ABSTRACT
BACKGROUND: The importance of alcohol and cannabis consumption for the effectiveness of treatment of chronic hepatitis C virus (HCV) infection with direct acting antivirals (DAAs) in people on opioid substitution therapy (OST) has not been investigated in detail. METHODS: We investigated sustained virological response (SVR) rates and proportion of lost to follow-up (LTFU) between OST (n = 739) and non-OST patients (n = 7008) in the German Hepatitis C-Registry (Deutsches Hepatitis C-Register, DHC-R), which is a national multicenter prospective non-interventional real-world registry. Non-OST patients comprised patients with former/current drug use (non-OST/DU; n = 1500) and patients never consuming drugs (non-OST/NDU; n = 5508). FINDINGS: SVR 12/24 rates (intention to treat [ITT]) in patients consuming no or less than 30 g/day (women) or 40 g/day (men) were significantly higher in non-OST/NDU (range 91%-92%) vs OST patients (range 83%-86%), mainly due to significantly higher LTFU rates in OST (range 11%-12%) compared with non-OST/NDU (range 2%-3%). In non-OST/NDU with high alcohol consumption of more than 30/40 g/day, SVR 12/24 rates (ITT) were lower (85%) but did not differ to OST (85%) with high alcohol consumption. No significant differences could be seen for SVR 12/24 in per-protocol (PP) analysis independent of alcohol consumption or amount of alcohol intake. Cannabis use did not significantly influence SVR 12/24 in ITT or PP or LTFU. CONCLUSIONS: High SVR rates could be achieved in both OST and non-OST patients irrespective of alcohol or cannabis consumption. However, LTFU is more likely in patients with current or former drug use than in patients without drug history and in patients with high alcohol consumption but occurred mainly after end of antiviral treatment (EOT), leaving a high chance for HCV elimination in these patients.
ABSTRACT
Bile acids (BA) have recently been shown to increase energy expenditure in mice, but this concept has not been tested in humans. Therefore, we investigated the relationship between plasma BA levels and energy expenditure in humans. Type 2 diabetic (T2DM) patients (n = 12) and gender, age and BMI-matched healthy controls (n = 12) were studied before and after 8 weeks of treatment with a BA sequestrant. In addition, patients with liver cirrhosis (n = 46) were investigated, since these display elevated plasma BA together with increased energy expenditure. This group was compared to gender-, age- and BMI-matched healthy controls (n = 20). Fasting plasma levels of total BA and individual BA species as well as resting energy expenditure were determined. In response to treatment with the BA sequestrant, plasma deoxycholic acid (DCA) levels decreased in controls (-60%, p < 0.05) and T2DM (-32%, p < 0.05), while chenodeoxycholic acid (CDCA) decreased in controls only (-33%, p < 0.05). Energy expenditure did not differ between T2DM and controls at baseline and, in contrast to plasma BA levels, was unaffected by treatment with the BA sequestrant. Total BA as well as individual BA species did not correlate with energy expenditure at any time throughout the study. Patients with cirrhosis displayed on average an increase in energy expenditure of 18% compared to values predicted by the Harris-Benedict equation, and plasma levels of total BA (up to 12-fold) and individual BA (up to 20-fold) were increased over a wide range. However, neither total nor individual plasma BA levels correlated with energy expenditure. In addition, energy expenditure was identical in patients with a cholestatic versus a non-cholestatic origin of liver disease while plasma total BA levels differed four-fold between the groups. In conclusion, in the various (patho)physiological conditions studied, plasma BA levels were not associated with changes in energy expenditure. Therefore, our data do not support an important role of circulating BA in the control of human energy metabolism.
