Clinical and endoscopic characteristics of patients undergoing gastrointestinal endoscopic procedures in Egypt: a nationwide multicenter study.

BACKGROUND: Egypt faces a significant public health burden due to chronic liver diseases (CLD) and peptic ulcer disease. CLD, primarily caused by Hepatitis C virus (HCV) infection, affects over 2.9% of the population nationwide, with regional variations. Steatotic liver disease is rapidly emerging as a significant contributor to CLD, especially in urban areas. Acid-related disorders are another widespread condition that can significantly impact the quality of life. These factors and others significantly influence the indications and findings of gastrointestinal endoscopic procedures performed in Egypt. AIM: We aimed to evaluate the clinico-demographic data, indications, and endoscopic findings in Egyptian patients undergoing gastrointestinal endoscopic procedures in various regions of Egypt. METHODS: This study employed a retrospective multicenter cross-sectional design. Data was collected from patients referred for gastrointestinal endoscopy across 15 tertiary gastrointestinal endoscopy units in various governorates throughout Egypt. RESULTS: 5910 patients aged 38-63 were enrolled in the study; 75% underwent esophagogastroduodenoscopy (EGD), while 25% underwent a colonoscopy. In all studied patients, the most frequent indications for EGD were dyspepsia (19.5%), followed by hematemesis (19.06%), and melena (17.07%). The final EGD diagnoses for the recruited patients were portal hypertension-related sequelae (60.3%), followed by acid-related diseases (55%), while 10.44% of patients had a normally apparent endoscopy. Male gender, old age, and the presence of chronic liver diseases were more common in patients from upper than lower Egypt governorates. Hematochezia (38.11%) was the most reported indication for colonoscopy, followed by anemia of unknown origin (25.11%). IBD and hemorrhoids (22.34% and 21.86%, respectively) were the most prevalent diagnoses among studied patients, while normal colonoscopy findings were encountered in 18.21% of them. CONCLUSION: This is the largest study describing the situation of endoscopic procedures in Egypt. our study highlights the significant impact of regional variations in disease burden on the utilization and outcomes of GI endoscopy in Egypt. The high prevalence of chronic liver disease is reflected in the EGD findings, while the colonoscopy results suggest a potential need for increased awareness of colorectal diseases.

Why MASLD Lags Behind MAFLD: A Critical Analysis of Diagnostic Criteria Evolution in Metabolic Dysfunction-Associated Liver Diseases.

Emerging in the 1800s under the label "fat in the liver" and later gaining prominence in the 1980 as non-alcoholic fatty liver disease (NAFLD), the disease predominantly attributed to metabolic dysfunction presents a formidable health issue marked by substantial morbidity and mortality. It was 2020 when a change of one letter "NAFLD" to metabolic dysfunction-associated fatty liver disease "MAFLD" linked with the change in the definition and diagnostic criteria began a new controversy around the globe. Metabolic dysfunction-associated fatty liver disease (MAFLD) criteria represent a substantial departure from previous diagnostic measures of NAFLD, and provide the first set of positive criteria for diagnosis of the disease in adults and children that emphasise the key attribute of metabolic dysfunction in the pathogenesis, and acknowledges that the disease is a continuum across the life span. In 2023, an adapted version of the diagnostic criteria of MAFLD was proposed to define a slightly modified term; metabolic dysfunction-associated steatotic liver disease (MASLD). The MASLD criteria did not provide any conceptual advantage, and emerging evidence suggests that it actually performs worse than the MAFLD criteria. This raises the intriguing question of why MASLD was unable to take advantage of being second? In this review, we will explore the possible reasons for this unique case and highlight the current evidence supporting the use of MAFLD instead of MASLD in defining metabolic dysfunction-associated fatty liver diseases.

Enhancing colorectal cancer prevention: a national assessment of public awareness in Egypt.

BACKGROUND: Despite the increasing incidence of colorectal cancer (CRC) in the Egyptian population, it still seems that there is a significant lack of awareness regarding the disease. This study aimed to assess the Egyptian population's awareness of CRC regarding its risk factors, the screening procedures, and the appropriate responses to its diagnosis. METHOD: A cross-sectional study was conducted in Egypt between July 2022 and March 2023 and recruited a convenient sample of adults from seven governorates representing different geographic areas, and socioeconomic and educational backgrounds with the help of the validated Bowel Cancer Awareness Measure (CAM) version 2.1. The modified Arabic questionnaire was validated through a pilot study including 30 patients. Then it was presented through a Google form before being shared via online methods and face-to-face interviews. The questionnaire provided both numerical and categorical data, which were analyzed accordingly. The Chi-square, the Fisher exact, and the Man-Whitney test were used to compare colorectal cancer poor and good knowledge groups. Logistic regression analysis was conducted to predict the factors that affected the awareness level of the study population. RESULTS: Nine hundred forty individuals participated in the survey. Their ages ranged from 18 to 86 years old, with an average of 37.38 ± 12.22 years. The mean Knowledge score was 14.29 ± 7.05 out of 37 with most of our participants (71%) having poor knowledge about CRC. Most of the participants (64.1%) chose colonoscopy as the best screening modality, followed by an abdominal CT (27.8%), and fecal occult blood (15.5%). The study revealed significant differences between participants with good and poor knowledge of colorectal cancer. (78.5%) of participants with good CRC knowledge lived in cities, (85.4%) attained university or higher educational level, and (87.2%) of them were nonsmokers (p < 0.05%). CONCLUSION: In general, there was a lack of awareness about Colorectal cancer among the Egyptian population especially among rural and lower educational levels, and more health education campaigns are required to enhance CRC prevention efforts in Egypt.

The role of PRDM1 gene polymorphism in the progression of hepatocellular carcinoma in Egyptian patients.

In Egypt, hepatocellular carcinoma (HCC) ranks as the second largest cause of cancer mortality. PRDM1 is a tumor suppressor gene essential for the differentiation and regulation activity of plasma cells and T cells. It plays a vital role in T cell exhaustion of chronic viral infection and HCC. We aimed to study the role of PRDM1 gene polymorphism in HCV and HCC-related to hepatitis C virus (HCV) progress in Egyptians. The case-control study included 300 Egyptian patients divided into 100 HCC,100 cirrhosis, and 100 control. Laboratory investigations were done for some clinicopathological biomarkers, including liver function tests, complete blood picture, serum alpha-fetoprotein, and hepatitis markers (HBsAg, anti-HCV-Ab). TaqMan allelic discrimination assay technique was used to genotype PRDM1 gene polymorphism. Multivariant analysis (logistic regression) assessed the association between the polymorphisms with HCC progression and designed the suggested model for HCC prediction. The frequencies of the G allele and GG phenotype in the control group were significantly more than that of the HCC and cirrhosis group. However, GA genotypes and A allele frequencies significantly increased in the HCC patients than in cirrhosis and controls. In addition, by comparing the HCC group and the non-HCC group (controls and cirrhotic patients), the subjects carrying AA or GA have 2 times more risk to develop HCC than those carrying GG genotypes (odd ratio = 2.045% and 95% confidence interval are (1.123-3.722) p = 0.019). Multivariate analysis results suggested a model of Aspartate transaminase (AST), Albumin, and PRDM1 polymorphism to predict the risk of HCC in Egyptians. In addition, PRDM1 polymorphism has an association with HCC prognosis (tumor size). For PRDM1 polymorphism, the A allele and AA might be considered as HCC-related to the HCV risk factor. In addition, AST, Albumin, and PRDM1 polymorphism predict the risk of HCC in Egyptians Therefore, the polymorphism might help in identifying the susceptible Egyptians to HCC. In addition, polymorphism might have a role in HCC prognosis.

Evaluation of factors affecting patients' refusal of HCV treatment in a cohort of Egyptian patients.

BACKGROUND: Treatment refusal, defined as active refusal of a patient to receive treatment despite physician recommendations, has not been extensively evaluated before in hepatitis C virus in the era of direct acting antivirals. OBJECTIVE: To investigate the reasons for refusal to receive hepatitis C virus treatment in Egypt. METHODS: an observational study conducted between July 2018 and November 2019 in Egypt. Enrollment was done to all patients who refused to get hepatitis C virus treatment during the national screening and treatment campaign. Reasons for their refusal were identified using a questionnaire as an instrument for data collection. RESULTS: Out of the 220 280 Egyptian hepatitis C virus patients who did not show up to start treatment and were contacted to get therapy, only 84 patients (0.038%) refused to receive treatment. The main reason for their refusal was having concerns about treatment (82.14%) and their main concern was the fear of adverse events (85.5%). Other causes of refusal were non-satisfactory experience at treatment centers (13.09%) and patients preferred to receive complementary and alternative medicines (4.7%). Most patients (65.4%) trusted the efficacy of directly acting antivirals for hepatitis C. None of the study participants was found to suffer from any psychiatric morbidity and the average score of the GHQ-12 was 10.7155. CONCLUSION: Proper health education and awareness regarding hepatitis C virus treatment safety and efficacy is needed to increase treatment acceptance rates.

Diagnostic Significance of hsa-miR-21-5p, hsa-miR-192-5p, hsa-miR-155-5p, hsa-miR-199a-5p Panel and Ratios in Hepatocellular Carcinoma on Top of Liver Cirrhosis in HCV-Infected Patients.

Early hepatocellular carcinoma (HCC) diagnosis is challenging. Moreover, for patients with alpha-fetoprotein (AFP)-negative HCC, this challenge is augmented. MicroRNAs (miRs) profiles may serve as potential HCC molecular markers. We aimed to assess plasma homo sapiens-(hsa)-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p-expression levels as a panel of biomarkers for HCC in chronic hepatitis C virus (CHCV) patients with liver cirrhosis (LC), especially AFP-negative HCC cases, as a step toward non-protein coding (nc) RNA precision medicine. SUBJECTS AND METHODS: 79 patients enrolled with CHCV infection with LC, subclassified into an LC group without HCC (n = 40) and LC with HCC (n = 39). Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p, hsa-miR-155-5p, hsa-miR-192-5p, and hsa-miR-199a-5p. RESULTS: Plasma hsa-miR-21-5p and hsa-miR-155-5p demonstrated significant upregulation, while hsa-miR-199a-5p demonstrated significant downregulation in the HCC group (n = 39) when compared to the LC group (n = 40). hsa-miR-21-5p expression was positively correlated with serum AFP, insulin, and insulin resistance (r = 0.5, p < 0.001, r = 0.334, p = 0.01, and r = 0.303, p = 0.02, respectively). According to the ROC curves, for differentiating HCC from LC, combining AFP with each of hsa-miR-21-5p, hsa-miR-155-5p, and miR199a-5p improved the diagnostic sensitivity to 87%, 82%, and 84%, respectively, vs. 69% for AFP alone, with acceptable specificities of 77.5%, 77.5%, and 80%, respectively, and AUC = 0.89, 0.85, and 0.90, respectively vs. 0.85 for AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios discriminated HCC from LC at AUC = 0.76 and 0.71, respectively, with sensitivities = 94% and 92% and specificities = 48% and 53%, respectively. Upregulation of plasma hsa-miR-21-5p was considered as an independent risk factor for HCC development [OR = 1.198(1.063-1.329), p = 0.002]. CONCLUSIONS: Combining each of hsa-miR-21-5p, hsa-miR-155-5p, and hsa-miR-199a-5p with AFP made it possible to identify HCC development in the LC patients' cohort with higher sensitivity than using AFP alone. hsa-miR-21-5p/hsa-miR-199a-5p and hsa-miR-155-5p/hsa-miR-199a-5p ratios are potential HCC molecular markers for AFP-negative HCC patients. hsa-miR-21-5p was linked, clinically and via in silico proof, to insulin metabolism, inflammation, dyslipidemia, and tumorigenesis in the HCC patients' group as well as for an upregulated independent risk factor for the emergence of HCC from LC in the CHCV patients.

Clinical, histological and molecular profiling of different stages of alcohol-related liver disease.

OBJECTIVE: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. DESIGN: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. RESULTS: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. CONCLUSIONS: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

High success rates for the use of ombitasvir/paritaprevir/ritonavir containing regimens in treatment of naïve and experienced chronic hepatitis C genotype 4: Real world results.

INTRODUCTION AND AIMS: Treatment of hepatitis C virus (HCV) genotype 4 patient with fixed dose combination of ombitasvir-paritaprevir-ritonavir plus ribavirin (OBV/rPTV/RBV) has been proven efficacy and safety in many clinical trials. The current study reports the efficacy and safety of OBV/rPTV/RBV (for treatment-naïve), and OBV/rPTV/RBV/sofosbuvir (SOF) (for treatment-experienced), in chronic HCV genotype 4 patients in real life settings. METHODS: Prospective cohort study including all adult chronic HCV genotype 4 patients who were scheduled to receive OBV/rPTV/RBV ± SOF for 12 or 24 weeks in New Cairo Viral Hepatitis Treatment Center. The primary efficacy endpoint was a virologic response at posttreatment week 12 (SVR12). Changes in hematological parameters, liver biochemical profile and fibrosis-4 index (FIB-4), as well as clinical and laboratory adverse events (AEs) across follow up visits (week 4, end of treatment [EOT], and SVR12), were recorded. RESULTS: Our study included 325 patients (age; 47.63 ± 12.63 years, 55.38% [n = 180] men). Most of the included patients (89.85%, n = 292) were treatment naïve and only 7% (n = 23) had liver cirrhosis. Overall, SVR12 was attained by 98.44% (316 of 321) of the patients; 97.15% (307 of 316) of patients who received 12 weeks of OBV/rPTV/RBV ± SOF and 100% (9 of 9) of patients who received 24 weeks of OBV/rPTV/RBV as assessed by modified intention to treat analysis. There was a significant improvement of baseline alanine aminotransferase, aspartate aminotransferase, hemoglobin, FIB-4 at SVR12 (P < 0.05). The most common reported AEs were anemia (n = 106), fatigue (n = 41) and elevated indirect bilirubin (n = 37). CONCLUSION: OBV/rPTV/RBV (±SOF) is a highly effective therapy for chronic HCV patients in real life settings.

Helicobacter pylori Infection in Africa: Update of the Current Situation and Challenges.

BACKGROUND: The burden of Helicobacter pylori infection (HPI) in Africa remains high with varying levels of prevalence among children and adults reported in different regions of the continent. Persistent and uneradicated HPI could result in gastric cancer, although less severe pathological outcomes have been reported among Africans - the so-called "African enigma." SUMMARY: Analysis of endoscopic findings of the upper gastrointestinal tract demonstrates similarities with that of patients from the West. Thus, it could be asserted that the true picture of HPI in Africa is yet to be unveiled due to several challenges including inadequate health-care system, lack of treatment guidelines and standardized protocol for diagnosis, and lack of data. This review explores the prevalence, diagnosis, treatment, and health-care system in Africa as it relates to HPI, thus providing an update and highlighting the need for an African HPI guideline. KEY MESSAGES: There is high prevalence of Helicobacter pylori infection (HPI) in Africa with an increasing burden of antibiotic resistance. Various methods including invasive and noninvasive methods are deployed in the diagnosis of HPI in Africa. There is a need for consensus on diagnosis and treatment of HPI in Africa.

Clinical study evaluating the efficacy of ivermectin in COVID-19 treatment: A randomized controlled study.

Researchers around the world are working at record speed to find the best ways to treat and prevent coronavirus disease 2019 (COVID-19). This study aimed to evaluate the efficacy of ivermectin for the treatment of hospitalized mild to moderate COVID-19 infected patients. This was a randomized open-label controlled study that included 164 patients with COVID-19. Patients were randomized into two groups where Group 1 (Ivermectin group) included patients who received ivermectin 12 mg once daily for 3 days with standard care and Group 2 (control group) included patients who received standard protocol of treatment alone for 14 days. The main outcomes were mortality, the length of hospital stay, and the need for mechanical ventilation. All patients were followed up for 1 month. Overall, 82 individuals were randomized to receive ivermectin plus standard of care and 82 to receive standard of care alone. Patients in the ivermectin group had a shorter length of hospital stay (8.82 ± 4.94 days) than the control group (10.97 ± 5.28 days), but this was not statistically significant (p = 0.085). Three patients (3.7%) in each group required mechanical ventilation (p = 1.00). The death rate was three patients in the ivermectin group (3.7%) versus four patients (4.9%) in the control group without any significant difference between the two groups (p = 1.00). Although there was no statistically significant difference in any endpoints by ivermectin doses (12 mg/day for 3 days); there was an observed trend to reducing hospital stay in the ivermectin-treated group.

Pregnancy outcome of anti-HCV direct-acting antivirals: Real-life data from an Egyptian cohort.

We aimed to assess the pregnancy outcome in women with chronic HCV who had negative pregnancy test prior to the anti-HCV course and had unintended pregnancy while on HCV treatment. Hundred patients with a mean age of 30 ± 6.7 y were included and advised to withhold antivirals and continue follow-up in viral hepatitis and obstetrics centres till delivery. All patients received a 12-weeks regimen of anti-HCV [sofosbuvir plus daclatasvir (SOF/DCV): n = 95, SOF/DCV plus ribavirin: n = 3, and paritaprevir/ritonavir/ombitasvir plus ribavirin: n = 2]. Only nine patients completed the full antiviral course against medical advice, and 91 stopped between on-treatment weeks 4 and 8. Eighty-eight patients delivered full-term babies, eight had preterm babies and two had abortions. Of the nine patients who completed the full course of DAAs, seven (77.8%) delivered normal babies, attended their post-treatment week 12 visit, and all (100%) achieved sustained virological response. No major antiviral-related adverse events were reported.

Current situation of viral hepatitis in Egypt.

An estimated 8-10 million people suffer from viral hepatitis in Egypt. Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the major causes of viral hepatitis in Egypt as 50% or more of the Egyptian population are already exposed to HAV infection by the age of 15. In addition, over 60% of the Egyptian population test seropositive for anti-HEV in the first decade of life. HEV mainly causes self-limiting hepatitis; however, cases of fulminant hepatitis and liver failure were reported in Egypt. Hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis D virus (HDV) are the main causes of chronic hepatitis, liver cirrhosis, and liver cancer (hepatocellular carcinoma [HCC]) in Egypt. Globally, Egypt had the highest age-standardized death rate due to cirrhosis from 1990 to 2017. The prevalence rate of HBV (1.3%-1.5%) has declined after national infantile immunization. Coinfection of HBV patients with HDV is common in Egypt because HDV antibodies (IgG) vary in range from 8.3% to 43% among total HBV patients. After the conduction of multiple national programs to control HCV infection, a lower rate of HCV prevalence (4.6%) was recently reported. Data about the incidence of HCV after treatment with direct antiviral agents (DAAs) are lacking. An HCC incidence of 29/1000/year in cirrhotic patients after DAA treatment is reported. A higher rate of infiltrative pattern among HCC patients after DAA treatment is also recognized. Viral hepatitis is one of the major public health concerns in Egypt that needs more attention and funding from health policymakers.

Alcohol-Related Liver Disease Is Rarely Detected at Early Stages Compared With Liver Diseases of Other Etiologies Worldwide.

BACKGROUND & AIMS: Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. METHODS: We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. RESULTS: Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). CONCLUSIONS: In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

Novel scores combining AFP with non-invasive markers for prediction of liver fibrosis in chronic hepatitis C patients.

Serum levels of alpha-fetoprotein (AFP) were reported to increase in patients with significant or advanced hepatic fibrosis. Combination of non-invasive tests decreases the use of liver biopsy in large proportion of chronic HCV patients. The aim of the study was to compare and combine AFP with commonly used non-invasive fibrosis tests in novel scores for prediction of different stages of hepatic fibrosis. Six hundred and fifty two treatment naïve chronic hepatitis C patients were enrolled. Demographic data, basic pre-treatment laboratory tests including complete blood count (CBC), liver biochemical profile and renal functions test, international normalized ratio (INR) in addition to AFP, liver stiffness measurement (LSM) by Fibroscan and liver biopsies were retrospectively analyzed. AST to Platelet Ratio Index (APRI) and FIB-4 scores were calculated. Different predictive models using multivariate logistic regression analysis were generated and presented in equations (scores) composed of a combination of AFP, LSM plus FIB-4/APRI scores. AFP was correlating significantly with LSM, FIB-4, and APRI scores. Areas under receiver operating characteristic curves (AUROCs) for predicting significant hepatic fibrosis, advanced hepatic fibrosis, and cirrhosis were 0.897, 0.931, and 0.955, respectively, for equations (scores) containing AFP, LSM, and FIB-4. AUROCs for predicting significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis were 0.897, 0.929, and 0.959, respectively, for equations (scores) containing AFP, LSM, and APRI. The study shows that combining AFP to serum biomarkers and LSM increases their diagnostic performance for prediction of different stages of liver fibrosis.

After successful hepatitis C virus antiviral therapy: It looks that normal alanine aminotransferase level is not the normal.

BACKGROUND: Normal serum alanine aminotransferase (ALT) levels differ with age, gender, and body mass index. Adjusting the upper limits of normal (ULN) for ALT needs further research in different populations. Aim of this work was to monitor the effect of successful chronic hepatitis C (CHC) treatment on the ALT levels in patients with normal pretreatment ALT. METHODS: Data of 1160 CHC patients with persistent pretreatment normal liver enzymes were retrospectively analyzed. Treatment response to direct acting antiviral agents (DAAs) therapy was recorded. Changes in ALT levels before and after treatment were analyzed by patients' demographic, laboratory, and radiologic characteristics. Areas under the receiver operating characteristic curve (AUROC) of ALT after treatment were used to generate a new ALT ULN. RESULTS: Males were 568 (49%) and females 592 (51%) with a mean age of 50.7 years. After treatment, mean (±SD) of ALT levels significantly decreased from (26.3±7.8) to (19.1±10.9). This reduction was more significant in interferon-free than interferon-based regimens. ROC curve analyses suggested a new ALT ULN cut off (26.4 IU/L) in the treated patients (sensitivity=78.6%, specificity=83.8%, AUROC=0.89. This cutoff dropped to 14.7 IU/L in cirrhotic patients (sensitivity=77.4%, specificity=44.7%, AUROC=0.612). The identified cutoffs were 16.3 IU/L (sensitivity=66.7%, specificity=47.5%, AUROC=0.499) and 15.5 IU/L (sensitivity=76.5%, specificity=51.3%, AUROC=0.576) in males and females, respectively. CONCLUSION: The current ALT ULN needs readjustment to identify new normal cutoffs in CHC patients. Posttreatment cutoffs differ according to gender, pretreatment liver affection, and treatment regimen.