Long-term Antiviral Therapy Research Articles

Varicella zoster vasculopathy causing recurrent ischaemic strokes in an immunocompetent patient.

A 66-year-old woman reported 10 days of generalised weakness, falls and memory 'glitches'. She had developed left-sided ophthalmic herpes zoster 3 months before but was otherwise well. MR scan of brain showed acute left-sided ischaemic strokes and CT cerebral angiogram identified marked stenoses of the left anterior and middle cerebral arteries. We suspected varicella-zoster virus vasculopathy, confirmed by cerebrospinal fluid analysis. Initially she had further ischaemic strokes despite intravenous acyclovir, prednisone, aspirin and clopidogrel. However, after prolonged acyclovir and prednisone, there were no new infarcts though imaging of left anterior and middle cerebral artery vessel walls showed persistent inflammation. Varicella zoster vasculopathy can cause recurrent ischaemic strokes, even in immunocompetent people with no cardiovascular risk factors, and despite long-term antiviral therapy.

HBcrAg is associated with prognosis of hepatitis B virus-related hepatocellular carcinoma in patients after hepatectomy undergoing antiviral therapy.

Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.

Reply to correspondence on "Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients".

Reply to correspondence on "Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients".

Timing of antiviral therapy in patients with hepatitis B virus related hepatocellular carcinoma undergoing hepatectomy.

Globally, hepatocellular carcinoma (HCC) is among the most prevalent and deadly cancers. Hepatitis B virus (HBV) infection is an important etiology and disease progression factor for HCC. Hepatectomy is a widely accepted curative treatment for HCC, but the long-term survival rate is still unsatisfactory due to the high recurrence rate after resection. Preoperative or postoperative antiviral therapy plays an important role in improving the prognosis for HBV-related HCC patients who underwent hepatectomy. However, many patients miss out on the chance to receive long-term preoperative antiviral medication because their HBV and HCC infections are discovered concurrently, necessitating the start of remedial antiviral therapy in the perioperative phase. Therefore, it is of great value to know when antiviral therapy is more appropriate and whether perioperative rescue antiviral therapy can achieve the effect of preoperative long-term antiviral therapy.

High accuracy model for HBsAg loss based on longitudinal trajectories of serum qHBsAg throughout long-term antiviral therapy

ObjectiveHepatitis B surface antigen (HBsAg) loss is the optimal outcome for patients with chronic hepatitis B (CHB) but this rarely occurs with currently approved therapies. We aimed to develop and...

Risk predictive model for the development of hepatocellular carcinoma before initiating long-term antiviral therapy in patients with chronic hepatitis B virus infection.

It is generally acknowledged that antiviral therapy can reduce the incidence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), there remains a subset of patients with chronic HBV infection who develop HCC despite receiving antiviral treatment. This study aimed to develop a model capable of predicting the long-term occurrence of HCC in patients with chronic HBV infection before initiating antiviral therapy. A total of 1450 patients with chronic HBV infection, who received initial antiviral therapy between April 2006 and March 2023 and completed long-term follow-ups, were nonselectively enrolled in this study. Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis was used to construct the model. The results were validated in an external cohort (n = 210) and compared with existing models. The median follow-up time for all patients was 60 months, with a maximum follow-up time of 144 months, during which, 32 cases of HCC occurred. The nomogram model for predicting HCC based on GGT, AFP, cirrhosis, gender, age, and hepatitis B e antibody (TARGET-HCC) was constructed, demonstrating a good predictive performance. In the derivation cohort, the C-index was 0.906 (95% CI = 0.869-0.944), and in the validation cohort, it was 0.780 (95% CI = 0.673-0.886). Compared with existing models, TARGET-HCC showed promising predictive performance. Additionally, the time-dependent feature importance curve indicated that gender consistently remained the most stable predictor for HCC throughout the initial decade of antiviral therapy. This simple predictive model based on noninvasive clinical features can assist clinicians in identifying high-risk patients with chronic HBV infection for HCC before the initiation of antiviral therapy.

Correspondence to editorial on "Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients".

Correspondence to editorial on "Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients".

Assessment of liver fibrosis by transient elastography among human immunodeficiency virus/hepatitis B virus and hepatitis B virus-mono-infected patients on tenofovir therapy in Jos, Nigeria

Objectives: Chronic hepatitis B (CHB) infection, both in human immunodeficiency virus (HIV) coinfection and hepatitis B virus (HBV)-mono-infection, is associated with a risk of progression to chronic liver disease. In Nigeria, there is a paucity of data on transient elastography (TE) in HIV/HBV and HBVmono-infected patients. This study aimed at assessing liver fibrosis using TE in relation to liver function biomarkers and HBV deoxyribonucleic acid (DNA) among HIV/HBV and HBV-mono-infected patients on long-term antiviral therapy. Material and Methods: This was a cross-sectional study among HBV–HIV and HBV-mono-infected adult’s patients receiving a tenofovir-containing antiretroviral and mono-tenofovir ≥12 months at three selected tertiary hospitals in Jos Metropolis from February 2018 to May 2019, after obtaining ethical approval from the Institutional Review Boards and informed consents. The patients’ HBV DNA, platelet count, hematological, and biochemical parameters were assessed, and liver stiffness was measured by TE in kilopascals (kPa), and valid TE measurements were interpreted as: normal (F0– 1 0–4), minimal fibrosis (F2 5–7.4), moderate (F3 7.5.9.4), and severe fibrosis and cirrhosis (F4 ≥9.5). Results: A total of 101 (50 HIV/HBV and 51 HBV-mono-infected) were enrolled during the study period, comprising 42.6% males and 57.4% females. The median age interquartile range among HIV/HBV coinfected was 40.5 years (36.0–45.3) and HBV-mono-infected was 41.0 years (35.0–49.0). The median platelet count was low in the HBV-mono-infected group 195 × 109/L (168–257), P = 0.034. The overall prevalence of severe liver fibrosis (≥9.5 kPa) was 13/101 (13.0%), and among HIV/HBV-coinfected and HBV-mono-infected patients, the prevalence was 4/50 (8.0%) and 9/51 (17.6%), respectively. The plasma HBV DNA was &lt;20 copies/mL in 38/50 (76.0%) HIV/HBV coinfected individuals and in 30/51 (58.8%) of HBV-mono-infected patients. In addition, 10/50 (20.0%) HIV/HBV coinfected and 19/50 (37.3%) HBV-mono-infected patients had plasma HBV DNA levels of 20–20,000 copies/mL. In the case of HIV/HBV coinfection, the prevalence of severe fibrosis (≥9.5) was 4/50 (8.0%), while in HBV-mono-infected patients, the prevalence was was 9/51 (17.6%). The overall prevalence of thrombocytopenia was observed in 4/101 cases (3.9%): 1/50 (2.0%) in HIV/HBV coinfected individuals and 3/51 (5.9%) in HBV-mono-infected patients. Conclusion: Severe liver fibrosis as observed among HIV/HBV-coinfected and HBV-mono-infected patients in this study affirmed the necessity of routine HBV screening in clinics and it highlights the immense potentials of tenofovir therapy in the treatment of CHB patients.

Long-term antiviral therapy is associated with changes in the profile of transcriptionally active HBV integration in the livers of patients with CHB.

Hepatitis B virus (HBV) integration exists throughout the clinical course of chronic hepatitis B (CHB). This study investigated the effects of long-term antiviral therapy on the level and profiles of transcriptionally active HBV integration. Serial liver biopsies and paired blood samples were obtained from 16, 16, and 22 patients with CHB at baseline, 78, and 260 weeks of entecavir monotherapy or combined with pegylated interferon alfa, respectively. Serum HBV biomarkers were longitudinally assessed. RNA-seq and HIVID2 program was used to identify HBV-host chimeric RNAs transcribed from integrated DNA. The counts of HBV integration reads were positively related to both serum HBV DNA levels (r = 0.695, p = 0.004) and HBeAg titers (r = 0.724, p = 0.021) at baseline, but the positive correlation exited only to the serum HBsAg levels after 260 weeks of antiviral therapy (r = 0.662, p = 0.001). After 78 weeks of antiviral therapy, the levels of HBV integration expression decreased by 12.25 folds from baseline. The viral junction points were enriched at the S and HBx genes after the long-term antiviral therapy. HBs-FN1 became one of the main transcripts, with the mean proportion of HBs-FN1 in all integrated expression increased from 2.79% at baseline to 10.54% at Week 260 of antiviral treatment. Antiviral therapy may reduce but not eliminate the HBV integration events and integration expression. Certain integration events, such as HBs-FN1 can persist in long-term antiviral treatment.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection: How to achieve a better outcome.

Although the benefits of antiviral therapy for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) have been proven, researchers have not confirmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time (at least 24 wk) and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC. To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC. A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi'an Jiaotong University from January 2016 to June 2019 was conducted. Considering the history of antiviral therapy, patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups. Kaplan-Meier analysis revealed significant differences in overall survival (P < 0.0001) and disease-free survival (P = 0.035) between the two groups. Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival (hazard ratio = 0.27; 95% confidence interval: 0.08-0.88; P = 0.030). In patients with HBV-related HCC, it is ideal to receive preoperative long-term antiviral therapy, which helps patients tolerate more extensive hepatectomy; however, remedial antiviral therapy, which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL, can also result in improved outcomes.

Simplified Criteria to Assess Long-Term Antiviral Treatment Indication in Chronic HBV-Infected Pregnant Women in Cambodia.

Pregnant women identified to carry hepatitis B surface antigen (HBsAg) should be linked to care for the determination of the need for long-term antiviral therapy (LTT). We assessed the performance of simplified criteria, free from HBV DNA quantification, to select women eligible for LTT using different international guidelines as a reference. A retrospective analysis of HBV-infected pregnant women enrolled in the phase 4 ANRS TA-PROHM study was conducted in Cambodia. Sensitivity, specificity, and AUROC were computed to compare three simplified criteria (TREAT-B, HBcrAg/ALT, and TA-PROHM) with the American (AASLD) and European (EASL) guidelines as a reference. An additional assessment was performed at 6 months postpartum. Of 651 HBsAg-positive women, 209 (32%) received peripartum antiviral prophylaxis using tenofovir disoproxil fumarate (TDF). During pregnancy, 9% and 12% of women were eligible for LTT according to AASLD and EASL guidelines, respectively; 21% and 24% of women were eligible for prophylactic TDF and 2% and 5% in those ineligible (p < 0.001). Using the AASLD guidelines, the AUROC of TREAT-B, HBcrAg/ALT, and TA-PROHM scores were 0.88 (95%CI, 0.85-0.90), 0.90 (95%CI, 0.87-0.92), and 0.76 (95%CI, 0.73-0.80), respectively. Using the EASL guidelines, the AUROCs were lower: 0.73 (95%CI, 0.69-0.76), 0.76 (95%CI, 0.73-0.80), and 0.71 (95%CI, 0.67-0.74), respectively. Among those ineligible for prophylactic TDF, only 2% to 6% present an indication for LTT at 24 weeks postpartum. Few pregnant women are eligible for LTT, and the use of simplified criteria could represent an efficient triage option in decentralized areas to identify those negative for whom there is no urgent indication for LTT and focus on those positive for whom other exams must be conducted to confirm LTT indication.

Serum hepatitis B virus pregenomic RNA profiles in patients with chronic hepatitis B on long-term antiviral therapy

Objective: To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy. Methods: 100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ (2) test and Fisher's exact test were used to compare categorical variables. Results: HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks (n = 54) during subsequent treatment compared to those who did not (n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients (P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy (r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion: HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

Impact of HBV Integration on Hepatocellular Carcinoma After Long-Term Antiviral Therapy.

Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved. We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels. After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC. HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.

Metformin Treatment Leads to Increased HIV Transcription and Gene Expression through Increased CREB Phosphorylation and Recruitment to the HIV LTR Promoter.

Antiretroviral therapy has effectively suppressed HIV infection and replication and prolonged the lifespan of HIV-infected individuals. In the meantime, various complications including type 2 diabetes associated with the long-term antiviral therapy have shown steady increases. Metformin has been the front-line anti-hyperglycemic drug of choice and the most widely prescribed medication for the treatment of type 2 diabetes. However, little is known about the effects of Metformin on HIV infection and replication. In this study, we showed that Metformin treatment enhanced HIV gene expression and transcription in HIV-transfected 293T and HIV-infected Jurkat and human PBMC. Moreover, we demonstrated that Metformin treatment resulted in increased CREB expression and phosphorylation, and TBP expression. Furthermore, we showed that Metformin treatment increased the recruitment of phosphorylated CREB and TBP to the HIV LTR promoter. Lastly, we showed that inhibition of CREB phosphorylation/activation significantly abrogated Metformin-enhanced HIV gene expression. Taken together, these results demonstrated that Metformin treatment increased HIV transcription, gene expression, and production through increased CREB phosphorylation and recruitment to the HIV LTR promoter. These findings may help design the clinical management plan and HIV cure strategy of using Metformin to treat type 2 diabetes, a comorbidity with an increasing prevalence, in people living with HIV.

Risk factors for relapse after discontinuation of tenofovir or entecavir in hepatitis B e antigen-negative patients.

This study aimed to define the relapse frequency and risk determinants in chronic hepatitis B (CHB) patients who discontinued nucleoside analog (NA) treatment, were HBeAg-negative, and had achieved both a virological and biochemical response. This retrospective cohort study reviewed patients with HBeAg-negative CHB who received antiviral therapy for at least 65 months between January 1, 2013, and December 31, 2020. These patients discontinued treatment after demonstrating a biochemical and virological response and were evaluated at 6, 12, and 24 months post-treatment discontinuation. Sixty-seven patients with CHB who received NA therapy for at least 65 months, discontinued treatment, and had undetectable HBV DNA and normal ALT values were evaluated. After cessation of NA therapy, a relapse was observed in 38 patients (56.7%). The relapse rate was 71.0% in patients treated with tenofovir disoproxil fumarate (TDF) as the last NA type and 37.9% in patients treated with entecavir (ETV) (p=0.017). The cutoff value for the best estimate of age for predicting relapse was 42 years. The relapse rate was 69.2% in patients aged ≥42 years and 39.2% in patients aged <42 years (p=0.007). The relapse rate was 51.3% in patients with a pre-treatment fibrosis score of 2, 56.0% in those with a fibrosis score of 3, and 100% in those with a fibrosis score of 4 (p=0.089). Among HBeAg-negative CHB patients who achieved a virological and biochemical response to long-term antiviral therapy, those aged 42 years and older, those with high fibrosis scores before treatment, and those who used TDF before treatment cessation should be closely monitored for relapse, especially in the first 12 months after stopping NA treatment.

An Early Prosthetic Valve Endocarditis in Presence of COVID-19-Associated Pneumonia

Introduction. Coronavirus disease (COVID-19)-associated pneumonia was a dangerous disease at the beginning of 2021. However, there are almost no records of early infectious endocarditis of prosthetic heart valve in the presence of such a disease. We present an interesting clinical case of successful treatment of complicated pathology.&#x0D; The COVID-19 outbreak involved unique clinical complications that were superimposed on the progressive heart failure due to prosthetic mitral valve dysfunction (its detachment) which did not allow time for active antiinflammatory therapy. Urgent replacement of the prosthesis made it possible to eliminate the infection and paved the way for successful long-term antibacterial, antifungal and antiviral therapy.&#x0D; The aim. To determine the features of management of patients with complex clinical pathology: prosthetic valve endocarditis associated with COVID-19 and severe lung inflammation in the early postoperative period.&#x0D; Case report. This work presents rare clinical case. A 46-year old male patient underwent successful surgery (mitral valve replacement with posterior leaflet preservation and left atrium resection) at the Department of Surgical Treatment of Acquired Heart Diseases of the National Amosov Institute of Cardiovascular Surgery and was discharged in satisfactory condition. One month later, he was hospitalized again and diagnosed with an early infectious endocarditis of prosthetic mitral valve and bilateral polysegmental COVID-19-associated pneumonia. After a week of medicinal preparation (antibacterial therapy), the patient underwent repeat mitral valve replacement in the presence of progressive heart insufficiency due to increasing paravalvular insufficiency. Postoperative period elapsed without significant complications. The patient was discharged in satisfactory condition on day 15 after surgery and primary rehabilitation.&#x0D; Conclusion. Having a specific etiology, pneumonia significantly damaged mitral prosthesis structures by increasing paravalvular insufficiency. Consequently, the patient underwent life-saving repeat mitral valve replacement in the presence of COVID-19-associated pneumonia and under massive antibacterial treatment which continued for 60 days after the patient’s discharge. An important element of successful treatment of COVID-19-associated pneumonia is the selection of adequate antibacterial, antifungal and antiviral drugs.

Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: a retrospective cohort study.

Low-level viremia (LLV), a special case of poor response to antiviral therapy, has become a focus of liver disease research; however, most studies have focused on poor response to antiviral therapy, and little attention has been paid to LLV. Therefore, this study aimed to investigate the factors influencing LLV in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) monotherapy. Clinical data of CHB patients receiving ETV treatment for at least 1year at the outpatient department of the Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were collected. Patients were divided into LLV (180 cases) and sustained virological response (SVR) groups (337 cases) according to the hepatitis B virus (HBV) DNA load at the end of the observation period. Demographic features and laboratory markers were also examined. Univariate and multivariate logistic regression analyses were performed to examine factors influencing LLV in patients receiving long-term ETV monotherapy. Significant differences were noted between the LLV and SVR groups in terms of age, sex, presence or absence of cirrhosis, HBeAg positivity rate, baseline HBV DNA load, and baseline HBsAg level before treatment. Multivariate logistic regression analysis showed that baseline HBeAg status, HBV DNA load, and HBsAg quantification were pretreatment risk factors for LLV in long-term ETV antiviral therapy. CHB patients with a high HBV DNA load, high HBsAg quantification, and positive HBeAg results tend to have a high risk of LLV despite long-term ETV antiviral treatment and should be dynamically monitored.

RESULTS OF ANTIFIBROTIC THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B+C

Modern antiviral therapy regimens for patients with chronic viral hepatitis aim to achieve either long-term suppression of pathogen replication (e.g., nucleoside analogs in chronic hepatitis B) or complete elimination of the virus (such as direct-acting antiviral drugs in chronic hepatitis C). However, antiviral agents do not have a significant impact on the complete restoration of biochemical processes or the prevention of further progression of morphological changes in the liver. These limitations emphasize the ongoing need for new therapeutic strategies that target the processes of fibrogenesis.&#x0D; The aim of the work is to assess the possibility of the effect of the drug "Bicyclol" on fibrotic changes in patients with chronic hepatitis B+C using a non-invasive scale of the rate of fibrosis.&#x0D; Materials and methods&#x0D; An analysis of the dynamics of 62 patients with chronic hepatitis B and C (HCV+C) was conducted. All patients received long-term antiviral therapy consisting of pegylated interferon for 48 weeks. In the main group (Group I), patients with chronic hepatitis B and C were prescribed the drug "Bicyclol" after completing antiviral treatment with interferon. The control group (Group II) followed the principles of proper nutrition and took traditional hepatoprotectors. Based on the identified correlations, a non-invasive scale was proposed to assess the individual risk of liver fibrosis progression.&#x0D; Research results&#x0D; Against the background of the use of an antiviral treatment regimen, the normalization of cytolysis indicators was observed in most patients with CHB+C, but in some patients it was short-lived. Treatment with the drug "Bicyclol" contributed to a further decrease in cytolysis indicators, in the vast majority of patients with CHB+C, the activity of ALT and AST reached the upper limit of the norm. In patients with CHB+C who received only basic treatment without an antifibrotic component, a tendency to maintain an elevated level of transaminases was observed.&#x0D; Conclusions.&#x0D; Thus, the use of the hepatoprotector "Bicyclol" for 12 months ensures a decrease in cytolysis in the liver, is accompanied by a decrease in the severity of fibrosis, and in some patients - its reverse development. The use of the proposed prognostic scale makes it possible to assess the need for early appointment of antifibrotic therapy.

P76 Management of aciclovir-resistant mucocutaneous herpes simplex virus infection: a systematic review

Abstract Aciclovir resistance results in immunocompromised hosts due to long-term antiviral therapy and ongoing viral replication. Aciclovir resistance in herpes simplex virus (HSV) poses a major concern, as this can lead to chronic and recalcitrant infection that significantly impacts on the quality of life. While different treatment options exist, there are currently no standardized clinical treatment guidelines for mucocutaneous aciclovir-resistant (ACV-R) HSV infection. This systematic review seeks to identify safe and effective treatments for mucocutaneous ACV-R HSV infection. For this systematic review, PubMed/MEDLINE and Embase were searched in September 2022 for all articles published between 1 January 1980 and 1 September 2022. Studies were included if they described the use of a medication for the treatment of mucocutaneous ACV-R HSV infection. From the initial search that yielded 1066 studies, 86 met the inclusion criteria and were selected. Of the 86 studies, 6 were clinical trials and 80 were case reports/series. A total of 318 patients were included in our review. Foscarnet [intravenous (IV) and topical] was studied in 5 clinical trials and 25 case reports/series, leading to complete response in most patients, with adverse effects including renal toxicity and electrolyte abnormalities. Vidarabine (IV) was found to be inferior to foscarnet in a clinical trial and reported in two case reports. Common side-effects included nausea, anaemia and renal impairment. Trifluridine (topical) was studied in a clinical trial and a case report, showing complete response in some patients. Cidofovir (IV, topical, intralesional) was studied in 21 case reports/series, showing complete response in most patients, with renal impairment as the most common adverse effect. Imiquimod (topical) was studied in eight case reports/series, showing complete response and no side-effects. Pritelivir (oral) was reported in two case reports/series, showing complete response and no side-effects. Combination treatment was reported in 10 case reports/series with variable clinical response. Our review also identified reports of less widely used treatments. These include artesunate, zidovudine, varicella-zoster virus vaccine, leflunomide and surgical excision, which achieved variable response rates but have not been widely studied. While foscarnet and cidofovir have the most robust evidence, IV administration of these agents is associated with significant side-effects and may be limiting. Intralesional and topical formulations of cidofovir, trifluridine and imiquimod are alternative options appropriate for outpatient management. Pritelivir is a novel and promising treatment of mucocutaneous ACV-R HSV infection.

BI03 (P76) Management of aciclovir-resistant mucocutaneous herpes simplex virus infection: a systematic review

Abstract Aciclovir resistance results in immunocompromised hosts due to long-term antiviral therapy and ongoing viral replication. Aciclovir resistance in herpes simplex virus (HSV) poses a major concern, as this can lead to chronic and recalcitrant infection that significantly impacts on quality of life. While different treatment options exist, there are currently no standardized clinical treatment guidelines for mucocutaneous aciclovir-resistant (ACV-R) HSV infection. This systematic review seeks to identify safe and effective treatments for mucocutaneous ACV-R HSV infection. For this systematic review, PubMed/MEDLINE and Embase were searched in September 2022 for all articles published between 1 January 1980 and 1 September 2022. Studies were included if they described the use of medications for the treatment of mucocutaneous ACV-R HSV infection. From the initial search that yielded 1066 studies, 86 met the inclusion criteria and were selected. Of the 86 studies, six were clinical trials and 80 were case reports/series. A total of 318 patients were included in our review. Foscarnet [intravenous (IV) and topical] was studied in five clinical trials and 25 case reports/series, leading to complete response in most patients, with adverse effects including renal toxicity and electrolyte abnormalities. Vidarabine (IV) was found to be inferior to foscarnet in a clinical trial and reported in two case reports. Common side-effects included nausea, anaemia and renal impairment. Trifluridine (topical) was studied in a clinical trial and a case report, showing complete response in some patients. Cidofovir (IV, topical, intralesional) was studied in 21 case reports/series, showing complete response in most patients, with renal impairment as the most common adverse effect. Imiquimod (topical) was studied in eight case reports/series, showing complete response and no side-effects. Pritelivir (oral) was reported in two case reports/series, showing complete response and no side-effects. Combination treatment was reported in 10 case reports/series with variable clinical response. Our review also identified reports of less widely used treatments. These include artesunate, zidovudine, varicella-zoster virus vaccine, leflunomide and surgical excision, which achieved variable response rates but have not been widely studied. While foscarnet and cidofovir have the most robust evidence, IV administration of these agents is associated with significant side-effects and may be limiting. Intralesional and topical formulations of cidofovir, trifluridine and imiquimod are alternative options appropriate for outpatient management. Pritelivir is a novel and promising treatment of mucocutaneous ACV-R HSV infection.