Antiviral Long-term Treatment Research Articles

Neurocognitive Functioning is Impaired in Perinatally HIV-Infected Youth.

The present study examined neurocognitive differences between Perinatally HIV (PHIV)-infected-youth and age and gender matched healthy controls. Despite early, long-term anti-viral treatment (ART), significant neurocognitive deficiencies remain for PHIV-infected-youth reaching adulthood compared to controls. Participants were assessed with a comprehensive neuropsychological battery. An Overall Neurocognitive Composite Score and a Global Deficit Score (GDS) were created. Sleep, depression, and developmental level of intellectual functioning were also examined. PHIV-youth performed more poorly than controls in all neurocognitive domains. Very large effect sizes were observed for the Overall Neurocognitive Composite Score and GDS. PHIV-infected-youth appear to be significantly more depressed compared to controls, but there were no differences in amount or type of sleep observed. Despite early, long-term anti-viral treatment (ART), neurocognitive deficiencies remain for PHIV-infected-young-adults. The verbal learning domain was significantly impaired with implications for functioning. The PHIV-infected-youth were also depressed and not receiving treatment for depression.

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.

The efficacy of antiviral treatment in chronic hepatitis B patients with hepatic steatosis

Background & aimsWith a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. MethodsCHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. ResultsIn total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245–0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. ConclusionsAmong CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B

ObjectiveThe association between baseline pretreatment serum HBV DNA levels and on-treatment hepatocellular carcinoma (HCC) risk remains controversial in patients with chronic hepatitis B (CHB). We aimed to investigate the association...

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.

Monitoring the effect of antiviral treatment on the development of cirrhosis and hepatocellular carcinoma in chronic hepatitis B patients.

Despite the availability of treatment and vaccines for chronic hepatitis B infection, it remains a public health problem. The use of nucleos(t)ide antiviral agents is effective in preventing complications such as cirrhosis and hepatocellular carcinoma, but despite the reduction, the risk persists. The objective of this study was to assess alterations in aspartate aminotransferase to platelet ratio index and Fibrosis-4 scores and examine the effectiveness of risk estimates for HCC in chronic hepatitis B scores in predicting the risk of hepatocellular carcinoma among chronic hepatitis B patients undergoing prolonged antiviral treatment. This is a retrospective 10-year follow-up study that included chronic hepatitis B patients who received antiviral treatment. The alterations in aspartate aminotransferase to platelet ratio index and Fibrosis-4 scores were examined for the first, fifth, and tenth years. In addition, the expected long-term risk of hepatocellular carcinoma, if antiviral treatment was not initiated, was calculated using the risk estimates for HCC in chronic hepatitis B scores before treatment, and the incidence of hepatocellular carcinoma despite long-term antiviral treatment was compared with these values. The study included a total of 218 chronic hepatitis B patients. A noteworthy decline in aspartate aminotransferase to platelet ratio index and Fibrosis-4 scores was noted across all fibrosis groups, irrespective of the initial degree of fibrosis, during the first year of antiviral treatment. Following the calculation using risk estimates for HCC in chronic hepatitis B scores, one case was observed compared to the expected 15.04 cases of hepatocellular carcinoma. We showed that both aspartate aminotransferase to platelet ratio index and Fibrosis-4 scores significantly decreased until the fifth year of antiviral treatment, with a prominent decline occurring in the first year. This study demonstrates that the impact of antiviral treatment on fibrosis can be monitored using noninvasive fibrosis scores.

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.

Antiviral Therapy Favors a Lower Risk of Liver Cirrhosis in HBeAg-negative Chronic Hepatitis B with Normal Alanine Transaminase and HBV DNA Positivity.

Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking. HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC). This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7-100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11-0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14-0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10-0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01-0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01-0.67) and 93% (95% CI: 0.01-0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did. Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.

Hepatitis B virus associated cirrhosis: overview of prognostic and management

Hepatitis B virus (HBV) infection is a global public health problem ; two billion people worldwide have evidence of past or present infection with HBV, and 296 million individuals are chronic carriers (i.e., positive for hepatitis B surface antigen [HBsAg]), of whom approximately 887,000 dies annually from HBV-related liver disease: chronic hepatitis B-associated cirrhosis and hepatocellular carcinoma. There are described some risk factors to the development of cirrhosis to HBV-infected persons: alcohol consumption, HBeAg status, metabolic syndrome, HBV genotypes and variants, and the level of HBV replication. The observation of a strong association between the development and decompensation of cirrhosis as well as between the development of HCC and the level of HBV replication suggests that suppression of HBV replication by long-term antiviral treatment may decrease the risk of complications in patients with HBV-related cirrhosis. The indication for antiviral treatment is given if any HBV DNA levels are detectable in the serum of HBV-infected patients with cirrhosis. Into the new era of antiviral treatment with nucleos(t)ide analogs we can prevent the development of cirrhosis in patients with chronic HBV infection and hepatic decompensation in many patients with HBV-related cirrhosis.

Effect of dietary branched chain amino acids on liver related mortality: Results from a large cohort of North American patients with advanced HCV infection.

Branched chain amino acids (BCAA) supplementation may reduce the incidence of liver failure and hepatocellular carcinoma in patients with cirrhosis. We aimed to determine whether long-term dietary intake of BCAA is associated with liver-related mortality in a well-characterized cohort of North American patients with advanced fibrosis or compensated cirrhosis. We performed a retrospective cohort study using extended follow-up data from the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. The analysis included 656 patients who completed two Food Frequency Questionnaires. The primary exposure was BCAA intake measured in grams (g) per 1000 kilocalories (kcal) of energy intake (range 3.0-34.8 g/1000 kcal). During a median follow-up of 5.0 years, the incidence of liver-related death or transplantation was not significantly different among the four quartiles of BCAA intake before and after adjustment of confounders (AHR 1.02, 95% CI 0.81-1.27, P-value for trend = 0.89). There remains no association when BCAA was modeled as a ratio of BCAA to total protein intake or as absolute BCAA intake. Finally, BCAA intake was not associated with the risk of hepatocellular carcinoma, encephalopathy or clinical hepatic decompensation. We concluded that dietary BCAA intake was not associated with liver-related outcomes in HCV-infected patients with advanced fibrosis or compensated cirrhosis. The precise effect of BCAA in patients with liver disease warrants further study.

Prevalence and Associated Factors of Low-Level Viremia in Chronic Hepatitis B Patients After Long-Term Therapy with Nucleos(t)ide Analogs.

Low-level viremia is usually defined as a detectable but lower than 2000 IU/mL hepatitis B virus DNA level after 12 months or longer duration of antiviral therapy in chronic hepatitis B patients. In this study, we aimed to clarify the factors associated with lowlevel viremia in patients during long-term monotherapy with tenofovir disoproxil fumarate or entecavir. Chronic hepatitis B patients having received entecavir or tenofovir disoproxil fumarate treatment for 12 months or more were enrolled from October 2019 to October 2021 at a tertiary hospital in Shanghai, China. In accordance with their hepatitis B virus DNA levels, chronic hepatitis B patients were grouped into 3 categories, hepatitis B virus DNA > 2000 IU/mL, low-level viremia, and complete virological response (hepatitis B virus DNA < 10 IU/mL). Compared with complete virological response patients, factors related to lowlevel viremia were evaluated. This study enrolled a total of 160 chronic hepatitis B patients, whose duration of treatment ranged from 12 to 144 months. In total, 107 patients achieved complete virological response, 51 showed low-level viremia, and 2 showed hepatitis B virus DNA > 2000 IU/mL. After multivariate logistic regression analysis, hepatitis e antigen-positivity (odds ratio = 6.479, 95% CI: 2.480-16.922, P = .000), entecavir treatment (odds ratio = 4.742, 95% CI: 1.855-12.118, P = .001), and duration of therapy (odds ratio = 0.168, 95% CI: 0.072-0.388, P = .000) were independently associated with low-level viremia. Having received long-term antiviral treatment, low-level viremia still occurred in 31.9% of patients. Longer duration of therapy was a protective factor, and HBeAg-positivity and entecavir treatment were risk factors for low-level viremia.

Results of long-term antiviral prophylactic treatment on the course of herpes zoster ophthalmicus with ocular involvement: A case series in a tertiary uveitis clinic – A 1-year follow-up

Results of long-term antiviral prophylactic treatment on the course of herpes zoster ophthalmicus with ocular involvement: A case series in a tertiary uveitis clinic – A 1-year follow-up

A Mac-2 Binding Protein Glycosylation Isomer-Based Risk Model Predicts Hepatocellular Carcinoma in HBV-Related Cirrhotic Patients on Antiviral Therapy.

Simple SummaryMac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 cirrhotic patients receiving entecavir or tenofovir monotherapy to construct an HCC risk score. The ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi at 12 months of treatment, was developed. The ASPAM-B scores accurately classified patients into low (0–3.5), medium (4–7) and high (>7) risk (p < 0.001). The values of AUROC for predicting 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively. All AUROCs between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3–9 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received antiviral treatment.Mac-2 binding protein glycosylation isomer (M2BPGi) has not been used in a risk score to predict hepatocellular carcinoma (HCC). We enrolled 1003 patients with chronic hepatitis B and cirrhosis receiving entecavir or tenofovir therapy for more than12 months to construct an HCC risk score. In the development cohort, Cox regression analysis identified male gender, age, platelet count, AFP and M2BPGi levels at 12 months of treatment as independent risk factors of HCC. We developed the HCC risk prediction model, the ASPAM-B score, based on age, sex, platelet count, AFP and M2BPGi levels at 12 months of treatment, with the total scores ranging from 0 to 11.5. This risk model accurately classified patients into low (0–3.5), medium (4–7), and high (>7) risk in the development and validation groups (p < 0.001). The areas under the receiver operating characteristic curve (AUROC) of 3-, 5- and 9-year risks of HCC were 0.742, 0.728 and 0.719, respectively, in the development cohort. All AUROC between the ASPAM-B and APA-B, PAGE-B, RWS-HCC and THRI scores at 3–9 years were significantly different. The M2BPGi-based risk model exhibited good discriminant function in predicting HCC in cirrhotic patients who received long-term antiviral treatment.

The decline of HBV RNA associated with HBeAg seroconversion and double-negative HBV DNA and RNA in chronic hepatitis B patients who received entecavir therapy: a 10-year retrospective cohort study.

BackgroundWhether the decline of hepatitis B virus (HBV) RNA was associated with antiviral efficacy in chronic hepatitis B (CHB) patients receiving long-term nucleos(t)ide analogues (NAs) therapy remains unclear. We observed the levels of serum HBV RNA in CHB patients treated with entecavir (ETV) for 10 years and explored the clinical significance of HBV RNA during long-term antiviral treatment.MethodsA total of 33 hepatitis B surface antigen (HBsAg)-positive CHB patients treated with ETV for up to 10 years were recruited for this study. Liver function, HBsAg, hepatitis B envelope antigen (HBeAg), HBV DNA, and HBV RNA were measured at the baseline and each follow-up points. Antiviral efficacy was defined as negative HBV DNA (<20 IU/mL) and HBV RNA (<300 Copies/mL).Results(I) Serum HBV DNA and HBV RNA declined with the duration of antiviral treatment over 10 years (P<0.001). (II) There were positive correlations between serum HBV DNA and HBV RNA at each follow-up point (r=0.62 and P<0.001 at baseline, r=0.77 and P<0.001 at week 24, r=0.71 and P<0.001 at week 48, r=0.81 and P<0.001 at week 96, r=0.60 and P<0.01 at year 5 and r=0.77 and P<0.001 at year 10). (III) HBeAg and HBsAg levels at baseline and 10th year after ETV treatment have significant difference (P<0.05 and P<0.01). (IV) The decline of HBV RNA after ETV treatment was associated with HBeAg seroconversion, the area under the ROC curves (AUROCs) of the declines of HBV RNA were 0.25 at the baseline, 0.62 at week 24, 0.78 at week 48 and 0.86 at week 96, respectively. (V) The decline of HBV RNA after ETV treatment was associated with antiviral efficacy, the AUROCs of the declines of HBV RNA were 0.33 at the baseline, 0.74 at week 24, 0.83 at week 48 and 0.86 at week 96, respectively.ConclusionsSerum HBV DNA and HBV RNA declined with the duration of antiviral treatment over 10 years. The decline of HBV RNA was associated with HBeAg seroconversion and antiviral efficacy in CHB patients receiving long-term ETV therapy, and the earliest prediction point was week 24.

Role of Serum M2BPGi Levels in Predicting Persistence of Advanced Fibrosis in Chronic Hepatitis B Virus Infection.

Serum mac-2-binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis assessment in patients with different liver diseases. For chronic hepatitis B infection (CHB), advanced fibrosis or cirrhosis is a risk factor for liver cancer and hepatic decompensation. We aimed to assess the role of serum M2BPGi in prediction of persistence of advanced fibrosis in CHB patients despite potent antiviral therapy. CHB patients with advanced fibrosis or cirrhosis who were put on nucleos(t)ide analogs for ≥ 3years with normal alanine aminotransferase and undetectable serum HBV DNA were prospectively recruited. Assessment of liver fibrosis with transient elastography (TE) and M2BPGi measurements were performed at baseline and repeated at 3years. Advanced fibrosis and cirrhosis were defined by liver stiffness (LS) ≥ 9.0kPa and ≥ 12.0kPa, respectively. A total of 143 patients (M:F = 101:42; median age 58.7years; 53.8% cirrhotic) were recruited and completed paired assessment. The median value of baseline LS and M2BPGi were 12.0 (IQR: 10.5-18.2) kPa and 0.99 cut-off-index (IQR: 0.75-1.74) (COI), respectively, with 96% concordance for diagnosing F3/F4. Ninety-six (67.1%) patients had persistent advanced fibrosis or cirrhosis at 3years despite continuation of long-term antiviral treatment. Upon multivariate analysis, baseline M2BPGi (OR 2.128, 95% CI 1.037-4.366) and presence of central obesity (OR 4.648, 95% CI 1.742-12.402) were significantly associated with persistent advanced fibrosis or cirrhosis at 3years. Baseline M2BPGi ≥ 1.265 COI has 50.6% sensitivity and 79.4% specificity for predicting persistent advanced fibrosis or cirrhosis at 3years (area under the receiver-operating characteristic curve: 0.695). The presence of central obesity in combination with baseline M2BPGi ≥ 1.265 COI was associated with 95.7% patients having persistent advanced fibrosis or cirrhosis at 3years. HCC development was observed in five patients during follow-up and was associated with bigger median increase in the level of serum M2BPGi compared to patients without HCC (46% vs 6.2%, P = 0.038). Persistent advanced fibrosis or cirrhosis was observed in two-thirds of CHB patients despite potent antiviral therapy. High serum M2BPGi and central obesity were associated with more than twofold and fourfold increase in risk of persistent advanced fibrosis or cirrhosis, respectively.

A multivariate parametric empirical Bayes screening approach for early detection of hepatocellular carcinoma using multiple longitudinal biomarkers.

The early detection of hepatocellular carcinoma (HCC) is critical to improving outcomes since advanced HCC has limited treatment options. Current guidelines recommend HCC ultrasound surveillance every 6 months in high-risk patients however the sensitivity for detecting early stage HCC in clinical practice is poor. Blood-based biomarkers are a promising direction since they are more easily standardized and less resource intensive. Combining of multiple biomarkers is more likely to achieve the sensitivity required for a clinically useful screening algorithm and the longitudinal trajectory of biomarkers contains valuable information that should be utilized. We propose a multivariate parametric empirical Bayes (mPEB) screening approach that defines personalized thresholds for each patient at each screening visit to identify significant deviations that trigger additional testing with more sensitive imaging. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial provides a valuable source of data to study HCC screening algorithms. We study the performance of the mPEB algorithm applied to serum -fetoprotein, a widely used HCC surveillance biomarker, and des- carboxy prothrombin, an HCC risk biomarker that is FDA approved but not used in practice in the United States. Using cross-validation, we found that the mPEB algorithm demonstrated moderate but improved sensitivity compared to alternative screening approaches. Future research will validate the clinical utility of the approach in larger cohort studies with additional biomarkers.

Recent Advances in the Discovery and Development of Anti-HIV Natural Products.

Acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection is a serious public problem threatening global health. At present, although "cocktail therapy" has achieved significant clinical effects, HIV still cannot be completely eradicated. Furthermore, long-term antiviral treatment has caused problems such as toxic side effects, the emergence of drug-resistant viruses, and poor patient compliance. Therefore, it is highly necessary to continue to search for high-efficient, low-toxic anti-HIV drugs with new mechanisms. Natural products have the merits of diverse scaffolds, biological activities, and low toxicity that are deemed the important sources of drug discovery. Thus, finding lead compounds from natural products followed by structure optimization has become one of the important ways of modern drug discovery. Nowadays, many natural products have been found, such as berberine, gnidimacrin, betulone, and kuwanon-L, which exert effective anti-HIV activity through immune regulation, inhibition of related functional enzymes in HIV replication, and anti-oxidation. This paper reviewed these natural products, their related chemical structure optimization, and their anti-HIV mechanisms.

Challenges in the discontinuation of chronic hepatitis B antiviral agents.

Long-term antiviral treatment of chronic hepatitis B patients has been proven to be beneficial in reducing liver-related complications. However, lengthy periods of daily administration of medication have some inevitable drawbacks, including decreased medication adherence, increased cost of treatment, and possible long-term side effects. Currently, discontinuation of antiviral agent has become the strategy of interest to many hepatologists, as it might alleviate the aforementioned drawbacks and increase the probability of achieving functional cure. This review focuses on the current evidence of the outcomes following stopping antiviral treatment and the factors associated with subsequent hepatitis B virus relapse, hepatitis B surface antigen clearance, and unmet needs.

Herpes simplex virus, varicella-zoster virus and cytomegalovirus keratitis: Facts for the clinician

Keratitis due to Herpes simplex virus (HSK), Varicella-Zoster virus (VZK) and Cytomegalovirus remains a frequent source of concern for many ophthalmologists. They are a frequent cause of emergency consultations at eye care centers and carry the risk of permanent loss of visual acuity or visual quality and/or chronic neurotrophic keratitis, resulting in a significant decrease in the quality of life. HSK and VZK can affect the corneal epithelium, stroma, or endothelium or a combination of layers. In contrast, most cases of CMV keratitis present as isolated endothelitis (CMVE), a clinical entity that has been described within the last 2 decades. These three types of viral keratitis are characterized by a high frequency of recurrences and each new episode increases the risk of sequelae. Hence, ophthalmologists must adapt the treatment to the clinical presentation of each recurrent episode in order to mitigate the immediate consequences of viral replication and the immune response on corneal transparency. In patients with frequent recurrences, preventive long-term antiviral treatment is strongly recommended. However, in some rare cases, continuous exposure to antivirals may promote the emergence of resistant viral strains, which can be difficult to manage. In the future, the introduction of new antiviral drugs, with differing modes of action compared to current medical therapy, could be an alternative until a truly effective preventive solution, such as a vaccine, is available.

The Prognostic Role of On-Treatment Liver Stiffness for Hepatocellular Carcinoma Development in Patients with Chronic Hepatitis B.

BackgroundDynamic changes in fibrosis markers occur under long-term antiviral treatment (AVT) for chronic hepatitis B. We evaluated prognostic values of on-treatment liver stiffness (LS) compared to ultrasonography findings and determined its optimal cutoff.MethodsThe cumulative probability of hepatocellular carcinoma (HCC) was assessed among 880 patients receiving entecavir or tenofovir for ≥2 years. LS was measured using transient elastography.ResultsAfter ≥2 years’ AVT, the proportion of patients with cirrhosis on ultrasonography decreased from 54.7% to 44.9% and the mean LS decreased from 13.6 to 8.2 kPa (both p<0.001). However, unlike cirrhosis on ultrasonography before AVT (p<0.001), that after ≥2 years’ AVT did not discriminate HCC risk (p=0.792). Using the Contal and O’Quigley’s method, pre-AVT and on-treatment LS of 12.0 and 6.4 kPa, respectively, were chosen as optimal cutoffs to successfully discriminate HCC risk (both p<0.001). However, through stratification using both pre-AVT and on-treatment LS, the prognosis was finally determined according to on-treatment LS of 6.4 kPa, regardless of pre-AVT LS of 12.0 kPa. Using on-treatment LS of 12 kPa suggested by Caucasians with CHB receiving long-term AVT, patients with higher LS were more likely to develop HCC than those with lower LS (p=0.017); however, there was no significant difference between those with on-treatment LS of 6.4–11.9 and ≥ 12.0 kPa (p=0.920).ConclusionFor HCC risk stratification in patients receiving long-term AVT, on-treatment LS cutoff should be lowered to 6.4 kPa, which is more predictive than 12 kPa or cirrhosis on ultrasonography. Further studies are required for validation.