ABSTRACT
Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.
Subject(s)
Alanine/administration & dosage , Antiviral Agents/administration & dosage , Hepatitis B, Chronic/drug therapy , Tenofovir/analogs & derivatives , Alanine/adverse effects , Alanine/pharmacology , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Asia , Drug Resistance, Viral , Hepatitis B, Chronic/virology , Humans , Randomized Controlled Trials as Topic , Tenofovir/administration & dosage , Tenofovir/adverse effects , Tenofovir/pharmacologyABSTRACT
Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.
Subject(s)
Hepatitis B/diagnosis , Hepatitis B/therapy , Asia , Consensus , DNA, Viral/blood , Hepatitis B e Antigens/blood , Hepatitis B virus , HumansABSTRACT
Background. HIV patients on highly active antiretroviral therapy (HAART) containing protease inhibitors (PIs) had been often associated with lipodystrophy. However, there are only few studies on association of nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI and NNRTI) with lipodystrophy. Study Design. One hundred and one HIV male patients were categorised into ART naïve (n = 22), zidovudine (n = 22), stavudine (n = 18), tenofovir (n = 15), and PIs (n = 24) based HAART. Their clinicoepidemiological data had been entered in preformed pro forma. The body composition, using TANITA machine and metabolic parameters like lipid profile, blood sugars was analysed. Results. Clinically, lipoatrophy of face was most prevalent in HIV patients on stavudine (15 patients, 83.3%) and PIs (20 patients, 83.3%) based HAART. The mean BMI among study population was in normal range. Excess visceral fat was most prevalent among patients on PIs, 4 patients (16.7%). The waist-hip ratio was significantly higher in PIs (P = 0.01) based HAART. There was no significant difference among different study populations in terms of BMI (P = 0.917), body water (P = 0.318), body fat (P = 0.172), bone mass (P = 0.200), and muscle mass (P = 0.070). Hypertriglyceridiemia was found in stavudine, tenofovir, and protease inhibitors regimens. Low levels of high density lipoprotein (HDL) was found zidovudine, stavudine, and PIs regimens. Fasting and postprandial hyperglycaemia was found PIs and impaired glucose tolerance in stavudine regimen. Conclusion. Patients on PIs were associated with truncal obesity and lipoatrophy of face, along with dyslipidemia and hyperglycaemia. Stavudine based regimen is associated with hypertriglyceridiemia and low HDL along with lipoatrophy of face.