Dietary fatty acid oxidation is decreased in non-alcoholic fatty liver disease: A palmitate breath test study.

BACKGROUND & AIM: Hepatic fat excess in non-alcoholic fatty liver disease (NAFLD) reflects an imbalance between fat accumulation and disposal. Conflicting data exist for the role of fatty acid oxidation (FAO), one of the disposal pathways, and have mostly come from the studies delivering fatty acids (FAs) intravenously. Whether FAO of orally provided FAs is affected in NAFLD is unknown. METHODS: We performed a breath test study to measure FAO in subjects with NAFLD and healthy controls. Subjects ingested [1-13 C] palmitic acid (PA, 10 mg/kg) in a liquid meal and the rate of 13 CO2 appearance in expired air was measured over 6 hours by a BreathID device (Exalenz) to obtain the cumulative percent dose recovered (CPDR), the total amount of ingested 13 C recovered. CPDR was corrected by the results of a [1-13 C] acetate breath test, performed 1-4 weeks later, to calculate the rate of PA ß-oxidation. RESULTS: Palmitic acid oxidation was 27% lower in 43 subjects with NAFLD compared to 11 controls (CPDR 9.5 ± 2.4% vs 13.1 ± 3.7%, P = .0001) and this persisted after correcting for acetate (29.3 ± 10.5 vs 36.6 ± 13.9, P = .03). The decrease in FAO was not because of the delayed transit as the time to peak 13 C detection did not differ between groups (4.9 ± 1.2 hours vs 4.7 ± 0.8 hours, P = .7). Rates of PA oxidation were not correlated with obesity, hepatic or adipose insulin resistance, alanine aminotransferase, liver fat content and NAFLD histology. CONCLUSION: Fatty acid oxidation of orally delivered FA is decreased in NAFLD compared to healthy controls, likely reflecting decreased ß-oxidation. The use of a breath test offers non-invasive dynamic assessment of FAO.

Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

BACKGROUND: Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. AIM: We aimed to evaluate disease progression and outcomes in NCPH. METHODS: Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. RESULTS: Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. CONCLUSIONS: Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.

Tenofovir alafenamide as part of a salvage regimen in a patient with multi-drug resistant HIV and tenofovir-DF-associated renal tubulopathy.

We describe a patient with two recent episodes of tenofovir disoproxil fumarate (TDF)-associated acute kidney injury and six-class drug-resistant HIV infection who achieved and maintained viral suppression without worsening kidney function on a regimen including tenofovir alafenamide (TAF) through 48 weeks of therapy. The safety and efficacy of TAF in patients with TDF-associated renal tubulopathy and multiple drug resistant HIV has not yet been described. TAF may represent a useful option to maximally suppress HIV in patients with these complications.