Changes in the Etiologies of Liver Cancer in Upper Egypt over a Decade from 2010 to 2020: A Single Tertiary Care Center Study.

Yasser Fouad The profile of liver diseases in Egypt is changing dramatically and viral hepatitis is declining, while the fatty liver disease is increasing dramatically. However, the impact of these changes on the profile of hepatocellular carcinoma (HCC) remains uncertain. Therefore, we determined the temporal trends in the etiologies of HCC in Egypt over a decade. We retrospectively analyzed data from consecutive patients who were diagnosed with HCC over 10 years (2010-2020) in a large center in Upper Egypt. Standard tests were utilized to diagnose hepatitis C virus (HCV) and hepatitis B virus. In the absence of other liver disorders, the presence of obesity, or diabetes in the absence of other risk factors, metabolic dysfunction-associated fatty liver disease (MAFLD) was diagnosed. A total of 1,368 HCC patients were included, in which 985 (72%) had HCV, 58 (4%) had hepatitis B virus, and 143 (10.5%) had MAFLD, 1 patient had hemochromatosis, 1 had autoimmune liver disease, and 180 (13%) patients were with unknown cause. The annual proportions of MAFLD-related HCC were increased significantly between 8.3% in 2010 and 20.6% in 2020 ( p = 0.001), while HCV-related HCC declined from 84.8 to 66.7% ( p = 0.001). Throughout the study period, there were significant increases in the age at diagnosis of HCC, the proportion of female patients, obesity, diabetes, and less severe liver dysfunction at diagnosis ( p < 0.05 for all). With the decline of HCV, MAFLD is becoming a major cause of HCC in Egypt, which has increased substantially over the past 10 years. This study urges the creation of comprehensive action strategies to address this growing burden.

Screening for maternal cytomegalovirus infection during pregnancy and pregnancy outcome in patients with liver disease: an observational study.

BACKGROUND: Cytomegalovirus (CMV) infection among pregnant females could induce CMV hepatitis with possible changes in liver stiffness measurement (LSM) which could be reversibly increased during normal pregnancies, particularly in the third trimester. This study aimed to detect the prevalence of CMV infection among pregnant females with and without chronic liver disease and to evaluate the effects of CMV infection on LSM and pregnancy outcomes in comparison to non-CMV-infected pregnant females. METHODS: This is an observational prospective study that included 201 pregnant ladies presented to the liver disease with pregnancy clinic, Cairo University from March 2018 to April 2019. We assessed the laboratory results, abdominal ultrasonography, LSM using ARFI elastography, and pregnancy outcomes. RESULTS: Two hundred and one pregnant ladies were divided into ; group 1: pregnant ladies with normal pregnancy (n = 128), group 2: pregnant ladies with chronic liver diseases not related to pregnancy (n = 35), and group 3: pregnant ladies with pregnancy-related liver diseases (n = 38). Positive CMV serology (either/or, +ve CMV-IgM, IgG) was detected in 106/201 patients (52.74%), and fifteen of them had an active infection (IgG +, IgM+, PCR+). Pregnant females with chronic liver diseases not related to pregnancy had significantly higher serum levels of CMV IgM, IgG, and PCR. Moreover, LSM had a significant correlation with CMV IgG and CM_PCR in normal pregnant ladies. Maternal mortality occurred only in pregnant females with chronic liver diseases in 5.7% (2/35). CONCLUSION: Maternal CMV infection carries a significant risk to pregnant females with chronic liver disease. Routine CMV screening for women planning to be pregnant, especially those with chronic liver disease could help to avoid bad maternal and fetal outcomes.

Hepatologists' awareness and knowledge toward NAFLD and the familiarity with renaming from NAFLD to MAFLD.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic; it is a negative diagnosis that depends mainly on the presence of hepatic steatosis with or without inflammation after exclusion of other chronic liver diseases and excess alcohol intake. However, the new definition of MAFLD is a shift towards a diagnosis of inclusion based on the presence of metabolic dysfunction, regardless of alcohol consumption or other concomitant liver diseases. Given the growing relevance of the disease, data on hepatologists' views and understanding of NAFLD are limited, we aimed to determine hepatologists' awareness and expertise of NAFLD screening, diagnosis, and therapeutic options as well as the influence of changing the NAFLD name to MAFLD on awareness of the fatty liver disease (FLD). OBJECTIVE: Most of the hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, necessitating a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer a better awareness of FLD. METHODS: A multicenter online questionnaire of 655 hepatologists was carried out, giving a sample of 207 respondents. A survey composed of 36 questions was used to assess the level of hepatologists' awareness and practices in the screening, diagnosis, and management of NAFLD/MAFLD, as well as their familiarity with the nomenclature change from NAFLD to MAFLD. RESULTS: A total of 207 hepatologists were included, of which 107 (51.4%) were males, with a mean age was 36.4 years. 50.2% (n=104) of the hepatologists were oriented with NAFLD. Only 41 (19.8%) realized that NAFLD may frequently result in severe hepatic disease. NAFLD is rarely screened by the majority of the participating hepatologists (118, 57%), and (135, 65.2%) of them use liver biopsy for diagnosis of NAFLD. In (104, 50.2%) of hepatologists, changing the nomenclature of NAFLD was relatively familiar. Furthermore, 71.9% of hepatologists thought that the new nomenclature offers a better awareness of FLD. CONCLUSION: A small percentage of hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, and around half of them realize that NAFLD necessitates a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.

HCV/HIV coinfected Egyptian patients: a cross-sectional study of their main characteristics and barriers to HCV treatment initiation.

BACKGROUND: This study investigates different barriers preventing a cohort of Egyptian HIV/HCV coinfected patients from accessing HCV treatment, despite being available and free of charge, aiming to improve the long-term outcomes of coinfected patients and decreasing their liver-related morbidity and mortality. METHODS: This study included HIV patients who were referred to Kasr Alainy Viral Hepatitis Center to receive HCV treatment and who had to continue pretreatment assessment in order to receive direct acting antiviral agents free of charge. Patients who did not attend within 90 d were questioned via a telephone interview. Questions addressed sociodemographic status, HIV status and the main barriers to accessing healthcare. RESULTS: Overall, 474 HIV/HCV coinfected patients were eligible for HCV treatment and 223 (47.1%) patients did not complete work-up for HCV treatment. Fear of community stigma concerning HIV/HCV was the most important barrier to compliance with treatment (73.3%), followed by lack of a supportive work environment and employment opportunities (51.5%), whereas 39.3% stopped follow-up due to the lack of integrated services in the healthcare facility. CONCLUSIONS: Managing HCV in HCV/HIV coinfected patients still represents a major challenge, not only for healthcare providers, but also at a community level, to improve community awareness and manage the major obstacle facing those patients regarding community stigma.

Current status of hepatitis C virus among people living with human immunodeficiency virus in Egypt.

BACKGROUND: Human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infection is increasing due to their similar routes of transmission. Co-infection poses a big challenge. Information on the prevalence of HCV infection in Egyptian HIV individuals is scarce. METHODS: A cross-sectional study was conducted on 1004 HIV individuals who were recruited from July 2018 to March 2019. Blood samples obtained from HIV individuals were subsequently screened for HCV antibodies using the Murex anti-HCV (version 4) enzyme-linked immunosorbent assay test. HCV RNA was performed only on anti-HCV antibody-positive samples. Logistic regression was used to identify factors associated with HCV seroprevalence using SPSS (IBM, Armonk, NY, USA). RESULTS: Among 1004 participants, 349 exhibited a positive result for anti-HCV antibodies (34.8% [95% confidence interval 31.81 to 37.8]). The most commonly self-reported risk factor of HIV infection by the co-infected participants was intravenous drug use (IDU) (303/349 [86.8%]). In multinomial analysis, risk factors identified as statistically associated with HCV seroprevalence include IDU, history of surgical operations and dental procedures and HIV viral load (p<0.001, 0.032, <0.001 and 0.006, respectively). Under combination antiretroviral therapy (cART), the proportion of HIV mono-infected individuals with an undetectable HIV viral load was significantly higher than those with co-infection (p<0.0007). We also found that HIV-HCV co-infected participants exhibited significantly higher CD4+ cell counts than those with HIV mono-infection (p=0.04). CONCLUSIONS: The prevalence of HIV-HCV co-infection is higher in Egypt compared with other countries in Africa. It is essential to screen all HIV-infected patients for HCV infection for early identification, counselling and initiation of anti-HCV treatment.

Long-term clinical outcomes in sustained responders with chronic hepatitis C after treatment with direct-acting antivirals.

OBJECTIVE: Little is known about how the achievement of sustained virological response (SVR) after treatment with direct-antiviral agents (DAAs) affects fibrosis and clinical outcomes in the long term. Our study aimed to evaluate the impact of achieving SVR on long-term changes in fibrosis and clinical outcomes in CHC patients treated with different DAAs-based regimens. METHODS: a prospective, 3-year follow-up study of 113 CHC patients who had achieved SVR after treatment with different DAAs-based regimens between January and June 2015 was conducted. The clinical outcomes of SVR on the biochemical profile, changes in fibrosis, ALBI score and grade and occurrence of liver-related events were analyzed. RESULTS: Overall, liver function parameters and serum alpha-fetoprotein level showed improvement from baseline to SVR12 and remained steady thereafter. Moreover, the ALBI score showed nonsignificant change at baseline to SVR12 (P = 0.2) but it was significantly better at 3-years follow-up than at SVR12 (P = 0.001). Regarding liver stiffness (LS) by transient elastography, a significant decrease in TE values was observed between baseline to SVR12 (P ≤ 0.0001) as well as between SVR12 to 3-years follow-up (P = 0.0005). Stratified by fibrosis stage, patients with advanced fibrosis and cirrhosis showed a more pronounced and significant improvement of LS during follow-up after SVR compared to patients with less advanced fibrosis stage. During the follow-up period, 3 (5.2%) cirrhotic patients developed liver-related events, including 2 (3.4%) patients with de novo HCC and one (1.7%) patient experienced ascites for the first time. CONCLUSION: This 3-year follow-up study provides evidence for the durability of SVR, improvement of liver function parameters and ALBI score and grade in patients with an advanced stage of fibrosis, in particular, and reduction of the clinical events after successful treatment with DAAs.

Improvement in Liver Stiffness in Pediatric Patients with Hepatitis C Virus after Treatment with Direct Acting Antivirals.

OBJECTIVES: To assess the degree of liver stiffness using transient elastography in Egyptian children infected with hepatitis C virus (HCV) at baseline and 1 year after achievement of sustained virologic response (SVR) with direct acting antivirals. STUDY DESIGN: This prospective study included children infected with HCV who received treatment with sofosbuvir/ledipasvir and achieved SVR. At baseline and 1 year after achievement of SVR, the extent of hepatic fibrosis was assessed by transient elastography using FibroScan to measure liver stiffness, in addition to noninvasive markers including aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. RESULTS: The study included 23 cases that had variable degrees of fibrosis at baseline; their ages ranged between 10 and 18 years. At baseline, 13 patients had F1; 3 patients had F1-F2; 1 patient had F2; 3 patients had F3; 2 had F3-F4; and 2 patients with F4. One year after achievement of SVR, there was a statistically significant improvement in liver stiffness, APRI, and FIB-4 index (P = .03, <.001, .02, respectively). In 13 patients (56.5%), the liver stiffness improved; in 7 patients, it was stationary; and the remaining 3 patients showed mild increase in liver stiffness that was, however, associated with improvement in APRI and FIB-4 index. Comorbid conditions and previous treatment with interferon were not associated with increased liver stiffness 1 year after SVR. CONCLUSIONS: Egyptian children infected with HCV genotype 4 achieved significant regression in liver stiffness after treatment with direct acting antivirals.

Analysis of clinical and virologic features in Hepatitis B e Antigen (HbeAg)-negative and HbeAg-positive Egyptian chronic hepatitis B patients.

BACKGROUND: HBeAg-negative chronic hepatitis B infection has a divergent clinical course from that of HBeAg-positive infection. OBJECTIVES: To analyze the frequency and to compare the different features of HBeAg-negative and HBeAg-positive chronic hepatitis B patients. METHODS: One hundred and twenty one Egyptian patients with chronic hepatitis B (CHB), underwent laboratory investigations and transient elastography (TE). Comparisons according to HBeAg status were conducted regarding their demographic, liver biochemical and virologic characters. RESULT: 97 patients (80.2%) were HBeAg-negative while 24 patients (19.8%) were HBeAg-positive. HBeAg-negative patients were significantly older in age than CHBeAg-positive patients (p=0.001). ALT levels in HBeAg-negative patients were significantly lower than those in HBeAg-positive patients (p=0.02), whereas serum albumin was lower in the HBeAg-positive group (p=0.03). The percentage of HBV DNA higher than 20000 IU/mL in HBeAg-negative patients was lower than those in HBeAg-positive patients (p=0.24). Stages of fibrosis by TE showed that 30.9% of HBeAg-negative and 41.7% of HBeAg-positive had a fibrosis score >F2. Four patients (3.3%) were diagnosed with HCC; all of whom were HBeAg-negative. CONCLUSION: HBeAg-negative patients compared with HBeAg-positive patients had older age, lower ALT and serum HBVDNA levels, but more incidence of HCC.

Diagnostic accuracy of acoustic radiation force impulse elastography (ARFI) in comparison to other non-invasive modalities in staging of liver fibrosis in chronic HCV patients: single-center experience.

PURPOSE: To evaluate the reliability of ARFI elastography for liver fibrosis staging and compare it to other non-invasive assessment of hepatic fibrosis (FIB-4 and APRI) in chronic HCV (CHC) patients. METHODS: A single-center, prospective study included 2103 CHC patients. Liver stiffness (LS) was evaluated by TE and ARFI elastography. FIB-4 and APRI were calculated. The area under the receiver-operating characteristic curve (AUROCs) was used to assess the diagnostic performance of ARFI elastography for staging of liver fibrosis using TE as a reference standard. RESULTS: The best cut off values of ARFI elastography for diagnosis of ≥ F2, ≥ F3and F4 were 1.36 m/s, 1.45 m/s, and 1.7 m/s with AUROCs of 0.89, 0.94 and 0.95, respectively. ARFI elastography cut offs are lower in patients with normal ALT level compared to those with ALT level (1.1-< 3 ULN) and those with ALT level ≥ 3ULN (1.35 m/s vs 1.39 m/s vs 1.54 for F ≥ 2, 1.44 m/s vs 1.58 m/s vs 1.6 m/s for F3, 1.69 m/s, 1.84 m/s, 1.86 m/s for F4). FIB-4 (0.82-0.86) and APRI (0.78-0.82) yielded lower AUC in prediction of significant fibrosis and cirrhosis than ARFI elastography (0.89-0.95). CONCLUSION: ARFI elastography is a reliable method for non-invasive staging of liver fibrosis in CHC patients when compared to TE with a good diagnostic performance comparable to FIB-4 and APRI scores for the prediction of significant fibrosis and cirrhosis.

Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort.

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.

Changes in liver stiffness measurements and fibrosis scores following sofosbuvir based treatment regimens without interferon.

BACKGROUND AND AIM: Accurate evaluation of the degree of liver fibrosis in patients with chronic liver diseases is crucial, as liver fibrosis is important in order to make therapeutic decisions, determine prognosis of liver disease and to follow-up disease progression. Multiple non-invasive methods have been used successfully in the prediction of fibrosis; however, early changes in non-invasive biomarkers of hepatic fibrosis under effective antiviral therapy are widely unknown. The aim of this study is to evaluate changes of transient elastography values as well as FIB-4 and AST to platelet ratio index (APRI) in patients treated with Sofosbuvir-based treatment regimen. METHODS: This is a retrospective study including 337 chronic HCV Egyptian patients with genotype 4 mainly. They were treated with Sofosbuvir-based treatment regimen. Transient elastography values were recorded as well as FIB-4 and APRI were calculated at baseline and SVR12. RESULTS: There was a significant improvement of platelets counts, ALT and AST levels, which in turn cause significant improvement in FIB-4 and APRI scores at SVR12. Liver stiffness measurements were significantly lower in SVR12 (14.8 ± 10.7 vs 11.8 ± 8.8 kPa, P = 0.000). About 77% of responders and 81.1% of cirrhotic patients showed improvement in liver stiffness measurements at SVR12.Univariate and multivariate regression analysis showed that failure to achieve improvement in liver stiffness measurements were significantly associated with relapsers and low baseline liver stiffness measurement. CONCLUSION: Sofosbuvir-based treatment resulted in a clinically significant improvement in parameters of liver fibrosis.