Concordance with the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention and colorectal cancer risk in Morocco: A large, population-based case-control study.

The present study aimed to investigate associations between adherence to the recommendations on cancer prevention from the WCRF/AICR and colorectal cancer (CRC) risk in Morocco. Incident CRC cases (n = 1,516) and controls (n = 1,516) matched on age, sex and center, were recruited between September 2009 and February 2017 at five major hospitals located in Morocco. In-person interviews were conducted to assess habitual diet using a validated Food Frequency Questionnaire, physical activity and anthropometric measurements. Adherence to the WCRF/AIRC Recommendations was ranged from 0 (no adherence) to 6 (maximal adherence) and incorporating six WCRF/AICR components (food groups, physical activity and BMI). Multivariable odd ratios (ORA ) and 95% confidence intervals (CI) were calculated using conditional multivariate logistic regression models, with low adherence as referent, adjusting for potential confounding factors. Compared to those with the lowest adherence score, individuals in the highest WCRF/AICR score category had a statistically significant reduced risk for colon cancer (ORA = 0.63, 95% CI 0.53-0.76); rectal cancer (ORA = 0.52, 95% CI 0.43-0.63) and CRC overall (ORA = 0.58, 95% CI 0.51-0.66). For individual score components, when comparing the lowest with the highest adherence category, CRC risk was significantly lower in the highest adherence category for body fatness (ORA = 0.73; 95% CI 0.62-0.85), physical activity (ORA = 0.70; 95% CI 0.60-0.82), plant foods (ORA = 0.50; 95% CI 0.39-0.63) and red/processed meat (ORA = 0.81; 95% CI 0.71-0.92). Our analysis indicated that greater adherence to the WCRF/AICR recommendations for cancer prevention may lower CRC risk in Morocco.

Genetic variations in toll-like receptors 7 and 8 modulate natural hepatitis C outcomes and liver disease progression.

BACKGROUND & AIMS: The natural outcomes of hepatitis C virus (HCV) as well as the progression of the liver disease are highly variable and depend primarily on an efficient immune response. As toll-like receptors seven (TLR7) and eight (TLR8) are important effectors of the innate immunity, this study aims to evaluate the association between TLR7 and TLR8 polymorphisms and the HCV infection outcomes in Moroccan subjects. METHODS: In this case-control study, 643 subjects including 293 mild chronic hepatitis patients, 119 with advanced liver disease (AdLD), 93 with HCV spontaneous clearance and 138 healthy controls were genotyped using TaqMan SNPs assays. RESULTS: Patients carrying TLR7 rs179008-A allele were more likely to clear the virus spontaneously (P = .0001 for women, and P < .001 for men). Besides, carriage of TLR7 rs179009-A allele was associated with a twofold increase in spontaneous viral clearance in female patients (P = .0002), but not in men. In addition, we observed that TLR7 rs179008-T and rs179009-G alleles increased the risk of disease progression in both sexes (P < .05). TLR8 rs3764880-G allele was associated with spontaneous HCV clearance in both sexes (P < .0001) albeit with an apparently stronger association in males (OR = 6.02 for men vs 2.2 for women). In males, TLR8 rs3764879-C and TLR8 rs3764880-A alleles were significantly associated with AdLD status (P < .05). CONCLUSIONS: Our results suggest that variations in TLR7 and TLR8 genes modulate the clearance and progression of HCV infection with different magnitudes between sexes. Our results refine, therefore, our understanding of the sex-specific differences observed regarding the susceptibility to chronic hepatitis.

Morocco underwent a drift of circulating hepatitis C virus subtypes in recent decades.

Hepatitis C virus (HCV) isolates circulating in Morocco are poorly documented. To determine the subgenotype distribution of HCV in chronically infected patients, serum samples from 185 anti-HCV-positive patients were analyzed. Determination of the HCV genotype and subtype was performed by sequencing the 5'UTR, NS5B and core regions. According to the NS5B phylogeny, the HCV strains primarily belonged to subtypes 1b (75.2%), 2i (19.1%) and 2k (2.8%). Using a Bayesian approach, the mean date of appearance of the most recent common ancestor was estimated to be 1910 for HCV-1b and 1854 for HCV-2i. Although it is currently the most frequent genotype in Morocco and the dominant form in hepatocellular carcinoma, it thus appears that HCV-1b was introduced into the population subsequently to HCV-2i.

The -94Ins/DelATTG polymorphism in NFκB1 promoter modulates chronic hepatitis C and liver disease progression.

Infection with Hepatitis C Virus (HCV) is one of the most important risk factor of hepatocellular carcinoma (HCC). HCV is suspected to induce HCC primarily through chronic inflammation and promotion of cirrhosis, a well-known pre-neoplastic condition. The NF-κB pathway is a key regulator of immune and inflammatory processes and plays a pivotal role in oncogenesis. Genetic variations affecting the pathway may alter NF-κB activity in response to HCV infection and contribute to liver tumorigenesis. The present study aims to evaluate the association between -94Ins/DelATTG (rs28362491) polymorphism in NF-κB1 gene promoter region and 2758G>A (rs696) single nucleotide polymorphism in the 3'UTR region of NFκBIA and the outcomes of HCV infection. In this case-control study, 559 subjects (343 patients with HCV infection including 237 mild chronic hepatitis patients and 106 patients with Advanced Liver Disease (AdLD), 78 individuals who naturally cleared HCV and 138 healthy subjects) were genotyped for the NFκB1 and NFκBIA SNPs using PCR-RFLP. Logistic regression was used to assess the association between polymorphisms and the outcome and progression of the infection. Variation at rs696 was not associated with HCV resolution or progression (P>0.05). By contrast, the Ins/Ins genotype was associated with a 4-fold increase of AdLD risk when compared to mild chronic hepatitis C (OR=4.69; 95% CI, 2.15-10.19; P=0.0001) and the risk was more pronounced when compared to healthy controls (OR=5.02; 95% CI, 2.30-10.98; P=0.00005). Furthermore, carriage of Ins allele at rs28362491 was significantly associated with higher viral loads (P=0.003). Our results suggest that variation in NFκB1 gene promoter modulates the progression of chronic hepatitis C toward advanced liver disease.

[Primary anorectal melanoma]. / Mélanome anorectal primitif.

OBJECTIVE: To specify the clinical and therapeutic aspects of anorectal melanoma. METHODS: Nine cases of malignant anorectal melanoma were managed in the department of gastroenterology of the Ibn Rochd university hospital in Casablanca between 1984 and 2002. RESULTS: There were 5 men and 4 women, with a mean age of 61 years. Clinical symptoms were dominated by rectal bleeding (7 cases) and rectal syndrome (5 cases). The tumor was blackish in 4 cases. Extension staging showed metastases in the liver in one patient and in the bones in another. One patient had undergone abdominoperineal resection, two transanal tumor resection, and in one patient radiotherapy was applied. Five patients refused any treatment. The outcome was marked by remission in 2 cases with an event free survival respectively of 10 and 21 months. Three patients died because of visceral metastases. Four patients were lost to follow-up. DISCUSSION: The prognosis of anorectal melanoma is frightening because of late diagnosis and high malignancy potential. Treatment is based essentially on surgery.

The adiponutrin I148M variant is a risk factor for HCV-associated liver cancer in North-African patients.

Recent reports revealed an association between variation in the PNPLA3 gene and alcohol-induced hepatocellular carcinoma among Europeans. We have assessed whether the PNPLA3 rs738409 (I148M) polymorphism may also affect the resolution and/or the progression of hepatitis C in a Moroccan cohort. Genotype and allele frequencies at rs738409 were determined using a TaqMan 5' allelic discrimination assay in 437 individuals. Among them, 230 patients had a persistent infection with hepatitis C virus (HCV) with 129 patients affected by a chronic hepatitis and 101 patients by a hepatocellular carcinoma (HCC). In addition, we analyzed 75 individuals who naturally cleared HCV and 132 healthy subjects. Variation at rs738409 was not associated with significant changes in resolution rate of hepatitis C. By contrast, M/M genotype, present at higher frequencies (22.8%) in HCC patients than in patients with chronic hepatitis C (8.5%, P = 0.004) or control individuals (9.1%, P = 0.005) was associated with a 3-fold increase of liver cancer risk. In North African subjects, the PNPLA3 I148M variant apparently stimulates liver cancer development without interfering on the HCV clearance process. This polymorphism may, therefore, represent a valuable genetic marker to monitor liver cancer risk in populations from the Southern bank of the Mediterranean.

Chronic permanent hypoxemia predisposes to mild elevation of liver stiffness.

AIM: To evaluate the impact of long term permanent hypoxemia noticed in patients with non operated congenital cyanogenic cyanotic cardiopathy on liver stiffness. METHODS: We included ten adult patients with non operated inoperate cyanotic cardiopathy and ten matched patients for age and gender admitted to the gastroenterology department for proctologic diseases; Clinical and laboratory data were collected [age, gender, body mass index, oxygen saturation, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), glycemia and cholesterol]. Measurement of hepatic stiffness by transient elastography was carried out in all patients using the Fibroscan device. All patients underwent an echocardiography to eliminate congestive heart failure. RESULTS: Among the patients with cyanotic cardiopathy, median liver stiffness 5.9 ± 1.3 kPa was greater than control group (4.7 ± 0.4 kPa) (P = 0.008). Median levels of GOT, GPT, gamma-glutamyltransferase, glycemia and cholesterol were comparable in cardiopathy and control group. In regression analysis including age, gender, body mass index, oxygen saturation, GOT, GPT, glycemia, cholesterol showed that only oxygen saturation was related to liver stiffness (r = -0.63 P = 0.002). CONCLUSION: Chronic permanent hypoxemia can induce mild increase of liver stiffness, but further studies are needed to explore the histological aspects of liver injury induced by chronic permanent hypoxemia.

Amino acid substitutions in the Hepatitis C virus core region of genotype 1b in Moroccan patients.

The aim of the present study was to identify basic amino acid in the core region in subtype 1b-infected, treatment-naive patients from Morocco and to search for their eventual association with liver cancer. The survey included 151 patients (86 patients with chronic hepatitis and 65 patients with hepatocellular carcinoma, HCC). We performed direct sequencing, and compared the data obtained with the consensus sequence of core protein. Several recurrent amino acid substitutions were observed. The Arg70 was changed for a Gln in 22 of 112 patients (19.6%) and Leu91 was changed to Met in 23 of 112 patients (20.5%). Besides, the threonine at position 75 (Thr75) was mutated for alanine or serine in 43 (38.4%) and 40 (35.7%) of the patients, respectively. Overall, there was no significant difference between patients with chronic hepatitis and those with HCC regarding amino acids substitution number (24% vs. 33%, respectively, P = 0.457). Our study provides the first inventory of predominant amino acid substitutions in the HCV core region genotype 1b. The impact of single or combined mutations on the resistance to treatment or on disease progression is still unknown and deserves more attention in the future.

Genetic variation in the interleukin-28B gene is associated with spontaneous clearance and progression of hepatitis C virus in Moroccan patients.

BACKGROUND: Genetic variation in the IL28B gene has been strongly associated with treatment outcomes, spontaneous clearance and progression of the hepatitis C virus infection (HCV). The aim of the present study was to investigate the role of polymorphisms at this locus with progression and outcome of HCV infection in a Moroccan population. METHODS: We analyzed a cohort of 438 individuals among them 232 patients with persistent HCV infection, of whom 115 patients had mild chronic hepatitis and 117 had advanced liver disease (cirrhosis and hepatocellular carcinoma), 68 individuals who had naturally cleared HCV and 138 healthy subjects. The IL28B SNPs rs12979860 and rs8099917 were genotyped using a TaqMan 5' allelic discrimination assay. RESULTS: The protective rs12979860-C and rs8099917-T alleles were more common in subjects with spontaneous clearance (77.9% vs 55.2%; p = 0.00001 and 95.6% vs 83.2%; p = 0.0025, respectively). Individuals with clearance were 4.69 (95% CI, 1.99-11.07) times more likely to have the C/C genotype for rs12979860 polymorphism (p = 0.0017) and 3.55 (95% CI, 0.19-66.89) times more likely to have the T/T genotype at rs8099917. Patients with advanced liver disease carried the rs12979860-T/T genotype more frequently than patients with mild chronic hepatitis C (OR = 1.89; 95% CI, 0.99-3.61; p = 0.0532) and this risk was even more pronounced when we compared them with healthy controls (OR = 4.27; 95% CI, 2.08-8.76; p = 0.0005). The rs8099917-G allele was also associated with advanced liver disease (OR = 2.34; 95% CI, 1.40-3.93; p = 0.0100). CONCLUSIONS: In the Moroccan population, polymorphisms near the IL28B gene play a role both in spontaneous clearance and progression of HCV infection.

Risk factors for liver fibrosis among human immunodeficiency virus monoinfected patients using the FIB4 index in Morocco.

AIM: To study the prevalence and risk factors of significant hepatic fibrosis in Moroccan human immunodeficiency virus (HIV) monoinfected patients. METHODS: We conducted a cross-sectional study among HIV monoinfected patients (negative for hepatitis B surface antigen and hepatitis C antibody). Clinical and laboratory data were collected from the data base of the Infectious Diseases Unit in Ibn Rochd Hospital Center [age, gender, duration of HIV infection, CD4 T lymphocyte count, HIV viral load, glycemia and current or prior use of antiretroviral and antiretroviral therapy (ART) duration]. The primary outcome was a FIB4 score > 1.45. Multivariable logistic regression identified independent risk factors for FIB4 > 1.45. RESULTS: A FIB4 score > 1.45 was identified in 96 among 619 (15.5%). HIV monoinfected patients followed up between September 1990 and September 2012. Multivariate analysis showed that only a viral load > 75 (OR = 2.23, 95%CI: 1.36-3.67), CD4 > 200 cells/mm(3) (OR = 0.39, 95%CI: 0.21-0.72) and age at FIB4 index calculation (OR = 1.10, 95%CI: 1.07-1.13) were independently associated with the occurrence of FIB4 index (> 1.45). Gender, duration of HIV infection, glycemia, use of antiretroviral therapy and ART duration were not associated with significant fibrosis by FIB4. CONCLUSION: FIB4 score > 1.45 was found in 15.5% of Moroccan HIV monoinfected patients. Age, HIV viremia > 75 copies/mL and CD4 count > 200 cells/mm(3) are associated with liver fibrosis. Further studies are needed to explore mechanisms for fibrosis in HIV monoinfected patients.