Randomised clinical study: the effects of oral taurine 6g/day vs placebo on portal hypertension

Schwarzer, R; Kivaranovic, Danijel; Mandorfer, Mattias; Paternostro, Rafael; Wolrab, Denise; Heinisch, B.; Reiberger, Thomas; Ferlitsch, Monika; Gerner, Christopher; Trauner, Michael; Peck‐Radosavljevic, Markus; Ferlitsch, Arnulf

doi:10.1111/apt.14377

Cited by 41 publications

(26 citation statements)

References 35 publications

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“…The Vienna Hepatic Hemodynamic Laboratory at the Medical University of Vienna performed the HVPG measurements according to a standardised operating procedure . HVPG measurements were performed in the absence of nonselective beta blockers and nitrates.…”

Section: Methodsmentioning

confidence: 99%

Impact of patatin‐like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension

Mandorfer

Scheiner

Stättermayer

et al. 2018

Aliment Pharmacol Ther

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SummaryBackgroundThe rs738409 C>G p.I148M variant in the patatin‐like phospholipase domain containing 3 (PNPLA3)‐gene promotes triglyceride accumulation in hepatocytes and hepatic stellate cell activation and has previously been linked to hepatic steatosis/liver fibrosis.AimTo investigate its impact on hepatic decompensation and (liver‐related) mortality in patients who had already developed portal hypertension. Moreover, we assessed its link with hepatic steatosis as evaluated by controlled attenuation parameter.MethodsWe performed a retrospective analysis in prospectively characterised patients with viral hepatitis/fatty liver disease‐induced portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) diagnosed at the Medical University of Vienna who underwent HVPG measurement (until 2013; n = 372; longitudinal study) or simultaneous HVPG and controlled attenuation parameter measurement (2014‐2017; n = 153; cross‐sectional study).ResultsWhile survival was similar between PNPLA3‐C/C and ‐C/G patients, we observed substantially increased mortality in PNPLA3‐G/G patients. PNPLA3‐G/G had no impact on mortality in the subgroup of patients with viral hepatitis; however, we observed a strong independent association between PNPLA3‐G/G and hepatic decompensation (adjusted subdistribution hazard ratio [aSHR]: 2.1, 95% confidence interval [95% CI]: 1.1‐4; P = 0.024) as well as mortality (overall: aSHR: 2.2, 95% CI: 1.22‐3.98; P = 0.009; liver‐related: aSHR: 2.2, 95% CI: 1.08‐4.46; P = 0.029) in patients with fatty liver disease. Interestingly, even in the subgroup of patients who had already progressed to clinically significant portal hypertension (HVPG ≥ 10 mm Hg), PNPLA3‐G/G substantially increased mortality (aSHR: 2.33, 95% CI: 1.27‐4.29; P = 0.006). PNPLA3‐genotype had no influence on controlled attenuation parameter or the prevalence of values ≥248 dB/m.Conclusion PNPLA3‐G/G‐genotype seems to double the risks of hepatic decompensation and (liver‐related) mortality in patients with portal hypertension due to fatty liver disease. Further studies are warranted to investigate potential underlying pathophysiological mechanisms unrelated to hepatic steatosis.

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Section: Methodsmentioning

confidence: 99%

Impact of patatin‐like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension

Mandorfer

Scheiner

Stättermayer

et al. 2018

Aliment Pharmacol Ther

Self Cite

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“…In addition, it is possible that certain populations have been underrepresented across the available meta-analysed studies. The studies were conducted in Europe [28][29]31], Asia [27,30] and the Middle East [25][26], yet there were no studies conducted in larger continents, such as the North and South America, Africa or Australasia, where similar risks of mortality due to cardiovascular disease are present and increased in certain ethnic groups [55]. This could be partly addressed with changes in dietary supplementation, including changes in taurine intake.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis

Waldron

Patterson²,

Tallent³

et al. 2018

Curr Hypertens Rep

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There is growing evidence that taurine deficiency is associated with hypertension and that oral supplementation can have antihypertensive effects in humans. However, these investigations have been conducted across a number of decades and populations and have not been collectively reviewed. A search was performed using various databases in May 2018 and later screened using search criteria for eligibility. There were seven peer-reviewed studies meeting the inclusion criteria, encompassing 103 participants of varying age and health statuses. Taurine ingestion reduced SBP (Hedges' g = - 0.70, 95% CI - 0.98 to - 0.41, P < 0.0001) and DBP (Hedges' g = - 0.62, 95% CI - 0.91 to - 0.34, P < 0.0001). These results translated to mean ~ 3 mmHg reductions in both SBP (range = 0-15 mmHg) and DBP (range = 0-7 mmHg) following a range of doses (1 to 6 g/day) and supplementation periods (1 day to 12 weeks), with no adverse events reported. These preliminary findings suggest that ingestion of taurine at the stated doses and supplementation periods can reduce blood pressure to a clinically relevant magnitude, without any adverse side effects. Future studies are needed to establish the effects of oral taurine supplementation on targeted pathologies and the optimal supplementation doses and periods.

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“…1 The data suggested that taurine may be a useful interventional tool for replacing non-selective beta blockers (NSBBs) when use of NSBBs is contraindicated. Another important aspect of this work was measurement of steady state serum taurine concentration; day 28 serum level of taurine (7.79 ng/lL) was 10-fold higher than placebo group (0.73 ng/lL) 1 As a clinical pharmacologist, I had a few questions: on dose selection, influence of the dose on absorption, distribution and excretion of taurine which would be critical for efficacy; likelihood of interference in the absorption of co-medications. A quick introspection/rationalisation to these may be beneficial for the design of future studies of taurine.…”

Section: Editorsmentioning

confidence: 99%

Letter: high oral dose of taurine for portal hypertension in cirrhotic patients—some clinical pharmacology considerations

Srinivas

2018

Aliment Pharmacol Ther

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Randomised clinical study: the effects of oral taurine 6g/day vs placebo on portal hypertension

Abstract: Taurine is safe and may reduce portal pressure in cirrhotic patients. More studies on the underlying mechanisms of action and long-term effects of taurine supplementation are warranted.

Cited by 41 publications

References 35 publications

Impact of patatin‐like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension

Impact of patatin‐like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension

The Effects of Oral Taurine on Resting Blood Pressure in Humans: a Meta-Analysis

Letter: high oral dose of taurine for portal hypertension in cirrhotic patients—some clinical pharmacology considerations

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