The effects of synbiotics on the liver steatosis, inflammation, and gut microbiome of metabolic dysfunction-associated liver disease patients-randomized trial.

INTRODUCTION: Metabolic Dysfunction-associated Liver Disease (MASLD) represents a spectrum of conditions from simple fat accumulation to non-alcoholic steatohepatitis. The possible role of the intestinal microbiome on MASLD development has been in focus. Our study aimed to examine the effects of synbiotics on the liver steatosis, inflammation, and stool microbiome. METHODS: A double-blind, placebo-controlled study was conducted involving 84 MASLD patients, defined by an elastometric attenuation coefficient (ATT) greater than 0.63 dB/cm/MHz with an alanine aminotransferase level above 40 U/L for men and 35 U/L for women. The patients were divided into an intervention group treated with a synbiotic with 64x109 CFU of Lactobacillus and Bifidobacterium and 6.4g of inulin and a control group treated with a placebo. RESULTS: Using synbiotics for 12 weeks significantly decreased liver steatosis (ΔATT -0.006±0.023 vs -0.016±0.021 dB/cm/MHz, p=0.046). The group of patients treated with synbiotics showed a significant decrease in the level of high-sensitive C-reactive protein (Δhs-CRP 0 vs -0.7 mg/L, p≤0.001). Synbiotics enriched the microbiome of patients in the intervention group with the genera Lactobacillus, Bifidobacterium, Faecalibacterium, and Streptococcus, by 81%, 55%, 51%, and 40%, respectively, with a reduction of Ruminococcus and Enterobacterium by 35% and 40%. Synbiotic treatment significantly shortened the gut transition time (ΔGTT -5h vs. -10h, p=0.031). CONCLUSION: Synbiotics could be an effective and safe option that could have place in MASLD treatment.

The Impact of Synbiotic Treatment on the Levels of Gut-Derived Uremic Toxins, Inflammation, and Gut Microbiome of Chronic Kidney Disease Patients-A Randomized Trial.

OBJECTIVE: Altering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study. METHODS: A total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach. RESULTS: Synbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS -21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (-39.5 vs. -8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted. CONCLUSION: Synbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.

Micro-elimination of HCV as a possible therapeutic strategy: our experience and a review of literature.

BACKGROUND: Serbia has an intermediate estimated prevalence of chronic hepatitis C (CHC) infection, approximately 1.13%, with hepatitis C remaining one of the leading causes of liver-related morbidity and mortality in Serbia with impaired quality of life and overwhelming cost of treating its complications As the availability of new treatment options and resources for screening remains limited, micro-elimination of CHC becomes a top priority. METHODS: Review of the available published data related to the clinical and epidemiological situation of the hepatitis C infection in Serbia, including the unpublished data from the databases of four major reference centres in Serbia (Clinical Center Serbia, Clinical Center Nis, Clinical Center Vojvodina and Clinical Center Kragujevac). RESULTS: Currently in Serbia, micro-elimination appears to be realistic in the patients with haemophilia, who represent a small, well-defined subpopulation, under constant monitoring by the healthcare system. Other feasible targets for micro-elimination of CHC infection in Serbia are patients on hemodialysis, prisoners and people who inject drugs. CONCLUSIONS: Micro-elimination is feasible in Serbia, especially in the subpopulation of patients with haemophilia. This may represent an initial step towards achieving the WHO objective to eliminate hepatitis C infection by 2030.

Mortality predictors of patients suffering of acute pancreatitis and development of intraabdominal hypertension

Background/aim: Intraabdominal hypertension (IAH) occurs frequently in patients with acute pancreatitis and adds to their morbidity and mortality. The main aim of the study was to identify the determination of the predictive factors connected to IAH that influence the evolution of acute pancreatitis. Materials and methods: The prospective cohort study was conducted on 100 patients who had acute pancreatitis. According to obtained intraabdominal pressure (IAP) values, the patients were divided into two groups: one group (n = 40) with normal IAP values and the other (IAH group, n = 60) with increased IAP values. Deceased patients were specially analyzed within the IAH group in order to determine mortality predictors. Results: Statistical significance of IAP (P = 0.048), lactates (P = 0.048), peak pressure (P = 0.043), abdominal perfusion pressure (P = 0.05), and mean arterial pressure (P = 0.041) was greater for deceased than for surviving patients in the IAH group. High mortality appears for patients younger than 65 years old, with lactate level higher than 3.22 mmol/L and filtration gradient (GF) lower than 67 mmHg. Conclusion: Age, lactates, GF, and APACHE II score are determined as mortality predictors for patients suffering from acute pancreatitis who developed IAH. The mortality rate is higher when the level of GF is decreasing and the level of lactate increasing.

Remodeling of extracellular matrix of the lamina propria in the uninvolved human rectal mucosa 10 and 20 cm away from the malignant tumor.

In recent years, it has been demonstrated that malignancy arises and advances through the molecular interplay between tumor cells and non-malignant elements of the tumor stroma, that is, fibroblasts and extracellular matrix. However, in contrast to the mounting evidence about the role of tumor stroma in the genesis and progression of the malignant disease, there are very few data regarding the uninvolved stromal tissue in the remote surrounding of the tumor. Using the objective morphometric approach in patients with adenocarcinoma, we demonstrate the remodeling of extracellular matrix of the lamina propria in the uninvolved rectal mucosa 10 and 20 cm away from the neoplasm. We show that the representation of basic extracellular matrix constituents (reticular and collagen fibers and ground substance) is decreased. Also, the diameter of empty spaces that appear within the extracellular matrix of the lamina propria is increased. These spaces do not represent the blood or lymphatic vessel elements. Very likely, they reflect the development of tissue edema in the remote, uninvolved lamina propria of the mucosa in patients with the malignant tumor of the rectum. We hypothesize that the remodeling of extracellular matrix in lamina propria of the rectal mucosa may increase its stiffness, modulating the mechano-signal transduction, and thus promote the progression of the malignant disease.

The influence of intraabdominal pressure on the mortality rate of patients with acute pancreatitis.

BACKGROUND/AIM: Intraabdominal hypertension (IAH) is a common clinical finding in patients with acute pancreatitis and is associated with poor prognosis. This study aimed to determine the impact of intraabdominal pressure (IAP) on the mortality rate in patients with acute pancreatitis in an intensive care unit. MATERIALS AND METHODS: A total of 50 patients with acute pancreatitis were included in this prospective cohort study. Based on the obtained values of IAP, the patients were divided into two groups: those with normal IAP (n = 14) and increased IAP (n = 36). Mean values of IAP were compared with examined variables. RESULTS: The mortality rate of the study group was 40%. Comparing the IAP and treatment outcomes, it was proved that there were statistically highly significant differences (P = 0.012). Increasing the value of IAP increased the mortality rate. Deceased patients in the IAH group had greater statistical significance of APACHE II score (P = 0.016), abdominal perfusion pressure (P = 0.048), lactate (P = 0.049), hematocrit (P = 0.039), Ranson's criteria on admission (P = 0.017), Ranson's criteria after 48 h (P = 0.010), Sequential Organ Failure Assessment score (P = 0.014), and body mass index (P = 0.012) compared to the surviving patients. CONCLUSION: IAP has an impact on the increase of mortality rates in patients with acute pancreatitis.

Boceprevir in genotype 1 chronic hepatitis C: first experiences in Serbia.

INTRODUCTION: The triple therapy which consists of one of the protease inhibitor plus pegylated interferon and ribavirin (P/R) is the standard of care for the treatment of chronic hepatitis C virus (HCV) genotype 1 (G1) infection both in treatment-naïve and experienced patients. OBJECTIVE: The aim of this study was to analyze the efficacy and tolerability of this regime in hospital practice in Serbia. METHODS: From July 2012 to October 2012, 20 previously treated patients with advanced fibrosis and HCV G1 infection were included in the triple antiviral regimen in six referral centers in Serbia. All patients were treated with response guide therapy (RGT) regime according to the boceprevir treatment protocol. During the 4-week lead-in period all patients received peginterferon plus ribavirin. After the lead-in pe- riod boceprevir was added in the dosage of 800 mg three times a day orally.The subsequent treatment varied according to virologic response and fibrosis. During the therapy HCV RNA level was measured at week 4, 8, 12, 24 of the treatment for the assessment of virologic response profile. All patients who completed therapy were assessed at the end of the treatment and at the end of an additional 24-week treatment-free period for a sustained virologic response (SVR). RESULTS: The total of 20 patients with advanced fibrosis was treated. Among patients with an undetectable HCV RNA level at week 8 the rate of SVR was 100%. No patient with decrease in the HCV RNA level < 1 log 10 IU/ml at treatment week 4 achieved SVR. The overall rate of SVR was 55%. The safety profile of the treatment regimen was good. Anemia was reported in 25% of patients. There was no life-threatening treatment adverse event. CONCLUSION: Boceprevir in combination with P/R achieved fairly good SVR rates in patients that were"most difficult to treat"who failed on dual therapy and was effective among patients with cirrhosis.

COLITIS AND "DIAPHRAGM DISEASE" OF THE COLON IN HEMODIALYSIS PATIENT DUE TO PROLONGED USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUG.

INTRODUCTION: The use of non-steroidal anti-inflammatory drugs may lead to stricture of the small intestine and less frequently of the colon. Colonic strictures have not been described in patients on dialysis and the aim of this report is to show the case of dialysis patient who was followed for recurrent and prolonged diarrhea. CASE REPORT: We present the patient on chronic dialysis for 15 years who used non-steroidal anti-inflammatory drugs due to chronic pain and who developed recurrent diarrhea. Diagnosis was made by endoscopy and confirmed by histology. Specific therapy was applied with a good response. CONCLUSION: Although not described in the literature, non-steroidal anti-inflammatory drug-induced colitis and/or diaphragm disease could be a potential reason for recurrent or prolonged diarrhea in dialysis patients.

Morphometric study of uninvolved rectal mucosa 10 cm and 20 cm away from the malignant tumor.

Recently, many details of the interplay between tumor cells and tumor-associated stromal elements leading to the progression of malignant disease were elucidated. In contrast, little is known about the role of uninvolved stromal tissue in the remote surrounding of the malignant tumor. Therefore, we performed a computer-aided morphometric study of rectal mucosa in samples taken 10 cm and 20 cm away from the malignant tumor during endoscopic examination of 23 patients older than 60 years. The samples of rectal mucosa from 10 healthy persons of corresponding age subjected to diagnostic rectoscopy during active screening for asymptomatic cancer were used as control. All structural elements of the rectal mucosa were studied and the number of nucleated cells in the lamina propria per 0.1 mm² of tissue was assessed. Our study revealed a reduced number of cells in the lamina propria of the rectal mucosa 10 cm and 20 cm away from the tumor lesion in both male and female patients. The decreased mucosal height and increased crypt number were registered in female patients 10 cm away from the tumor. The connective tissue of lamina propria showed a disorderly organization: the collagen fibers were frail, loosely arranged and signs of tissue edema were present. Small blood vessels and capillaries were much more frequently seen than in healthy tissue. Our results demonstrate the complex interactions between the cancer and remote mucosal tissue of the affected organ.

[Importance of adherence for efficacy of hepatitis C combined therapy].

INTRODUCTION: Dual antiviral therapy with pegylated interferon alfa-2a and ribavirin leads do sustained elimination of hepatitis C virus infection in over 50% patients with genotypes 1 and 4 and in over 80% with genotypes 2 and 3. In addition to genotype, for predicting success of therapy, important factors are baseline HCV RNA level, age, sex, stage of fibrosis, insulin resistance, degree of fat in liver, and patient's weight and genetics. Also, adherence to therapy could be a very important factor associated with success of therapy. OBJECTIVE: The aim of this study was to assess importance of therapy adherence and reduced doses of pegylated interferon alfa-2a and ribavirin on sustained virological response. METHODS: One hundred and sixteen patients with chronic hepatitis C were analyzed. Sustained virological response was analyzed in relation to whether the patients received a full cumulative dose of pegylated interferon alfa-2a, a full cumulative dose of pegylated interferon alfa-2a and ribavirin, and a full cumulative dose of pegylated interferon alfa-2a and at least 60% the expected cumulative dose of ribavirin. RESULTS: At the end of the follow-up period, sustained virological response was achieved in 26 (96.3%) patients who received full cumulative dose of pegylated interferon alfa-2a and in 66 (74.2%) who did not (p < 0.05). Sustained virological response was achieved in 18 (94.7%) patients who received full cumulative dose of pegylated inteferon alfa-2a and ribavirin, and in 73 (76%) who did not (p < 0.05). Sustained virological response was achieved in 25 (96.2%) patients who received full cumulative dose of pegylated inteferon alfa-2a and at least 60% of cumulative dose of ribavirin and in 66 (74.2%) who did not (p < 0.05). CONCLUSION: These findings indicate that adherence to therapy for chronic hepatitis C is a very important factor for achieving sustained virological response.

Microsatellite instability affecting the T17 repeats in intron 8 of HSP110, as well as five mononucleotide repeats in patients with colorectal carcinoma.

AIM: To investigate mononucleotide markers: BAT-25, BAT-26, NR-21, NR-22 and NR-24 in patients with colorectal cancer (CRC), and the status of HSP110T17, KRAS, BRAF and the MLH1 promoter mutations in microsatellite unstable CRC. METHODS: Genetic assessments were performed on samples obtained following resection of CRC in 200 patients. RESULTS: Allelic variations of HSP110T17 were found in all 18 patients with microsatellite instabilities (MSIs) in at least three markers (high-frequency MSI). By contrast, mutations of HSP110T17 were absent in all 20 patients with no MSI frequency. Eight out of 182 patients with low (instability in one marker) or no frequency MSI had allelic shifts due to polymorphisms of BAT-25 (1.5%), NR-21 (1.75%) and NR-24 (1.5%). BRAF mutations were associated with >5 bp shortening of HSP110T17. CONCLUSION: Patients with high-frequency MSI CRC had allelic variations of HSP110T17. BRAF mutations occur along with greater shortening in HSP110T17 during oncogenesis via the MSI pathway.

The influence of single and combined IL28B polymorphisms on response to treatment of chronic hepatitis C.

BACKGROUND: Three single nucleotide polymorphisms (SNPs) near IL28B gene were shown to be highly predictive of sustained virological response (SVR) in patients with chronic hepatitis C virus (HCV) infection. OBJECTIVES: This study attempted to demonstrate the role of single and combined IL28B polymorphisms (rs8099917, rs12979860 and rs12980275) and other host and viral factors in predicting response to treatment, in Caucasian patients infected with HCV genotype 1. STUDY DESIGN: The IL28B genotypes at 3 SNPs were determined in 106 patients who underwent standard 48-week therapy and out of which 55.7% achieved SVR. RESULTS: Patients carrying genotypes CCrs12979860 or AArs12980275 were 3.5 and 3 times more likely to achieve SVR, respectively. Genotypes GGrs8099917 and TTrs12979860 were identified as predictors of treatment failure. The presence of IL28B profiles including at least one of the favourable genotypes was identified as the most important factor associated with SVR, followed by younger age and lower grade of histological activity. Of all patients who achieved SVR, 88.1% was carrying one of these IL28B profiles. The strongest PPV of single SNPs for achieving SVR was observed for CCrs12979860 (76.9%). The presence of GGrs8099917 showed the strongest NPV of 85.7%. The correlation of SNPs with other host and viral factors revealed association of TTrs8099917 and lower AST levels. CONCLUSIONS: Results of this study confirm that all investigated IL28B polymorphisms are associated with treatment response and that presence of any of the favourable IL28B genotypes can be considered independent pretreatment determinant of the effectiveness of therapy.

Clinical and pathological tools for identifying microsatellite instability in colorectal cancer.

AIM: To assess practical accuracy of revised Bethesda criteria (BGrev), pathological predictive model (MsPath), and histopathological parameters for detection of high-frequency of microsatellite instability (MSI-H) phenotype in patients with colorectal carcinoma (CRC). METHOD: Tumors from 150 patients with CRC were analyzed for MSI using a fluorescence-based pentaplex polymerase chain reaction technique. For all patients, we evaluated age, sex, family history of cancer, localization, tumor differentiation, mucin production, lymphocytic infiltration (TIL), and Union for International Cancer Control stage. Patients were classified according to the BGrev, and the groups were compared. The utility of the BGrev, MsPath, and clinical and histopathological parameters for predicting microsatellite tumor status were assessed by univariate logistic regression analysis and by calculating the sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values. RESULTS: Fifteen out of 45 patients who met and 4 of 105 patients who did not meet the BGrev criteria had MSI-H CRC. Sensitivity, specificity, PPV, and NPV for BGrev were 78.9%, 77%, 30%, and 70%, respectively. MSI histology (the third BGrev criterion without age limit) was as sensitive as BGrev, but more specific. MsPath model was more sensitive than BGrev (86%), with similar specificity. Any BGrev criterion fulfillment, mucinous differentiation, and right-sided CRC were singled out as independent factors to identify MSI-H colorectal cancer. CONCLUSION: The BGrev, MsPath model, and MSI histology are useful tools for selecting patients for MSI testing.

Ultrasound measurement of visceral fat in patients with primary biliary cirrhosis.

BACKGROUND/AIM: Primary biliary cirrhosis (PBC) is a progressive, chronic liver disease with elevated serum lipids, but it is unclear whether hyperlipidemia in PBC patients is associated with atherosclerosis. Metabolic syndrome promotes development of atherosclerotic cardiovascular disease related to abdominal type obesity and insulin resistance. The aim of our study was to assess abdominal adiposity in patients with PBC. METHODS: The study included 40 patients with PBC and 50 healthy controls. Age, sex and anthropometric measurements (weight, height, body mass index and waist circumference) were registered for all patients and controls. We used ultrasonography to measure subcutaneous (SF) and visceral fat (VF) diameter, subcutaneous area (SA) and visceral area (VA), as well as perirenal fat diameter (PF). RESULTS: Values of SF, VF and PF thicknesses in PBC patients were 19.23 +/- 5.85 mm, 10.92 +/- 3.63 mm, and 7.03 +/- 1.82 mm, respectively. In controls these measurements were 22.73 +/- 6.70 mm, 16.84 +/-5.51 mm and 10.50 +/- 2.70 mm respectively. In PBC patients SA and VA were calculated to 983.64 +/- 322.68 mm2 and 403.64 +/- 166.97 mm2 and in controls 1124.89 +/- 366.01 mm2 and 720.57 +/- 272.50 mm2 respectively. Significant difference was found for VF, VA and RF values. CONCLUSIONS: Considering that the amount of visceral fat plays an important role in development of metabolic syndrome and cardiovascular diseases, we concluded that the lower amount of visceral fat in PBC patients could be related to lower incidence of cardiovascular events, despite hyperlipidemia.

Neuroendocrine gastric carcinoma in a young patient.

BACKGROUND: Neuroendocrine tumors cover a spectrum of neoplasms showing wide variations in their clinicopathological and pathogenetic features, as well as prognosis. They may develop throughout the whole gastrointestinal tract. CASE REPORT: We described a case of gastric neuroendocrine carcinoma in a 29-year-old male. The patient presented with chronic continuous abdominal pain and weight loss over a 6-month period. Preoperative diagnosis, operative findings, histology and immunohistochemistry of the tumor confirmed the diagnosis of the rare neuroendocrine gastric carcinoma, stage T2N1. CONCLUSION: Case reports of this rare tumor are important, because of the paucity of studies noted in the gastrointestinal literature as a result of poor identification prior to the advent of modern immunohistochemistry. Significance of accurately diagnosing gastrointestinal neuroendocrine tumors is crucial for an appropriate treatment.

[Splenomegaly and thrombocytopenia in patients with liver cirrhosis].

BACKGROUND/AIM: Splenomegaly is a frequent finding in patients with liver cirrhosis and portal hypertension and may cause hypersplenism. The occurrence of thrombocytopenia in those patients can be considered as an event with multiple etiologies. Two mechanisms may act alone or synergistically with splenic sequestration. One is central which involves either myelosuppression because of hepatitis viruses or the toxic effects of alcohol abuse on the bone marrow. The second one involves the presence of antibodies against platelets. It also depends upon the stage and etiology of liver disease. The aim of the study was to investigate a correlation between the platelet count and spleen size and the risk factors for thrombocytopenia in patients with liver cirrhosis. METHODS: We studied 40 patients with decompensated liver cirrhosis who were hospitalized in the Department of Gastroenterohepatology. The liver function was graded according to Child Pugh score. Spleen size was defined ultrasonografically on the basis of craniocaudal length. Suspicion of portal hypertension was present when longitudinal spleen length was more than 11 cm. Thrombocytopenia was determined by platelet count under 150,000/mL. RESULTS: We did not find any significant correlation between hepatic dysfunction and spleen size (p = 0.9), and between hepatic dysfunction and thrombocytopenia (p = 0.17). Our study did not find any significant correlation between spleen size and peripheral platelet count (p = 0.5), but we found a significant correlation between thrombocytopenia and etiology of cirrhosis - decreased platelet count was more common among patients with cirrhosis of alcoholic etiology than in other etiologies of cirrhosis (p = 0.001). CONCLUSION: According to our study, liver cirrhosis, portal hypertension and thrombocytopenia could be present even in the absence of enlarged spleen suggesting the involvement of other mechanisms of decreasing platelet account.

Old age as a privilege of the "selfish ones".

In the past couple of centuries, scientists proposed great number of aging theories but neither of them appears to be fully satisfactory. In the statistical sense, we are dealing with an even greater challenge because large array of factors affects the aging process. Although at this point the most of these factors are well known, it is the very fact of their innumerability that complicates approaches to the issue at hand. Both in life and in medicine, the cause behind an effect can rarely be unequivocally determined. Thus, it appears that through out human history longevity has been primarily affected by eradication of diseases, especially by eradication of infectious diseases and introduction of the vaccines. For that reason, maybe we should not be referring to this issue as the «fountain of youth¼ but rather as the «vaccine of youth¼. The postulate that genetic instability is the precipitating factor both of aging and cancer has withstood many tests and keeps on being reaffirmed. For this reason, it is legitimate to pose a question of whether long-lived individuals may be those with «selfish¼ genes and more stable genetic material. They certainly cannot avoid aging, but aging in such individuals could be delayed due to steady character of their genome, which is less susceptible to mutations. On the population level, they constitute minority because stable genome would represent an obstacle to successful evolution of the species. If this was not the case, we might not be writing all these texts today.

Morphometric study of healthy jejunal and ileal mucosa in adult and aged subjects.

Small intestine mucosa is often affected with malabsorptive, autoimmune and inflammatory pathological processes. However, morphometric data on the healthy human small intestine mucosa, especially ileum, are scarce. We aimed to obtain histoquantitative data on the healthy jejunal and ileal mucosa and assess the effects of gender and ageing on these parameters. Computer-aided morphometric analysis was performed on 24 jejunal and 25 ileal biopsy samples collected upon routine endoscopy screening of healthy persons with a family history of intestinal malignancy. Subjects were distributed in four groups according to age and sex: adult (<60 years) and elderly (>60 years) males, and adult (<60 years) and elderly (>60 years) females. Results were statistically analyzed with Mann-Whitney U test. Jejunal mucosal thickness was significantly reduced in elderly subjects (p<0.05), especially in elderly females compared to adult ones (p<0.05). Jejunal villi were significantly wider in adult than in the elderly subjects (p<0.05), whereas ileal villi were significantly wider in elderly compared to adult subjects (p<0.01) and in male compared to female subjects (p<0.05). No statistically significant differences were found in other histoquantitative parameters (mucosa epithelium height, crypt numerical density, villous height, crypts and villous perimeter, diameter and epithelium height) of jejunal and ileal mucosa. This study provides complete morphometric data on the healthy human jejunum and the first relevant data on the healthy ileal mucosa, thus representing a valuable morphometric reference for future histoquantitative studies of human small bowel mucosa in both healthy and disease affected individuals.