The long-term effect on surgery-free survival of biological compared to conventional therapy in Crohn's disease in real world-data: a retrospective study.

BACKGROUND: The introduction of biological drugs has led to great expectations and growing optimism in the possibility that this new therapeutic strategy could favourably change the natural history of Inflammatory Bowel Disease (IBD) and, in particular, that it could lead to a significant reduction in surgery in the short and long term. This study aims to assess the impact of biological versus conventional therapy on surgery-free survival time (from the diagnosis to the first bowel resection) and on the overall risk of surgery in patients with Crohn's disease (CD) who were never with the surgical option. METHODS: This is a retrospective, double-arm study including CD patients treated with either biological or conventional therapy (mesalamine, immunomodulators, antibiotics, or steroids). All CD patients admitted at the GI Unit of the S. Salvatore Hospital (L'Aquila. Italy) and treated with biological therapy since 1998 were included in the biological arm. Data concerning the CD patients receiving a conventional therapy were retrospectively collected from our database. These patients were divided into a pre-1998 and post-1998 group. Our primary outcome was the evaluation of the surgery-free survival since CD diagnosis to the first bowel resection. Surgery-free time and event incidence rates were calculated and compared among all groups, both in the original population and in the propensity-matched population. RESULTS: Two hundred three CD patients (49 biological, 93 conventional post-1998, 61 conventional pre-1998) were included in the study. Kaplan-Meier survivorship estimate shows that patients in the biological arm had a longer surgery-free survival compared to those in the conventional arm (p = 0.03). However, after propensity matching analysis, conducted on 143 patients, no significant difference was found in surgery-free survival (p = 0.3). A sub-group analysis showed shorter surgery-free survival in patients on conventional therapy in the pre-biologic era only (p = 0.02; Hazard Ratio 2.9; CI 1.01-8.54) while no significant difference was found between the biologic and conventional post-biologic groups (p = 0.15; Hazard Ratio 2.1; CI 0.69-6.44). CONCLUSION: This study shows that the introduction of biological therapy has only a slight impact on the eventual occurrence of surgery in CD patients over a long observation period. Nevertheless, biological therapy appears to delay the first intestinal resection.

The connection between diverticulosis and colonic superficial neoplastic lesions in patients who underwent screening colonoscopy.

PURPOSE: If could be a potential pathophysiological connection between colonic diverticula and colonic superficial neoplastic lesions, beyond the shared risk factors, has been a subject of debate in the last years. This study tries to evaluate the association between diverticulosis and colonic neoplastic lesions. METHODS: This is a cross-sectional study including asymptomatic patients who underwent a screening colonoscopy (patients with a positive fecal occult blood test under the regional program of colorectal cancer (CRC) screening), surveillance after polypectomy resection, or familiarity (first-degree relatives) between 2020 and 2021 to evaluate the association between diverticula and colonic polyps. A multivariate analysis with multiple logistic regression and odds ratio (OR) to study the independent association between adenomas and adenocarcinomas was performed. RESULTS: One thousand five hundred one patients were included. A statistically significant association between adenomas or CRC alone and colonic diverticula was found (p = 0.045). On a multivariate analysis of demographic (age, gender) and clinical parameters (familiarity for diverticula and adenoma/CRC), only age was significantly associated with the development of colorectal adenomas or cancer (OR 1.05, 95% CI 1.03-1.07, p < 0.0001). CONCLUSIONS: This study showed a statistically significant association between diverticula and colonic adenomas. However, it is impossible to establish a cause-effect relationship due to the intrinsic characteristics of this study design. A study with a prospective design including both patients with diverticulosis and without colonic diverticula aimed at establishing the incidence of adenoma and CRC could help to answer this relevant clinical question, since a potential association could indicate the need for closer endoscopic surveillance.

Evaluation of factors associated with trust in telemedicine in patients with inflammatory bowel disease during COVID-19 pandemic: a multicenter cross-sectional survey.

OBJECTIVE: Telemedicine (TM) has had a powerful impact in recent years, particularly on managing chronic diseases such as inflammatory bowel disease (IBD). Knowing patients' expectations and concerns is essential to increase their confidence in this mode of medical care. PATIENTS AND METHODS: We interviewed a large cohort of IBD patients enrolled at two Italian tertiary referral centers to investigate their trust in TM. RESULTS: A total of 376 patients completed the survey and were included in the study: 293 (77.9%) considered TM valuable for managing their disease, and 307 (85%) wanted to have TM service at their center. However, only 99 patients (26.3%) believed that TM guarantees the same level of care as the in-person visit. Among the socio-demographic variables, those independently associated with trust in TM were the higher education qualification (p=0.02) and the level of competence in information and communication technologies (ICT) (p=0.03). CONCLUSIONS: Our findings highlighted the importance of equipping IBD patients with basic ICT skills to utilize TM services and increase their confidence in ICT with the help of caregivers. Additionally, to improve the perceived value of TM, it will be helpful to use additional tools such as telemonitoring of disease activity using patients' reported outcomes or remote measurement of fecal calprotectin.

Worse impact of second wave COVID-19 pandemic in adults but not in children with inflammatory bowel disease: an Italian single tertiary center experience.

OBJECTIVE: From September 2020, a second wave of COVID-19 pandemic started. We aimed at exploring the impact of SARS-CoV-2 infection in IBD patients during the two waves. PATIENTS AND METHODS: All IBD patients with a confirmed diagnosis of SARS-CoV-2 infection were enrolled. They were sorted into two groups (those infected before September 2020, and those from September 2020 to January 2021) and compared by demographic and clinical data. RESULTS: Twenty-five patients (out of about 600 with a follow-up visit) were infected with SARS-CoV-2 (4.1%). Sixteen were male and the mean age was 46.5 ± 14.3 years (range 24-74). Six were smokers and 11 had comorbidities; 2 were on steroids and 17 on immunosuppressants or biologics. Three patients (12%) needed hospitalization and other three patients were treated with azithromycin, steroids and LMWH, all of them during the second wave. No patient died or developed any sequelae. Two subjects were infected during the first wave (0.3 vs. 3.83, p<0.0001). Non-significant differences were found between the two groups. CONCLUSIONS: A higher number of IBD patients were infected during the second wave. No patient developed a severe form of pneumonia, even those treated with immunosuppressants or biologics. No risk factor for hospitalization was found.

Is mesalazine treatment effective in the prevention of diverticulitis? A review.

Diverticulitis is the most severe form of Diverticular disease (DD). An effective treatment strategy for its prevention has not yet been defined. This review aimed to provide a viewpoint on the role of mesalazine, also note as 5-aminosalicylic acid (5-ASA), in the prevention of diverticulitis. A systematic electronic search of relevant articles was performed using PubMed, Embase, Scopus, and Cochrane. Randomized controlled trials (RCTs), open trials, and retrospective studies, published between January 1999 and January 2020, were identified. Twelve eligible studies that analyzed primary or secondary outcomes of diverticulitis were included. The population included patients with symptomatic uncomplicated diverticular disease (SUDD), or patients with a history of diverticulitis. All studies compared 5-ASA to placebo, rifaximin, or other treatments. Two studies, including 359 patients, assessed the efficacy of 5-ASA in preventing the first appearance of diverticulitis in patients with SUDD. Of these, one showed that 5-ASA was effective, and one did not. Ten studies, including 2.995 patients, assessed the efficacy of 5-ASA treatment in preventing the recurrence of diverticulitis in patients with a history of diverticulitis. Four studies showed that 5-ASA had a certain degree of efficacy. All four RCTs demonstrated that 5-ASA did not significantly reduce the rate of diverticulitis recurrence. In a retrospective trial, 5-ASA was less effective than rifaximin in preventing diverticulitis recurrence. In an open trial, there was no difference between 5-ASA and probiotic treatment. Overall, there is currently conflicting evidence regarding the efficacy of 5-ASA treatment in the prevention of diverticulitis and further RCTs are needed.

Systematic review: interferon-free regimens for patients with HCV-related Child C cirrhosis.

BACKGROUND: It is unclear whether the efficacy and long-term outcome of treating patients with hepatitis C virus (HCV)-positive cirrhosis with the new protease inhibitors will extend to those with Child C cirrhosis. AIM: To assess the effectiveness of the interferon-free regimens in Child C cirrhotic patients with HCV infection. METHODS: A systematic Medline search was conducted to retrieve studies describing the treatment of Child C patients with direct-acting agents. Citations from identified studies were cross-referenced and abstracts from European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Disease (AASLD) meetings were checked. Extracted data were evaluated using a meta-analysis to calculate a weighted response rate. RESULTS: Seven full-text records and two conference abstracts were retained for analysis from the 649 records identified. Data from an Italian real-life trial were also interrogated. Information on treatment outcome was available for 228 of the 240 Child C patients evaluated in the 10 trials. Overall, the weighted mean sustained virological response (SVR12) was 74.9% (95% CI: 65.6-82.4%). Neither duration of treatment (24 or 12 weeks), nor addition of ribavirin influenced these rates. The weighted SVR12 was 65.4% (95% CI: 46.8-80.2) after sofosbuvir/simeprevir, 76.0% (95% CI: 54.4-89.3%) after sofosbuvir/daclatasvir and 83.0% (95% CI: 73.4-89.6) after sofosbuvir/ledipasvir. Some studies did not provide information on the rate of post-treatment relapse or functional improvement. However, in those studies that did provide such data, a relapse was documented in 12.1% of patients and an improvement of ≥2 points on the model for end-stage liver disease (MELD) score in 61.1% of patients. CONCLUSION: The improvement in MELD scores strongly suggests HCV-positive patients with Child C cirrhosis should be treated with these agents.

HBsAg kinetics in chronic hepatitis D during interferon therapy: on-treatment prediction of response.

BACKGROUND: Therapy of chronic hepatitis D with Interferon is successful when testing for HDV-RNA turns negative. This end-point is disputed. AIM: To assess the role of serum hepatitis B surface antigen (HBsAg) in the clearance of HDV-RNA in pegylated interferon (Peg-IFN)-treated chronic hepatitis D (CHD). METHODS: Sixty-two patients with CHD, treated with Peg-IFN, were considered. The patients belonged to three groups: 14 patients cleared the HBsAg and HDV-RNA (responders, R), 12 cleared the HDV-RNA remaining positive for HBsAg (partial responders, PR) and 36 cleared neither the HBsAg nor the HDV-RNA (nonresponders, NR). RESULTS: In responders, at baseline the median value (mv) of HBsAg and HDV-RNA was 1187 and 188 663 IU/mL. By month 6 of therapy, HBsAg declined to less than 1000 IU/mL and HDV-RNA was undetectable in 12 patients. In NR, the pre-therapy median value of HBsAg and HDV viremia was 6577 and 676 319 IU/mL. There was no significant reduction of antigen at month 6; after a decline, HDV-RNA rebounded to baseline levels. In PR, the median value of baseline HBsAg was 7031 IU/mL; it declined at month 6 in the majority. HDV-RNA progressively declined from an initial median value of 171 405 IU/mL. HBsAg <1000 IU/mL at month 6 discriminated responders and PR from NR (P < 0.001). By ROC curve, the threshold of 0.105 log reduction of HBsAg associated with 1.610 log reduction of HDV-RNA from baseline to month 6 predicted the clearance of this marker. CONCLUSIONS: A reduction of serum HBsAg is mandatory for the definitive clearance of the HDV-RNA. Quantitative HBsAg may predict the long-term response to Peg-IFN therapy and provide a guide to prolong or stop treatment.

Renal tuberculosis: a case report.

Tuberculosis or TB (tubercle bacillus) remains a major public health problem in developing countries. Over the last decades extrapulmonary locations of the disease have become more frequent due to the increased prevalence of acquired immune deficiency syndrome and the increase number of organ transplants. The urogenital localization represents about 27% of all extra-pulmonary localizations of TB and may be due either to a disseminated infection or to a primitive genitourinary localization. The majority of patients, has pyuria, sometimes with hematuria. The diagnosis of urinary tuberculosis is based on the finding of pyuria in the absence of infection by common bacteria. The initial medical treatment includes isoniazide, rifampicin, pyrazinamide, ethambutol and streptomycin. This disease should be suspected in patients with unexplained urinary tract infections, especially if immunocompromised and/or coming from endemic areas.

HCV genotype 1 subtypes (1a and 1b): similarities and differences in clinical features and therapeutic outcome.

AIM: To evaluate similarities and differences in HCV-1 subtypes 1a and 1b in the presenting clinical features and the response to peg-interferon and ribavirin (Peg/RIBA). PATIENTS AND METHODS: A total of 1,233 naïve patients with HCV genotype-1 infection, 159 (13%) with subtype 1a and 1,074 (87%) with subtype 1b were treated with Peg-IFN/RIBA at 12 Italian centers. Covariates included in the logistic model were age, gender, BMI, serum alanine aminotransferase, serum gamma-glutamiltranspeptidase (γGT), platelets counts, liver fibrosis, the occurrence of type 2 diabetes, baseline viremia, and IL28B genotype. RESULTS: At multivariate analysis, baseline characteristics differentiating patients with HCV-1a versus HCV-1b were young age, male gender, no F4 fibrosis, and no diabetes. SVR was achieved by 37% of patients with subtype 1b and 45% of those with subtype 1a, a nonsignificant difference of 8% (p = 0.069). In patients with subtype 1a, predictors of SVR were IL28B CC (OR 5.78, CI 1.98-16.83), RVR (OR 4.18, CI 1.66-10.55), female gender (OR 2.83, CI 1.83-6.78), and HCVRNA (OR 0.55, CI 0.32-0.96). In patients with subtype 1b, the ranking of predictors was levels RVR (OR 6.49, CI 4.32-9.73), IL28B CC (OR 3.32, CI 2.15-4.58), γGT (OR 1.59, CI 0.14-2.22), HCVRNA (OR 0.61, CI 0.47-0.79), and age (OR 0.01, CI 0.02-0.42). CONCLUSION: In Italy HCV-1 subtype 1a prevails in young male patients with less advanced liver damage, findings that imply a more recent spreading of the infection with this viral strain. The two HCV-1 subtypes appear equally responsive to Peg-IFN/RIBA, with IL28B genotyping and monitoring of RVR mostly influencing the therapeutic response.

Influence of preoperative biliary drainage on surgical outcome after pancreaticoduodenectomy: single centre experience.

PURPOSE: Controversy prevails on the impact of preoperative biliary drainage (PBD) on postoperative complications and clinical outcome of pancreatic cancer. We determined whether PBD is associated with increased morbidity and mortality rates after pancreaticoduodenectomy. METHODS: A total of 131 consecutive patients who underwent pancreaticoduodenectomy (93 jaundiced, 38 with no jaundice) were included in this study. Overall, 57 % of jaundiced patients underwent PBD, while 43 % were not drained. The impact of PBD on postoperative morbidity and mortality was evaluated by means of logistic regression analysis. The Kaplan-Meier method was applied to determine the effect of PBD on survival of patients with malignant lesions. RESULTS: Mortality and morbidity rate was 3 % and 54.6 %, respectively. PBD was demonstrated to be the unique predictor of complications (odds ration [OR] = 10.18; 95 % confidence interval [CI], 3.65-28.39, p < 0.001). The jaundiced patients who were drained exhibited high frequencies of wound infection (p < 0.001), post-pancreatectomy haemorrhage (p = 0.0185) and hyperglycaemia (p < 0.001). In addition, an increased frequency of pancreatic fistula emerged among drained patients compared to those who were not drained (p = 0.036). PBD did not affect survival of patient with malignant lesions. CONCLUSIONS: With the exception of the classical indications, PBD should be carefully evaluated in patients with resectable pancreatic cancer.

Long-term outcome of hepatitis B virus-related Chronic Hepatitis under protracted nucleos(t)ide analogues.

Long-term outcome of patients with chronic hepatitis B virus (HBV) infection under continuous nucleos(t)ide analogues (NUCs) has been poorly elucidated. We enrolled 121 anti-HBe-positive patients into a prospective surveillance programme while on (>36 months) NUCs therapy. HBV-DNA clearance, add-on therapy and safety were evaluated. Development of cirrhosis, events of liver decompensation and hepatocellular carcinoma (HCC) during the follow-up were the main endpoints, as the complication-free survival. At baseline, 74 patients (61%) had chronic hepatitis, the remainders a cirrhotic liver. HBV-DNA levels >38 000 IU/mL were discovered in 103 patients. At enrolment, 79 patients were naïve to NUCs treatment. Lamivudine monotherapy (n = 70) or a different NUC (n = 51) was administered. At month 6 of therapy, HBV-DNA clearance was documented in 88 patients (73%). Treatment schedule was modified in 52 patients due to breakthrough or suboptimal response. During a mean follow-up of 6 ± 3 years, viral clearance was achieved in the majority of patients. Ten of 74 patients (13.5%) with chronic hepatitis progressed to cirrhosis, 1 patient developed a HCC. In the 47 patients with cirrhosis at presentation, HCC occurred in 14 (30%) and liver decompensation in 5 (11%). The 5 and 10-year event-free survivals were, respectively, 89.3% (95% CI, 81.7 -96.9) and 75.6% (95% CI, 61.5 -89.7) for patients with chronic hepatitis, and 70.2% (95% CI, 56.3 -84.1) and 40.4% (95% CI, 16.9 -63.9) for those with cirrhosis. Protracted, effective treatment with oral NUCs affects the natural history of chronic HBV infection by reducing the incidence of cirrhosis and risk of complications, but does not guarantee against the development of HCC in cirrhosis at presentation.

Estimates of HCV-1 patients attaining RVR following dual therapy with peg-interferon and ribavirin.

BACKGROUND: Given the significant side-effects and healthcare costs associated with telaprevir- or boceprevir-combination therapy, identifying patients likely to respond to dual therapy peg-interferon (Peg-IFN)/ribavirin is highly desirable. Since the perception of how large the pool of patients who may achieve rapid virologic response (RVR) is vaguely ascertained, we searched the literature for this information. METHODS: Studies on patients treated with Peg-IFN/ribavirin were identified by searching MEDLINE and analyzed by meta-analysis. The primary end point was weighted estimates of RVR. The influence on race/ethnicity, baseline viremia, type of Peg-IFN, ribavirin dosage, and significant hepatic fibrosis on the results was evaluated. RESULTS: Across 38 studies on 13,219 patients, the fraction of RVR patients was 19.6 %. The only baseline factor influencing RVR was race/ethnicity, with higher rates in Asian (26.7 %) and Caucasian patients (22.5 %). Of the 1,735 RVR patients, 85.1 % attained sustained virologic response (SVR). In these, SVR was influenced by ribavirin dose (86.8 vs. 72.8 % for high or low), type of Peg-IFN (91.8 % for alpha-2b vs. 82.9 % for alpha-2a), and treatment duration (91.7 % for 48 weeks vs. 79.4 % for 24 weeks). CONCLUSIONS: One fifth to one fourth of hepatitis C virus genotype 1 (HCV-1) patients can be safely treated with dual therapy of Peg-IFN/ribavirin, and may be spared from cost and inconvenience of regimens considering the addition of HCV protease inhibitors.

Clock gene expression levels and relationship with clinical and pathological features in colorectal cancer patients.

The clock gene machinery controls cellular metabolism, proliferation, and key functions, such as DNA damage recognition and repair. Dysfunction of the circadian clock is involved in tumorigenesis, and altered expression of some clock genes has been found in cancer patients. The aim of this study was to evaluate the expression levels of core clock genes in colorectal cancer (CRC). Quantitative real-time polymerase chain reaction (qPCR) was used to examine ARNTL1, CLOCK, PER1, PER2, PER3, CRY1, CRY2, Timeless (TIM), TIPIN, and CSNK1? expression levels in the tumor tissue and matched apparently healthy mucosa of CRC patients. In the tumor tissue of CRC patients, compared to their matched healthy mucosa, expression levels of ARNTL1 (p=.002), PER1 (p=.002), PER2 (p=.011), PER3 (p=.003), and CRY2 (p=.012) were lower, whereas the expression level of TIM (p=.044) was higher. No significant difference was observed in the expression levels of CLOCK (p=.778), CRY1 (p=.600), CSNK1 (p=.903), and TIPIN (p=.136). As to the clinical and pathological features, a significant association was found between low CRY1 expression levels in tumor mucosa and age (p=.026), and female sex (p=.005), whereas high CRY1 expression levels in tumor mucosa were associated with cancer location in the distal colon (p?=?.015). Moreover, high TIM mRNA levels in the tumor mucosa were prevalent whenever proximal lymph nodes were involved (p= .013) and associated with TNM stages III-IV (p=.005) and microsatellite instability (p=.015). Significantly poorer survival rates were evidenced for CRC patients with lower expression in the tumor tissue of PER1 (p=.010), PER3 (p= .010), and CSNKIE (p=.024). In conclusion, abnormal expression levels of core clock genes in CRC tissue may be related to the process of tumorigenesis and exert an influence on host/tumor interactions.

Common themes in glycoconjugate assembly using the biogenesis of O-antigen lipopolysaccharide as a model system.

The biosynthesis of glycoconjugates is remarkably conserved in all types of cells since the biochemical reactions involved exhibit similar characteristics, which can be summarized as follows: (a) the saccharide moiety is formed as a lipid-linked, membrane-associated glycan; (b) the lipid component in most cases is a polyisoprenoid phosphate; (c) the assembly of the lipid-linked saccharide intermediate depends on reactions taking place at both sides of the cell membrane, which requires the obligatory transmembrane movement of amphipathic molecules across the lipid bilayer. These general characteristics are present in the biosynthesis of the O-antigen component of the bacterial lipopolysaccharide, which serves as a model system to investigate the molecular and mechanistic basis of glycoconjugate synthesis, as summarized in this mini-review.

Unawareness of HBV infection among inpatients in a Southern Italian hospital.

Hepatitis B virus (HBV) infection may run undetected. Unawareness of an ongoing infection delays the diagnosis of HBV-related liver disease and favours the spread of the virus. We have evaluated among hepatitis B surface antigen-positive (HBsAg) inpatients admitted to a Southern Italian hospital the proportion of those aware of their carrier status and correlated the status to signs of liver disease. All patients admitted to the San Giovanni Rotondo Hospital from March 2008 to July 2009 were tested for HBV and hepatitis C virus (HCV) markers, and those positive for HBsAg were interviewed and underwent examinations for liver function and abdominal ultrasound. Overall, of 25,000 patients admitted during the observation period 311 (1.2%) were positive for HBsAg, most of them (98%) being anti-HBe positive. HCV and HDV co-infections were ascertained in 2.9% and 0.6% of cases, respectively. Two hundred and fifty-three subjects (81%) agreed to undergo further investigation, 132 of them (52%) were HBV-DNA positive. One hundred and two patients (40.3%) were unaware of their infection; this was encountered among 29% of HBV-DNA-positive and 52% of HBV-DNA-negative subjects (P < 0.01). Subjects already aware of their infection were more likely to present with abnormal alanine aminotransferase (ALT) levels (27%vs 15%), serological presence of HBV-DNA (63.6% vs. 36%) and liver cirrhosis (30%vs. 13%). A high proportion of HBsAg-positive patients (40.3%) were unaware of their infection, which had evolved to the stage of liver cirrhosis in a consistent percentage of them.

The -A2518G polymorphism of monocyte chemoattractant protein-1 is associated with Crohn's disease.

OBJECTIVES: The -A2518G variation in monocyte chemoattractant protein (MCP)-1 gene promoter has been associated with autoimmune diseases. Our aim was to investigate the gene polymorphism and MCP-1 plasma levels in patients with inflammatory bowel disease (IBD). METHODS: Family-based and case-control association analyses of the -A2518G polymorphism (rs1024611) were performed in 1,936 subjects (770 patients with Crohn's disease (CD), 316 patients with ulcerative colitis (UC), 302 healthy relatives (151 CD trios), and 548 healthy controls (HCs)). Extensive gene sequencing was also undertaken, and a further six single-nucleotide polymorphisms (SNPs) were genotyped in 435 CD patients and 189 HCs. MCP-1 protein plasma levels in 234 CD patients, 117 UC patients, and 108 HCs were assessed by an immunosorbent assay. RESULTS: Five SNPs in strong linkage disequilibrium (D'>0.85) were associated with CD, with the strongest signal found at the -A2518G SNP. The frequency of the G allele was significantly lower in CD patients (22.1%), compared with HCs (29.8%), both at case-control (P=6 x 10(-6)) and at transmission disequilibrium test analyses (T/U 41/88; P=4 x 10(-4)). No difference in alleles (26.1%) and genotype frequencies were found in UC patients. MCP-1 plasma levels in CD and UC patients were similar to those in HCs (P=0.38), irrespective of disease activity, or MCP-1 genotypes. However, 30 CD (13%) and 20 UC patients (17%) with extensive colonic involvement had plasma levels significantly higher than HCs (P=0.02). CONCLUSIONS: The -A2518G polymorphism seems to be associated with CD but does not influence MCP-1 plasma levels, which in contrast are increased in UC and CD with extensive colonic involvement.

Sustained virological responses following standard anti-viral therapy in decompensated HCV-infected cirrhotic patients.

BACKGROUND: Little data is available about predictors of sustained virological response (SVR) during anti-viral therapy of patients with decompensated HCV cirrhosis. AIMS: To determine whether rapid and early virological responses (RVR and EVR) could predict SVR and help optimize treatment in these patients. METHODS: A total of 94 cirrhotics underwent treatment with peg-interferon alfa-2b (1.5 microg/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for genotypes 1/4 or genotypes 2/3, respectively. RESULTS: Overall, SVR was achieved in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 (P < 0.01). At treatment week 4, 34 patients had undetectable HCV-RNA, 10 with genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%), 6 and 18 with genotypes 1 and non-1. At the multivariate analysis, only EVR, genotypes 2 and 3, and adherence to full course and dosage of therapy retained their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0-217.3), 4.2 (95% CI 1.2-15.3) and 9.1 (95% CI 2.2-38.0), respectively. CONCLUSION: In decompensated cirrhotic patients, anti-viral therapy with current regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment ought to be pursued among patients who attain an EVR, and maintain a full course and dosage of therapy.

Early discontinuation of ribavirin in HCV-2 and HCV-3 patients responding to Peg-interferon alpha-2a and ribavirin.

Guidelines for the treatment of patients infected with hepatitis C virus of genotypes 2 and 3 (HCV-2 and HCV-3, respectively) recommend a 24-week course of Peg-interferon (Peg-IFN) alpha-2a combined with ribavirin, despite 50% of patients in registration trials attaining a sustained virologic response (SVR) following Peg-IFN alpha-2a monotherapy. The aim of this study was to delineate patient characteristics that might help to identify individuals likely to benefit from ribavirin discontinuation. One hundred and forty-four HCV-2- and HCV-3-infected patients initiated Peg-IFN alpha-2a (180 microg/week) and ribavirin (1000 or 1200 mg/day); those with viral clearance at week 4 were randomized to either Peg-IFN alpha-2a monotherapy (n = 59) or continuing combination therapy (n = 61) until week 12. Overall, all but one patient with a rapid virologic response (RVR) responded by the end of therapy and the overall SVR rates were lower after discontinuation of ribavirin (54%vs 82%; P < 0.001). In RVR patients who discontinued ribavirin, low baseline viraemia helped predict SVR (odds ratio 11.2, 95% CI 2.7-47.1). SVR rates were similar in patients receiving mono- or combination therapy with low (< or =300,000 IU/mL) and intermediate viraemia (86%vs 81% and 70%vs 71%, 86% refers to low viraemic patients receiving monotherapy and 81% to those receiving combination therapy. Similarly, 70% refers to patients with intermediate viraemic levels receiving monotherapy and 71% to those receiving combination therapy), but different in those with high (>700,000 IU/mL) viraemia (37%vs 88%; P = 0.004). Thus in HCV-2- and HCV-3-infected patients, withdrawal of ribavirin and continuation of Peg-IFN alpha-2a monotherapy may be appropriate to attain an SVR, providing viraemia is cleared early during therapy and associated with low baseline viral load. These results warrant future investigations, as discontinuing ribavirin could lead to considerable savings in cost and quality of life related to over-treatment.

Polymorphism of the IRGM gene might predispose to fistulizing behavior in Crohn's disease.

OBJECTIVES: Recently, genome-wide association analyses have identified single nucleotide polymorphisms in the IRGM gene (rs1000113 and rs4958847) as strong candidate susceptibility factors for Crohn's disease (CD). The aim of our study was to test whether these variants are associated with inflammatory bowel disease (IBD) in adult- and childhood-onset Italian patients. METHODS: Allele and genotype frequencies of rs1000113 and rs4958847 were determined in 823 CD (265 younger than 19 years at diagnosis), 353 ulcerative colitis (UC) (130 younger than 19 years at diagnosis), and 578 controls. Genotype distributions were examined both within IBD clinical sub-phenotypes and CARD15 genotypes. RESULTS: rs1000113 and rs4958847 were both associated with adult-onset (P=2 x 10(-4); P=2.5 x 10(-3), respectively) and childhood-onset (P=4 x 10(-4); P=8 x 10(-3), respectively) CD cohorts. Similarly, the genotype frequencies remained significantly different for both variants (adult rs1000113, P=1 x 10(-4); rs4958847, P=1 x 10(-3); pediatric rs1000113, P=2.3 x 10(-4); rs4958847, P=9.6 x 10(-3)). At logistic regression, the rs4958847 polymorphism was associated with fistulizing behavior (P=0.037, OR=1.54, CI=1.02-2.31) and perianal fistulas (P=0.045, OR=1.55, CI=1.01-2.38). Conversely, no association with UC and sub-phenotypes was shown. CONCLUSIONS: We replicated the previously reported associations between CD and rs1000113 and rs4958847, confirming that IRGM is a susceptibility locus only for CD, either adult- or early-onset in the Italian population; furthermore, we have also shown its influence on specific clinical features (fistulizing disease).

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

BACKGROUND: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. METHODS: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. RESULTS: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. CONCLUSION: DLG5 30Q is associated with a small reduction in risk of CD in women.