Journal of gastrointestinal and liver diseases : JGLD最新文献

Background and aims: Adipokines are among the biomarkers that have been studied in chronic pancreatitis (CP), as well as in pancreatic cancer (PC). So far, the existing findings are contradictory and inconclusive. Therefore, we assessed the levels of three major adipokines in CP in comparison to controls and PC, adiponectin, leptin, and resistin.

Methods: A systematic electronic search was carried out in November 2022 using PubMed, Embase, and Scopus, reviewing observational studies. By using the Newcastle-Ottawa Scale, the included studies' quality was evaluated (NOS). In the examination of the estimated overall effect size, we employed the random-effects model in conjunction with the mean difference (MD) analysis. The MD with 95% confidence interval (CI) served as the primary summary outcome.

Results: Our systematic review included a total of 14 studies, out of which nine were considered in our meta-analysis. A significant MD related to leptin levels in CP patients vs. controls (-1.299, 95%CI: -2.493 - -0.105), resistin levels in CP patients vs. controls (8.356, 95%CI: 3.700-13.012), and adiponectin levels in PC patients vs. controls (11.240, 95%CI: 5.872-16.60) was reported. However, no significant MD was reported in leptin levels between CP vs. PC patients (-0.936, 95%CI: -3.325-1.454), as well as adiponectin levels in CP patients vs. controls (0.422. 95%CI -5.651-6.535]) and in CP vs. PC patients (-6.252, 95%CI -13.269-0.766).

Conclusions: CP was significantly associated with decreased leptin levels and increased resistin levels. Furthermore, increased levels of adiponectin are associated with PC. Yet, no significant MD was seen for leptin and adiponectin levels between CP and PC patients, and likewise for adiponectin levels between CP patients and controls. Results should be interpreted with caution due to the high heterogeneity between the included studies.

The role of the liver in drug metabolism makes individuals with hepatic dysfunction more susceptible to adverse drug reactions, necessitating careful consideration in analgesic selection and dosing. Acetaminophen, despite being a common cause of liver failure, is considered safe within recommended dosages. Nonsteroidal anti-inflammatory drugs (NSAIDs), while effective, pose risks in cirrhosis due to complications like renal failure and gastrointestinal bleeding. Cyclooxygenase-2 inhibitors have limited data, and their use is discouraged due to cardiovascular concerns. Opiates, though potent, require cautious use in cirrhosis due to altered metabolism, potential adverse effects, and the risk of addiction. Tricyclic antidepressants like nortriptyline and desipramine can be utilized for neuropathic pain, while SSRIs and SNRIs are not recommended. Anticonvulsants such as gabapentin and pregabalin are preferred for neuropathic pain, with gabapentin being the first-line choice. Topical analgesics, including NSAIDs, lidocaine, and rubefacients, are deemed safe for use in cirrhosis, offering localized relief with minimal systemic effects. Nonpharmacological approaches addressing medical, psychological, and socio-economic factors are crucial adjuvants to analgesic therapy in advanced liver diseases. Physiotherapy, psychotherapy, behavioral therapy, relaxation techniques, acupuncture, and traditional practices like yoga and massage, as well as novel modalities, contribute to a holistic pain management strategy. This review provides healthcare professionals with valuable insights into the complex landscape of analgesic therapy in cirrhosis. Meticulous consideration of drug metabolism, hepatic safety, and individual patient factors is paramount in optimizing pain management strategies for this challenging patient population.

Background and aims: Vedolizumab is a humanized gut selective drug that targets α4β7 integrin and has been used successfully in the treatment of inflammatory bowel disease (IBD). Pivotal studies have already demonstrated the drug's safety, but some real-life cohorts have shown an increase in arthralgia and arthritis in patients using vedolizumab. These findings raised the question of whether these joint symptoms are extraintestinal manifestations of IBD (since the drug acts only in the gut) or if they are associated with the use of vedolizumab. This systematic review and meta-analysis aimed to assess the incidence of arthralgia/arthritis in patients receiving vedolizumab and to investigate whether these events are indeed drug related.

Methods: Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of joint manifestations in patients with Crohn's disease (CD) or ulcerative colitis (UC) who were treated with vedolizumab. The considered outcomes were arthritis and arthralgia. We used RevMan to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI).

Results: The search strategy yielded 4,206 articles. After removal of duplicates and screening of results, 6 randomized studies met the inclusion criteria. A total of 3,134 patients with moderately to severe IBD were included. Of those, 2,119 were randomized to receive vedolizumab and 1,015 to placebo. In the intervention group, 210 patients developed arthritis or arthralgia of any kind while 84 patients developed those symptoms in the placebo group (RR=1.09; 95%CI: 0.86-1.38; p=0.49, I2=0%), showing no significant association. Results also showed no significant association between exposure and the studied outcome after comparing CD (RR=1.02; 95%CI: 0.76-1.37, p=0.89, I2=0%) and UC (RR=1.24; 95%CI: 0.81-1.89, p=0.32, I2=43%) separately.

Conclusions: The meta-analysis showed no association of these symptoms to the treatment with vedolizumab. Therefore, the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, with the body's response to the drugs or with the exclusion of corticosteroids or anti-TNF from concomitant treatment with vedolizumab. Further studies with larger sample sizes are required, especially randomized clinical trials comparing anti-TNF, corticosteroid and immunomodulators to evaluate the incidence of joint manifestations in patients with IBD and even other rheumatological manifestations that may be associated as well.

Background and aims: Prediabetes is often underdiagnosed and underreported due to its asymptomatic state in over 80% of individuals. Considering its role in promoting cancer incidence and limited evidence linking prediabetes and colorectal cancer (CRC), we conducted a systematic review and meta-analysis to evaluate the incidence of colorectal cancer in people with prediabetes.

Methods: A comprehensive search through PubMed/Medline, Embase, Scopus, and Google Scholar was performed until June 1, 2022, to screen for studies reporting CRC incidence/risk in prediabetics. Binary random-effects models were used to perform meta-analysis and subgroup analyses. Sensitivity analysis was done using leave-one-out method. The quality of the studies was assessed by the Newcastle Ottawa Scale for observational studies.

Results: Seven prospective and one retrospective study comprising 15 cohorts and a pooled number of 854,876 cases and 219,0511 controls were included in the analysis (2 Japan, 2 Korea, 1 Sweden, 1 UK, 1 China, and 1 USA). After combining all the studies, the forest plots for adjusted analysis shows a statistically significant increase in odds of having CRC with prediabetes (OR=1.16; 1.08-1.25, p< 0.01; I2=56.06%) and unadjusted analysis also shows a statistically significant increase in odds of having CRC with prediabetes (OR=1.62; 1.35-1.95, p< 0.01; I2=85.72% ). Sensitivity analysis using the Leave-one-out method did confirm equivalent results. Subgroup analysis based on type of study, the odds of developing CRC was higher in prospective studies (OR=1.175; 1.065-1.298) (p=0.001) than retrospective studies (OR=1.162; 1.033- 1.306) (p=0.012). The odds of developing CRC were not significantly higher in ages >60 (OR=1.446; 0.887-2.356) (p=0.139) compared to less than 60 years. The strongest association b/w prediabetes and CRC was found on a median 5-10 years (aOR=1.257; 1.029-1.534) (p=0.025) follow-up compared to < 5 years and 10 years and higher.

Conclusions: This study showed that the odds of developing CRC is 16% higher in patients with prediabetes than those with normal blood glucose. Lifestyle modifications such as weight loss, proper diet, and exercise are essential to control prediabetes. This study further warrants a specific prediabetes screening for patients already at high risk of colorectal cancer with other risk factors.

Background and aims: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, including elexacaftor/ivacaftor/tezacaftor (ETI) and lumacaftor/ivacaftor (LI), have revolutionized the treatment of cystic fibrosis. However, their impact on liver function remains unclear, with varying effects reported across studies. The aim of this study was to systematically review the effects of CFTR modulators on liver function in cystic fibrosis patients by evaluating changes in key hepatic biomarkers.

Methods: A comprehensive literature search was conducted in Europe PubMed Central and PubMed databases for studies published between January 1, 2010, and December 31, 2023. Eligible studies included those assessing the impact of CFTR modulators on liver biomarkers in cystic fibrosis patients. Meta-analyses were performed where possible.

Results: Six studies encompassing 195 patients were included, with significant heterogeneity in study design, population, and outcomes. The review found mixed results for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GGT) levels, with some studies reporting increases and others decreases. LI therapy was associated with significant reductions in GGT and alkaline phosphatase (AP) levels, while ETI therapy showed significant increases in bilirubin levels. Albumin levels increased significantly with both therapies.

Conclusions: CFTR modulators have varying effects on liver function biomarkers in cystic fibrosis patients, with LI therapy generally showing more favorable outcomes on liver health. The significant heterogeneity among studies underscores the need for more standardized research to better understand these effects and guide clinical management.