Introduction Of Antiviral Therapy Research Articles

Total serum bile acids predict therapy for HBeAg-negative chronic hepatitis B patients with borderline ALT and high HBV DNA.

The introduction of antiviral therapy in chronic hepatitis B (CHB) infection depends on precise evaluation of hepatic lesions. Total serum bile acids (TSBAs) are highly sensitive in monitoring liver dysfunction. We evaluated the predictive role of TSBAs for hepatic lesions in CHB patients with borderline alanine aminotransferase (ALT) and high level of hepatitis B virus (HBV) DNA copies. 328 CHB patients were enrolled, 241 were hepatitis B e antigen (HBeAg)-positive and 87 were HBeAg-negative. Patients were further divided into two entities according to inflammation/fibrosis evaluated by liver biopsy, low-grade (inflammation grade < 2 and fibrosis stage < 2) and high-grade (inflammation grade ≥ 2 or/and fibrosis stage ≥ 2) cohorts. TSBAs were compared with noninvasive tools including aspartate aminnotransferase (AST)-to-platelet ratio index (APRI), fibrosis-4 (FIB-4) and red cell distribution width (RDW)-to-platelet ratio (RPR) to predict high-grade hepatic lesions in CHB subgroups. TSBAs, APRI, FIB-4 and RPR were statistically different between low- and high-grade patients in HBeAg-positive cohort. Only TSBAs showed significant difference between low and high grade in HBeAg-negative patients. Similarly, APRI, FIB-4 and RPR were correlated with different division of inflammation/fibrosis only in HBeAg-positive while TSBAs were correlated with inflammation/fibrosis levels in both HBeAg-positive and HBeAg-negative groups. Of the four indicators, the receiver operating characteristic (ROC) curve analysis showed that TSBAs have the maximum AUC (area under the curve) in HBeAg-negative group but the minimum in HBeAg-positive cohort. TSBAs can be used for predicting antiviral therapy in CHB patients with HBeAg-negative, borderline ALT and high HBV DNA.

Hepatitis B virus‐related hepatocellular carcinoma in the era of antiviral therapy: The emerging role of non‐viral risk factors

Hepatocellular carcinoma (HCC), one of the major malignant lethal tumours, is most prevalent in Asian patients with chronic hepatitis B virus (HBV) infection. Both viral and non-viral factors contribute to the development of HCC. It is established that viral factors associated with HBV DNA level, HBV genotype, designated gene mutation, HBV DNA integration, HBx protein, hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg) and HBV RNA are correlated with hepatocarcinogenesis. Before the introduction of antiviral therapy, viral factors once attracted more attention during the development of HCC. With the widespread use of antiviral therapy, predominantly nucleos(t)ide analogues (NAs), most patients with chronic hepatitis B (CHB) have achieved sustained viral control. The role of non-viral factors, especially modifiable factors, is anticipated to be reinforced in the future. Herein, we reviewed the modifiable non-viral risk factors of HBV-related HCC, in the hope of providing substantial evidence for further development of novel precautionary measures for HCC. In addition, the therapeutic interventions for reducing the risk of HCC, like potential conventional pharmaceutical interventions and lifestyle modification are also discussed in this review. Future studies that would explore the specific mechanism of HBV-related HCC development in patients with satisfactory viral control and related precision treatment are warranted.

CD49b, a Major Marker of Regulatory T-Cells Type 1, Predicts the Response to Antiviral Therapy of Recurrent Hepatitis C after Liver Transplantation

The TRANSPEG study was a prospective study to assess the efficacy of antiviral therapy in patients with a recurrent hepatitis C virus (HCV) after liver transplantation. The influence of regulatory T-cells (Tregs) on the response to antiviral therapy was analyzed. Patients were considered as a function of their sustained virological response (SVR) at 18 months after treatment initiation. A transcriptomic analysis was performed to assess Treg markers (Tr1 and FoxP3+) in serum, PBMC, and liver biopsies. 100 patients had been included in the TRANSPEG study. Data from 27 of these patients were available. The results showed that the expression of CD49b (a predominant marker of Tr1) before the introduction of antiviral therapy was significantly associated with SVR. Responders displayed lower serum levels of CD49b than nonresponders (P < 0.02). These findings were confirmed in PBMC and liver biopsies even if in a nonsignificant manner for the limited number of samples. The assessment of CD49b levels is thus predictive of the response to antiviral therapy. This data suggests that CD49b may be a marker of the failure of the immune response and antiviral therapy during HCV recurrence. The assessment of CD49b could help to select patients who require earlier and more intensive antiviral therapy.

AIDS and HIV Infection after Thirty Years.

AIDS and HIV Infection after Thirty Years.

Serum Aspartate Aminotransferase Level and Previous Histopathological Findings Enable Reduction of Protocol Liver Biopsies after Liver Transplantation for Hepatitis C

Hepatitis C virus (HCV) infection remains the leading indication for liver transplantation (LT) worldwide. Recurrent hepatitis C following LT is universal, and significant fibrosis (SF, Metavir fibrosis stage ≥2) apparent on protocol biopsy typically prompts antiviral therapy. To determine the optimal timing of protocol liver biopsies in this setting. A total of 151 patients who underwent LT related to HCV infection between July 2004 and December 2009 were analyzed retrospectively. Data regarding protocol liver biopsies at six, 12 and 24 months post-LT, conventional laboratory parameters and demographic information were obtained. The 151 patients included in the present study had significantly lower serum aspartate aminotransferase (AST) levels than the four patients who progressed to receive antiviral treatment for SF before six months post-LT (P<0.001). AST level, but not alanine aminotransferase level, histological activity or fibrosis stage at the six-month biopsy was independently associated with the progression to SF at 12 months (P<0.05). However, AST level, histological activity and fibrosis stage at the 12-month biopsy emerged as independent parameters associated with progression to SF at 24 months (P<0.05). The protocol liver biopsy at six months could be eliminated, especially in patients who consistently exhibit low AST levels. Histological activity, the presence or absence of fibrosis, and AST values at the 12-month biopsy may lead to the decision to defer the protocol biopsy at 24 months or result in earlier introduction of antiviral therapy.

Pitfalls in the diagnosis of neonatal herpes infection and learning from our mistake/a report of a case of disseminated neonatal herpes simplex with treatment failure

IntroductionHerpes Simplex Virus (HSV) infection is a serious neonatal infection with high mortality and morbidity. The fact that it has a relatively low prevalence in neonates, it may not be...

Polymerase Chain Reaction Monitoring Reduces the Incidence of Cytomegalovirus Disease and the Duration and Side Effects of Antiviral Therapy After Bone Marrow Transplantation

Culture-based preemptive therapy with ganciclovir was shown to reduce the incidence of cytomegalovirus (CMV) disease after bone marrow transplantation (BMT). Culture techniques did not detect CMV in 12% to 13% of patients before the onset of CMV disease. In a prospective study, 71 patients either received preemptive therapy based on polymerase chain reaction (PCR) technique (37 patients) or on culture assays (34 patients). In both groups, therapy was continued until clinical signs disappeared and PCR negativity was documented. Twenty-two patients in the PCR group and 15 patients in the culture group received antiviral therapy. PCR allowed detection of the virus (median day, +32 v day +49; P = .006) and introduction of antiviral therapy (median day, +44 v day +54; P = .02) earlier than did culture assays. The incidences of CMV disease (2 of 37 v 8 of 34 in PCR group v culture group, respectively; P = .02) and CMV-associated mortality (0 of 37 v 5 of 34 in PCR group v culture group, respectively; P = .02) were decreased, and the duration of ganciclovir therapy (P < .001) was shorter in the PCR-monitored group. Incidence and median duration of severe neutropenia (less than 500/microL) were lower in the PCR group (two v eight episodes, P = .02; median duration, 1.5 v 5 days, P = .04), as was the incidence of nonviral infections during/after antiviral therapy (2 of 37 v 9 of 34; P = .012). Thus, preemptive therapy based on more sensitive detection methods such as the PCR assay reduces the incidence of CMV disease and CMV-related mortality. Additionally, stopping and withholding antiviral therapy in a PCR-negative patient is safe and allows reduction of the duration and side effects of antiviral therapy.

Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation

Culture-based preemptive therapy with ganciclovir was shown to reduce the incidence of cytomegalovirus (CMV) disease after bone marrow transplantation (BMT). Culture techniques did not detect CMV in 12% to 13% of patients before the onset of CMV disease. In a prospective study, 71 patients either received preemptive therapy based on polymerase chain reaction (PCR) technique (37 patients) or on culture assays (34 patients). In both groups, therapy was continued until clinical signs disappeared and PCR negativity was documented. Twenty-two patients in the PCR group and 15 patients in the culture group received antiviral therapy. PCR allowed detection of the virus (median day, +32 v day +49; P = .006) and introduction of antiviral therapy (median day, +44 v day +54; P = .02) earlier than did culture assays. The incidences of CMV disease (2 of 37 v 8 of 34 in PCR group v culture group, respectively; P = .02) and CMV-associated mortality (0 of 37 v 5 of 34 in PCR group v culture group, respectively; P = .02) were decreased, and the duration of ganciclovir therapy (P &lt; .001) was shorter in the PCR-monitored group. Incidence and median duration of severe neutropenia (less than 500/microL) were lower in the PCR group (two v eight episodes, P = .02; median duration, 1.5 v 5 days, P = .04), as was the incidence of nonviral infections during/after antiviral therapy (2 of 37 v 9 of 34; P = .012). Thus, preemptive therapy based on more sensitive detection methods such as the PCR assay reduces the incidence of CMV disease and CMV-related mortality. Additionally, stopping and withholding antiviral therapy in a PCR-negative patient is safe and allows reduction of the duration and side effects of antiviral therapy.

Effect of zidovudine on survival of patients with AIDS in Australia

Since the first case of AIDS in Australia was diagnosed in December 1982, there have been substantial improvements in the treatment of AIDS-related conditions. In particular, zidovudine was widely introduced into clinical practice in Australia in June 1987. In order to evaluate its effect, we compared the survival of patients diagnosed before and after July 31, 1987 using data available in early 1989. Survival distributions were compared by means of Kaplan-Meier curves and by fitting exponential survival models incorporating a special feature of the data. Before August 1, 1987 the overall distribution of survival times for patients with AIDS in Australia is well described by an exponential distribution with a mean of 1.04 years. The corresponding median survival time for this period was 8.8 months. For patients diagnosed with AIDS after July 31, 1987 the median survival time had not been attained by December 31, 1988. However, the estimated mean survival time increased to 2.7 years. Survival times were found to be remarkably stable over the different regions of Australia. We have shown that substantial improvements in survival of patients diagnosed with AIDS in Australia are associated with the widespread availability of zidovudine from mid 1987. To the best of our knowledge this study is the first of its kind to show a major shift in the distribution of survival associated with the introduction of antiviral therapy.

Suggestions for future research directions resulting from this workshop

Herpes simplex virus (HSV) infections of the central nervous system are a significant cause of mortality and morbidity. The introduction of antiviral therapy has improved the outcome for patients with life-threatening disease. Neonatal HSV infection is usually acquired at the time of delivery by contact of the fetus with infected maternal genital secretions resulting in disease that can be localized to the skin, eye, and mouth, and can lead to encephalitis or become disseminated. A total of 291 babies with neonatal HSV infection have been evaluated over a period of 14 years with mortality and morbidity rates determined at one year. Vidarabine therapy decreased the incidence of mortality and improved morbidity rates; however, further improvement in mortality rates with acyclovir therapy has not been apparent. No significant clinical toxicity appeared in either treatment group. In order to improve outcome, earlier intervention and prophylactic strategies must be developed. For patients with herpes simplex encephalitis, acyclovir therapy is superior to vidarabine therapy for biopsy-proven disease. When outcome is compared for 136 vidarabine- and 46 acyclovir-treated, biopsy-proven patients, mortality rates are decreased to 20 percent with acyclovir, and approximately 40 percent of survivors are evaluated as normal at one year after therapy. Despite better outcome with antiviral therapy for the treatment of biopsy-proven herpes simplex encephalitis, further improvement is required.