Partial Response to Entecavir and Tenofovir in Na?ve Patients with Chronic Hepatitis B: Clinical Relevance and Management

Entecavir and tenofovir are the currently recommended first line analogues for treatment of na?ve patients with chronic hepatitis B. Despite their overall efficacy and high genetic barrier granting for a low risk of resistance, both regimens will fail to completely suppress HBV DNA at week 48 in 10% of HBeAg-negative and 30% of HBeAg-positive patients. A pre-treatment level >8 log₁₀ IU/mL HBV DNA and poor medication adherence were the most significant predictors of a partial virological response (PVR). While the clinical relevance of PVR is still poorly understood, nucleos(t)ide (NUC)-naive PVR patients who maintained detectable levels of viremia in follow up, were at risk of developing resistance to ETV. Patients with a suboptimal decline of viremia during the first 48?weeks of therapy with ETV and/or a residual viremia >1,000?IU/mL, can be protected by a rescue switch to TDF. Resistance to TDF has not been described so far, yet the long-term risk of PVR in TDF-treated patients remains unclear.     

Virologic Response and Safety of Tenofovir Versus Entecavir in Treatment-Na?ve Chronic Hepatitis B patients

Background/Aims:

This study aimed to evaluate the antiviral response and safety of tenofovir (TDF) versus entecavir (ETV) in treatment-naïve CHB patients.

Patients and Methods:

We performed a retrospective cohort study of treatment-naive CHB patients who were treated with TDF or ETV. We analyzed virologic, biochemical, and serologic responses at 3, 6, and 12 months.

Results:

A total of 107 patients (TDF group = 49, ETV group = 58) were included. Baseline characteristics were similar between the two groups. The estimated proportion of complete virologic response (CVR) in the TDF or ETV group was 44.9% versus 39.7% at 6 months and 89.6% versus 83.2% at 12 months, respectively (P = 0.991). Viral breakthrough was not observed in both groups. One patient in the TDF group and two patients in the ETV group experienced HBeAg loss, respectively (P = 0.657). High HBV DNA level at baseline was a significant negative predictor of virologic response by Cox regression analysis (P = 0.007). The safety profile was similar between the two groups. There was no case with serious adverse event.

Conclusions:

Both TDF and ETV were effective in achieving CVR and had a favorable safety profile in treatment-naïve CHB patients. High viral load at baseline was a negative predictive factor of CVR.     

Does Adherence Change When No One is Looking? Comparing Announced and Unannounced Tenofovir Levels in a PrEP Trial

Differences between unannounced and announced tenofovir levels as measures of PrEP adherence are not well understood. In an ancillary adherence study involving one urban site (Kampala) and two rural sites (Kabwohe and Tororo) from the Partners PrEP study, 268 specimen pairs from chronologically proximal clinic and home visits were tested for plasma tenofovir levels. Comparing clinic and home specimens, 89 versus 89 % were classified as detectable (>0.31 ng/ml; p = 0.77), 87 versus 86 % as recent dosing (>10 ng/ml; p = 0.80), and 82 versus 80 % as steady-state (>40 ng/ml; p = 0.44). Mean difference between announced and unannounced drug levels, adjusted for specimen collection time was 3.2 ng/ml (p = 0.50) for Kabwohe, 23.2 ng/ml (p = 0.003) for Kampala and ?3.3 ng/ml p = 0.69) for Tororo. In the setting of high adherence, plasma tenofovir levels tested at the clinic were categorically similar as levels tested at home; however, differences were seen between urban and rural settings.     

Tenofovir in the Treatment of Na?ve and Refractory Chronic Hepatitis B: A Single Center Experience in Saudi Arabia

Background/Aims:

Tenofovir disoproxil fumarate (TDF) is a nucleotide analog used in the treatment of chronic hepatitis B (CHB) infection. This study evaluated the efficacy of TDF in achieving undetectable HBV DNA after 48 weeks of treatment in a Saudi cohort of CHB patients.

Patients and Methods:

This retrospective study included patients treated at a tertiary care center in Saudi Arabia from January 2009 to December 2012. Of the 68 eligible patients, 51 were treatment naïve and 17 were treatment-refractory. Twenty-three patients tested positive for HBeAg. The remaining 45 patients were HBeAg-negative.

Results:

The mean HBV DNA viral load decreased from 95 million IU/mL at baseline to 263 IU/mL after 48 weeks of treatment (P < 0.001). Overall, 62% of patients achieved a complete virological response (CVR) and 37% a partial virological response (PVR). Respective CVR and PVR rates according to subgroup were: HBeAg-positive (21.7% and 78.3%) and HBeAg-negative (84.4% and 15.6%). At 48 weeks, HBV DNA was undetectable in 66.7% of treatment-naïve and 53% of treatment-refractory patients (P = 0.3). Seroconversion occurred in 13 (57%) of HBeAg-positive patients. Two (3%) of the HBeAg-negative patients lost HBsAg at follow up. Mean alanine aminotransferase decreased significantly from 134 U/L before treatment to 37 U/L at 48 weeks (P < 0.001). Significant adverse events were not encountered during the study period.

Conclusion:

Forty-eight weeks of treatment with TDF reduced HBV DNA to undetectable levels in more than half of our patients regardless of whether they were treatment-naïve or refractory. HBeAg-negative (vs positive) patients experienced a better response rate.     

有拉米夫定耐药性的乙型肝炎病毒变异患者用Tenofovir治疗强烈影响病毒复制

Tenofovir(特洛福韦)是一种无环簇核苷类逆转录酶抑制剂,类似于阿德福韦。据认为可被直接结合进入病毒DNA链,引起病毒DNA链合成提前终止。该药新近已被美国、澳大利     

Assessing Adherence in the CAPRISA 004 Tenofovir Gel HIV Prevention Trial: Results of a Nested Case–Control Study

Adherence undeniably impacts product effectiveness in microbicide trials, but the connection has proven challenging to quantify using routinely collected behavioral data. We explored this relationship using a nested case–control study in the CAPRISA 004 Tenofovir (TFV) gel HIV prevention trial. Detailed 3-month recall data on sex events, condom and gel use were collected from 72 incident cases and 205 uninfected controls. We then assessed how the relationship between self-reported adherence and HIV acquisition differed between the TFV and placebo gel groups, an interaction effect that should exist if effectiveness increases with adherence. The CAPRISA 004 trial determined that randomization to TFV gel was associated with a significant reduction in risk of HIV acquisition. In our nested case–control study, however, we did not observe a meaningful decrease in the relative odds of infection—TFV versus placebo—as self-reported adherence increased. To the contrary, exploratory sub-group analysis of the case–control data identified greater evidence for a protective effect of TFV gel among participants reporting less than 80 % adherence to the protocol-defined regimen (odds ratio (OR) 0.30; 95 % CI 0.11–0.78) than among those reporting ≥80 % adherence (Odds Ratio 0.81; 95 % CI 0.34–1.92). The small number of cases may have inhibited our ability to detect the hypothesized interaction between adherence and effectiveness. Nonetheless, our results re-emphasize the challenges faced by investigators when adherence may be miss-measured, miss-reported, or confounded with the risk of HIV.     

Clinical Course of Partial Virologic Response with Prolonged Tenofovir Therapy in Nuclos(t)ides-Naïve Patients with Chronic Hepatitis B

Digestive Diseases and Sciences - The clinical course of chronic hepatitis B (CHB) patients with partial virologic response (PVR) during tenofovir disoproxil fumarate (TDF) therapy remains unclear....     

Anomaly and tumor of kidney and urinary tract

2007475 MRI manifestations of renal oncocytoma.JI Jiansong(纪建松) , et al. Dept Radiol, Sir Run RunShaw Hosp, Zhejiang Univ, Hangzhou 310016. Chin JRadiol 2007;41(10):1087 -1089. Objective To analyze the MRI findings of renal on-cocytoma, and to improve the ability for the diagnosis.Methods We retrospectively reviewed MRI findings ofsults Sixcases had a solitary lesion, and 1 of themac-companied with renal clear-cell carcinoma. Tumors ap-peared as round with diameter 1.5 to 3.8 cm,…     

Relationships between serum adiponectin and soluble TNF-α receptors and glucose and lipid oxidation in lean and obese subjects

Insulin resistance might be associated with an impaired ability of insulin to stimulate glucose oxidation and inhibit lipid oxidation. Insulin action is also inversely associated with TNF-α system and positively related to adiponectin. The aim of the present study was to analyze the associations between serum adiponectin, soluble TNF-α receptors concentrations and the whole-body insulin sensitivity, lipid and glucose oxidation, non-oxidative glucose metabolism (NOGM) and metabolic flexibility in lean and obese subjects. We examined 53 subjects: 25 lean (BMI < 25 kg × m⁻²) and 28 with overweight or obesity (BMI > 25 kg × m⁻²) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese subjects had lower insulin sensitivity, adiponectin and higher sTNFR1 (all P < 0.001) and sTNFR2 (P = 0.001). Insulin sensitivity was positively related to adiponectin (r = 0.49, P < 0.001) and negatively related to sTNFR1 (r = −0.40, P = 0.004) and sTNFR2 (r = −0.52, P < 0.001). Adiponectin was related to the rate of glucose (r = 0.47, P < 0.001) and lipid (r = −0.40, P = 0.003) oxidation during the clamp, NOGM (r = 0.41, P = 0.002) and metabolic flexibility (r = 0.36, P = 0.007). Serum sTNFR1 and sTNFR2 were associated with the rate of glucose (r = −0.45, P = 0.001; r = −0.51, P < 0.001, respectively) and lipid (r = 0.52, P < 0.001; r = 0.46, P = 0.001, respectively) oxidation during hyperinsulinemia, NOGM (r = −0.31, P = 0.02; r = −0.43, P = 0.002, respectively) and metabolic flexibility (r = −0.47 and r = −0.51, respectively, both P < 0.001) in an opposite manner than adiponectin. Our data suggest that soluble TNF-α receptors and adiponectin have multiple effects on glucose and lipid metabolism in obesity.     

Periodontitis and diabetes mellitus—an awareness and perception study among endocrinologists and diabetologists

International Journal of Diabetes in Developing Countries - Periodontitis is a chronic inflammatory disease caused by pathogenic dental plaque which causes microbial dysbiosis leading to...