CD133+ stem cell mobilization after partial hepatectomy depends on resection extent and underlying disease.

BACKGROUND: Bone marrow stem cells (BMSC) can participate to liver regeneration. However, conflicting results have been reported on this topic in patients undergoing liver resection. AIMS: To assess the impact of liver resection extent and presence of underlying liver disease in modulating BMSC mobilization. METHODS: We enrolled 29 patients undergoing liver resection of different extents, 5 surgical controls and 10 blood donors. Circulating CD133+ BMSC were measured by flow cytometry at different time-points after surgery. The hepatic commitment of mobilized BMSC was investigated by polymerase chain reaction. Liver specimens were collected during surgery for histopathological analysis. Hepatocyte growth factor and granulocyte-colony stimulating factor serum levels were measured by enzyme-linked immunosorbent assay. RESULTS: BMSC mobilization was found in patients undergoing major liver resection, especially in the presence of underlying disease. Ductular reactions were noted in patients with chronic hepatopathy and the hepatic progenitor-like cells expressed CD133, NCAM, cytokeratin-19, and alpha-fetoprotein. Hepatocyte growth factor and granulocyte-colony stimulating factor levels increased following liver resection and the contemporaneous presence of liver disease was associated with their highest raise. CONCLUSIONS: Liver repair is mainly an endogenous process. BMSC become important in case of extensive resection, especially in the presence of underlying hepatopathy and hepatic progenitor-like cells activation. Hepatocyte growth factor and granulocyte-colony stimulating factor seem to be involved in the dynamics underlying hepatic regeneration and BMSC recruitment.

Thrombotic risk factors in patients with liver cirrhosis: correlation with MELD scoring system and portal vein thrombosis development.

BACKGROUND/AIMS: Prognostic scores currently used in cirrhotic patients do not include thrombotic risk factors (TRFs). Predicting factors of portal vein thrombosis (PVT) development are still unknown. We wanted to describe TRFs as a function of liver disease severity using the MELD score and assess the role of local and systemic TRFs as predictors of PVT development in cirrhotic patients. METHODS: One hundred consecutive patients with liver cirrhosis were included in the study. TRFs, D-dimers, MELD score, portal vein patency and flow velocity were evaluated in all subjects at baseline and every 6 months thereafter. Variables able to predict PVT development within 1 year were identified by means of multiple logistic regression. RESULTS: The plasma levels of protein C and antithrombin were lower and the concentration of D-dimers was higher in patients with advanced disease. Plasma levels of antithrombin, protein C and protein S resulted significantly lower in PVT group at univariate analysis, but reduced portal vein flow velocity was the only variable independently associated with PVT development. CONCLUSIONS: Lower concentrations of natural coagulation inhibitors are frequently detected in patients with liver cirrhosis. A reduced portal flow velocity seems to be the most important predictive variable for PVT development in patients with cirrhosis.

Small intestinal bacterial overgrowth recurrence after antibiotic therapy.

OBJECTIVES: Current treatment for small intestinal bacterial overgrowth (SIBO) is based on courses of broad-spectrum antibiotics. No data concerning SIBO recurrence are available. The aims of the present study were to investigate SIBO recurrence as assessed by glucose breath test (GBT) after antibiotic treatment and conditions associated to SIBO recurrence. METHODS: Eighty consecutive patients affected by SIBO and decontaminated by rifaximin (1,200 mg per day for 1 wk) were enrolled. Diagnosis of SIBO was based on GBT. GBT was reassessed at 3, 6, and 9 months after evidence of GBT normalization. GBT positivity recurrence, predisposing conditions, and gastrointestinal symptoms were evaluated. RESULTS: Ten (10/80, 12.6%), 22 (22/80, 27.5%), and 35 (35/80, 43.7%) patients showed positivity to GBT at 3, 6, and 9 months after successful antibiotic treatment, respectively. At multivariate analysis, older age (OR 1.09, 95% CI 1.02-1.16), history of appendectomy (OR 5.9, 95% CI 1.45-24.19), and chronic use of proton pump inhibitors (PPIs) (OR 3.52, 95% CI 1.07-11.64) were significantly associated to GBT positivity recurrence. All gastrointestinal symptoms significantly increased at 3, 6, and 9 months in patients with evidence of GBT positivity recurrence. CONCLUSIONS: GBT positivity recurrence rate was high after antibiotic treatment. Older age, history of appendectomy, and chronic use of PPIs were associated with GBT positivity recurrence. Patients with evidence of GBT positivity recurrence showed gastrointestinal symptoms relapse thus suggesting SIBO recurrence.

Stem cell-based therapy in gastroenterology and hepatology.

Protagonists of a new scientific era, stem cells are promising tools on which regenerative medicine relies for the treatment of human pathologies. Stem cells can be obtained from various sources, including embryos, fetal tissues, umbilical cord blood, and also terminally differentiated organs. Once forced to expand and differentiate into functional progenies, stem cells may become suitable for cell replacement and tissue engineering. The manipulation and/or stimulation of adult stem cells seems to be particularly promising, as it could improve the endogenous regenerative potential without risks of rejection and overcome the ethical and political issues related to embryonic stem cell research. Stem cells are already leaving the bench and reaching the bedside, despite an incomplete knowledge of the genetic control program driving their fate and plasticity. In gastroenterology and hepatology, the first attempts to translate stem cell basic research into novel therapeutic strategies have been made for the treatment of several disorders, such as inflammatory bowel diseases, diabetes mellitus, celiachy and acute or chronic hepatopaties. Nonetheless, critical aspects need to be further addressed, including the long-term safety, tolerability and efficacy of cell-based treatments, as well as their carcinogenic potential. Aim of this review is to summarize the state-of-the-arts on gastrointestinal and hepatic stem cells and on stem cell-based therapies in gastroenterology and hepatology, highlighting both the benefits and the potential risks of these new tools for the treatment and prevention of human diseases.

Association between hypothyroidism and small intestinal bacterial overgrowth.

OBJECTIVES: Small intestinal bacterial overgrowth is defined as an abnormally high bacterial population level in the small intestine. Intestinal motor dysfunction associated with hypothyroidism could predispose to bacterial overgrowth. Luminal bacteria could modulate gastrointestinal symptoms and interfere with levothyroxine absorption. The aims of the present study were to assess the prevalence and clinical pattern of bacterial overgrowth in patients with a history of overt hypothyroidism and the effects of bacterial overgrowth decontamination on thyroid hormone levels. METHODS: A total of 50 consecutive patients with a history of overt hypothyroidism due to autoimmune thyroiditis was enrolled. Diagnosis of bacterial overgrowth was based on positivity to a hydrogen glucose breath test. Bacterial overgrowth positive patients were treated with 1,200 mg rifaximin each day for a week. A glucose breath test, gastrointestinal symptoms, and thyroid hormone plasma levels were reassessed 1 month after treatment. RESULTS: A total of 27 patients with a history of hypothyroidism demonstrated a positive result to the breath test (27 of 50, 54%), compared with two in the control group (two of 40, 5%). The difference was statistically significant (P < 0.001). Abdominal discomfort, flatulence, and bloating were significantly more prevalent in the bacterial overgrowth positive group. These symptoms significantly improved after antibiotic decontamination. Thyroid hormone plasma levels were not significantly affected by successful bacterial overgrowth decontamination. CONCLUSIONS: The history of overt hypothyroidism is associated with bacterial overgrowth development. Excess bacteria could influence clinical gastrointestinal manifestations. Bacterial overgrowth decontamination is associated with improved gastrointestinal symptoms. However, fermenting carbohydrate luminal bacteria do not interfere with thyroid hormone levels.