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