Probiotics for patients with compensated liver cirrhosis: A double-blind placebo-controlled study

The syndrome we refer to as Hepatic Encephalopathy (HE) was first characterized by a team of Nobel Prize winning physiologists led by Pavlov and Nencki at the Imperial Institute of Experimental Medicine in Russia in the 1890's. This focused upon the key observation that performing a portocaval shunt, which bypassed nitrogen-rich blood away from the liver, induced elevated blood and brain ammonia concentrations in association with profound neurobehavioral changes. There exists however a spectrum of metabolic encephalopathies attributable to a variety (or even absence) of liver hepatocellular dysfunctions and it is this spectrum rather than a single disease entity that has come to be defined as HE. Differences in the underlying pathophysiology, treatment responses and outcomes can therefore be highly variable between acute and chronic HE. The term also fails to articulate quite how systemic the syndrome of HE can be and how it can be influenced by the gastrointestinal, renal, nervous, or immune systems without any change in background liver function. The pathogenesis of HE therefore encapsulates a complex network of interdependent organ systems which as yet remain poorly characterized. There is nonetheless a growing recognition that there is a complex but influential synergistic relationship between ammonia, inflammation (sterile and non-sterile) and oxidative stress in the pathogenesis HE which develops in an environment of functional immunoparesis in patients with liver dysfunction. Therapeutic strategies are thus moving further away from the traditional specialty of hepatology and more towards novel immune and inflammatory targets which will be discussed in this review. ( J CLIN EXP HEPATOL 2015;5:S7-S20) H epatic encephalopathy (HE) is the term used to encapsulate the broad spectrum of neuropsychiatric disturbances associated with both acute and chronic liver failure (ALF and CLF, respectively), as well as porto-systemic bypass in the absence of hepatocellular disease. The clinical manifestations of HE can be extremely heterogeneous in nature, with symptoms presenting anywhere on a continuum spanning from seemingly normal cognitive performance, right the way through to states of confusion, stupor and coma. In between these extremes, patients with HE may exhibit signs such as inattentiveness, blunted affect, impairment of memory or reversal of the sleep-wake cycle, as well as physical manifestations such as tremor, myoclonus, asterixis and deep tendon hyperreflexia.ALF is defined by the onset of coagulopathy alongside any degree of encephalopathy in patients with no evidence of pre-existing liver disease. 1 The presence of HE in those with ALF is prognostic, with up to a quarter of cases developing raised intracranial pressure. 2 Patients presenting with ALF are at risk of developing its cardinal, lifethreatening feature, cerebral edema. Left untreated, cerebral edema can rapidly progress to cause herniation of the uncus through the falx cerebri, leading to compression of the brainstem and, ultimately, death. H...

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“…124 However, in other studies no changes in the reduction of the plasma proinflammatory milieu 125 or outcomes have been demonstrated. 126 …”

Section: Probioticsmentioning

confidence: 99%

Pathogenesis of Hepatic Encephalopathy: Role of Ammonia and Systemic Inflammation

Aldridge

Tranah

Shawcross

2015

Journal of Clinical and Experimental Hepatology

235

190

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“…No significant differences were observed in plasmatic levels of creatinine, aminotransferases, bilirubin, and albumin or in the international normalized ratio. This RCT showed that patients with compensated liver cirrhosis are not benefited by the use of supplemental probiotics (Pereg et al, 2011).…”

Section: Probiotics In Compensated Cirrhosismentioning

confidence: 96%

“…Endotoxemia secondary to bacterial infection has been proposed as a possible trigger for variceal hemorrhage because it can impair homeostasis and increase portal pressure (Pereg et al, 2011).…”

Section: Probiotics In Variceal Bleedingmentioning

confidence: 99%

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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“…A multistrain probiotic had no benefit in these patients except for a nonsignificant trend toward reduction in serum ammonia levels in those with elevated ammonia. 38 Preoperative and postoperative use of probiotics in cirrhosis and hepatocellular carcinoma patients who underwent tumor resection was associated with a lower serum TNF-α level and quicker recovery of hepatic function. 39 Use of VSL#3 for 2 months in cirrhosis patients with an elevated hepatic venous pressure gradient (>10 mm of Hg) did not reduce hepatic venous pressure gradient, although reductions in plasma endotoxemia and cytokines (TNF-α, interleukin 6, and interleukin 8) were noted.…”

Section: Other Liver Diseasesmentioning

confidence: 97%