Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: Given the poor synthetic function of cirrhotic liver, successful resection for patients with hepatocellular carcinoma (HCC) necessitates the ability to achieve resections with tumor free margins. AIM: To validate post hepatectomy liver failure score (PHLF), compare it to other established systems and to stratify risks in patients with cirrhosis who underwent curative liver resection for HCC. METHODS: Between December 2010 and January 2017, 120 patients underwent curative resection for HCC in patients with cirrhosis were included, the pre-operative, operative and post-operative factors were recorded to stratify patients' risks of decompensation, survival, and PHLF. RESULTS: The preoperative model for end-stage liver disease (MELD) score [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (OR = 2.5, 95%CI: 1.5-4.2, P = 0.001) were significant independent predictors of hepatic decompensation after resection. While the preoperative MELD score [hazard ratio (HR) = 1.37, 95%CI: 1.16-1.62, P < 0.001] and different grades of PHLF (grade A: HR = 2.33, 95%CI: 0.59-9.24; Grade B: HR = 3.15, 95%CI: 1.11-8.95; Grade C: HR = 373.41, 95%CI: 66.23-2105.43; P < 0.001) and HCC recurrence (HR = 11.67, 95%CI: 4.19-32.52, P < 0.001) were significant independent predictors for survival. CONCLUSION: Preoperative MELD score and tumor diameter can independently predict hepatic decompensation. While, preoperative MELD score, different grades of PHLF and HCC recurrence can precisely predict survival.

Optimization of biliary drainage in inoperable distal malignant strictures.

BACKGROUND: Given most patients with distal malignant biliary obstruction present in the non-resectable stage, palliative endoscopic biliary drainage with fully covered metal stent (FCMS) or uncovered metal stent (UCMS) is the only available measure to improve patients' quality of life. Half covered metal stent (HCMS) has been recently introduced commercially. The adverse effects and stent function between FCMS and UCMS have been extensively discussed. AIM: To study the duration of stent patency of HCMS and compare it with FCMS and UCMS to optimize biliary drainage in inoperable patients with distal malignant obstruction. Secondary aims in our study included evaluation of patients' survival and the rates of adverse events for each type of stent. METHODS: We studied 210 patients and randomized them into three equal groups; HCMS, FCMS and UCMS were inserted endoscopically. RESULTS: Stent occlusion occurred in (18.6%, 17.1% and 15.7% in HCMS, FCMS and UCMS groups, respectively, P = 0.9). Stent migration occurred only in patients with FCMS (8.6% of patients). Cholangitis and cholecystitis occurred in 11.4% and 5.7% of patients, respectively, in FCMS. Tumor growth occurred only in 10 cases among patients with UCMS after a median of 140 d, sludge occurred in nine, seven and one patients in HCMS, FCMS and UCMS, respectively (P = 0.04). CONCLUSION: Given the prolonged stent functioning time, the use of HCMS is preferred over the use of UCMS and FCMS for optimizing biliary drainage in patients with distal malignant biliary obstruction.

Cost Analysis of Biliary Drainage Using Metal versus Plastic Stents in Hepatocellular Carcinoma Patients with Obstructive Jaundice.

BACKGROUND: The optimal method of biliary drainage for biliary obstruction caused by hepatocellular carcinoma (HCC) is controversial, and the possible endoscopic application of plastic and metal stents is the least invasive procedure to improve patients' quality of life. AIM: Our objective was to study cost evaluation based on a clinical efficacy of both procedures in a randomized trial comparing both approaches in patients with biliary obstruction caused by HCC. METHODS: The strategy of management was based on clinical effectiveness of biliary drainage with either metal or plastic stents in 90 patients over a 1-year follow-up period. Total (direct and indirect) costs were evaluated. RESULTS: The direct costs were EGP 40,857.84 and 21,802.62 per patient with plastic and metal stents, respectively. Concerning the indirect costs, EGP 888 and 454 were spent for each patient with plastic and metal stents, respectively. The differences in the costs resulted from patients with plastic stent insertion requiring more second endoscopic retrograde cholangiopancreatography procedures and more medication, medical consultation, and hospitalization during the year of follow-up. CONCLUSIONS: Based on this analysis, the use of metal stents rather than plastic stents in biliary drainage is more cost effective for this group of patients.

Direct-acting antiviral drugs improve the female sexual burden associated with chronic HCV infection.

Background: The impact of patient cure by direct-acting antiviral agents (DAAs) on female sexual dysfunction (FSD) associated with HCV hasn't been studied.Aim: To study the impact of DAAs on associated FSD in patients with chronic HCV infection.Methods: In patients with chronic HCV infection who were eligible for DAAs, the self-administered female-sexual-function index (FSFI) questionnaire was completed by 300 sexually active females' patients before treatment and compared to equal number of age and socioeconomically matched controls. FSFI questionnaire results after treatment were compared to patients' baseline results.Results: The mean total score for the patients was significantly lower than that for controls (16.77 ± 1.36 versus 17.52 ± 0.99, P < 0.001). Patients after treatment with DAAs significantly scored better results than baseline results in the total score and all domains of the questionnaire and significantly less patients had FSD compared to baseline (2.7% versus 29.3% P < 0.05). Patients' mean FSFI score significantly improved after cure (18.8 ± 0.27 vs. 16.77 ± 1.36, P < 0.001).Conclusion: Hepatitis C has negative impacts on FSF and affecting all domains of FSFI. The DAAS improve the sexual burden associated with hepatitis C in patients who achieved sustained virologic response.

Optimizing the Diagnostic Role of Alpha-Fetoprotein and Abdominal Ultrasound by Adding Overexpressed Blood mRNA Matrix Metalloproteinase-12 for Diagnosis of HCV-Related Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Matrix metalloproteinase-12 (MMP-12) is involved in tumor invasiveness and metastasis and significantly overexpressed in hepatocellular carcinoma (HCC) tissues. We aimed to investigate the diagnostic and prognostic value of blood mRNA MMP-12 overexpression in patients with HCC. PATIENTS AND METHODS: From January 2017 to June 2017, 100 patients with HCC (HCV-related cirrhosis) and 100 patients with HCV-related cirrhosis (without HCC) were included in this study. All patients were subjected to triphasic CT abdomen when indicated, liver profile, alpha-fetoprotein (AFP), and molecular characterization of metalloproteinase-12 expression. RESULTS: There were no statistically significant differences between both groups regarding CBC parameters and liver profile (p value > 0.05). There was a statistically significant difference between patients with and without HCC regarding blood mRNA MMP-12 overexpression (p value < 0.01), blood mRNA MMP-12, and/or AFP (sensitivity 84.0%, specificity 60.0%, PPV 51.2%, and NPP 88.2%). The accuracy of mRNA MMP-12 and/or AFP in detection of HCC was 68.0%. CONCLUSION: Blood mRNA MMP-12 has a good sensitivity and a bad specificity but is accurate in HCC diagnosis. Adding blood mRNA MMP-12 to AFP optimizes the current screening program to improve early diagnosis of HCC and hence better prognosis.

Male Sexual Dysfunction Among Egyptian Patients with Chronic Hepatitis C Virus Infection Before and After Direct-Acting Antiviral Drugs.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a global health burden that affects quality of life, with a negative impact on sexual functioning (SF). AIM: To study male sexual dysfunction (MSD) among Egyptian men with chronic HCV infection and the impact of therapy with direct-acting antiviral drugs (DAAs) on their sexual health. METHODS: The self-administered International Index of Erectile Function (IIEF) questionnaire was completed by 400 sexually active male patients with chronic HCV infection without liver cirrhosis before the initiation of therapy with DAAs and then again at the completion of therapy. We compared these baseline questionnaires with those completed by a similar number of age-matched and socioeconomic status-matched controls. In the patients with HCV infection, we also compared IIEF questionnaires completed before and after DAA therapy. MAIN OUTCOME MEASURE: We determined the proportions of patients and controls who were dissatisfied with their sexual life and the impact of clearing HCV infection on MSD and evaluated the impact of DAA therapy on the total IIEF score and scores in all IIEF domains. RESULTS: Men with chronic HCV infection before DAA treatment had significantly higher erectile dysfunction (ED) scores compared with controls, and scores increased with age (P < .0001). The average scores in all IIEF domains was significantly lower in the patients compared with controls in all age groups. Men with chronic HCV infection had significantly higher ED scores before cure than after cure (P < .0001). CLINICAL IMPLICATIONS: Given the high prevalence of MSD in patients with chronic HCV infection, and given that curing the HCV virus can improve the MSD associated with HCV infection, it is recommended that sexual quality of life in men with HCV be addressed as part of the evaluation protocol before initiation of DAA treatment and again after cure in an effort to improve this particular aspect of quality of life. STRENGTHS & LIMITATIONS: This is the first study to report on MSD in the era of DAA therapy in Egyptian men with chronic HCV infection before the development of cirrhosis, with a relatively large study population. The use of a detailed version of the IIEF questionnaire reinforces the validity of our study. CONCLUSION: Chronic HCV infection negatively impacts MSD, affecting all domains of the IIEF, and effects increase with age. The MSD associated with HCV infection is significantly improved in patients who are cleared of the virus. These findings require further confirmation and need to be addressed as part of a comprehensive therapeutic plan to improve patients' quality of life. Elshimi E, Morad W, Mohamad NE. Male Sexual Dysfunction Among Egyptian Patients with Chronic Hepatitis C Virus Infection Before and After Direct-Acting Antiviral Drugs. J Sex Rev 2019;16:402-409.

Female sexual dysfunction among Egyptian patients with chronic hepatitis C.

INTRODUCTION: Chronic hepatitis C is associated with many extrahepatic manifestations that impact and impair the quality of life. Hepatitis C virus (HCV) infection has a high prevalence in Egypt and carries with the diagnosis many social impacts and stigmatization correlates that further impair social function. This might negatively impact patients and their sexual function. Sexuality and sexual function have not been studied well in patients with HCV, especially in women. AIM: To investigate sexual dysfunction in Egyptian women with chronic hepatitis C. MAIN OUTCOME MEASURES: Female Sexual Function Index (FSFI) scores of patients with hepatitis C, both total and for individual domains, were compared with those of controls. METHODS: The self-administered FSFI questionnaire was completed by 112 sexually active female patients with chronic hepatitis C without liver cirrhosis prior to initiation of therapy by pegylated interferon and ribavirin. Their results were compared to those of 225 age- and socioeconomic class-matched sexually active healthy females. RESULTS: Significantly more patients than controls had questionnaire scores below the threshold of female sexual dysfunction (FSD) (79% vs. 21%, P < 0.05), and the mean total score for the patients was significantly lower than that for controls (19.54 ± 6.2 vs. 28.43 ± 4.9 P < 0.001). The patients' scores in all domains of the questionnaire were significantly lower than those of the controls. CONCLUSION: Chronic hepatitis C negatively impacts female sexual function, affecting all domains of the sex cycle; this warrants further studies and needs to be addressed as part of a comprehensive therapy plan to improve patients' quality of life.

Bile acids induce overexpression of homeobox gene CDX-2 and vascular endothelial growth factor (VEGF) in human Barrett's esophageal mucosa and adenocarcinoma cell line.

OBJECTIVE: Barrett's esophagus (BE) is an acquired precancerous condition that develops from mucosal injury incurred after chronic gastroesophageal acid and bile reflux. The mechanism of progression of carcinogenesis in BE is still not fully understood. Recently, the role of bile acids and the homeobox gene transcription factor CDX-2 has been suggested in the pathogenesis of BE. The aims of the present study were 1) to compare the mRNA and protein expression of CDX-2 in biopsies obtained from patients with BE and normal squamous epithelium and 2) to study the effect of two different bile salts, ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA), on the mRNA expression of CDX-2 and vascular endothelial growth factor (VEGF) in Barrett's the adenocarcinoma cell line (OE-33). MATERIAL AND METHODS: CDX-2 expression was measured in Barrett's mucosa and normal esophageal mucosa obtained from 15 patients with BE histologically diagnosed by immunohistochemistry, Western blot, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In in vitro experiments, OE-33 cells were incubated with DCA (100 microM) and UDCA (100 microM) in neutral and shortly acidified media (pulse acidification). The expression of CDX-2 and VEGF was assessed by quantitative RT-PCR. RESULTS: Both mRNA and protein expression of CDX-2 were significantly up-regulated in Barrett's mucosa as compared to normal esophageal mucosa. In neutral medium, OE-33 cells showed an increase in CDX-2 expression after incubation with DCA or UDCA. After short acidification of the medium, expression of CDX-2 in OE-33 cells was significantly higher than that in cells incubated in neutral pH. The addition of DCA and UDCA did not cause any further alteration in CDX-2 expression. In neutral and acidified medium, VEGF mRNA expression was only significantly up-regulated by DCA, but not by UDCA. CONCLUSIONS: Bile acids, especially in acidic medium, increase expression of CDX-2. DCA appears to be a stronger stimulant of the expression of VEGF than UDCA in the Barrett's carcinoma cell line, indicating a stronger carcinogenic potential of this bile salt.