Shousha, H. I., H. Ayman, and M. B. Hashem, "Climate Changes and COVID-19.", Advances in experimental medicine and biology, vol. 1458, pp. 217-231, 2024. Abstract

Climatic change, which influences population growth and land usage, has been theorized to be linked to the emergence and spread of new viruses like the currently unfolding COVID-19 pandemic. In this chapter, we explain how climate change may have altered the beginning, transmission, and maybe even the sickness consequences of the COVID-19 pandemic. Where possible, we also provide mechanistic explanations for how this may have occurred. We have presented evidence that suggests climate change may have had a role in the establishment and transmission of SARS-CoV-2 infection, and most possibly even in some of its clinical effects. Human activities bringing people into closer contact with bats and animals like pangolins that potentially represent the intermediate hosts, and evidence that climate-induced changes in vegetation are the main reservoir source of coronaviruses for human infection, are among the explanations. Although there are still unsubstantiated indications that the first viral pathogen may have escaped from a laboratory, it is possible that this encounter took place in the field or in marketplaces in the instance of COVID-19. We also present the argument that climate change is working to enhance transmission between diseased and uninfected humans, and this is true regardless of the source of the original development of the disease. Changes in temperature and humidity make it easier for viruses to survive, and the impacts of industrial pollution induce people to cough and sneeze, which releases highly infectious aerosols into the air. These three factors combine to make this a more likely scenario than it would otherwise be. We suggest that changes in climate are contributing to create conditions that are favorable for the development of more severe symptoms of illness. It is more difficult to build the argument for this circumstance, and much of it is indirect. However, climate change has caused some communities to adjust their nutritional habits, both in terms of the quantity of food they eat and the quality of the foods they consume. The effects frequently become apparent as a result of alterations that are imposed on the microbiome of the gut, which, in turn, influence the types of immune responses that are produced. The incidence of comorbidities like diabetes and animal vectors like bats that transmit other illnesses that modify vulnerability to SARS-CoV-2 are also two examples of the factors that have been affected by climate change. In order to curb the development of infectious illnesses caused by new viruses, it is necessary to understand the connection between environmental dynamics and the emergence of new coronaviruses. This knowledge should lead to initiatives aimed at reducing global greenhouse gas emissions.

El-Kassas, M., E. M. F. Barakat, H. I. Shousha, M. Kohla, M. Said, E. F. Moustafa, A. Tawheed, M. A. A. Shamkh, M. M. Nabeel, E. Elkhateeb, et al., "Characteristics and survival of patients with viral versus nonviral associated hepatocellular carcinoma: a multicenter cohort study.", European journal of gastroenterology & hepatology, vol. 37, issue 1, pp. 83-93, 2025. Abstract

BACKGROUND: Viral hepatitis B and C are the leading causes of hepatocellular carcinoma (HCC). With obesity, metabolic-related disorders are increasingly associated with a higher incidence of nonviral HCC. This study aimed to investigate the characteristics, tumor features, treatment outcomes, and survival of patients with viral versus nonviral HCC.

METHODS: This multicenter cohort study was conducted at six tertiary care centers. Patients were recruited between February 2007 and June 2022 and follow-up was recorded until death or the study end (July 2023). The patients were divided into viral-related and nonviral HCC groups. We studied baseline patient characteristics, tumor characteristics, treatment, and overall survival (OS).

RESULTS: This study included 2233 patients, 1913 patients with viral and 320 patients with nonviral HCC. Patients with nonviral HCC presented with more advanced Barcelona Clinic Liver Cancer (BCLC) stages (BCLC stage C or D were present in 26.3% and 53.8% of patients with viral and nonviral HCC, respectively) that affected the median OS (19.167 vs. 13.830 months, P-value <0.001 for viral and nonviral HCC, respectively). The OS did not differ between patients with viral and nonviral HCC treated with resection, percutaneous ablation, trans-arterial chemoembolization, or Sorafinib. The independent factors affecting the survival of nonviral HCC were albumin-bilirubin score (hazard ratio = 2.323, 95% confidence interval (CI): 1.696-3.181, P-value <0.001), tumor size (hazard ratio = 1.085, 95% CI: 1.019-1.156, P-value 0.011), and alpha-fetoprotein (hazard ratio = 1.000, 95% CI: 1.000-1.000, P-value 0.042).

CONCLUSION: Patients with nonviral HCC had higher BMI, worse performance status, BCLC stage, and tumor response than those with viral HCC.

Ramadan, A., M. Kaddah, H. Shousha, and M. El-Kassas, "Personalized treatment approaches in hepatocellular carcinoma.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 26, issue 1, pp. 122-128, 2025. Abstract

Personalized medicine is an emerging field that provides novel approaches to disease's early diagnosis, prevention, treatment, and prognosis based on the patient's criteria in gene expression, environmental factors, lifestyle, and diet. To date, hepatocellular carcinoma (HCC) is a significant global health burden, with an increasing incidence and significant death rates, despite advancements in surveillance, diagnosis, and therapeutic approaches. The majority of HCC lesions develop in patients with liver cirrhosis, carrying the risks of mortality associated with both the tumor burden and the cirrhosis. New therapeutic agents involving immune checkpoint inhibitors and targeted agents have been developed for sequential or concomitant application for advanced HCC but only a tiny percentage of patients benefit from each approach. Moreover, clinicians encounter difficulties determining the most appropriate regimen for each patient. This emphasizes the need for a personalized treatment approach. In other words, patients should no longer undergo treatment based on their tumor's histology but depending on the distinct molecular targets specific to their tumor biology. However, the utilization of precision medicine in managing HCC is still challenging. This review aims to discuss the role of personalized medicine in diagnosing, managing, and defining the prognosis of HCC. We also discuss the role of liquid biopsy and their clinical applications for immunotherapies in HCC. More clinical studies are still necessary to improve the precision of biomarkers used in the treatment decision for patients with HCC.

Shousha, H. I., E. M. F. Barakat, E. Rewisha, M. El-Kassas, E. F. Moustafa, M. Said, A. O. Abdelaziz, S. R. Askar, E. Elkhateeb, A. Tawheed, et al., "Survival of patients with non-viral hepatocellular carcinoma treated with trans-arterial chemoembolization: A multicenter cohort study.", Arab journal of gastroenterology : the official publication of the Pan-Arab Association of Gastroenterology, vol. 26, issue 1, pp. 94-103, 2025. Abstract

BACKGROUND AND STUDY AIMS: Few studies have considered patients treated with trans-arterial chemoembolization (TACE) for non-viral-induced hepatocellular carcinoma (HCC), with some reporting that those patients may have larger tumors, emphasizing the need for determination of the factors affecting survival in such patients. This work aims to study the characteristics and survival of patients with non-viral related HCC treated with TACE.

PATIENTS AND METHODS: This is a multicenter observational study. Patients (166) with non-viral related HCC treated with TACE were recruited from six tertiary care centers (January 2008- June 2022). Follow-up continued until death or the end of the study (August 2023).

RESULTS: The patients had a mean age of 60.2 ± 9.5 years, a male predominance of 79.5 %. The mean size of the lesions was 5.71 ± 3.02 cm, and 42.8 % of the patients had a single lesion. After a median follow-up period of 27.02 months (IQR 14.99-39.37), the median overall survival (OS) was 42.14 months. The Cox regression hazard model revealed that the independent factors affecting survival were: multiple focal lesions, exceeding five in number, have a substantially higher hazard of death (HR = 8.5, p-value = 0.001) compared to those with a single focal lesion. HAP score grade D exhibited a threefold increase in the hazard of death (HR = 3.8, p-value 0.007). Individuals who did not respond positively to treatment faced a significantly higher risk of death (HR = 10.76, p-value 0.001). Albumin-bilirubin score (ALBI), Easy ALBI, platelet albumin (PAL), platelet albumin bilirubin score (PALBI), The hepatoma arterial-embolisation (HAP) and Tumor burden score were found not to impact the survival of our patients.

CONCLUSION: Tumor burden is an important determinant of survival after TACE in patients with non-viral HCC. HAP score can be implemented in selecting patients who would benefit from TACE.

Barakat, E. M. F., M. Kohla, H. Dabees, H. I. Shousha, E. F. Moustafa, M. El-Kassas, M. S. Aziz, E. Elkhateeb, A. O. Abdelaziz, M. O. Abdelmalek, et al., "Tyrosine kinase inhibitors were well-tolerated among patients with different etiologies of advanced HCC with lower survival in non-viral patients.", Scientific reports, vol. 15, issue 1, pp. 20323, 2025. Abstract

We studied the characteristics and survival of patients with sorafenib-treated HCC and impact of underlying etiology on outcomes. This retrospective multicenter study recruited patients with sorafenib-treated advanced HCC (12/2016 to 4/2023) till death or the study end (2/2024). Time to progression (TTP) and overall survival (OS) were recorded. We evaluated; Clinico-laboratory and imaging predictors of OS, The impact of underlying etiology on tumor variables, outcomes and tolerance for sorafenib > 6 months. This study included 706 patients. Median duration of Sorafenib therapy was 240.00 (90.00-360.00) days. Median OS was 314.00(146.00-601.00) days. Median TTP was 180.00(90.00-330.00) days. COX regression revealed that the independent factors of mortality were baseline AST, Tumor size, hepatic vein thrombosis (HVT), development of jaundice and shifting to Regorafenib. Advanced HCCs were more common on top of non-cirrhotic non-viral and HBV-related liver disease. Adverse events, TTP and tumor response didn't differ with the underlying etiology. Median OS was lower in non-viral-related HCC than HCV-related HCC (218.00 versus 326.50 days, P-value = 0.048). Patients who continued sorafenib > 6 months had lower AFP, HVT, adverse effects and better tumor response after 3 months. OS is lower in non-viral Sorafenib-treated HCC compared with viral-related HCC and Sorafenib was well-tolerated among different HCC etiologies.

El-Kassas, M., R. Khalifa, K. M. AlNaamani, H. Shousha, Y. Yilmaz, F. M. Sanai, M. Almattooq, A. Labidi, M. W. I. Akroush, N. Debzi, et al., "Multidisciplinary Team Management of Hepatocellular Carcinoma in the MENA Region: Current Practices, Challenges, and Gaps.", Journal of hepatocellular carcinoma, vol. 12, pp. 1315-1335, 2025. Abstract

PURPOSE: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, with a high disease burden in the Middle East and North Africa (MENA) region. Multidisciplinary teams (MDTs) are essential for optimizing HCC management; however, their implementation and impact may vary across healthcare settings. This study evaluates the structure, decision-making processes, and challenges faced by MDTs in HCC treatment centers across the MENA region.

PATIENTS AND METHODS: This cross-sectional, multicenter study surveyed representatives from 53 HCC treatment centers across 38 cities in 11 MENA countries. A structured questionnaire was electronically distributed to assess MDT composition, meeting frequency, decision-making processes, adherence to clinical guidelines, patient management pathways, and challenges in HCC treatment.

RESULTS: Among the surveyed centers, 84.9% (n=45) reported having an established MDT. The most common specialties involved in MDT composition were hepatology (100%), interventional radiology (97.8%), medical oncology (91.1%), and hepatobiliary surgery (80%). Barcelona Clinic Liver Cancer staging was used in 95.6% of centers. Despite acknowledging MDT benefits, major challenges were documented by participants, including resource limitations (13.2%), financial constraints (13.2%), patient nonadherence (9.4%), and limited access to advanced technology (11.3%). Telemedicine was underutilized (9.4% of centers), and only 15.1% experienced participation in clinical trials.

CONCLUSION: Our result highlights the pivotal role of MDTs in HCC management in the MENA region, demonstrating adherence to evidence-based guidelines and exposing critical gaps in resource availability, technology integration, and patient-centered decision-making. Strengthening MDTs through enhanced resource allocation, digital health adoption, and increased clinical trial participation is essential to improving HCC outcomes in the region.

El-Kassas, M., H. Shousha, and L. R. Roberts, "Addressing Africa's marginalisation in hepatocellular carcinoma clinical trials.", The lancet. Gastroenterology & hepatology, 2025.
Sedhom, S. S., L. M. El Wakeel, E. M. F. Barakat, H. I. Shousha, M. A. Shamkh, S. H. Salama, D. Z. Zaky, and A. A. El Kholy, "The impact of choline supplementation on oxidative stress and clinical outcomes among patients with non-alcoholic fatty liver disease: a randomized controlled study.", Therapeutic advances in chronic disease, vol. 16, pp. 20406223251358659, 2025. Abstract

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by the accumulation of fat in the liver. Nutrition, particularly micronutrients, plays a crucial role in the development and progression of NAFLD.

OBJECTIVES: This study aimed to assess the impact of choline supplementation on oxidative stress, inflammation, and clinical outcomes in patients with NAFLD.

DESIGN: A randomized, controlled, single-blinded study.

METHODS: Eligible NAFLD patients were randomized to; ( = 39), received conventional management plus phosphatidylcholine (PC) 2400 mg/day for 12 weeks, or c ( = 40), received conventional management for 12 weeks, and 10 healthy volunteers were included. Anthropometric, clinical, and laboratory evaluations were performed at baseline and after treatment.

RESULTS: After 12 weeks, choline group showed significant differences versus controls by improvement in controlled attenuation parameter (304 vs 332 dB/m,  < 0.001) and fibrosis score (5.3 vs 6.8 kPa,  < 0.001), reduction in thiobarbituric acid reactive substances levels (1.9 vs 3.8 nmol/mL,  < 0.001), a decline in leptin levels (1.3 vs 2.1 ng/mL,  < 0.001) and liver enzyme (alanine aminotransferase and aspartate aminotransferase),  < 0.001 and 0.004 respectively). Also, the lipid profile improved by a significant decline in triglyceride levels in choline versus controls 133 versus 158,  = 0.048.

CONCLUSION: Choline supplementation in NAFLD patients demonstrated a favorable impact on hepatic steatosis, oxidative stress, inflammatory markers, liver enzyme levels, and lipid profile. These findings suggest that choline may be a promising therapeutic option for NAFLD management. Further large-scale, long-term studies are warranted to investigate the clinical benefits of choline supplementation in NAFLD patients.

TRIAL REGISTRATION: The study was registered at clinicaltrials.gov and given the ID number: NCT05200156.

El-Kassas, M., R. Khalifa, M. A. Medhat, Y. Yilmaz, A. Tumi, A. Labidi, M. Almattooq, F. M. Sanai, M. Elbadry, M. O. Mohammed, et al., "Mapping artificial intelligence adoption in hepatology practice and research: challenges and opportunities in MENA region.", Frontiers in medicine, vol. 12, pp. 1630831, 2025. Abstract

BACKGROUND: Artificial intelligence (AI) is increasingly relevant to hepatology, yet real-world adoption in the Middle East and North Africa (MENA) is uncertain. We assessed awareness, use, perceived value, barriers, and policy priorities among hepatology clinicians in the region.

METHODS: A cross-sectional online survey targeted hepatologists and gastroenterologists across 17 MENA countries. The survey assessed clinical and research applications of AI, perceived benefits, clinical and research use, barriers, ethical considerations, and institutional readiness. Descriptive statistics and thematic analysis were performed.

RESULTS: Of 285 invited professionals, 236 completed the survey (response rate: 82.8%). While 73.2% recognized the transformative potential of AI, only 14.4% used AI tools daily, primarily for imaging analysis and disease prediction. AI tools were used in research by 39.8% of respondents, mainly for data analysis, manuscript writing assistance, and predictive modeling. Major barriers included inadequate training (60.6%), limited AI tool access (53%), and insufficient infrastructure (53%). Ethical concerns focused on data privacy, diagnostic accuracy, and over-reliance on automation. Despite these challenges, 70.3% expressed strong interest in AI training., and 43.6% anticipating routine clinical integration within 1-3 years.

CONCLUSION: MENA hepatologists are optimistic about AI but report limited routine use and substantial readiness gaps. Priorities include scalable training, interoperable infrastructure and standards, clear governance with human-in-the-loop safeguards, and region-specific validation to enable safe, equitable implementation.

Abdelhamed, W., H. Shousha, and M. El-Kassas, "Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end?", Liver research (Beijing, China), vol. 8, issue 3, pp. 141-151, 2024. Abstract
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Hepatocellular carcinoma (HCC) is the sixth most prevalent form of cancer globally and the third leading cause of cancer-related mortality. The incidence of portal vein tumor thrombosis (PVTT) in HCC patients is 21% at one year and 46% at three years. The presence of PVTT has consistently been associated with a poor prognosis for HCC patients over the past decades. Notably, HCC prognosis is influenced not only by the presence of PVTT but also by the degree or extent of PVTT. Currently, there is a lack of global consensus or established protocols regarding the optimal management of HCC with associated PVTT. The Barcelona Clinic for Liver Cancer classifies HCC patients with PVTT as stage C, indicating an advanced stage, and limiting treatment recommendations for these patients to systemic therapy. In recent years, there has been an increase in the availability of therapeutic options for HCC patients with PVTT. Treatment modalities include systemic therapy, transarterial chemoembolization, surgical resection, stereotactic body radiotherapy, transarterial radioembolization, and liver transplantation. An ideal therapy for each patient necessitates a multidisciplinary approach. This review article presents the latest updates in managing HCC patients with PVTT.

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