Assessment of Renal Function in Post-Liver Transplant HCV-Positive Patients Treated with Direct Acting Antivirals.

PURPOSE: Direct acting antiviral agents (DAAs) have greatly improved the clearance of hepatitis C virus (HCV) infection. The effect of DAAs on renal function in post-liver transplant HCV-positive patients remains questionable, especially considering the possibility of drug interactions between immunosuppressants and DAAs. PATIENTS AND METHODS: A retrospective observational study included 84 post-liver transplant patients with HCV infection. Patients were divided into two groups: group I received sofosbuvir plus ribavirin for 24 weeks, group II received sofosbuvir plus daclatasvir for 12 weeks. Laboratory data and eGFR were determined before, at the end, and 6 months after completion of treatment. RESULTS: The treatment was well tolerated with 100% sustained virologic response (SVR 12). There was no statistically significant difference between the two groups regarding clinical and laboratory data before treatment. Mean eGFR significantly reduced from 87.36 mL/min to 76.16 mL/min in group I (P=0.001). However, within 6 months after treatment, mean eGFR recovered to 81.51 mL/min, which was not significant when compared to baseline eGFR (P=0.09). Mean eGFR in group II showed non-significant change. There were no significant changes in immunosuppressive drug levels and eGFR in either group of patients, who received either ciclosporin or tacrolimus before and at the end of treatment. CONCLUSION: DDAs in post-liver transplant patients with HCV infection were well tolerated and associated with stable renal function. Moreover, sofosbuvir plus daclatasvir regimen showed relatively better renal safety compared to sofosbuvir plus ribavirin.

XRCC1 Gene Polymorphism Increases the Risk of Hepatocellular Carcinoma in Egyptian Population.

Several major risk factors for hepatocellular carcinoma (HCC) have been identified, including chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Nevertheless, only a fraction of infected patients develops HCC during their lifetime suggesting that genetic factors might modulate HCC development. X-ray repair cross complementing group1 (XRCC1) participates in the repair pathways of DNA. AIM: to investigate the association between XRCC1 gene polymorphism and HCC in Egyptian chronic hepatitis C patients. METHODS: This study was assessed on 40 patients with HCC secondary to chronic HCV infection who were compared to 20 cirrhotic HCV patients and 40- age and gender- matched healthy control group. After collection of relevant clinical data and basic laboratory tests, c.1517G>C SNP of XRCC1 gene polymorphism was performed by (PCR-RFLP) technique. RESULTS: A statistically higher frequency of XRCC1 (CC, GC) genotypes and increased (C) allele frequency in patients with HCC was found in comparison to cirrhotic HCV patients as well as control group. In addition, patients with the XRCC1 (CC, GC) genotypes had significantly higher number and larger size of tumor foci and significantly higher Child Pugh grades. Multivariate analysis showed that the presence of c.1517G>C SNP of XRCC1 gene is an independent risk for the development of HCC in chronic HCV patients with 3.7 fold increased risk of HCC development. IN CONCLUSION: XRCC1 gene polymorphism could be associated with increased risk of HCC development in chronic HCV Egyptian patients.
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Interleukin 28A.rs12980602 and interleukin 28B.rs8103142 genotypes could be protective against HCV infection among Egyptians.

Previous studies showed that interleukin (IL)-28B gene polymorphisms were associated with hepatitis C Virus (HCV) infection and treatment outcomes. We tested whether single-nucleotide polymorphisms (SNPs) in IL-28A and IL-28B are associated with HCV infection among Egyptians with HCV genotype 4 infections. We enrolled 144 chronic HCV patients, 72 spontaneously resolved HCV subjects, and 69 healthy controls. Four SNPs in IL-28A and IL-28B genes (IL-28A.rs12980602, IL-28B.rs12979860, IL-28B.rs8099917, and IL-28B.rs8103142) were genotyped. The most frequent IL-28B haplotype "TCT" was significantly more frequent in HCV-infected subjects than in HCV negative subjects (62.2% vs. 48.6%, respectively; p = 0.005). The frequency of IL-28A.rs12980602 "T" allele was significantly higher than the "C" allele in healthy controls compared to HCV-infected subjects (p < 0.001) with the "TT" genotype significantly higher in healthy controls compared to HCV-infected subjects (p < 0.001) with no association with viral load (p = 0.11) among chronically infected subjects. The results, also, confirmed the previous role of IL-28B SNPs in predicting HCV infection outcome. Importantly, IL-28B.rs8099917 "TT" genotype was significantly associated with low viral load in HCV-infected subjects, while the remaining three SNPs did not. The three IL-28B SNPs were in linkage disequilibrium (D' > 0.68; r2 > 0.43) for all comparisons in HCV patients, while there was no linkage disequilibrium of IL-28A polymorphisms and the three IL-28B SNPs. In conclusion, IL-28A.rs12980602 and IL-28B.rs8103142 TT genotype could be protective against HCV infection. Also, IL-28B.rs12979860, IL-28B.rs8099917, and IL-28B.rs8103142 SNPs predicted the outcome of HCV infection among genotype-4-infected Egyptians. Moreover, IL-28B.rs8099917 SNP affected the viral load in chronic HCV patients.

High spontaneous clearance of symptomatic iatrogenic acute hepatitis C genotype 4 infection.

Acute hepatitis C (AHC) infection resolves spontaneously in 15% to 40% of patients. Factors favoring spontaneous viral clearance remain undefined. In this study, predictors of spontaneous viral clearance in patients with symptomatic AHC were investigated. Epidemiological, clinical, and virologic parameters were also examined. Patients with symptomatic AHC were enrolled and followed up prospectively. The patients were followed up every 2 weeks in the first month and then monthly for the following 5 months, with a follow-up visit 6 months after the last hepatitis C virus (HCV)-RNA negative sample for those who had cleared the virus. Interleukin (IL)-28B.rs12979860 single-nucleotide polymorphism and HCV genotype were tested at baseline. HCV-RNA was tested during each visit. Patients who remained RNA-positive at 24 weeks were treated with pegylated interferon plus ribavirin for 24 weeks. A total of 30 patients, mostly with iatrogenically acquired AHC genotype 4 infections completed 6-months' follow-up, to either spontaneous clearance or start of treatment. The mean age of the patients was 37 ± 13 years. In total, 67% of patients were females, and the mean incubation period was 7.6 ± 3.5 weeks. Viral clearance occurred spontaneously in 19 (63.3%) patients. The average time to clearance was 24.3 ± 9.6 weeks. A total of 11 patients received therapy, and 8 (72.7%) cleared the virus and had a sustained virologic response to the treatment 24 weeks after the therapy. A total of three patients were treatment nonresponders. IL28B.rs12979860 CC genotype, female gender, and viremia level were not associated with self-limiting AHC in this cohort. In conclusion, patients with symptomatic AHC genotype 4 infection caused by an iatrogenic exposure had higher rates of spontaneous resolution than previously reported. Predicting spontaneous viral clearance after iatrogenic AHC exposure was not possible in this population.

Long-term rifaximin therapy as a primary prevention of hepatorenal syndrome.

BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of liver cirrhosis, with poor survival. Rifaximin is a gut-selective broad-spectrum antibiotic. AIM: The aim of this study was to evaluate the role of rifaximin as a primary prevention of HRS. PATIENTS AND METHODS: Eighty patients with liver cirrhosis and ascites were enrolled. They were randomized into two groups: control (n=40) and rifaximin group (n=40). Baseline liver function tests, renal function tests, complete blood count, international normalized ratio, urine analysis, and abdominal ultrasonography were carried out. Rifaximin 550 mg was administered twice daily for 12 weeks. Renal functions were measured every 4 weeks with monitoring of HRS occurrence and possible precipitating factor. RESULTS: Both groups were matched for age, sex, virology, serum bilirubin, serum albumin, aspartate aminotransferase, alanine aminotransferase, hemoglobin, white blood cells, platelets, international normalized ratio, potassium, and Child-Pugh score. In contrast to the rifaximin group, the control group showed statistically significant serial blood urea nitrogen (18.84±7.17, 19.85±6.10, 21.54±4.79, and 22.96±5.82 mg/dl; P=0.001) and serum creatinine (0.94±0.25, 1.02±0.24, 1.12±0.16, and 1.21±0.17 mg/dl; P=0.001) levels. The overall blood urea nitrogen and serum creatinine change was statistically higher in the control group than the rifaximin group (20.8 vs. 18.24 mg/dl and 1.07 vs. 0.99 mg/dl, respectively). HRS developed more in the control group than the rifaximin group [9 (22.5%) vs. 2 (5%); P=0.048]. In both groups, HRS was precipitated by spontaneous bacterial peritonitis mainly and large volume paracentesis. The Child-Pugh score, control group, baseline serum sodium, and creatinine were predictors of HRS. CONCLUSION: Rifaximin may be useful as a primary prevention of HRS.

IL17A gene polymorphism, serum IL17 and total IgE in Egyptian population with chronic HCV and hepatocellular carcinoma.

BACKGROUND: Chronic infections with HCV (CHC) induce a chronic inflammation which can lead to liver fibrosis and subsequently cirrhosis. A recent study suggests a role of IL-17 polymorphism and serum IL17 in hepatitis B related HCC. These data indicate that the IL-17 G-197A polymorphism may be a good indicator for susceptibility to cancer development. AIM: To investigate the role of the IL17A gene polymorphism, serum IL17 and total IgE in Egyptian population with chronic infections with HCV and HCC. SUBJECTS AND METHODS: This study was carried out on 40 patients with chronic HCV, 35 patients with hepatocellular carcinoma and 20 healthy persons as control. All subjects were submitted to History taking, clinical examination, abdominal ultrasound, laboratory tests including CBC, liver function tests, alpha fetoprotien, determination of IL17gene polymorphisms by PCR-RFLP, IL17 by ELISA and IgE by immunonephelometric assay. RESULTS: In reference to AA genotype, the frequencies of GG, GA+GG genotypes in the cases with HCC were significantly different from that of the controls (p=0.012, 0.011) and carry 6.12,4.9 respectively fold increase for HCC risk and that of chronic HCV without HCC (p=0.005, 0.004) respectively. However, there was no significant difference in allele frequency in the studied groups (p=0.095). Cases with HCC significantly have higher levels of serum IL17 and IgE than both healthy control and chronic HCV. In conclusion, the present study showed the GG, GG+GA genotypes of IL17A gene is a risk factor for HCC development may be through increased IL17 and IgE and further studies with larger sample size and different populations are recommended.

Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians.

BACKGROUND/PURPOSE: Single-nucleotide polymorphisms (SNPs) around the interferon lambda 3 (IFNL3; also known as interleukin 28B; IL28B) gene are associated with spontaneous hepatitis C virus (HCV) clearance. Interferon lambda 4 (IFNL4).ss469415590, in linkage disequilibrium (LD) with IFNL3.rs12979860 among the Caucasian population, has recently been identified as a potential functional variant. Our objective was to assess the LD between IFNL3.rs12979860 and IFNL4.ss469415590 and to compare their effect on the outcome of HCV infection among Egyptians, mainly infected with HCV genotype 4. METHODS: One-hundred and eighty-five Egyptian HCV patients (77 spontaneous resolvers and 108 chronic subjects), and 122 healthy controls were genotyped for both IL28B.rs12979860 and IFNL4.ss469415590. Logistic regression models including factors with univariate association with the outcome of infection were calculated for each genetic marker. The LD was also calculated for the 122 healthy controls. RESULTS: The CC genotype of IFNL3.rs12979860 was more frequent among individuals with HCV spontaneous resolution than among those with chronic infection (57 vs. 27%; adjusted OR 3.84; 95% CI 2.02-7.30; p < 0.0001). Also, the TT/TT genotype of IFNL4.ss469415590 was more frequent among individuals with spontaneous resolution (49 vs. 20%; adjusted OR 4.17; 95% CI 2.12-8.19; p < 0.0001). Both markers were in LD (D' = 0.96; r (2) = 0.84). CONCLUSION: The IFNL3.rs12979860 and IFNL4.ss469415590 variants have comparable effects on spontaneous resolution of HCV among Egyptians, for whom both markers are closely linked.

Utility and cost-effectiveness of screening for hepatocellular carcinoma in a resource-limited setting.

The utility, efficacy and cost-effectiveness of establishing a prospective screening program for hepatocellular carcinoma (HCC) in a low-cost setting as Egypt has not been previously studied. Eligible patients in this observational study were screened by ultrasound and alpha-fetoprotein (AFP) every 6 months. A focal lesion on ultrasound or AFP >200 ng/ml or significant increase in 6 months indicated a recall. Characteristics of cases detected on screening were compared to patients diagnosed outside the screening program. Of 1,920 eligible patients, 1,286 patients participated and 102 patients (7.9 %) developed HCC, with an annual incidence of 5.3 %. Ninety-one (89.2 %) were BCLC stage 0 or A and 11 (10.8 %) stage D. Ultrasound detected a hepatic focal lesion in 99 patients, of which 74 were confirmed to be HCC, and AFP added another 28 HCC cases. The annual cost of detecting a treatable HCC case by ultrasound was 3,980 EGP ( 400) and by both ultrasound and AFP 4,645 EGP ( 500). Adding the cost of treatment, the cost/quality-adjusted life year (QALY) gained was 7,907 EGP ( 800)/QALY for screening with ultrasound only, and 8,430 EGP ( 850)/QALY for using both ultrasound and AFP, which in both cases is <50 % of the per capita GDP and <20 % of the accepted cost/QALY for Egypt. Screening for HCC is feasible and is highly cost-effective in a resource-limited setting. Adding AFP to ultrasound increased detection with a trivial addition to cost/QALY.

Schistosoma mansoni coinfection could have a protective effect against mixed cryoglobulinaemia in hepatitis C patients.

BACKGROUND/AIM: The association between mixed cryogloblinaemia and chronic hepatitis C virus (HCV) infection has been established. However, the factors underlying its great geographical heterogeneity of prevalence have not yet been identified. Concomitant HCV and Schistosoma mansoni infections are common in Egypt. Chronic helminthic infections have been found to decrease the incidence and manifestations of immune-related diseases. To date, no study has focused on the influence of S. mansoni coinfection on the risk of cryoglobulinaemia in hepatitis C patients. METHODS: A cohort of 119 consecutively recruited chronic hepatitis C-infected patients was studied. Patients' sera were assessed for S. mansoni antibodies and cryoglobulins (CGs) were determined and characterized. RESULTS: Cryoglobulins were detected in 18 of 119 patients (15.1%) included in this study. They were detected in 12 of 45 hepatitis C (26.7%) and six of 74 coinfected patients (8.1%), which was statistically significant, P=0.01. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also found to be significantly lower in the CG-positive group compared with the CG-negative group, P=<0.01. CGs were detected in seven of 21 (33.3%) and in 11 of 98 (11.2%) hepatitis C female and male patients, respectively, indicating a significantly positive association with the female gender, P=0.02. A logistic regression adjusted for gender, AST and ALT showed that hepatitis C patients without schistosomal coinfection are more likely to have cryoglobulinaemia, odds ratio=4.12, 95% confidence interval=1.42-11.95. CONCLUSION: There is an apparent protective effect of S. mansoni coinfection against mixed cryoglobulinaemia in chronic hepatitis C patients.

Predictors of employment after liver transplantation.

Employment after orthotopic liver transplantation (OLT) indicates recipients' physical/psychosocial adjustment. Our aim was to determine clinical, socioeconomic and health-related quality of life parameters influencing employment after OLT. Questionnaire on demographics, medical conditions, alcohol and drug use before/after OLT, and a validated 12-Item Short Form Health Survey (SF-12) were mailed to 126 adult OLT patients. Stepwise logistic regression was conducted to identify best predictors of post-OLT employment. Among non-retirees, 49% were employed after OLT. The predictors of employment were: employment status, income, disability status before OLT and Model of End Stage Liver Disease score. These variables had prediction rate of 82%. Individuals working during the five yr prior to OLT were likely to return to work (p<0.0001), particularly those who held a job for >6 months prior to OLT (p<0.0001), income>$80 000 before OLT compared with <$30 000 (p=0.036). Patients receiving Social Security Insurance (SSI) payment for >or=6 months prior to OLT, were less likely to work (p=0.0005). Severity/duration of liver dysfunction prior to OLT did not correlate with employment. Sense of physical health was poorer in those employed after OLT than in unemployed (p=0.0003). Socioeconomic factors were the most important predictors of post-OLT employment.