Background Direct-acting antivirals (DAAs) have revolutionized the therapy of HCV infection with higher sustained virological response (SVR) rates. Fibrosis regression after achieving SVR to DAA remains to be evaluated in chronic hepatitis C patients. One of the main inquiries here is what occurs with liver fibrosis after achieving a SVR, albeit the current DAA was not intended to be antifibrotic. Liver biopsy was replaced by various non-invasive methods, like FIB4 score and fibroscan. The aim of the study was to evaluate the impact of SVR following DAAs on liver fibrosis in chronic HCV patients. Results Five hundred of 1170 F4 treated patients (42.7%) improved and became 190 F3, 90 F2, and 220 F1. Also, 40 of 60 F3 patients improved and became 10 F2 and 30 F1. Also, 350 of 1230 treated patients (28.4%) transited from significant fibrosis (≥F3) to non-significant fibrosis (≤F2). There was a significant improvement of FIB-4 (p<0.001) in the improved group after DAAs were proved by liver stiffness measurement. Conclusion Treatment of chronic HCV with DAAs is associated with regression of liver fibrosis as about 28% of patients improved from significant fibrosis (≥F3) to non-significant fibrosis (≤F2) after treatment.

Background and AimsUlcerative colitis (UC) and Crohn's disease (CD) are the most common types of Inflammatory bowel disease (IBD), with variable responses to traditional therapies and unpredicted prognosis. In Egypt and most developing countries, the lack of recent epidemiological and prognostic data adversely affects management strategies. We collected and analyzed data of patients with IBD from multiple centers across Egypt to evaluate patients' clinical and epidemiological characteristics.MethodsThis retrospective multicenter study included patients diagnosed with IBD between May 2018 and August 2021, at 14 tertiary gastroenterology units across Egypt. Record analysis addressed a combination of clinico-epidemiological characteristics, biochemical tests, stool markers, endoscopic features, histological information, and different lines for IBD treatment.ResultsWe identified 1104 patients with an established diagnosis of IBD; 81% of them had UC, and 19% showed CD. The mean age of onset was 35.1 ± 12.5 years ranging from 5 to 88 years, the mean duration of illness at inclusion was 13.6 ± 16.7 years, gender distribution was almost equal with a significant male dominance (60.4%, p = 0.003) among patients with CD, 57% were living in rural areas, and 70.5% were from Delta and Coastal areas. Two hundred nineteen patients (19.8%) displayed comorbid conditions, primarily associated with CD. The most frequent complaints were diarrhea (73.2%), rectal bleeding (54.6%) that was significantly higher among patients with UC (64%, p &lt; 0.001), and 46.8% with abdominal pain (more often with CD: 71%, p &lt; 0.001). Conventional therapy was effective in treating 94.7% of patients. The main lesion in patients with CD was ileal (47.8%); patients with UC mainly exhibited proctosigmoiditis (28.4%). Dysplasia was detected in 7.2% of patients, mainly subjects with UC.ConclusionsTo our knowledge, our effort is the first and largest cohort of Egyptian patients with IBD to describe clinical and epidemiological characteristics, and diagnostic and management approaches. More extensive prospective studies are still needed to fully characterize disease distribution, environmental factors, and pathological features of the disease.

Inflammatory bowel disease (IBD) involves a variety of conditions, particularly Crohn’s disease (CD) and ulcerative colitis (UC). IBD is characterized by chronic inflammatory process of patient’s gut. This review aims to summarize the pharmacogenetics of biologics approved for IBD and the correlation with azathioprine-metabolizing enzymes and adverse reactions, therefore highlighting a likely relationship between particular polymorphisms and therapeutic response. Therefore, we reviewed and discussed the activities of TDM protocols which use monoclonal antibodies (mABs) with a particular attention on the integration of other actions aimed to exploit the most effective and safest medications for IBD cases. The pharmacotherapy of IBD (CD and UC) has experienced a great advancement with the advent of mABs which have peculiar pharmacokinetic properties differentiating them from chemical agents, like aminosalicylates, antimetabolites (e.g., azathioprine (AZA), 6-mercaptopurine (6MP)), and methotrexate), and immunosuppressant agents (steroids and cyclosporine). But clinical studies showed that biologicals might have pharmacokinetic variability which can affect the anticipated clinical outcomes, beyond primary resistance phenomena. Thus, therapeutic drug monitoring (TDM) protocols are applied to the doses of medications according to the required serum mABs levels. This aims to maximize the favorable effects of mABs and minimizing the toxicity. But, the presence of particular genetic polymorphisms in patients might determine a different outcome in response to treatment, indicating the heterogeneity of the effectiveness among IBD cases. Indeed, many reports demonstrated significant associations between polymorphisms and response to biologics. In conclusion, the improvement of TNF-, TNFR and IL-1 pharmacogenetics could be the best approach toward a targeted treatment for IBD. Pre-therapy genotyping has to be integrated with IBD therapeutic guidelines, as it is the most suitable approach to choose the most appropriate biologicals for each case. Also, the addition of pharmacodynamic markers (including serum, cellular, or tissue concentrations of TNF-alpha and IL-8) might boost the predictive performance of models and, eventually, control the disease with a significant improvement in quality of life (QOL).

Background Inflammatory Bowel disease (IBD) is a chronic progressive condition that prompts generous physical and mental morbidity. Choosing the best kind of management and medication dosage prevents new episodes of high disease activity during therapy because of adverse drug reactions (ADRs). This can lead to cessation or inefficacy of the treatment, or complete non-responsiveness to specific medications. Pharmacogenetics (PGx) is a well-established aspect in IBD. One of the exemplary instances of PGx is thiopurines, which are frequently utilized as IBD therapy. This study aimed to evaluate specific gene polymorphism involved in the toxicity and efficacy of Azathioprine (AZA) use in the management in Egyptian patients and to find the correlation between the polymorphism of Nudix Hydrolase15 (NUDT15) gene (rs116855232), The Thiopurine methyltransferase (TPMT) gene (rs1800460) and Inosine Triphosphatase (ITPA) gene (rs1127354) which are involved in the metabolism of the medications utilized in IBD management. Methods This prospective study was performed in 150 patients with IBD. All patients were treated with 2 mg/kg per day AZA (Imuran, GlaxoSmithKline®) for at least 3 months at therapeutic doses to induce remission. Subsequent treatment of AZA. The minimum follow-up period for those who did not experience ADR was one year. Among the studied patients, one hundred twenty-nine patients were treated with combination regimen of steroids (oral prednisone 1 mg/kg/day). Also, treatment failure was considered among the patients who could not tolerate AZA side effects, or there was no improvement after dose modification. Results The most identifiable adverse effect among the studied population was anemia followed by leukopenia and myelosuppression. SNPs genotype TPMT (rs1800460) and ITPA gene (rs1127354) were significantly related to adverse effects among IBD patients receiving Azathioprine treatment. There was a lack of any variants in the NUDT15 genotype among the Egyptian population. Conclusion Further research is required in to clarify the relationship between NUDT15 PGx and AZA-ADRs. The effect of NUDT15 PGx on toxicity and ADRs as yet necessitates to be elucidated. Studies with a larger sample size and involving different ethnicities are also necessary.

Background Hepatitis C virus (HCV) infection is considered one of the main causes of chronic liver diseases. HCV is responsible for 25% of HCC cases worldwide. DAAs represent an important step for HCV eradication. The aim was to study the role of IL-28B single nucleotide polymorphism in the prediction of HCC in patients with HCV-related cirrhosis after DAAs. Results This study was done at Mansoura Specialized Hospital: 50 cases HCC after DAAs, 50 cases without HCC after DAAs, and 100 controls. SNPs of the IL-28B gene were genotyped. There was an insignificant difference between HCC patients and the cirrhotic group as regards genotypes (p value = 0.26) and alleles (p value = 0.77). A significant association in SNP of IL-28B between healthy individuals and the cirrhotic group was detected. C C genotype (28%) and C T (64%) genotype were more prevalent in the healthy group than in the cirrhotic group 20% and 52% respectively while T T genotype was more prevalent in cirrhotic patients (28%) than controls (8%). C allele was protective against cirrhosis with 60% distribution in healthy individuals and 46% in the cirrhotic group. T allele was more prevalent in cirrhotic (54%) than the normal group (40%) Conclusion Although IL-28B SNP had a role in HCV-related cirrhosis progression, it did not predict the probability for HCC development following DAAs.