Background The current COVID-19 pandemic, caused by SARS-CoV-2, has emerged as a public health emergency. All nations are seriously challenged as the virus spreads rapidly across the globe with no regard for borders. The primary management of IBD involves treating uncontrolled inflammation with most patients requiring immune-based therapies. However, these therapies may weaken the immune system and potentially place IBD patients at increased risk of infections and infectious complications including those from COVID-19. Aim To summarise the scale of the COVID-19 pandemic, review unique concerns regarding IBD management and infection risk during the pandemic and assess COVID-19 management options and drug interactions in the IBD population. Methods A literature review on IBD, SARS-CoV-2 and COVID-19 was undertaken and relevant literature was summarised and critically examined. Results IBD patients do not appear to be more susceptible to SARS-CoV-2 infection and there is no evidence of an association between IBD therapies and increased risk of COVID-19. IBD medication adherence should be encouraged to prevent disease flare but where possible high-dose systemic corticosteroids should be avoided. Patients should exercise social distancing, optimise co-morbidities and be up to date with influenza and pneumococcal vaccines. If a patient develops COVID-19, immune suppressing medications should be withheld until infection resolution and if trial medications for COVID-19 are being considered, potential drug interactions should be checked. Conclusion IBD patient management presents a challenge in the current COVID-19 pandemic. The primary focus should remain on keeping bowel inflammation controlled and encouraging medication adherence.
Background Proton pump inhibitors (PPIs) have a significant impact on the gut microbiome, which in turn, might increase the risk of rheumatoid arthritis (RA). Aim To evaluate regular use of PPIs and risk of RA. Methods This is a prospective analysis of the US nurses who reported PPI use data, and were free of RA from the Nurses' Health Study (NHS 2002-2014) and NHS II (2003-2015). The exposure was regular use of PPI in the past 2 years, which was repeatedly evaluated in biennial surveys. RA was confirmed by the 1987 or 2010 American College of Rheumatology criteria. We estimated the hazard ratios (HRs) and confidence interval (CIs) with time-dependent Cox regression adjusting for potential confounders. Results We documented 421 cases of RA over 1 753 879 person-years of follow-up. Regular PPI users had a 44% higher risk of RA as compared with non-regular users (adjusted HR = 1.44; 95%CI, 1.10-1.89). The risk of RA increased with the total duration of PPI use (P-trend = 0.008). Compared with non-regular users, the adjusted HRs were 1.22 (95%CI, 0.93-1.62) for women with >0 to 4 years' use and 1.73 (95% CI, 1.14 to 2.61) for >4 years' use. Conclusions Regular use of PPI was associated with increased risk of RA in women, with a higher risk observed in individuals with a longer duration of PPI use. Due to the observational study design, large prospective trials are still required to confirm our finding.
Background Serum hepatitis B virus (HBV) RNA is a novel biomarker for evaluating treatment response. Detailed information regarding serum HBV RNA kinetics during treatment with nucles(t)ide analogues (NAs) is limited. Aims To ascertain serum HBV RNA kinetics during long-term NAs treatment and identify associated factors. Methods We enrolled 76 HBeAg-positive chronic hepatitis B patients receiving NAs from randomised controlled trials. Laboratory assays were undertaken every 3 months. Factors associated with serum HBV RNA kinetics were identified by generalised estimating equations. Results Baseline serum HBV RNA was 8.5 +/- 1.0 log(10) copies/mL. Decline in serum HBV RNA during NAs therapy was biphasic: the first phase (HBV DNA detectable) had a fast decrease (median slope, -0.207 log(10) copies/mL/month) and was followed by a second phase (HBV DNA undetectable) with slow decrease (median slope, -0.071 log(10) copies/mL/month). In the first phase, factors independently associated with lower initial serum HBV RNA were male sex (OR, 0.685,P = 0.044), low baseline HBsAg (OR, 0.525,P = 0.001) and rapid virological response (RVR) (OR, 0.624,P = 0.031). In the second phase, only RVR was independently associated with serum HBV RNA kinetics, including its lower initial level (OR, 0.694,P = 0.043) and greater decline (OR, 0.966,P = 0.002). Based on viral dynamics, time needed to achieve undetectable serum HBV RNA from baseline was 43.56 (IQR: 29.49-66.40) months. Conclusion RVR was a significant determinant for biphasic decline in serum HBV RNA during NAs treatment, which significantly influenced the treatment duration required to achieve undetectable serum HBV RNA.
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Background The incidence of elevated liver chemistries and the presence of the pre-existing chronic liver disease (CLD) have been variably reported in COVID-19. Aims To assess the prevalence of CLD, the incidence of elevated liver chemistries and the outcomes of patients with and without underlying CLD/elevated liver chemistries in COVID-19. Methods A comprehensive search of electronic databases from 1 December 2019 to 24 April 2020 was done. We included studies reporting underlying CLD or elevated liver chemistries and patient outcomes in COVID-19. Results 107 articles (n = 20 874 patients) were included for the systematic review. The pooled prevalence of underlying CLD was 3.6% (95% CI, 2.5-5.1) among the 15 407 COVID-19 patients. The pooled incidence of elevated liver chemistries in COVID-19 was 23.1% (19.3-27.3) at initial presentation. Additionally, 24.4% (13.5-40) developed elevated liver chemistries during the illness. The pooled incidence of drug-induced liver injury was 25.4% (14.2-41.4). The pooled prevalence of CLD among 1587 severely infected patients was 3.9% (3%-5.2%). The odds of developing severe COVID-19 in CLD patients was 0.81 (0.31-2.09;P = 0.67) compared to non-CLD patients. COVID-19 patients with elevated liver chemistries had increased risk of mortality (OR-3.46 [2.42-4.95,P < 0.001]) and severe disease (OR-2.87 [95% CI, 2.29-3.6,P < 0.001]) compared to patients without elevated liver chemistries. Conclusions Elevated liver chemistries are common at presentation and during COVID-19. The severity of elevated liver chemistries determines the outcome of COVID-19. The presence of CLD does not alter the outcome of COVID-19. Further studies are needed to analyse the outcomes of compensated and decompensated liver disease.
Background The outbreak of coronavirus disease 2019 (COVID-19) is a critical challenge for public health. The effect of COVID-19 on liver injury has not been fully presented. Aims To evaluate the dynamic changes in liver function and the relationship between liver function damage and prognosis in patients with COVID-19. Methods Retrospective analysis of clinical data of 675 patients with COVID-19 in Zhongnan Hospital of Wuhan University from January 3 to March 8, 2020. Patients were classified as normal, abnormal liver function and liver injury. Results Of 675 patients, 253 (37.5%) had abnormal liver function during hospitalisation, and 52 (7.7%) had liver injury. The dynamic changes of ALT and AST levels were more significant in patients with liver injury and in those who died. AST >3-fold ULN had the highest risk of death and mechanical ventilation. Compared to patients with normal AST levels, mortality and risk of mechanical ventilation significantly increased 19.27-fold (95% confidence interval [CI], 4.89-75.97;P < 0.0001) and 116.72-fold (95% CI, 31.58-431.46;P < 0.0001), respectively, in patients with AST above 3-fold ULN. Increased leucocytes, decreased lymphocytes and female sex were independently associated with liver injury. Conclusions The dynamic changes in liver function may have a significant correlation with the severity and prognosis of COVID-19. Increased index of liver injury was closely related to mortality and need for mechanical ventilation. Therefore, these indicators should be closely monitored during hospitalisation.
Background A critical aspect of liver transplantation in hepatitis B patients is to prevent graft reinfection with hepatitis B virus. The use of hepatitis B immune globulin after transplant was a significant milestone, which allowed prolonged graft and patient survival by controlling hepatitis B reinfection in liver grafts. The development of anti-viral treatments with oral nucleos(t)ide analogues, led to a further reduction in graft reinfection and improvement in patient survival. The combination of the aforementioned two therapies has been widely used in hepatitis B-associated liver transplants. Aim To address the post-transplant management of hepatitis B and provide updates on preventing graft reinfection. Methods We performed a literature search on Ovid and PubMed for RCTs or cohort studies in English, which investigated the effectiveness of hepatitis B immune globulin and anti-viral therapy on hepatitis B-associated transplants (1/2000-1/2020). Studies that met pre-established criteria were reviewed. Results Based on currently available evidence, an algorithm for post-transplant management with anti-viral therapy is proposed. Also, the management of recipients who received grafts from hepatitis B core antibody-positive donors is discussed. Conclusions The development of hepatitis B immune globulin and anti-viral treatments led to substantial improvement in graft and patient survival. The prevention of hepatitis B graft reinfection is complex and involves a broad interdisciplinary team.
Background Evidence for endoscopic balloon dilation of small intestinal strictures in Crohn's disease (CD) using balloon-assisted enteroscopy is scarce. Aim To evaluate endoscopic balloon dilation for the treatment of small intestinal CD strictures using balloon-assisted enteroscopy. Methods Citations in Embase, MEDLINE, and Cochrane were systematically reviewed. In a meta-analysis of 18 studies with 463 patients and 1189 endoscopic balloon dilations, technical success was defined as the ability to dilate a stricture. Individual data were also obtained on 218 patients to identify outcome-relevant risk factors. Results In the pooled per-study analysis, technical success rate of endoscopic balloon dilation was 94.9%, resulting in short-term clinical efficacy in 82.3% of patients. Major complications occurred in 5.3% of patients. During follow-up, 48.3% of patients reported symptom recurrence, 38.8% were re-dilated and 27.4% proceeded to surgery. On the per-patient-based multivariable analysis, that patients with disease activity in the small intestine had lower short-term clinical efficacy (odds ratio 0.32; 95% confidence interval 0.14-0.73,P = 0.007). Patients with concomitant active disease in the small and/or large intestine had an increased risk to proceed toward surgery (hazard ratio 1.85; 95% confidence interval 1.09-3.13,P = 0.02 and hazard ratio 1.77; 95% confidence interval 1.34-2.34,P < 0.001). Conclusions Balloon-assisted enteroscopy for dilatation of CD-associated small intestinal strictures has high short-term technical and clinical efficacy and low complication rates. However, up to two-thirds of patients need re-dilation or surgery.
Background Data on tenofovir alafenamide fumarate (TAF) therapy for preventing mother to child transmission of hepatitis B virus (HBV) are lacking. Aims To investigate the efficacy and safety of TAF therapy for preventing hepatitis B mother to child transmission. Methods Mothers with chronic HBV infection, positive for hepatitis B e-antigen and with HBV DNA >200 000 IU/mL received TAF for preventing mother to child transmission were enrolled retrospectively from multiple centres with data collection on mother-infant dyads up to postpartum week 24-28. Primary measurements were the mother to child transmission rate and infants' malformation rate. Secondary assessments included maternal HBV DNA reduction at delivery, and maternal or infant adverse events during follow up. Results Among 71 mothers enrolled, the mean (+/- SD) age was 30.3 (+/- 2.2) years. TAF therapy was initiated during the second or third trimester and continued to delivery with a mean (+/- SD) duration of 12.8 (+/- 4.0) weeks. At delivery, 85.9% (61/71) of the mothers achieved HBV DNA <200 000 IU/L. Seventy-three infants (two sets of twins) were born from mothers treated with TAF and none had congenital defects or malformations. All infants received HBV immunoglobulin and vaccine at birth with additional HBV vaccinations at one and six months. At age 24-28 weeks, all infants had negative hepatitis B surface antigen and undetectable levels of HBV DNA (<100 IU/mL). Body weight, height, and head circumferences were comparable to national standards for physical development. No severe adverse effects were reported in either mothers or infants. Conclusions TAF for highly viraemic mothers effectively prevented mother to child transmission of hepatitis B. There were no safety concerns for either mothers or infants with 24-28 weeks of follow up.
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