Vitamin D receptor rs3782905 and vitamin D binding protein rs7041 polymorphisms are associated with hepatocellular carcinoma susceptibility in cirrhotic HCV patients.

BACKGROUND: The severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are associated with genetic variations within vitamin D receptor (VDR) in several populations. This study aims to determine the significance of the VDRs (rs2228570, rs3782905, rs11568820) and DBP (rs7041) for the susceptibility to HCC in Egyptian patients with chronic HCV infection and their effect on the progression of liver cirrhosis to carcinogenesis. METHODS: Single nucleotide polymorphisms (SNPs) VDR (rs2228570, rs3782905), and DBP rs7041 were genotyped using restriction fragment length-PCR (RFLP-PCR) technique and VDR rs11568820 was genotyped using single strand polymorphism PCR (SSP PCR). These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls). RESULT: The VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly higher in HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are higher in HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported. CONCLUSION: Among the four investigated SNPs, there are associations between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. These SNPs are considered as risk factors in HCV induced liver cirrhosis and HCC. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. Future research with a larger sample size of subjects with HCV infection is advised, because chronic liver disease induced by HCV infection is the primary cause of HCC in Egypt. We recommend screening of these SNPs for prediction of LC and HCC development in HCV infected patients, which may improve the used therapeutic protocol. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.

Prognostic value of S100A4 and Glypican-3 in hepatocellular carcinoma in cirrhotic HCV patients.

AIMS: Both S100A4 and Glypican-3 have been known to be engaged in HCC development and progression. This study aimed to evaluate both S100A4 and GPC3 expression in HCC tissues as a prognostic markers. METHODS: Tissues from 70 patients of HCC in cirrhotic HCV patients were evaluated by immunohistochemistry using antibodies against SA100A4 and GPC3 and compared with tumor-adjacent tissue (controls). All cases were followed for 40 months. RESULTS: GPC3 was more expressed in HCC (79%) than S100A4 (21%). S100A4 was more significantly expressed in cases showing metastasis, microscopic vascular emboli, necrosis, and grade III tumors. There was no relationship between overall survival and both S100A4 and GPC3. The only significant independent predictor for recurrence was decompensation (OR 3.037), while metastasis was significantly predicted by S100A4 expression (OR 9.63) and necrosis (OR 8.33). CONCLUSION: S100A4 might be used as a prognostic marker for HCC, while GPC3 is a reliable marker of HCC diagnosis.

Association of MTHFR and TYMS gene polymorphisms with the susceptibility to HCC in Egyptian HCV cirrhotic patients.

Identification of host genetic factors influencing the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection may help to refine patients' selection to benefit from specific preventative measures and/or adapted screening policies. Thus, this study aimed to investigate the association of MTHFR c.677C > T and c.1298A > C in addition to TYMS 3'-UTR 6-bp ins/del polymorphisms with the susceptibility to HCV-related HCC in an Egyptian population. Polymerase chain reaction-restriction fragment length polymorphism was performed to genotype the polymorphisms in 194 HCV-infected patients subdivided into liver cirrhotic (LC, n = 104) and HCC (n = 90) patients as well as 100 healthy subjects. In healthy controls, the MTHFR c.677C > T polymorphism under the homozygous and recessive models (p = 0.005) and the c.1298A > C polymorphism under all the tested genetic models (p-values range from < 0.001 to 0.007) were associated with an increased risk of HCC. In LC patients, the MTHFR c.677C > T polymorphism under the homozygous, dominant, and recessive models (p-values range from 0.001 to 0.007), as well as MTHFR c.1298A > C under the homozygous model only (p = 0.014), increased the susceptibility to HCC. The C/C and T/C haplotypes of MTHFR c.677C > T and MTHFR c.1298A > C polymorphisms were contributed to an increased risk of healthy subjects to develop HCC (p-values range from < 0.001 to 0.015), while only the T/C haplotype was associated with the progression of HCC in LC patients (p = 0.001). In conclusion, MTHFR c.677C > T and c.1298A > C in addition to their haplotypes may contribute to the development of HCV-related HCC in an Egyptian population. These findings may aid in the early diagnosis and management of HCC.

Impact of successful HCV treatment using direct acting antivirals on recurrence of well ablated hepatocellular carcinoma.

BACKGROUND: There are many contradictory studies that dealt with hepatocellular carcinoma (HCC) recurrence rate of well ablated hepatitis C virus (HCV) related HCC. We aim to assess the recurrence rate of previously ablated HCC in patients who received direct acting antiviral (DAA) for their HCV. RESEARCH DESIGN AND METHODS: This is a retrospective data analysis of 523 HCV patients who have a history of successfully ablated HCC and eligible for HCV treatment. Retrieval was done to demographic/clinical data, HCV pretreatment investigations, HCV treatment outcome. Follow up for survival and HCC recurrence was done every 3 months using abdominal ultrasound and alfa-fetoprotein. RESULTS: Mean age was 53.83 years. Sofosbuvir/daclatasvir/ribavirin was the most used regimen (35.4%) with 438 patients (83.7%) achieved sustained virologic response (SVR). The median duration for surveillance was 159 weeks. Hundred and five patients developed recurrent HCC, with a crude recurrence rate of 20.1%. There was no difference between HCV responders and non-responders in crude recurrence rate (p = 0.94) but HCC developed earlier in non-responders (p = <0.01). CONCLUSION: Recurrence of HCC remains a threat in HCV patients even after achieving an SVR. Implementation of long-term surveillance programs is highly recommended.

Efficacy of combined Sofosbuvir and Daclatasvir in the treatment of COVID-19 patients with pneumonia: a multicenter Egyptian study.

BACKGROUND: Limited experimental and clinical evidence suggests a potential role for sofosbuvir/daclatasvir in treating COVID19. We aim to evaluate the efficacy of generic sofosbuvir/daclatasvir in treating COVID-19 patients with pneumonia. RESEARCH DESIGN AND METHODS: This multicenter prospective study involved 174 patients with COVID-19. Patients were randomized into two groups. Group A (96 patients) received sofosbuvir (400 mg)/daclatasvir (60 mg) for 14 days in combination with conventional therapy. Group B (78 patients) received conventional therapy alone. Clinical, laboratory, and radiological data were collected at baseline, after 7, 14, and 28 days of therapy. Primary endpoint was rate of clinical/virological cure. RESULTS: A lower mortality rate was observed in group (A) (14% vs 21%, P = 0.07). After 1 month of therapy, no differences were found in rates of ICU admission, oxygen therapy, or ventilation. Additionally, a statistically significant shorter duration of hospital stay (9% vs 12%, P < 0.01) and a faster achievement of PCR negativity at day 14 (84% versus 47%, P < 0.01) were noticed in group (A). CONCLUSION: Adding sofosbuvir/daclatasvir to conventional therapy of COVID-19 is promising. Their use is associated with shorter hospital stay, faster PCR negativity and may be reduced mortality.

New Year's greeting and overview of World Journal of Virology in 2021.

The 2020 year-end wrap-up session of Baishideng Publishing Group was held on December 31, 2020. All staff attended this session. We shared our key results area and made a business plan regarding the journal management. World Journal of Virology (WJV) is now abstracted and indexed in PubMed and PubMed Central. It received 23 manuscripts and published 9 papers which included 6 articles reporting coronavirus 19 in 2020. On the other hand, we made major strategies for WJV's development in 2021. At present, WJV only has 28 Editorial Board members and cannot receive many manuscripts. We must redouble our efforts to invite more highly influential scientists to join our Editorial Board member and write high-quality manuscripts.

Pregnancy outcome of anti-HCV direct-acting antivirals: Real-life data from an Egyptian cohort.

We aimed to assess the pregnancy outcome in women with chronic HCV who had negative pregnancy test prior to the anti-HCV course and had unintended pregnancy while on HCV treatment. Hundred patients with a mean age of 30 ± 6.7 y were included and advised to withhold antivirals and continue follow-up in viral hepatitis and obstetrics centres till delivery. All patients received a 12-weeks regimen of anti-HCV [sofosbuvir plus daclatasvir (SOF/DCV): n = 95, SOF/DCV plus ribavirin: n = 3, and paritaprevir/ritonavir/ombitasvir plus ribavirin: n = 2]. Only nine patients completed the full antiviral course against medical advice, and 91 stopped between on-treatment weeks 4 and 8. Eighty-eight patients delivered full-term babies, eight had preterm babies and two had abortions. Of the nine patients who completed the full course of DAAs, seven (77.8%) delivered normal babies, attended their post-treatment week 12 visit, and all (100%) achieved sustained virological response. No major antiviral-related adverse events were reported.

Effect of a combination of nitazoxanide, ribavirin, and ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-19.

This trial compared the rate and time of viral clearance in subjects receiving a combination of nitazoxanide, ribavirin, and ivermectin plus Zinc versus those receiving supportive treatment. This non-randomized controlled trial included 62 patients on the triple combination treatment versus 51 age- and sex-matched patients on routine supportive treatment. all of them confirmed cases by positive reverse-transcription polymerase chain reaction of a nasopharyngeal swab. Trial results showed that the clearance rates were 0% and 58.1% on the 7th day and 13.7% and 73.1% on the 15th day in the supportive treatment and combined antiviral groups, respectively. The cumulative clearance rates on the 15th day are 13.7% and 88.7% in the supportive treatment and combined antiviral groups, respectively. This trial concluded by stating that the combined use of nitazoxanide, ribavirin, and ivermectin plus zinc supplement effectively cleared the SARS-COV2 from the nasopharynx in a shorter time than symptomatic therapy.

Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients.

OBJECTIVES: This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence. METHODS: 114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done. RESULTS: VEGF level was higher than baseline after cTACE (P < 0.001), and DEB-TACE (P = 0.004). It was also significantly higher in patients with progressive disease (P < 0.001). VEGF level at cut off values of 97.3, 149.8, and 104.1 pg/ml could discriminate disease progression from treatment success with area under ROC curves of 0.806, 0.775, and 0.771, respectively. The sensitivity was 88.9%, 88.9%, and 77.8% and specificity was 62.5%, 64.6 and 66.7%, respectively. However, no relation to tumor recurrence in CR group could be detected after one year. CONCLUSION: VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

Interrelationship between Toll-like receptors and infection after orthotopic liver transplantation.

Early microbial recognition by the innate immune system is accomplished by Toll-like receptors (TLRs), with resultant initiation of a pro-inflammatory response against infecting organisms. In spite of presence of an abundance of Toll-like receptors on the surface of the liver, gut bacteria does not elicit an inflammatory reaction in healthy individuals due to tolerance to these TLRs, suggesting that the inflammatory responses seen in the liver are the result of breakdown of this tolerance. While orthotopic liver transplantation is often life saving in many instances, death following this procedure is most commonly due to infection that occurs in up to 80% of transplant recipients, most commonly due to microbial causes in up to 70% of cases and viral infections in 20%, while fungal infections affect only 8% of cases. The probability of acquiring infection following hepatic transplantation is heightened due to affection of the innate immune defense mechanisms of the host following this procedure. Single nucleotide polymorphisms of TLRs have been associated with increased likelihood of either development of post-transplant infection or eradication of infecting organism. However, conflicting reports from other studies reveal that prevalence of this single nucleotide polymorphism is not increased in infected patients.

Impact of Toll-like Receptors 2(TLR2) and TLR 4 Gene Variations on HCV Susceptibility, Response to Treatment and Development of Hepatocellular Carcinoma in Cirrhotic HCV Patients.

Background and Aims: Genetic polymorphisms of Toll-like receptors (TLRs) have been proposed to affect susceptibility to HCV infection and progression to end-stage liver disease. This study was conducted to clarify the association of SNPS of TLR2 and TLR4 with clinical outcome of hepatitis C, response to treatment and development of HCC.Methods: The current study examined 3295 individuals from 725 families that were categorized into groups comprising chronic HCV (CH), spontaneous viral clearance (SC) and control subjects. Treated patients were classified into responders (RT) and non-responders (NRT). In addition, patients with liver cirrhotic (LC), and hepatocellular carcinoma (HCC) were also included. All subjects were genotyped for five single nucleotide polymorphisms (SNPs) of TLR2 and four SNPs of TLR4 and their haplotypes using allelic discrimination real-time PCR.Results: Results demonstrated strong association with allele A of rs13105517 of TLR2 and allele C of rs10116253 of TLR4 with CH in comparison to SC group. However, The peak of risk of HCC was observed with allele C of rs3804099 of TLR2 and C allele of rs10116253 TLR4 (p < 0.001).A strong association was found with allele T of rs1816702 of TLR2 and allele A of rs5030728 of TLR4 in non responder group in comparison to responders (p < 0.001). Haplotypes CAGT of TLR4 and ATAC of TLR2 showed significant association with CH and HCC groups in comparison to other groups.Conclusions: This study shows an association of minor alleles of TLR2 and TLR4 with outcome of HCV infection, response to therapy and development of HCC in cirrhotic patients.

Methylation of tumour suppressor genes RUNX3, RASSF1A and E-Cadherin in HCV-related liver cirrhosis and hepatocellular carcinoma.

Background: HCV infection is related to aberrant methylation of several genes. RASSF1A, E-Cadherin and RUNX3 are tumour suppressor genes that may be inactivated by hypermethylation in many tumours including hepatocellular carcinoma (HCC). We hypothesized that methylation is a diagnostic biomarker for HCC in patients with HCV-related liver cirrhosis.Methods: We recruited 207 cases of HCV-related liver cirrhosis, 193 HCC patients and 53 healthy controls. Methylation-specific polymerase chain reaction for detection of circulating hypermethylated RASSF1A, E-Cadherinand RUNX3. Alpha fetoprotein (AFP) was measured by commercial immunoassay.Results: Significant hypermethylation of the three genes was found in the HCC group compared to both cirrhosis and healthy groups (P < 0.001), whereas no significant difference in hypermethylation was found between cirrhosis and healthy groups (P = 0.17, 0.50 and 0.14, respectively). No significant links were found between hypermethylated RASSF1A, E-Cadherin and RUNX3 and stages of Barcelona Clinic of Liver Cancer score (P =0.21, 0.63 and 0.98, respectively). No significant associations were found between AFP value and hypermethylated genes in cirrhosis and HCC groups (P = 0.82) except with E-Cadherin in HCC (P = 0.02). In multiple regression analysis, RASSF1A and E-Cadherin were predictors of HCC within cirrhosis cases, but only E-Cadherin was an independent risk factor for prediction of HCC in cases with low AFP (P = 0.01).Conclusions: The presence of hypermethylated serum RASSF1A, E-Cadherin and RUNX3 is linked to HCC in patients with HCV-related cirrhosis. Only E-Cadherin is an independent risk factor for prediction of HCC with low AFP. These findings may be of diagnostic value.

HLA Class II-DRB1 Alleles with Hepatitis C Virus Infection Outcome in Egypt: A Multicentre Family-based Study.

INTRODUCTION AND AIM: Hepatitis C virus (HCV) infection is a global medical problem. HLA -DRB1 alleles have an important role in immune response against HCV. The aim of this study is to clarify the contribution of HLA -DRB1 alleles in HCV susceptibility in a multicentre family-based study. MATERIAL AND METHODS: A total of 162 Egyptian families were recruited in this study with a total of 951 individuals (255 with chronic hepatitis C (CHC), 588 persons in the control group(-ve household contact to HCV) and 108 persons who spontaneously cleared the virus (SVC). All subjects were genotyped for HLA -DRB1 alleles by SSP-PCR and sequence based typing (SBT) methods. RESULTS: The carriage of alleles 3:01:01 and 13:01:01 were highly significant in CHC when compared to that of control and SVC groups [OR of 3 family = 5.1289, PC (Bonferroni correction ) = 0.0002 and 5.9847, PC = 0.0001 and OR of 13 family = 4.6860, PC = 0.0002 and OR = 6.5987, PC = 0.0001 respectively]. While DRB1*040501, DRB1*040101, DRB1*7:01:01 and DRB1*110101 alleles were more frequent in SVC group than CHC patients (OR = 0.4052, PC = 0.03, OR: OR = 0.0916,PC = 0.0006, OR = 0.1833,PC = 0.0006 and OR = 0.4061, PC = 0.0001 respectively). CONCLUSIONS: It was concluded that among the Egyptian families, HLA-DRB1*030101, and DRB1*130101 alleles associated with the risk of progression to CHC infection, while DRB1*040101, DRB1*040501, DRB1*7:01:01and DRB1*110101 act as protective alleles against HCV infection.

Diffusion-weighted magnetic resonance imaging and micro-RNA in the diagnosis of hepatic fibrosis in chronic hepatitis C virus.

BACKGROUND: Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs (miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis. AIM: To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C. METHODS: This prospective study included 208 patients and 82 age- and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring. RESULTS: The ADC value decreased significantly with the progression of fibrosis, from controls (F0) to patients with early fibrosis (F1 and F2) to those with late fibrosis (F3 and F4) (median 1.92, 1.53, and 1.25 × 10-3 mm2/s, respectively) (P = 0.001). The cut-off ADC value used to differentiate patients from controls was 1.83 × 10-3 mm2/s with an area under the curve (AUC) of 0.992. Combining ADC and miR-200b revealed the highest AUC (0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10-3 mm2/s with an AUC of 0.866. The combination of ADC and miR-200b revealed the best AUC (0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200b (r = - 0.61, P = 0.001), miR-21 (r = - 0.62, P = 0.001), and miR-29 (r = 0.52, P = 0.001). CONCLUSION: Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.

Mansoura simple scoring system for prediction of spontaneous bacterial peritonitis: lesson learnt.

BACKGROUND AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a common bacterial infection with life-threatening sequelae in cirrhotic ascites. The purpose of this retrospective cohort study was to recognize the predictors of SBP to build up a noninvasive system to exclude or establish an episode of SBP. PATIENTS AND METHODS: Of 1194 consecutive patients with cirrhotic ascites, only 966 patients were enrolled in this study. SBP was diagnosed once polymorphonuclear count was at least 250 cells/mm and/or there was a positive ascitic fluid culture result. Biochemical and clinical parameters were evaluated as predictors of SBP. A scoring system was established in the training group of 682 and validated in a second group of 284 participants. RESULTS: The incidence of SBP was 12.3 and 12% in the training and validation groups, respectively. Age of at least 55 years, mean platelet volume (MPV) of at least 8.5 fl, neutrophil-to-lymphocyte ratio (NLR) of at least 2.5, and C-reactive protein (CRP) of at least 40 mg/l were identified as independent predictors of SBP. A scoring system including these four variables (age, MPV, and NLR with 1 point each, whereas CRP with 2 points) achieves a specificity of 98.2% with a positive predictive value for the diagnosis of SBP of 88.1% (score≥4). At a threshold of 1 point, the negative predictive value is 97.5% with a sensitivity of 92.9%. SBP is not associated with a high Model for End-stage Liver Disease score (P=0.135). CONCLUSION: The combination of age, MPV, NLR, and CRP in a simple scoring system, Mansoura simple scoring system, supports quick and accurate exclusion or diagnosis of SBP.

Diagnosis of cirrhosis in patients with chronic hepatitis C genotype 4: Role of ABCB11 genotype polymorphism and plasma bile acid levels.

BACKGROUND/AIMS: Chronic hepatitis C (CHC)-related mortality generally results from cirrhosis and subsequent complications. We aimed to investigate the potential role of plasma bile acid levels and ABCB11 1331T > C (V444A, rs2287622) (ATP-binding cassette subfamily B, member 11) gene polymorphism in fibrosis prediction in CHC genotype 4 patients. MATERIALS AND METHODS: This case control study included 85 healthy control and the following 225 subjects: 170 adult patients infected with hepatitis C virus (HCV) and categorized into three groups according to liver biopsy; no fibrosis group (F0) (n=33), early fibrosis group (F1-F2) (n=61), and advanced fibrosis group (F3-F4) (n=76). Fasting bile acid levels, hepatitis C virus (HCV) genotyping, and ABCB11 1331T > C gene polymorphism were assessed. RESULTS: The frequency of the variant homozygote genotype CC in advanced fibrosis was significantly higher than that in early fibrosis (48.7% vs. 36.1%) (odd ratio, OR =2.58; 95% confidence interval, CI=1.07-6.20; p=0.03). C allele was significantly represented in advanced fibrosis (65.8%) compared with that in early fibrosis (51.6%) (OR=1.80, 95% CI=1.10-2.93, p=0.01). A significant elevation of plasma bile acid levels in advanced fibrosis was observed compared with those in early fibrosis (p≤0.001). Receiver operating characteristic curve for plasma bile acid levels at cutoff value of 75.5 µmol/L had a 59% specificity and 97.4% sensitivity as a predictor of advanced hepatic fibrosis (AUROC=0.78%). CONCLUSION: We concluded that Egyptian patients having chronic hepatitis C genotype 4 with CC genotype of ABCB11 SNP 1331T > C and high plasma bile acid levels at cutoff value of 75.5 µmol/L were associated with advanced hepatic fibrosis.

Does steatosis affect the performance of diffusion-weighted MRI values for fibrosis evaluation in patients with chronic hepatitis C genotype 4?

BACKGROUND/AIMS: To evaluate the effect of hepatic steatosis on the apparent diffusion coefficient (ADC) of hepatic fibrosis in patients with HCV genotype 4-related chronic hepatitis. MATERIALS AND METHODS: Overall, 268 chronic hepatitis C patients (164 males and 104 females) underwent liver biopsy for fibrosis assessment by the METAVIR score and grading for hepatic steatosis. They were classified into early fibrosis stage (F1, F2) and advanced fibrosis stage (F3, F4). Diffusion-weighted MRI (DWI) of the liver was performed using 1.5-Tesla scanners, and the ADC value of the patients with and without steatosis in different stages of fibrosis was estimated and compared. RESULTS: In patients with early fibrosis, the ADC value significantly decreased in patients with steatosis (1.52±0.17×10-3 mm2/s) compared to that in patients without steatosis (1.65±0.11×10-3 mm2/s) (p<0.001). In those with an advanced stage of fibrosis, the ADC value was also significantly decreased in patients with steatosis (1.07±0.16×10-3 mm2/s) compared with that in patients without steatosis (1.35±0.11×10-3 mm2/s) (p≤0.001). The cutoff value for ADC for steatosis prediction in the early fibrosis group was 1.585 according to the AUROC curve, with a sensitivity of 76.8% and a specificity of 73.5%. The cutoff value for ADC for steatosis prediction in patients with an advanced stage of fibrosis was 1.17×10-3 mm2/s, with a sensitivity of 97% and a specificity of 88.5%. CONCLUSION: Histologically detected hepatic steatosis should always be considered when assessing hepatic fibrosis using diffusion-weighted MRI to avoid the underestimation of the ADC value in patients with chronic hepatitis C genotype 4.

Prediction of Fibrosis Progression Rate in Patients with Chronic Hepatitis C Genotype 4: Role of Cirrhosis Risk Score and Host Factors.

The rate of liver fibrosis progression in chronic hepatitis C (CHC) patients is highly variable and affected by different factors. This study aimed to assess the role of cirrhosis risk score (CRS) based on 7 genetic variants (7 single-nucleotide polymorphisms [SNPs]) and host factors (age and sex) in the prediction of the rate of fibrosis progression in CHC. Duration of infection was determined in 115 patients. The fibrosis progression rate (FPR) per year was calculated as the ratio between fibrosis stage and the duration of infection. SNP genotyping were performed and CRS was determined based on it. FPR was significantly elevated in patients who acquired infection at age >40 years versus those who acquired infection at 30-40 years and those who acquired infection at <30 years. Median FPR was significantly higher in males than females (0.17 vs. 0.15) with P = 0.001. CRS value ≥0.8 is predictive of patients with high risk for cirrhosis, and CRS value <0.5 is predictive of patients with low risk for cirrhosis. There was significant positive correlation between CRS and FPR (P ≤ 0.001). CRS based on 7 SNPs at cutoff value ≥0.8, age at infection >40 years, and male sex are predictors of higher FPR.

Association of interferon gamma gene polymorphism and susceptibility to hepatitis C virus infection in Egyptian patients: A multicenter, family-based study.

BACKGROUND AND AIM: Polymorphisms in some genes may influence the persistence of hepatitis C virus (HCV) infection, clinical outcome, HCV replication, and liver damage. This study was conducted to investigate the role of the interferon gamma (IFN-γ) gene at (+874 T/A, -764 G/C, -179 C/A) single-nucleotide polymorphisms (SNPs) and its receptor (IFN-γR2) at (rs 2786067 A/C) SNP in the susceptibility of Egyptian families to HCV infection with high-resolution techniques. METHODS: In total, 517 Egyptian families, with 2246 subjects, were recruited to this study from the Upper and Lower Egypt governorates and were classified into three groups: 1034 patients with chronic hepatitis C virus, 108 subjects with spontaneous virus clearance (SVC), and 1104 subjects as a healthy control group. All subjects were genotyped for (+874 T/A, rs2430561, -764 G/C, rs2069707, -179 C/A, rs2069709, and rs 27860067, A/C) SNPs of the IFN-γ gene using the allelic discrimination real-time polymerase chain reaction technique and were confirmed using sequence-based typing. RESULTS: The carriage of T allele of (+874) IFN-γ is a risky allele and was significantly higher in chronic hepatitis C more than other two groups (odds ratio [OR]: 2.6646, P < 0.0002). On the other hand, the C allele of (-764, rs2069707) is a protective allele and was higher in SVC than the other two groups (OR: 0.2709, P < 0.0001). However, both (-179 C/A, rs 2069709) and (rs 27860067, A/C) SNPs are not polymorphic enough to be studied in the Egyptian population. CONCLUSIONS: HCV infection is associated with the T allele of (+874 rs2430561), while SVC of HCV is associated with the C allele of (-764, rs2069707) of the IFN-γ gene.

Profile of expression of certain markers of apoptosis in chronic hepatitis C and hepatitis B patients in an Egyptian population.

Increased peripheral blood mononuclear cell (PBMC) apoptosis during viral hepatitis has been suggested to cause impaired regulation of the immune response and maintenance of the infection. The purpose of this work was to study the expression of some apoptotic markers in chronic hepatitis B (CHB) and C (CHC) infections in order to understand the underlying mechanisms of immune failure and viral persistence. This study aims to evaluate the level of PBMC apoptosis and the expression of the apoptosis-related proteins Fas and Bcl-2 in CHB and CHC patients. This case control study was carried out on 38 cases (group I: 20 chronic HCV patients; group II: 18 chronic HBV patients) attending the Tropical Medicine Clinic, Mansoura University Hospital, in addition to 10 healthy controls. Morphological assessment of apoptosis of cultured PBMCs was done. The level of Fas and Bcl-2 expression by PBMCs was detected using flow cytometry. An increased level of apoptosis correlated with increased Fas expression, but no increase in Bcl-2 expression was found on the surface of PBMCs in CHC and CHB patients compared to controls. No significant difference in the level of apoptosis, Fas, or Bcl2 expression between CHC and CHB patients was detected. Modulation of apoptosis, particularly by manipulation of Fas receptor activation, may be of therapeutic benefit in chronic CHB and CHC.