treatment. The secondary outcomes included risk factors of overall death or liver transplantation and different treatment responses between tenofovir and entecavir treatment for CHBV. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. Results: A total of 15 PSM studies were identified, with 24,035 sample sizes in tenofovir group and 61,410 sample sizes in entecavir group, respectively. Pooled data indicated that, compared with entecavir, patients receiving tenofovir experienced significantly lower overall death or liver transplantation, with a pooled OR of 0.55 (95% CI: 0.45–0.68; p < 0.00001). Subgroup analysis by population also found similar results with pooled ORs of 0.52 (95% CI: 0.38–0.70; p < 0.0001) in entire cohort and 0.62 (95% CI: 0.50–0.77; p < 0.0001) in PSM cohort. Similarly, the subgroup analysis also found that HCC patients without cirrhosis receiving tenofovir experienced significantly lower overall death or liver transplantation than entecavir (OR: 0.56; 95% CI: 0.49–0.66), but no significant result was found in HCC patients with cirrhosis. In addition, both univariate (OR: 0.46; 95% CI: 0.31–0.69) and multivariable analyses (OR: 0.86; 95% CI: 0.82–0.91) also indicated significant reduction of overall death or liver transplantation in tenofovir group than entecavir group. Conclusion: Our analysis indicated that there was clinically meaningful difference in prognosis of HCC between patients who received entecavir and patients who received tenofovir. Patients who received tenofovir experienced much lower overall death or liver transplantation than patients who received entecavir. Tenofovir treatment may be one of independent favorable factors of prognosis for HCC patients with CHBV.

The Effects of the COVID-19 Pandemic on Clinical and Laboratory Follow-up of Patients Diagnosed With Chronic Hepatitis B: A Multicenter, Prospective, Observational Study

Background: Chronic hepatitis B (CHB) patients who are under the treatment of antiviral agents should be monitored in routine control visits. However, during the COVID-19 pandemic, the visits were interrupted. Objectives: This study aimed to investigate whether these patients were affected regarding clinical, laboratory, and treatment outcomes. Methods: This prospective study consisted of CHB patients aged &gt; 18 who were applied to 3 tertiary centers between 14 February and 30 March 2022. The patients were selected from the ones who regularly applied to outpatient clinics and under the treatment of antiviral agents before the pandemic. The demographic and laboratory values, including serologic, biochemistry, and molecular results, were compared between the 2 groups who came and did not come to control visits. Results: A total number of 220 patients were included. More than half (n = 142, 64.5%) were female. The median age was 44 years (19 - 73). A hundred and forty-two (64.5%) patients did not come to control visits during the pandemic. The most common reason was anxiety about COVID-19. The tenofovir treatment was replaced with entecavir (ETV) due to osteopenia and with alafenamide due to osteopenia and/or renal failure. The previous agents were re-started in 27 (79.5%) patients who discontinued the treatment. Conclusions: The COVID-19 pandemic negatively impacted the follow-up of CHB patients. In this regard, 15.5% of patients stopped their treatments. The patients who stopped their follow-ups and continued tenofovir disoproxil fumarate (TDF) had proteinuria and decreases in bone mineral density (BMD) and estimated glomerular filtration rate (eGFR) levels.

Incidence of Nephrotoxicity among People Living with Human Immunodeficiency Virus on Tenofovir Treatment in a Tertiary Hospital in the Philippines

Incidence of Nephrotoxicity among People Living with Human Immunodeficiency Virus on Tenofovir Treatment in a Tertiary Hospital in the Philippines

Long-term trends of alanine aminotransferase levels among persons living with human immunodeficiency virus/hepatitis B virus with and without hepatitis delta coinfection

BackgroundHepatitis delta virus (HDV) infection accelerates the progression of liver disease in persons living with HIV and hepatitis B virus (HBV) coinfection. We explored the association between HDV infection and alanine aminotransferase (ALT) elevation during tenofovir-containing antiretroviral treatment among persons living with HIV/HBV.Materials and methodsWe included persons living with HIV/HBV with and without HDV starting tenofovir-containing antiretroviral therapy (ART) in three European cohorts with at least 18 months of follow-up. We defined HDV infection as a positive anti-HDV antibody test. We assessed risk factors for ALT elevation ≥ 1.25x upper limit of normal after 5 years of tenofovir-treatment using multivariate logistic regression models. The difference in ALT trends between individuals with and without HDV was evaluated using linear mixed effects models.Results61/518 (11.8%) participants had an HDV infection. Among individuals with HDV, 63.9% had ALT elevation after 2 years and 55.6% after 5 years of tenofovir, whereas the estimates were 34.1% after two and 27.0% after 5 years in those without HDV. HDV coinfection (adjusted odds ratio 2.8, 95% confidence interval 1.4–5.8) and obesity at baseline (adjusted odds ratio 3.2, 95% confidence interval 1.2–8.0) were associated with ALT elevation after 5 years of tenofovir therapy. Mean ALT levels were consistently higher during follow-up in participants with HDV compared to those without HDV.ConclusionPersistent ALT elevation is common in persons living with HIV/HBV in Europe despite adequate HBV therapy. HDV coinfection and obesity are independent risk factors for persistent ALT elevation during long-term tenofovir treatment.

ANALYSIS OF THE METABOLIC SYNDROME AND ITS ASSOCIATION WITH CART IN HIV POSITIVE INDIVIDUALS RECEIVING VARIOUS CART REGIMENS WITH REVIEW OF LITERATURE.

Context: Many endocrine and metabolic disorders are seen in patients with HIV infection. Various comorbidities have been reported at a higher rate in HIV positive individuals, some at an earlier age. Since metabolic syndrome and its determinants are slowly developing, studies are needed in this regard. The study aimed to analyze various parameters associated with the metabolic syndrome in HIV positive individuals and stratifyAims: subjects based on their treatment regimens, and present a brief comparison based on the same. A cross sectional studySettings and Design: involving 155 participants was conducted at a tertiary care centre in Western India. Detailed history and clinicalMaterials and Methods: examination was carried out. Routine investigations were done and parameters of interest to the study were then analysed based on AHA/NHLBI denitions. Univariate analysis of all parameters. Multiple logistic regression for statistically signicant parameters.Statistical Analysis used: Results and Conclusion: Deranged HDL cholesterol was the most common component of the metabolic syndrome seen amongst all participants (53.8%) which was signicantly higher in the treatment naïve group (P = 0.001). The difference between the prevalence of metabolic syndrome between the ART naïve group and patients receiving ART was not signicant. Males had a signicantly higher prevalence of metabolic syndrome than females (26.3%&gt;12.4%, P = 0.026). There was a signicant difference in the prevalence between the Zidovudine and Tenofovir treatment groups(P=0.02). Patients on the TLE (Tenofovir, Lamivudine, and Efavirenz) regimen had the lowest prevalence (4.2%) of metabolic syndrome.

Risk of Hepatocellular Carcinoma With Tenofovir vs Entecavir Treatment for Chronic Hepatitis B Virus

Conventional meta-analyses with aggregated study-level data have yielded conflicting results for the comparative effectiveness of tenofovir disoproxil fumarate vs entecavir in reducing hepatocellular carcinoma (HCC) risk among patients with chronic hepatitis B virus. Within-study heterogeneity, between-study heterogeneity, and the inability of conventional meta-analyses to capture time-to-event data were associated with these results. To perform a reconstructed individual patient data meta-analysis of high-quality propensity score-matched studies to provide robust estimates for comparative HCC risk between groups receiving tenofovir or entecavir. Medline and Embase databases were searched from inception to October 6, 2021. The initial search yielded 3435 articles. Fourteen studies that used propensity score matching to balance baseline characteristics were included in the final analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Individual patient data were reconstructed from Kaplan-Meier curves. Risk of HCC was evaluated using random-effects hazard ratios (HRs) via a shared-frailty model and a Cox proportional hazards model stratified by study group. Restricted mean survival time (RMST) analysis was conducted to account for varying estimated treatment effect across time. The comparative risk of HCC with tenofovir vs entecavir treatment. From analysis of 14 studes with 24 269 patients (10 534 receiving tenofovir and 13 735 receiving entecavir; mean age, 49.86 [95% CI, 48.35-51.36] years; 65.05% [95% CI, 58.60%-71.00%] men), tenofovir was associated with decreased HCC incidence compared with entecavir (stratified Cox HR, 0.85 [95% CI, 0.76-0.94] at 5 years; P = .002). However, there was no significant difference in subanalysis of clinical cohort studies (stratified Cox HR, 0.92 [95% CI, 0.80-1.06] at 5 years; P = .24). Among administrative database studies, proportionality was violated, and HRs could not be obtained via Cox proporational hazards-based models. The mean time to HCC development in RMST analysis was 2.8 (95% CI, 1.8-3.7) weeks longer (P < .001) for tenofovir vs entecavir at 5 years. The RMST analyses for other subgroups revealed either insignificant or minimal differences (<3 weeks) in the mean time to HCC at 5 years. In this meta-analysis, there was no clinically meaningful difference in the risk of HCC between patients who received entecavir and patients who received tenofovir. There was no difference between tenofovir and entecavir among clinical cohort studies, whereas the mean time to HCC development was less than 3 weeks longer for patients who received tenofovir vs those who received entecavir at year 5 among administrative database studies. The choice between tenofovir or entecavir should be decided based on patient convenience and tolerability.

A Study on Pregenomic RNA and Factors Related to Hepatitis B Virus Infection Based on Real World

ObjectiveThis article aims to study the influencing factors of pgRNA and its change magnitude based on the real world.MethodsA total of 421 patients who were tested for pgRNA were selected. According to the baseline data, the subjects were divided into negative and positive groups. The Chi-square test and logistic regression were used to analyze the influencing factors of pgRNA status. Based on the follow-up data, the rank-sum test and linear regression were used to analyze the influencing factors of pgRNA change magnitude.ResultsA total of 153 (36.3%) of the 421 subjects were pgRNA-negative and 268 (63.7%) were pgRNA-positive. Logistic regression analysis showed that positive HBV DNA (OR: 40.51), positive HBeAg (OR: 66.24), tenofovir treatment (OR: 23.47), and entecavir treatment (OR: 14.90) were the independent risk factors for positive pgRNA. Univariate linear regression showed that the pgRNA change magnitude of patients treated with entecavir was higher than that of patients treated with tenofovir. Multivariate linear regression showed that age was an independent factor influencing pgRNA change magnitude.ConclusionsThe pgRNA of patients who were young, female, HBV DNA-positive, high-HBsAg, HBeAg-positive is higher than the detection line. HBV DNA and HBeAg are the independent risk factors of positive pgRNA. Different antiviral regimens and disease stages have significantly different effects on pgRNA status. There was a significant correlation between pgRNA and FIB-4, suggesting that pgRNA is related to liver fibrosis. The decrease in pgRNA was greater in young patients than in non-young patients. The decrease in pgRNA was greater in patients treated with tenofovir than in patients treated with entecavir.