Elsevier

Journal of Hepatology

Volume 53, Issue 5, November 2010, Pages 849-855
Journal of Hepatology

Research Article
Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy

https://doi.org/10.1016/j.jhep.2010.05.017Get rights and content

Background & Aims

Minimal hepatic encephalopathy (MHE) is the mildest form in the spectrum of hepatic encephalopathy. This cross-sectional study was carried out to elucidate the role of bacterial overgrowth of the small intestine and delayed intestinal transit among patients with MHE.

Methods

Two-hundred-thirty patients with cirrhosis were screened; 102 patients (44.4%) who met the eligibility criteria were included in the study. MHE was diagnosed when the psychometric hepatic encephalopathy score was ⩽−5. All patients underwent a glucose breath test for small intestinal bacterial overgrowth (SIBO) and lactulose breath test for oro-cecal transit time (OCTT).

Results

Fifty-seven (55.9%) patients with cirrhosis had MHE. Among these patients with MHE, 22 (38.6%) had SIBO, while 4 (8.9%) without MHE had SIBO (p = 0.001). The prevalence of SIBO was higher in patients with CTP classes B and C (69.2%) compared to those in CTP class A (30.8%); p = 0.054. OCTT was significantly prolonged in patients who had SIBO than in those who did not have SIBO (p <0.0001). Univariate analysis demonstrated that increased age, female gender, low educational status, low albumin, presence of SIBO, and prolonged OCTT were associated with the presence of MHE. Multivariate analysis demonstrated SIBO as the only factor associated with MHE.

Conclusions

Our study conclusively demonstrates high prevalence of SIBO in patients with cirrhosis with MHE. This study gives the rationale of treatment directed against SIBO and gut dysmotility, which may include non-absorbable antibiotics such as rifaximin, probiotics, and prokinetics.

Introduction

Minimal hepatic encephalopathy (MHE) is the mildest form of a portion of the spectrum of hepatic encephalopathy (HE) [1]. Patients with MHE have no recognizable clinical symptoms of HE but have mild cognitive and psychomotor deficits, which impairs health-related quality of life [2]. MHE also has prognostic significance and predicts the development of overt HE [3], [4].

The pathogenesis of MHE is believed to be similar to that of overt HE and ammonia, derived primarily from enteric bacterial flora, which plays a key role [5], [6]. Cirrhotic patients have substantial derangements in the gut microecology [7], [8], which has been attributed, at least in part, to a decrease in small intestinal motility [7], [8], [9], [10], [11], [12]. Gut flora also contribute to the pro-inflammatory state of cirrhosis even in the absence of overt infection [13]. Orthotopic liver transplantation has been shown to improve small bowel motility disorders in cirrhotic patients [14]. Modulation of gut flora may be an option for treating cirrhotic patients with MHE [2], [15], [16], [17].

SIBO and intestinal dysmotility have not been studied in cirrhotic patients with MHE to date. We hypothesized that SIBO might be associated with the presence of MHE among patients with cirrhosis of liver; we tested this hypothesis by comparing the presence of SIBO in cirrhotic patients with and without MHE and correlated it with oro-cecal transit time (OCTT). We believe that this information would help modulate gut flora with interventions such as pre- or probiotic supplementation, and antibiotic or prokinetic therapy in prevention or treatment of the development of MHE in cirrhotic patients.

Section snippets

Patients and methods

The Ethics Committee of the Postgraduate Institute of Medical Education and Research (PGIMER), a tertiary level health care center in Chandigarh, India, approved the study. Each subject gave a written informed consent before inclusion in the study. The guidelines were laid down by the Indian Council of Medical Research (1994) and the Helsinki declarations (modified 1989) were adhered to in all patients in the study. A cross-sectional study was utilized.

Psychometric hepatic encephalopathy score (PHES)

PHES has been validated in German [18], Spanish [19], and Indian [20] populations and can be performed in 15–20 min. PHES contains 6 tests: number connection test (NCT)-A, NCT-B, serial dotting test, digit symbol test, and the line tracing test for time (t) and for error (e). In the Indian version we replaced NCT-B with the figure connection test (FCT-A) because of concerns that some of our patients were not familiar with English alphabets and could not perform NCT-B. In principle, the FCT is

Results

Between January 1, 2007, and December 31, 2008, 230 patients with cirrhosis were screened, 102 patients (44.4%) who met the eligibility criteria were included in the study. Fig. 1 shows the flow of patients into the study and reasons for the exclusion of 128 patients (55.6%). The clinical and demographic characteristics of the patients screened and of those enrolled are shown in Table 1.

Of the 102 patients included in the study, 84 were men and 18 were women. Table 1 shows the causes of

Discussion

The results of this study confirm the high prevalence of MHE among patients with cirrhosis and that the prevalence of SIBO was significantly higher in cirrhotic patients with MHE than in those without MHE; multivariate analysis showed that SIBO was the only significant factor for the presence of MHE.

Author roles

RKD conceived the idea for the study, performed all analyses, interpreted data, and assisted in preparing the manuscript. AG performed psychometric testing, interpreted data, and assisted in preparing the manuscript. SR performed hydrogen breath tests, RA performed statistical analysis, and SK, AD and YC participated in the design of the study and critically reviewed the manuscript.

Conflict of interest

The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Acknowledgements

The paper was presented in the Annual Conference of Indian National Association for the Study of Liver (INASL), and International Liver Transplant Society (ILTS), New Delhi, March 27–29, 2009, and it received best Oral Presentation Award.

References (48)

  • A. Maheshwari et al.

    Autonomic neuropathy may be associated with delayed oro-cecal transit time in patients with cirrhosis

    Auton Neurosci

    (2005)
  • J.A. Reilly et al.

    Small intestinal transit in the portal hypertensive rat

    Gastroenterology

    (1991)
  • S.F. Solga

    Probiotics can treat hepatic encephalopathy

    Med. Hypotheses

    (2003)
  • A.M. Madrid et al.

    Long-Term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function

    Am J Gastroenterol

    (2001)
  • S. Prasad et al.

    Lactulose improves cognitive functions and health-related quality of life in cirrhotic patients with minimal hepatic encephalopathy

    Hepatology

    (2007)
  • A. Das et al.

    Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis

    J Gastroenterol Hepatol

    (2001)
  • A.H. Lockwood et al.

    Cerebral ammonia metabolism in patients with severe liver disease and minimal hepatic encephalopathy

    J Cereb Blood Flow Metab

    (1991)
  • R.K. Dhiman et al.

    Minimal hepatic encephalopathy

    Indian J Gastroenterol

    (2009)
  • C.S. Chang et al.

    Small intestine dysmotility and bacterial overgrowth in cirrhotic patients with spontaneous bacterial peritonitis

    Hepatology

    (1998)
  • J. Chesta et al.

    Abnormalities in proximal small bowel motility in patients with cirrhosis

    Hepatology

    (1993)
  • J.J. Stewart et al.

    Intestinal myoelectrical activity and transit time in chronic portal hypertension

    Am J Physiol

    (1992)
  • R. Sadik et al.

    Etiology of portal hypertension may influence gastrointestinal transit

    Scand J Gastroenterol

    (2003)
  • A.M. Madrid et al.

    Orthotopic liver transplantation improves small bowel motility disorders in cirrhotic patients

    Am J Gastroenterol

    (1997)
  • Q. Liu et al.

    Symbiotic modulation of gut flora: effect on minimal hepatic encephalopathy in patients with cirrhosis

    Hepatology

    (2004)
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