Prevalence of Small Intestinal Bacterial Overgrowth in Patients with Liver Cirrhosis

Vanya A Gerova, Ventsislav N Nakov, Simeon G Stoynov, Radislav V Nakov

Vanya A Gerova, Ventsislav N Nakov, Simeon G Stoynov, Radislav V Nakov, Clinical Center of Gastroenterology, University Hospital Queen Joanna, Medical University, Sofia 1527, Bulgaria

Correspondence to: Ventsislav N Nakov, MD, PhD, Clinical Center of Gastroenterology, University Hospital Queen Joanna, Medical University, 8 Byalo more Str, Sofia 1527, Bulgaria.
Received: May 9, 2013
Revised: June 3, 2013
Accepted: June 5, 2013
Published online: August 21, 2013


AIM: To assess the prevalence of small intestinal bacterial overgrowth (SIBO) and to analyze its relationship with the etiology of the disease and the severity of liver dysfunction in patients with liver cirrhosis (LC).

METHODS: Forty-three patients with LC (25 alcohol- and 18 viral-induced) and ten healthy subjects consented to participate in the study. According to Child-Pugh classification, 7 of the patients were with class A, 14 - class В and 22 - class С. SIBO was estimated indirectly by the lactulose hydrogene (H2) breath test.

RESULTS: In 4 of the patients no peak of H2 was recorded. In comparison to the control group of healthy subjects, LC patients had significantly higher basal breathed H2 (15.54±10.56 vs 6.24±3.39 ppm), p<0.05). The mean basal breathed H2 in cirrotic patients with evidence of SIBO was 29.33±6.69 ppm (range 21-42). Of the 39 patients with LC, 12 (31%) had SIBO compared to none of the healthy controls. No differences in SIBO regarding Child-Pugh score were found. SIBO was demonstrated in 45.5% of the alcohol- and only in 11.8% of the viral-induced LC (p<0.05).

CONCLUSION: SIBO is common in patients with LC and more frequent in the cases with alcoholic etiology, but it is not related to the severity of liver dysfunction. Future larger trials are needed to establish the exact role of these alterations in patients with LC.

Key words: Small intestinal bacterial overgrowth; Lactulose hydrogene breath test; Liver cirrhosis; Alcohol

© 2013 The Authors. Published by ACT Publishing Group Ltd.

Gerova VA, Nakov VN, Stoynov SG, Nakov RV. Prevalence of Small Intestinal Bacterial Overgrowth in Patients with Liver Cirrhosis. Journal of Gastroenterology and Hepatology Research 2013; 2(8): 740-743 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/460


Patients with liver cirrhosis (LC) have an increased risk of infections due to bacterial translocation (BT)[1]. Over 70% of the cases are caused by intestinal bacteria and can be prevented by selective bacterial decontamination with non-absorbed or absorbed antibiotics, which confirms that the gut is the main source of microorganisms[2]. The gut microflora not only takes part in the pathogenesis of overt infective episodes and of the clinical consequences of sepsis, but it also contributes to the pro-inflammatory state of cirrhosis even in the absence of overt infection[1]. Although accurate mechanisms of BT are unknown, small intestinal bacterial overgrowth (SIBO), gut dysmotility, increased intestinal permeability and impaired defense mechanisms are regarded as major risk factors for BT[1,2]. SIBO is common in LC due to various causes[3,4] and is an independent risk factor for systemic endotoxemia, implicated in various pathophysiological sequelae of cirrhotic patients[5].

Data on SIBO frequency in patients with LC and its association with the ethiology and degree of liver damage are scanty and contradictory. Some authors suggested that SIBO might be related to the degree of liver dysfunction[3,6,7], whereas others suggested that it was related to the portal hypertension[8]. The later may cause small bowel motility disturbances, which might be a predisposing factor for the SIBO.

The aim of this study was to assess the prevalence of SIBO using the lactulose hydrogene breath test (LHBT) and to analyze its relationship with the etiology of the disease and the severity of liver dysfunction in patients with LC.


The study included 43 patients with LC (33 males and 10 females; mean age 48 years, range 37-60), recruited from January 2008 to June 2009. The LC was diagnosed and staged by means of clinical presentation, laboratory results and abdominal ultrasound examination. The Child-Pugh (CP) score was used for an evaluation of the disease severity. Upper gastrointestinal endoscopy was performed to assess further complications of portal hypertension. The ascitic fluid was localized by ultrasonography and paracentesis was performed where possible. The presence of spontaneous bacterial peritonitis (SBP) was assessed by the number of polymorphonuclear leucocytes in the ascitic fluid over 250 cells/mm3.

Patients with anatomical predispositions for intestinal stasis, such as small intestinal diverticula on the small bowel series, were not included. In addition, the patients with diseases associated with impaired motility (diabetes mellitus, scleroderma), renal failure or previous abdominal surgery, as well as those who had received antibiotics, probiotics, lactulose, prokinetic or acid-suppressive drugs in the two weeks preceding the study were not included. Ten healthy persons (6 males and 4 females, mean age 46 years, range 32-60) were recruited as controls.

SIBO was estimated indirectly by the LHBT, using a breath gas analyzer (Gastrolyzer Breath Hydrogen Bedfont Scientific, UK). All participants were asked to avoid slowly absorbed carbohydrates in the day preceding the test. Basal breath specimens were obtained after an fasting overnight. Smoking and physical exercise were not permitted for 2 h before and during the test for a prevention of hyperventilation and consequent changes in breath hydrogen (H2) content. The H2 exhalation was measured for 3 h (in 15-minute intervals) following the ingestion of 10 g lactulose dissolved in 100 mL tap water. The results were expressed in parts per million (ppm).

The LHBT was considered as positive for SIBO on the basis of the following criteria: the baseline value of H2 above 20 ppm or/and early H2 peak (12 ppm increasing of breath H2 above the baseline value between 30 to 60 min after the lactulose ingestion) followed by a second peak or plateau[9,10].

Statistical analysis

All values were expressed as mean±standard deviation (SD) or proportions. Nonparametric Mann-Whitney U test for overall testing the difference between subject groups and Chi-square for comparing proportions were used. Each hypothesis was tested at a level of significance of 0.05.

Ethics approval

The study was approved by the Ethics Committee at the University Hospital Queen Joanna in Sofia, Bulgaria. Written informed consent was obtained from all patients and control subjects.


The baseline characteristics of the investigated subjects are shown in table 1.

In twenty-five patients the alcohol was identified as a cause, assessed by a history of drinking at least 80 g of alcohol daily for more than five years. All were HBs antigen negative and HCV antibody negative. In the remaining 18 patients LC was virus-related (Hepatitis B or Hepatitis C virus). Ascites was present in 32 of the cirrhotic patients (22 with CP C and 10 with CP B). Paracentesis was performed in 27 of the patients, because of small amount of ascitic fluid in the remaining 5 patients.

In 4/43 (9.3%) of the patients (one with CP class B, 3 with class C; 3 with alcoholic and 1 with viral LC; all with evidences of ascites) no peak of H2 was recorded (non-producers) and they were excluded from the final analysis.

The mean basal value of the H2 concentration in exhaled air was found to be higher in the cirrhotic patients compared to that of healthy individuals (15.54±10.56 vs 6.24±3.39 ppm, p<0.05). The evidence of SIBO was found in a third (31%) of the LC patients, but in none of the controls (p<0.05). The mean basal breathed H2 in cirrotic patients with evidence of SIBO was 29.33±6.69 ppm (range 21-42).

Data of SIBO were found in 34.4% (11/32) of patients with decompensated cirrhosis (CP class B/C) and in 14.3% (1/7) of patients with compensated cirrhosis (CP class A) (p=0.36). No differences in SIBO regarding CP score were found. There was not a significant diference in the incidence of SIBO between cirrhotic patients with and without ascites (31.3% vs 18.2%, respectively, p=0.46). The frequency of SIBO was significantly higher in the patients with alcohol-induced liver disease compared to that with viral-related LC (45.5% vs 11.8%, respectively, p<0.05) (Figure1).

SBP was diagnosed in 2/27 of ascitic patients. Both patients met the criteria for SIBO.


In normal individuals, intestinal peristalsis, gastric acid, and mucosal immunity prevent the development of SIBO. Abnormalities in one or more of these factors facilitate the manifestation of SIBO.

Data from our study clearly indicate that nearly one third of the patients with LC have evidence of SIBO compared to healthy subjects.

The microbiological analysis of the jejunal aspirate is regarded as a “gold” standard in diagnosis of SIBO. However, this method requires intubation and does not detect unculturable species. Moreover, it is cumbersome, time-consuming and generally not well tolerated. In the recent decades, breath tests are widely used in clinical practice to assess SIBO. They are simple, inexpensive, non-invasive, easily applicable, and withouth risk of contamination[11,12]. The LHBT has been used as an indirect indicator of SIBO in several settings such as Published studies are quite heterogenic showing prevalence of SIBO in 20%-60% in the cirrhotic patients[5,15]. Several alterations in defensive mechanisms in LC could be responsible for its occurrence, including prolonged small intestinal transit, achylia and hypochlorhydria, a decreasing of the Ig A secretion, abnormalities in bile secretion, and malnutrition caused by liver disfunction and alcoholism[16].

Although we did not find significant differences in prevalence of SIBO in regards to the severity of the LC, such relationship was previously reported as existing. SIBO is present in 30-61% of decompensated cirrhotics, and its prevalence is more frequent in advanced disease[3,6,7]. More advanced liver disease with impaired liver function, ascites, portal enteropathy, hypoalbuminemia are all factors facilitating SIBO. Despite the fact that all except for one of the cirrhotics with SIBO had ascites, we, like some authors did not find any association between prevalenve of SIBO and the presence or absence of ascites[6].

We found significant differences in the prevalence of SIBO between cirrhotic patients depending on the etiology of liver disease. In the present study, we have demonstrated that SIBO occurs significantly more frequently in patients with alcoholic LC (45.5%) compared to those with viral etiology of the disease (11.8%). Similar findings are also published even in the absence of decompensated disease, thus proving the leading role of chronic alcohol exposure perse.

A few studies are available in the literature investigating the relationship between alcohol consumption and intestinal bacterial growth. These studies suggest that chronic alcohol abuse can promote SIBO. Excessive alcohol consumption leads to quantitative and qualitative changes in the jejunal flora. The incidence of SIBO in alcoholic liver disease was three times higher than in healthy controls[14].

The studies, performed in “real life”, also demonstrated recent evidences of influence of alcohol on the dysregulation of intestinal antimicrobial molecules. This leads to enteric microbiome changes and induces alcoholic steatohepatitis[17]. Overgrowth of Gramnegative bacteria can result in increased production of endotoxin that can escape into portal circulation leading to increased plasma levels of endotoxin[18]. Alcohol consumption can affect the colonic microbiome composition and can suggest that dysbiosis may be an important mechanism of alcohol-induced endotoxemia. Futuremore, clinical and animal data indicate that gut-derived endotoxin and other luminal bacterial products are necessary cofactors for development of alcoholic liver disease[19]. On the other hand, SIBO could worsen liver function in alcohol-induced liver diseases by trigering and maintaining the necro-inflammatory liver alterations both through the metabolism of ethanol and through the activation of key hepatic innate immune cell populations[20].

In conclusion, the data from our study indicate that SIBO is present in nearly one third of patients with LC. SIBO is more frequent in the cases with alcoholic etiology, but is not related to the severity of liver dysfunction.

Ongoing research is needed to reveal mechanisms of the gut flora derangement in the patients with alcoholic liver disease. This could further facilitate the rationale of therapeutic usage of different antibiotics and probiotics in patients of alcoholic LC.


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Peer reviewers: Da Li, PhD, Professor, Department of Physiology, Institute of Basic Medical Sciences, China Medical University, Shenyang, 110001, China; Abdulrahman Abdullah Aljumah, Department of Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City and King Saud bin Abdulaziz University for Health Sciences, National Guard Health Affairs, Riyadh, Saudi Arabia.


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