Effects of the adjunctive probiotic <scp>VSL</scp>#3 on portal haemodynamics in patients with cirrhosis and large varices: a randomized trial

Gupta, Nitin; Kumar, Ashish; Sharma, Praveen; Garg, Vishal; Sharma, Barjesh Chander; Sarin, Shiv Kumar

doi:10.1111/liv.12172

Cited by 74 publications

(69 citation statements)

References 19 publications

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“…Probiotics are not drugs, but rather combinations of bacteria. In adjunctive therapy a beneficial effect has been observed in patients receiving propranolol and in addition VSL#3 as a probiotic therapy, with response rates to propranolol being subsequently improved [48]. On the other hand, probiotic administration alone did not show effects on portal pressure in compensated [49] and decompensated cirrhosis [50].…”

Section: Clinical Studiesmentioning

confidence: 99%

Infection as a Trigger for Portal Hypertension

Steib¹,

Schewe²,

Gerbes³

2015

Dig Dis

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Background: Microbial infections are a relevant problem for patients with liver cirrhosis. Different types of bacteria are responsible for different kinds of infections: Escherichia coli and Klebsiella pneumoniae are frequently observed in spontaneous bacterial peritonitis or urinary tract infections, and Streptococcus pneumoniae and Mycoplasma pneumoniae in pulmonary infections. Mortality is up to 4-fold higher in infected patients with liver cirrhosis than in patients without infections. Key Messages: Infections in patients with liver cirrhosis are due to three major reasons: bacterial translocation, immune deficiency and an increased incidence of systemic infections. Nonparenchymal liver cells like Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells are the first liver cells to come into contact with microbial products when systemic infection or bacterial translocation occurs. Kupffer cell (KC) activation by Toll-like receptor (TLR) agonists and endothelial sinusoidal dysfunction have been shown to be important mechanisms increasing portal pressure following intraperitoneal lipopolysaccharide pretreatment in cirrhotic rat livers. Reduced intrahepatic vasodilation and increased intrahepatic vasoconstriction are the relevant pathophysiological pathways. Thromboxane A₂ and leukotriene (LT) C₄/D₄ have been identified as important vasoconstrictors. Accordingly, treatment with montelukast to inhibit the cysteinyl-LT₁ receptor reduced portal pressure in cirrhotic rat livers. Clinical studies have demonstrated that activation of KCs, estimated by the amount of soluble CD163 in the blood, correlates with the risk for variceal bleeding. Additionally, intestinal decontamination with rifaximin in patients with alcohol-associated liver cirrhosis reduced the portal pressure and the risk for variceal bleeding. Conclusions: TLR activation of nonparenchymal liver cells by pathogens results in portal hypertension. This might explain the pathophysiologic correlation between microbial infections and portal hypertension in patients with liver cirrhosis. These findings are the basis for both better risk stratifying and new treatment options, such as specific inhibition of TLR for patients with liver cirrhosis and portal hypertension.

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Section: Clinical Studiesmentioning

confidence: 99%

Infection as a Trigger for Portal Hypertension

Steib¹,

Schewe²,

Gerbes³

2015

Dig Dis

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“…No relevant differences were observed in the frequency or type of adverse effects between the groups studied. In this study authors concluded that VSL#3 improved the response rate to propranolol therapy and was well tolerated by patients; however, the effects of supplemental probiotic therapy on portal pressure require further study (Gupta et al, 2013). …”

Section: Probiotics In Variceal Bleedingmentioning

confidence: 94%

“…The addition of probiotic therapy to propanolol improved its response rate on hepatic venous pressure gradient (HVPG) compared with adjunctive antibiotics. The mean decrease in HVPG was also greater in the probiotics-treated group (3.7 mmHg) than in the antibiotics-treated group (3.4 mmHg) and placebo group (2.1 mmHg) (Gupta et al, 2013).…”

Section: Probiotics In Decompensated Cirrhosismentioning

confidence: 97%

“…Therefore, the use of probiotics in patients who underwent a liver transplant requires careful analysis to ensure its safe use. (Pereg et al, 2011) Compensated cirrhosis 36 6 months 2 × 10 10 CFU Improvement in liver function tests and ammonia levels L. casei Shirota (Stadlbauer et al, 2008) Compensated cirrhosis 12 4 weeks 6.5 × 10 9 CFU/3 times/day Improvement in inflammatory markers and nuclear receptors L. sporogenes (Pawar et al, 2014) Decompensated cirrhosis 65 6 months 2 billion CFU/day Reduction in hospitalization rate and hepatic encephalopathy VSL#3 (Gupta et al, 2013) Portal hypertension 94 2 months 900 billion/day Increased response rate to propranolol and reduction in inflammatory markers E. faecalis JPC/C. butyricum/B.…”

Section: Probiotics In Liver Transplantationmentioning

confidence: 97%

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Current evidence on the use of probiotics in liver diseases

Chávez-Tapia

González-Rodríguez

Jeong

et al. 2015

Journal of Functional Foods

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“…Another approach is to restore intestinal bacterial diversity by supplementing probiotics. While the impact of the probiotic VSL#3 alone on HVPG led to conflicting studies [102,103], a RCT observed an increase in haemodynamic response to NSBB in patients receiving adjunctive probiotics [104]. …”

Section: Inflammation and Bacterial Translocationmentioning

confidence: 99%

Novel treatment options for portal hypertension

Schwabl

Laleman

2017

Gastroenterology Report

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Portal hypertension is most frequently associated with cirrhosis and is a major driver for associated complications, such as variceal bleeding, ascites or hepatic encephalopathy. As such, clinically significant portal hypertension forms the prelude to decompensation and impacts significantly on the prognosis of patients with liver cirrhosis. At present, non-selective β-blockers, vasopressin analogues and somatostatin analogues are the mainstay of treatment but these strategies are far from satisfactory and only target splanchnic hyperemia. In contrast, safe and reliable strategies to reduce the increased intrahepatic resistance in cirrhotic patients still represent a pending issue. In recent years, several preclinical and clinical trials have focused on this latter component and other therapeutic avenues. In this review, we highlight novel data in this context and address potentially interesting therapeutic options for the future.

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Effects of the adjunctive probiotic VSL#3 on portal haemodynamics in patients with cirrhosis and large varices: a randomized trial

Abstract: Adjunctive probiotic (VSL#3) improved the response rate to propranolol therapy and was safe and well tolerated in patients with cirrhosis. Adjunctive probiotic therapy merits further study for reduction in portal pressure.

Cited by 74 publications

References 19 publications

Infection as a Trigger for Portal Hypertension

Infection as a Trigger for Portal Hypertension

Current evidence on the use of probiotics in liver diseases

Novel treatment options for portal hypertension

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