Application of guidelines for the management of nonalcoholic fatty liver disease in three prospective cohorts of HIV-monoinfected patients.

OBJECTIVES: Current guidelines recommend use of a diagnostic algorithm to assess disease severity in cases of suspected nonalcoholic fatty liver disease (NAFLD). We applied this algorithm to HIV-monoinfected patients. METHODS: We analysed three prospective screening programmes for NAFLD carried out in the following cohorts: the Liver Disease in HIV (LIVEHIV) cohort in Montreal, the Modena HIV Metabolic Clinic (MHMC) cohort and the Liver Pathologies in HIV in Palermo (LHivPa) cohort. In the LIVEHIV and LHivPa cohorts, NAFLD was diagnosed if the controlled attenuation parameter (CAP) was ≥ 248 dB/m; in the MHMC cohort, it was diagnosed if the liver/spleen Hounsfield unit (HU) ratio on abdominal computerized tomography scan was < 1.1. Medium/high-risk fibrosis category was defined as fibrosis-4 (FIB-4) ≥ 1.30. Patients requiring specialist referral to hepatology were defined as either having NAFLD and being in the medium/high-risk fibrosis category or having elevated alanine aminotransferase (ALT). RESULTS: A total of 1534 HIV-infected adults without significant alcohol intake or viral hepatitis coinfection were included in the study. Of these, 313 (20.4%) patients had the metabolic comorbidities (obesity and/or diabetes) required for entry in the diagnostic algorithm. Among these patients, 123 (39.3%) required specialist referral to hepatology, according to guidelines. A total of 1062 patients with extended metabolic comorbidities (any among obesity, diabetes, hypertension and dyslipidaemia) represented most of the cases of NAFLD (79%), elevated ALT (75.9%) and medium/high-risk fibrosis category (75.4%). When the algorithm was extended to these patients, it was found that 341 (32.1%) would require specialist referral to hepatology. CONCLUSIONS: According to current guidelines, one in five HIV-monoinfected patients should undergo detailed assessment for NAFLD and disease severity. Moreover, one in ten should be referred to hepatology. Expansion of the algorithm to patients with any metabolic comorbidities may be considered.

Calcium and zinc ion release from polyalkenoate cements formed from zinc oxide/apatite mixtures.

Calcium and zinc ion release from hydroxyapatite-zinc oxide-poly(acrylic acid) (HAZnO-PAA) composite cements into deionised water was investigated as a function of HA content, PAA concentration, PAA molecular weight and maturation time. At any given maturation time, zinc ion release was constant until the HA content was at the maximum loading (60 wt%) resulting in the cement matrix breaking up, allowing exacerbated ion release. The calcium ion release increased with increased HA content in the composite until the maximum loading where the release drops off. Up to this point, the release of both ionic species was proportional to square root time for the initial 24 hour period, indicating that the release is diffusion controlled. In agreement with related data from conventional Glass Polyalkenoate Cements (GPCs), it is the concentration of the PAA, not the molecular weight, that influences ion release from these materials. However, unlike GPCs, the release of the active ions results in a pH rise in the deionised water, more conventionally seen with Bioglass and related bioactive glasses. It is this pH rise, caused by the ion exchange of Zn(2+) and Ca(2+) for H(+) from the water, leaving an excess of OH(-), that should result in a favourable bioactive response both in vitro and in-vivo.

Zinc ion release from novel hard tissue biomaterials.

Zinc polyalkenoate cements (ZPCs) and glass polyalkenoate cements (GPCs) are used routinely in dentistry, but have potential for orthopaedic applications as they set at body temperature without shrinkage or significant heat evolution. However, the materials have drawbacks; ZPCs are biocompatible in implant studies, but a fibrous collagen capsular layer forms adjacent to the cement. GPCs are bioactive in the bone environment as a result of the release of calcium, phosphate and fluoride ions, as well as the formation of a silicious gel phase, but research has shown that aluminum ions released result in defective bone mineralisation and as a consequence the ability of these cements to chemically bond to bone is lost. Two approaches have been developed to overcome these problems. The ZPC route considers a ZnO : hydroxyapatite (HA) : poly(acrylic acid) (PAA) mixture, the HA incorporated to improve bioactivity. The GPC route employs a calcium zinc silicate glass; the zinc taking the role that aluminum plays in conventional GPCs. This study has shown that cements can be formulated by an acid base reaction between PAA and both calcium zinc silicate glasses (GPCs) and a mixture of hydroxyapatite and zinc oxide (ZPCs). The moduli of these cements are comparable to both bone and conventional acrylic cements, highlighting their potential for biomedical applications. Unfortunately, both materials have previously been shown to be toxic by cell culture methods, as a result of high zinc ion release, and so it is necessary to study ion release profiles of the cements in order to determine the magnitude of this release. Considering the ZPCs, the modulus of the cement has an inversely proportional relationship to the zinc ion release. From the data presented it is clear that increases in polymer concentration results in lower amounts of zinc ions being released, whilst molar mass of the PAA has no influence. Therefore it would appear that polymer concentration has a significant influence over ion release. Generally, the amount of Zn(2+) released decreases with increasing HA content and/or decreasing ZnO content. Considering the GPCs, the materials are all seen to release large amounts of the active ion, when compared to the commercial versions. The extent of this release increases with temperature and agitation. The release could be minimised by an increased P : L mixing ratio, and an increased PAA concentration, which would produce a more cross-linked cement matrix. Minimising the release of the active ion should improve the in vitro bioactivity of both materials. However, for a full understanding of the clinical benefits of such materials, an in vivo study would be required.