Occult HBV infection in Morocco: from chronic hepatitis to hepatocellular carcinoma.

BACKGROUND & AIMS: Morocco is one of low to intermediate endemic areas for hepatitis B virus (HBV) infection, but no reports have been published on Occult HBV infection (OBI). To determine the prevalence of OBI and its clinical impact among patients with cryptogenic and HCV-related chronic liver disease in Morocco. METHODS: A total of 152 HBsAg-negative patients (60 patients with cryptogenic hepatitis and 92 HCV carriers) were enrolled in this study. Sera collected from all patients were tested for anti-HBc and anti-HBs antibodies. OBI was assessed in serum and liver tissue samples using highly sensitive PCR assays targeting Surface, X and core regions of the HBV genome and confirmed by Southern blot hybridization. RESULTS: A high rate of anti-HBc positivity was found among patients with HCV infection (57/92, 61.95%) compared to those with cryptogenic hepatitis (24/60, 40%) (P = 0.034). A high prevalence of OBI was found among patients with HCV infection (42/92, 45.65%) compared to those with cryptogenic hepatitis (17/60, 28.3%) (P = 0.013). In both groups, the prevalence of OBI increased in parallel with advancing stage of liver disease (χ2 = 6.73; P = 0.0095). The highest proportion of OBI was reached among HCV-related HCC cases (62.5%). Multivariate Cox regression analysis revealed that older age (≥56 years), positivity for anti-HBc and presence of OBI were independent risk factors for the development of HCC in HCV-infected patients. CONCLUSION: This study helps to understand the current status of OBI and its impact on the severity of liver disease in Moroccan patients.

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.

[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.

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.