A Machine Learning-Based Mortality Prediction Model for Patients with Chronic Hepatitis C Infection: An Exploratory Study.

Background: Chronic hepatitis C (HCV) infection presents global health challenges with significant morbidity and mortality implications. Successfully treating patients with cirrhosis may lead to mortality rates comparable to the general population. This study aims to utilize machine learning techniques to create predictive mortality models for individuals with chronic HCV infections. Methods: Data from chronic HCV patients at Sultan Qaboos University Hospital (2009-2017) underwent analysis. Data pre-processing handled missing values and scaled features using Python via Anaconda. Model training involved SelectKBest feature selection and algorithms such as logistic regression, random forest, gradient boosting, and SVM. The evaluation included diverse metrics, with 5-fold cross-validation, ensuring consistent performance assessment. Results: A cohort of 702 patients meeting the eligibility criteria, predominantly male, with a median age of 47, was analyzed across a follow-up period of 97.4 months. Survival probabilities at 12, 36, and 120 months were 90.0%, 84.0%, and 73.0%, respectively. Ten key features selected for mortality prediction included hemoglobin levels, alanine aminotransferase, comorbidities, HCV genotype, coinfections, follow-up duration, and treatment response. Machine learning models, including the logistic regression, random forest, gradient boosting, and support vector machine models, showed high discriminatory power, with logistic regression consistently achieving an AUC value of 0.929. Factors associated with increased mortality risk included cardiovascular diseases, coinfections, and failure to achieve a SVR, while lower ALT levels and specific HCV genotypes were linked to better survival outcomes. Conclusions: This study presents the use of machine learning models to predict mortality in chronic HCV patients, providing crucial insights for risk assessment and tailored treatments. Further validation and refinement of these models are essential to enhance their clinical utility, optimize patient care, and improve outcomes for individuals with chronic HCV infections.

Association of the Magnitude of Anti-SARS-CoV-2 Vaccine Side Effects with Sex, Allergy History, Chronic Diseases, Medication Intake, and SARS-CoV-2 Infection.

Vaccination provides the best protection against the increasing infections of SARS-CoV-2. The magnitude and type of anti-SARS-CoV-2 vaccine side effects (SEs) depend on parameters that are not fully understood. In this cross-sectional study, the associations between different anti-SARS-CoV-2 vaccine SEs and age, sex, the presence of chronic diseases, medication intake, history of allergies, and infections with SARS-CoV-2 were investigated. Our survey used the Google platform and had 866 participants, contacted through e-mails, social media and chain referral sampling (margin of error ≈ 4.38%, 99% confidence). More than 99% of the participants received the BNT162b2 and ChAdOx1-S vaccines. Being female, having chronic diseases, taking medicines routinely and the presence of a SARS-CoV-2 infection (p < 0.05) were associated with strong SEs after the BNT162b2 vaccine second dose. Having a history of allergies and a female sex (p < 0.01) were associated with strong SEs after the ChAdOx1-S vaccine second dose. Furthermore, the results reveal, for the first time, the associations between having a history of allergies, chronic diseases, medication usage, and SEs of a strong magnitude for the BNT162b2 and ChAdOx1-S vaccines. Additionally, this study supports the association of the female sex and infection with SARS-CoV-2 with an increased potential of developing stronger SEs with certain anti-SARS-CoV-2 vaccines.

Predictors of survival among patients with chronic hepatitis C at a tertiary care center in Oman.

BACKGROUND: Chronic hepatitis C (CHC) is a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. This study aimed to determine rates and predictors of survival among Omani patients with CHC at a tertiary hospital in Muscat, Oman. METHODS: This ambidirectional cohort study included all CHC patients who presented to the Sultan Qaboos University Hospital between January 2009 and December 2017. Baseline demographic, clinical, laboratory, and radiological data were analyzed. Patients were followed-up until death or the endpoint of the study (April 2022) to determine survival and associations with other parameters. RESULTS: A total of 702 CHC patients were included, of which 398 (56.7%) were under 50 years of age and 477 (67.9%) were male. Overall, 180 patients (25.6%) died by the study endpoint. The mean duration of follow-up was 93.3 ± 48.0 months. The 5-year survival rate was estimated to be 80.5%, while the 10-year survival was 73%. Sustained virological response and the absence of diabetes mellitus, chronic kidney disease, HCC, or other malignancies were associated with significantly better overall survival. The 3- and 5-year survival rate of patients with hepatitis C virus (HCV)-related HCC was 46.5% and 27.6%, respectively, with a median survival of 29.5 months. Co-infection with hepatitis B was associated with poor survival among this subgroup; conversely, early HCV screening and the presence of a single HCC lesion were associated with better overall survival. CONCLUSIONS: National policies for early CHC screening and rapid treatment are needed to improve survival rates in this population.

Differential Production of Midkine and Pleiotrophin by Innate APCs upon Stimulation through Nucleic Acid-Sensing TLRs.

Midkine (MK) and pleiotrophin (PTN) belong to the same family of cytokines. They have similar sequences and functions. Both have important roles in cellular proliferation, tumors, and diseases. They regulate and are expressed by some immune cells. We have recently demonstrated MK production by some human innate antigen-presenting cells (iAPCs), i.e., monocyte-derived dendritic cells (MDDCs) and macrophages stimulated through Toll-like receptor (TLR)-4, and plasmacytoid dendritic cells (pDCs) stimulated through TLR 7. While PTN production was only documented in tissue macrophages. TLRs 3, 7, 8, and 9 are nucleic acid sensing (NAS) TLRs that detect nucleic acids from cell damage and infection and induce iAPC responses. We investigated whether NAS TLRs can induce MK and PTN production by human iAPCs, namely monocytes, macrophages, MDDCs, myeloid dendritic cells (mDCs), and pDCs. Our results demonstrated for the first time that PTN is produced by all iAPCs upon TLR triggering (p < 0.01). IAPCs produced more PTN than MK (p < 0.01). NAS TLRs and iAPCs had differential abilities to induce the production of MK, which was induced in monocytes and pDCs by all NAS TLRs (p < 0.05) and in MDDCs by TLRs 7/8 (p < 0.05). TLR4 induced a stronger MK production than NAS TLRs (p ≤ 0.05). Monocytes produced higher levels of PTN after differentiation to macrophages and MDDCs (p < 0.05). The production of MK and PTN differs among iAPCs, with a higher production of PTN and a selective induction of MK production by NAS TLR. This highlights the potentially important role of iAPCs in angiogenesis, tumors, infections, and autoimmunity through the differential production of MK and PTN upon TLR triggering.

Mortality and complications in Omani patients with beta-thalassemia major: a long-term follow-up study.

BACKGROUND AND AIM: Beta thalassemia major (ß-TM) is a genetic blood disorder requiring lifelong blood transfusions.  The resulting iron overload damages multiple organs, particularly the heart and endocrine organs. This study aimed to describe and assess the predictors of survival and complications in Omani patients with ß-TM.   Methods: All ß-TM patients registered in the day care of Sultan Qaboos University Hospital were included in this retrospective study.   Results: There were 187 patients with ß-TM with a median follow-up of 24.9 years.  The median ages at diagnosis and the start of chelation were 0.7 and 4.8 years, respectively. The following complications developed at different time points [Median (age in years), Complication Free Probability at 20 years]: Death (20.0 years;85%), hypogonadism (15.9 years;50%), insulin-dependent or non-insulin dependent diabetes (20.0 years;88%), cardiac complications (20.3 years;91%), osteoporosis (20.7 years;96%), hypothyroidism (25.7 years;97%), liver complications (7.3 years;54%). The number of complications predicted death (P = 0.0038). Those born after 1980 had a lower risk of death (P = 0.005), hypogonadism (P = < 0.0001), and cardiac complications (P = 0.004). Higher serum ferritin at the start of chelation was associated with the development of diabetes (P = < 0. 001).   Conclusions: This long-term study shows complications development at different ages, and the number of complications is associated with survival. Later birth cohorts had a lower risk of death, hypogonadism, and cardiac complications. There was a persistent negative impact of delay in the start of iron chelation that is present even after a long follow-up. (www.actabiomedica.it).

Hepatitis B Related Liver Cirrhosis in Oman.

Objectives: An estimated 887 000 deaths were due to chronic hepatitis B (CHB) related complications in 2015 worldwide. Most of these deaths were related to decompensated liver cirrhosis and hepatocellular carcinoma (HCC). Oman is a country with an intermediate prevalence of CHB. The Hepatitis B vaccine was introduced in Oman in 1990, with a vaccine coverage rate of > 95% reported in 2005. Despite the association between CHB and liver cirrhosis and HCC, no available data from Oman demonstrates CHB-related liver cirrhosis. We sought to estimate the prevalence of CHB among patients with liver cirrhosis from Oman. Methods: We conducted a retrospective chart review of patients diagnosed with liver cirrhosis at Sultan Qaboos University Hospital and Armed Forces Hospital between January 2006 and April 2013. All pediatric and adult patients with liver cirrhosis were included. We collected demographic data and liver cirrhosis investigations. Results: A total of 419 patients were included. Two-thirds of the patients were males. The median age was 59 years. Omani patients represented the majority (97.1%) of patients with cirrhosis. Diabetes mellitus was present in almost half of the patients, and 22.2% indicated alcohol consumption. Evidence of previous or current hepatitis B virus (HBV) infection was found in about half of the cohort (51.3%). Only 3.3% of CHB patients were positive for hepatitis B e-Antigen. HBV DNA was detected in 47 patients (21.9%), of which 20 patients had a high viral load > 2000 IU/ml. More than a third (36.7%) had positive hepatitis B surface antibody (anti-HBs), indicating immunity to HBV, and 27.1% was due to previous HBV infection, 5.2% was immune due to vaccination, and 3.7% had positive anti-HBs and unknown anti-HBc status. Negative anti-HBs was found in 34.1% of the cohort and 29.9% had unknown immunity status. HBV coinfection with HCV was found in 24.7% of HBV patients with cirrhosis. Conclusions: Serological markers of CHB are common among liver cirrhosis patients in Oman. CHB related cirrhosis was more common in old age males than females (70.7% vs. 29.3%, respectively; p < 0.010). Evidence of past or present HBV infection was found in > 50% of the patients.

Human macrophages and monocyte-derived dendritic cells stimulate the proliferation of endothelial cells through midkine production.

The cytokine midkine (MK) is a growth factor that is involved in different physiological processes including tissue repair, inflammation, the development of different types of cancer and the proliferation of endothelial cells. The production of MK by primary human macrophages and monocyte-derived dendritic cells (MDDCs) was never described. We investigated whether MK is produced by primary human monocytes, macrophages and MDDCs and the capacity of macrophages and MDDCs to modulate the proliferation of endothelial cells through MK production. The TLR stimulation of human monocytes, macrophages and MDDCs induced an average of ≈200-fold increase in MK mRNA and the production of an average of 78.2, 62, 179 pg/ml MK by monocytes, macrophages and MDDCs respectively (p < 0.05). MK production was supported by its detection in CD11c+ cells, CLEC4C+ cells and CD68+ cells in biopsies of human tonsils showing reactive lymphoid follicular hyperplasia. JSH-23, which selectively inhibits NF-κB activity, decreased the TLR-induced production of MK in PMBCs, macrophages and MDDCs compared to the control (p < 0.05). The inhibition of MK production by macrophages and MDDCs using anti-MK siRNA decreased the capacity of their supernatants to stimulate the proliferation of endothelial cells (p = 0.01 and 0.04 respectively). This is the first study demonstrating that the cytokine MK is produced by primary human macrophages and MDDCs upon TLR triggering, and that these cells can stimulate endothelial cell proliferation through MK production. Our results also suggest that NF-κB plays a potential role in the production of MK in macrophages and MDDCs upon TLR stimulation. The production of MK by macrophages and MDDCs and the fact that these cells can enhance the proliferation of endothelial cells by producing MK are novel immunological phenomena that have potentially important therapeutic implications.

Prevalence and persistence of SARS-CoV2 antibodies among healthcare workers in Oman.

OBJECTIVES: The primary objective is to determine the prevalence of SARS-CoV-2 antibodies persistence among HCWs and specifically among asymptomatic HCWs. A secondary objective is to determine the duration of persistent SARS-CoV-2 antibodies post infection and factors affecting this duration. The findings are expected to open the door for further research into the role of SARS-CoV-2 antibodies during the current COVID-19 pandemic. METHODOLOGY: HCWs were divided into high, intermediate, and low risk based on their type and location of work. All participants filled a questionnaire. Blood samples were obtained for SARS-CoV-2 IgG/total antibodies. A documented SARS-CoV-2 PCR or Anti-SARS-CoV-2 IgG/total antibodies defined the primary outcome. The probability of persistence of antibody was calculated using the Kaplan-Meier estimator. Logistic and Cox regression were used where appropriate. RESULTS: A total of 1111 HCWs were included. The median age 37 years (IQR: 31-43). More than half (67.2%) were females. The primary outcome was seen in 373 (33.6%) participants with a median age of 36 years (IQR: 29-41). Only 37.2% of those with documented positive SARS-CoV-2 PCR had reactive serology, while only 16.2% of those with reactive serology had documented positive SARS-CoV-2 PCR. Male gender (OR 0.44, P < 0.001) and older age (OR 0.98, P < 0.019) were associated with a lower risk of acquiring SARS-CoV-2 infection. The probability of persistent SARS-CoV-2 antibodies at six months was 60.2% (95% CI: 49.5%-73.1%). Omanis had a higher probability of losing the antibody than others (HR 2.63, P = 0.021). CONCLUSION: We report a high prevalence of anti-SARS-CoV-2 antibodies among HCWs in Oman, specifically among asymptomatic HCWs. Community was the most likely source of infection. Therefore, the society must adhere to the roles and regulations set to reduce the risk of transmission. We demonstrate a high percentage of seroconversion post initial infection, and the persistence of SARS-CoV-2 antibodies at six months in more than half of those previously infected. We demonstrated a new interesting finding of fast decline of SARS-CoV2 antibody levels over time among different nationalities and this requires further research.

Risk Factors for Hepatitis B Virus Transmission in Oman.

OBJECTIVES: Hepatitis B virus (HBV) is a major public health problem worldwide. The prevalence of HBV is dependent on the modes of transmission. Chronic hepatitis B (CHB) infection can progress to liver cirrhosis and hepatocellular carcinoma. Oman is regarded as an intermediate endemic region and has had a neonatal vaccine against HBV since 1990. However, little research has been conducted regarding risk factors for HBV transmission. Our study aimed to identify the prevalence of major risk factors for acquiring HBV in Oman. METHODS: We conducted a retrospective chart review of all adult Omani patients diagnosed with CHB at two tertiary hospitals in Oman, Sultan Qaboos University Hospital and Armed Forces Hospital, between February 2009 and July 2013. The prevalence of major risk factors was identified by interviewing CHB patients using a standard questionnaire during their follow-up visits to the hepatology clinic at both hospitals. The risk factor frequency was stratified by age, gender, and educational level. RESULTS: A total of 274 patients were interviewed; 52.2% of the participants were males. The median age for men was 35.9 years and 35.1 years for women, with 75.5% aged 20-39 years old. The antenatal screening was the most common means of identifying HBV infection in females, and pre-blood donation screening was the most common in males. Intra-familial contact with HBV infected persons and behavioral risks such as body piercing (females) and barber shaving (males) were more common than nosocomial risk factors. Knowledge about HBV infection was scarce among our participants. More than half of the participants had a positive family history of HBV infection. There was a significant association between HBV infection and age groups, and educational levels (p < 0.050 and p < 0.001, respectively). Among those who were infected due to intra-familial contact or behavioral risk, there was a significant difference between the two sexes (p < 0.020) and between the three age groups (< 23, 23-28, >28) of HBV positive mothers (33.3%, 14.3%, and 6.6%, respectively; p < 0.050). There was also a statistically significant difference among different educational levels (p < 0.050). CONCLUSIONS: Direct contact of infected individuals within a family and exposure to high-risk behaviors such as piercing and barber shaving are the main reported risk factors for HBV infection in Omani patients. Reducing the vertical and horizontal transmission of HBV in Oman could be improved by implementing routine antenatal screening of pregnant women and a greater focus on contact screening, respectively.

Hepatocellular Carcinoma in Oman: An analysis of 284 cases.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the most common type of primary liver tumour worldwide and is increasing in incidence. This study aimed to describe the clinical characteristics of HCC among Omani patients, along with its major risk factors, outcomes and the role of surveillance. METHODS: This retrospective case-series study was conducted between January 2008 and December 2015 at the three main tertiary care hospitals in Oman. All adult Omani patients diagnosed with HCC and visited these hospitals during the study period were included. Relevant data were collected from the patients' electronic medical records. RESULTS: A total of 284 HCC patients were included in the analysis. The mean age was 61.02 ± 11.41 years and 67.6% were male. The majority had liver cirrhosis (79.9%), with the most common aetiologies being chronic hepatitis C (46.5%) and B (43.2%). Only 13.7% of cases were detected by the HCC surveillance programme. Approximately half of the patients (48.5%) had a single liver lesion and 31.9% had a liver tumour of >5 cm in size. Approximately half (49.2%) had alpha-fetoprotein levels of ≥200 ng/mL. The majority (72.5%) were diagnosed using multiphase computed tomography alone. Less than half of the patients (48.9%) were offered one or more HCC treatment modalities. CONCLUSION: The majority of Omani HCC patients were male and had cirrhosis due to viral hepatitis. In addition, few patients were identified by the national surveillance programme and presented with advanced disease precluding therapeutic or even palliative treatment.

Cystic Fibrosis Liver Disease: Know More.

Cystic fibrosis (CF) is a multisystem disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CFTR is expressed in the apical surface of cholangiocytes. Homozygous CFTR gene mutation results in viscous and acidic bile secretions secondary to deficient surface fluid and bicarbonate efflux. Viscous, inspissated bile causes ductular obstruction and hepatotoxicity from retained bile components, leading to fibrosis and ultimately cirrhosis, known as CF liver disease (CFLD). CFLD is the third leading cause of death in CF patients. CFLD manifestations can take many forms. They range from asymptomatic elevation of transaminases to cirrhosis and end-stage liver disease. CFLD is diagnosed after excluding other causes of chronic liver disease. To date, there is no effective therapy to prevent or treat CFLD. Management of CFLD emphasizes on optimizing nutritional status. Ursodeoxycholic acid is the only available treatment that may prevent progression of CFLD at present. All CF patients with CFLD need annual investigations and follow-up for early detection of the disease. Liver transplantation should be considered in patients with decompensated cirrhosis and portal hypertension, with acceptable long-term outcomes. Novel therapies of CFLD are promising. This review article aims to summarize the published literature on CFLD, its pathophysiology, clinical features and complications, and management including new therapeutic options.

Epidemiology of Chronic Hepatitis C Infections at a Tertiary Care Centre in Oman.

OBJECTIVES: Chronic hepatitis C (CHC) is a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. However, there is a lack of data regarding the epidemiology of CHC in Oman. This study aimed to describe the clinicopathological characteristics and outcomes of CHC-infected patients at a tertiary care hospital in Oman. METHODS: This retrospective descriptive hospital-based study included all CHC-infected patients who presented to the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, between January 2010 and December 2015. The baseline demographic, clinical, laboratory and radiological data of the patients were analysed. RESULTS: A total of 603 CHC-infected patients were identified during the study period; of these, 65.8% were male and the mean age was 44.8 ± 16.5 years. The main risk factors associated with CHC infection were intravenous drug abuse (23.9%) and a history of blood transfusions (20.7%). The most prevalent virus genotypes were 1 and 3 (44.0% and 35.1%, respectively). Upon initial presentation, 33.0% of the cohort had liver cirrhosis; of these, 48.7% had decompensated cirrhosis and 23.1% had HCCs. Liver transplantation was only performed for 7.5% of the cirrhosis patients, mostly as a curative treatment for HCC. CONCLUSION: The implementation of national policies to prevent hepatitis C transmission and encourage the early screening of at-risk patients is recommended to reduce the burden and consequences of this disease in Oman.

Increased CD86 but Not CD80 and PD-L1 Expression on Liver CD68+ Cells during Chronic HBV Infection.

BACKGROUND: The failure to establish potent anti-HBV T cell responses suggests the absence of an effective innate immune activation. Kupffer cells and liver-infiltrating monocytes/macrophages have an essential role in establishing anti-HBV responses. These cells express the costimulatory molecules CD80 and CD86. CD80 expression on antigen-presenting cells (APCs) induces Th1 cell differentiation, whereas CD86 expression drives the differentiation towards a Th2 profile. The relative expression of CD80, CD86 and PD-L1 on APCs, regulates T cell activation. Few studies investigated CD80 and CD86 expression on KCs and infiltrating monocytes/macrophages in HBV-infected liver and knowledge about the expression of PD-L1 on these cells is controversial. The expression of these molecules together in CD68+ cells has not been explored in HBV-infected livers. METHODS: Double staining immunohistochemistry was applied to liver biopsies of HBV-infected and control donors to explore CD80, CD86 and PD-L1 expression in the lobular and portal areas. RESULTS: Chronic HBV infection was associated with increased CD68+CD86+ cell count and percentage in the lobular areas, and no changes in the count and percentage of CD68+CD80+ and CD68+PD-L1+ cells, compared to the control group. While CD68+CD80+ cell count in portal areas correlated with the fibrosis score, CD68+CD80+ cell percentage in lobular areas correlated with the inflammation grade. CONCLUSION: The upregulation of CD86 but not CD80 and PD-L1 on CD68+ cells in HBV-infected livers, suggests that these cells do not support the induction of potent Th1. Moreover, the expression of CD80 on CD68+ cells correlates with liver inflammation and fibrosis.

A Potential Inhibitory Profile of Liver CD68+ Cells during HCV Infection as Observed by an Increased CD80 and PD-L1 but Not CD86 Expression.

AIM: The lack of potent innate immune responses during HCV infection might lead to a delay in initiating adaptive immune responses. Kupffer cells (KCs) and liver-infiltrating monocytes/macrophages (CD68+ cells) are essential to establish effective anti-HCV responses. They express co-stimulatory molecules, CD80 and CD86. CD86 upregulation induces activator responses that are then potentially regulated by CD80. The relative levels of expression of CD80, CD86 and the inhibitory molecule, PD-L1, on CD68+ cells modulate T cell activation. A few studies have explored CD80 and PD-L1 expression on KCs and infiltrating monocytes/macrophages in HCV-infected livers, and none investigated CD86 expression in these cells. These studies have identified these cells based on morphology only. We investigated the stimulatory/inhibitory profile of CD68+ cells in HCV-infected livers based on the balance of CD80, CD86 and PD-L1 expression. METHODS: CD80, CD86 and PD-L1 expression by CD68+ cells in the lobular and portal areas of the liver of chronic HCV-infected (n = 16) and control (n = 14) individuals was investigated using double staining immunohistochemistry. RESULTS: The count of CD68+ KCs in the lobular areas of the HCV-infected livers was lower than that in the control (p = 0.041). The frequencies of CD68+CD80+ cells and CD68+PD-L1+ cells in both lobular and total areas of the liver were higher in HCV-infected patients compared with those in the control group (p = 0.001, 0.031 and 0.007 respectively). Moreover, in the lobular areas of the HCV-infected livers, the frequency of CD68+CD80+ cells was higher than that of CD68+CD86+ and CD68+PD-L1+ cells. In addition, the frequencies of CD68+CD80+ and CD68+CD86+ cells were higher in the lobular areas than the portal areas. CONCLUSIONS: Our results show that CD68+ cells have an inhibitory profile in the HCV-infected livers. This might help explain the delayed T cell response and viral persistence during HCV infection.