Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis:Is the evidence of sufficient quality to develop recommendations?

BACKGROUND The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce. AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). METHODS A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI). RESULTS The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups. CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement

Red blood cell distribution width: a determinant of hospital mortality in pancreatitis

Objective: In recent years, there has been a great attention concerning red blood cell distribution width (RDW) in clinical decisions as well as determining the severity of diseases. This study was conducted to evaluate the primary level of RDW to predict hospital mortality in pancreatitis. Methods: This was a descriptive analytical study performed on 100 patients with acute pancreatitis in the emergency department of Imam Reza hospital of Tabriz University of Medical Sciences. In this study, the primary level of RDW in patients with acute pancreatitis presenting to the emergency ward was collected and after patients’ admission we followed them. Also, the admission outcome (mortality or discharge) of patients was registered, and finally we evaluated the predictive value of RDW in determining the patient’s outcome in hospital. Results: In our study, 47 patients were male, and 53 patients were female. Mean RDW in patients was 13.82 ± 1.69. Five patients died during the study. Mean RDW in dead patients and other patients was 16.44 ± 4.22 and 13.68 ± 1.37, respectively (P < 0.001). The cut-off point of 14.55 for RDW with 80% sensitivity and 85% specificity was determined for predicting mortality in patients. Conclusion: Based on our study results, the initial RDW level is an independent factor for predicting in-hospital mortality in pancreatitis but not for determining the need for surgery or admission to the intensive care unit (ICU)

Prevalence, awareness, treatment, and control of hypertension based on ACC/AHA versus JNC7 guidelines in the PERSIAN cohort study

In this cross-sectional population-based study, we used the baseline data of the Prospective Epidemiologic Research Studies in IrAN cohort study collected in Iran from 2014 to 2020. The main outcomes were the prevalence of hypertension and proportion of awareness, treatment, and control based on the 2017 ACC/AHA guideline compared to the seventh report of the Joint National Committee (JNC7). Of the total of 163,770 participants, aged 35–70 years, 55.2% were female. The sex-age standardized prevalence of hypertension was 22.3% (95% CI 20.6, 24.1) based on the JNC7 guideline and 36.5% (31.1, 41.8) based on the ACC/AHA guideline. A total of 24,312 participants [14.1% (10.1, 18.1)] were newly diagnosed based on the ACC/AHA guideline. Compared to adults diagnosed with hypertension based on the JNC7 guideline, the newly diagnosed participants were mainly young literate males who had low levels of risk factors and were free from conventional comorbidities of hypertension. About 30.7% (25.9, 35.4) of them (4.3% of the entire population) were eligible for pharmacologic intervention based on the ACC/AHA guideline. Implementation of the new guideline may impose additional burden on health systems. However, early detection and management of elevated blood pressure may reduce the ultimate burden of hypertension in Iran

Non-invasive serum fibrosis markers: A study in chronic hepatitis

Introduction: Chronic hepatitis is specified as inflammatory disease of the liver lasting for more than six months. Role of noninvasive fibrosis markers as prognostication factors of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis is the aim of this study. Methods: Two hundred twenty-one patients with chronic hepatitis involved in the study between 2011 and 2013. Routine biochemical indices and serum fibrosis markers such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score (FIB-4) were evaluated, and the histological grade and stage of the liver biopsy specimens were scored according to the Ishak scoring system. Diagnostic accuracies of these markers for prediction of significant fibrosis were assessed by Receiver Operating Characteristic (ROC) curve analysis. Results: Contemporaneous laboratory indices for imputing AAR, APRI, and FIB-4 were identified with liver biopsies. From all, 135 males (61.1%) and 86 females (38.9%), with mean age of 39.6±14.4 were studied. Significant correlation between stages of fibrosis and FIB-4, APRI and AAR were detected, with a correlation coefficient higher than that of other markers in the patients with Hepatitis B (r = 0.46), C (r = 0.58) and autoimmune hepatitis (r = 0.28). FIB-4 (AUROC = 0.84) and APRI (AUROC = 0.78) were superior to AAR at distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest diagnostic accuracy. Conclusion: Application of these markers was good at distinguishing significant fibrosis and decreased the need for staging liver biopsy specimens among patients with chronic hepatitis

Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis: Is the evidence of sufficient quality to develop recommendations?

BACKGROUND The standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce. AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). METHODS A systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI). RESULTS The pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups. CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement

Prevalence of Hepatitis B genotypes worldwide and in Iran: A meta-analysis

Background. Chronic hepatitis B is associated with different long-term outcomes in various regions. One of the critical predictors of clinical outcomes is the genotype of Hepatitis B virus (HBV). The current study investigated the frequency of worldwide and Iranian national HBV genotypes. Methods. Electronic search was performed through Medline (via Ovid), Embase, Web of Science, and Persian databases. Furthermore, the references of eligible articles were manually checked. The quantitative synthesis was conducted using the 2nd version of comprehensive Meta-analysis software (CMA.2). Results. In total, 5817 records were retrieved, and after removing duplicate studies, 3701 were screened at the title/abstract level. A total of 350 eligible studies were identified in the end.D genotype had the highest frequency (43.50%; 95% CI: 39.60 to 47.50), and the H genotype had the lowest frequency (1.2%; 95% CI: 0.6 to 2.7) globally. In 29 studies conducted in Iran (97.0%), genotype D was identified. Genotype E was the most prevalent in the African Region, followed by A in the American Region, B and C in the South-East Asian Region, D in the European Region, and C in the Western Pacific Region. Conclusion. The most prevalent genotype of HCV worldwide and in Iran is D. Furthermore, HBV genotype frequencies vary according to WHO regions. A prediction of progression could be made based on these results. Practical Implications. 1.According to the results of the meta-analyses, the D genotype had the highest frequency (43.50%; 95% CI: 39.60 to 47.50) and the genotype H had the lowest frequency (1.2%; 95% CI: 0.6 to 2.7) globally. 2.In 29 studies conducted in Iran (97.0%), genotype D was identified. 3. Genotype E was the most prevalent in the African Region, followed by A in the American Region, B and C in the South-East Asian Region, D in the European Region, and C in the Western Pacific Region