Hepatitis C Virus Cirrhotic Patients Research Articles

Apa1 (rs7975232) SNP in the vitamin D receptor is linked to hepatocellular carcinoma in hepatitis C virus cirrhosis

ABSTRACTBackground: As hepatocellular carcinoma (HCC) arising from chronic hepatitis C virus (HCV) infection in liver cirrhosis is a major problem in public health, early and rapid prediction of HCC is urgent. We hypothesized that a single nucleotide polymorphism in the Apa1 SNP in the vitamin D receptor may help diagnosis.Methods: We recruited 3 groups: 80 HCC patients with HCV cirrhosis, 80 HCV cirrhotic patients free of HCC and 80 healthy controls. Apa1 rs7975232 SNP was detected by PCR- RFLP technique. Routine laboratory markers were determined by standard methods.Results: The Apa1 CC genotype was more frequent (75%) in HCC than in the cirrhosis (35%) and control (20%) groups (P<0.0001). CC patients were more likely to have a more severe Child-Pugh score (P=0.027) and MELD score (P<0.05). In multivariate analysis, the CC genotype out-performed AFP is determining HCC.Conclusion: Apa1 CC genotype is linked to HCC in HCV C cirrhotic patients, and so has the potential to be an independent biomarker predictor for HCC occurrence in HCV cirrhosis.

Value of Child-Turcotte-Pugh Score in Prediction of Treatment Response in “Difficult to Treat” Chronic HCV Cirrhotic Patients

Background and aim: The direct-acting antivirals (DAAs) treatment has greatly improved sustained virologic response (SVR) in chronic non-cirrhotic hepatitis C virus (HCV) patients and to less extent in those with cirrhosis. There is a stressing need for predicting the outcome of DAAs treatment especially in “difficult to treat” patients. This work aimed to study the value of the Child-Turcotte-Pugh (CTP) score in the prediction of treatment outcome with DAAs in “difficult to treat” chronic HCV patients. Materials and methods: A retrospective cohort study was conducted where files of 120 “difficult to treat” patients were randomly selected from the follow-up clinic. Patients’ data were collected before and after treatment including history taking, clinical examination, laboratory investigations, and abdominal ultrasonography. Child-Turcotte-Pugh (CTP) scores were calculated. Results: There was no significant difference in mean Child score between patients with and without SVR before treatment, while this difference became significant after treatment. The patients without complications showed a highly significant decrease in their mean Child score after treatment, while patients with complications did not show any significant differences. Conclusion: The baseline Child-Turcotte-Pugh score cannot predict the treatment response of DAAs in “difficult to treat” chronic HCV patients, but it is significantly associated with the occurrence of complications.

Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients.

Background & aimsSerum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients.MethodsIn serum DPPIV activity (by enzymatic assay), IP-10 (by ELISA) and bile acids (BA) (by enzymatic assay) were analysed in 229 naive HCV genotype (GT) 1 patients and in 16 patients with cholestatic liver disease. In a prospective follow-up (FU) cohort of 27 HCV GT 1 patients peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ cells were measured by FACS.ResultsIn 229 HCV patients serum IP-10 levels correlated positively to DPPIV serum activity. Higher IP-10 levels and DPPIV activity were detected in cholestatic and in cirrhotic HCV patients. Increased IP-10 serum levels were associated with therapeutic non-response to antiviral treatment with pegylated-interferon and ribavirin. In the HCV FU cohort elevated IP-10 serum levels and increased BA were associated with higher frequencies of peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ T cells. Positive correlation between serum IP-10 levels and DPPIV activity was likewise validated in patients with cholestatic liver diseases.ConclusionsA strong correlation between elevated serum levels of IP-10 and DPPIV activity was seen in different cholestatic patient groups. Furthermore, in cholestatic HCV patients a functional link to increased numbers of peripheral CXCR3+ immune cells could be observed. The source of DPPIV release in cholestatic patients remains open.

Impact of the Uridine⁻Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients-A Pilot Study.

Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine–cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.

Role of circulating miR-182 and miR-150 as biomarkers for cirrhosis and hepatocellular carcinoma post HCV infection in Egyptian patients

In Egypt, liver diseases are exceptionally high, maintaining the highest prevalence of hepatitis C virus (HCV) worldwide, and increasing rates of hepatocellular carcinoma (HCC). Available diagnostic methods show poor performance in early diagnosis of HCC. Definite pathogenic factors contributing in the development of HCV are still lacking. MicroRNAs have been reported as promising biomarkers for cancers diagnosis and in virus-host interaction.This study was conducted to detect the role of miR-182 and miR-150 as biomarkers for development of cirrhosis and malignant transformation in HCV infected patients.The expression of miR-182 and miR-150 was evaluated using real-time quantitative PCR (qRT-PCR) in 120 subjects: 40 HCC patients, 40 hepatitis C patients (20 cirrhotic and 20 non-cirrhotic HCV genotype 4) and 40 healthy controls.In HCC, statistically significant decrease of miR-182 and miR-150 compared to non-cirrhotic HCV patients (p = 0.015, p = 0.006 respectively) and of miR-150 compared to controls (p = 0.039). In cirrhotic HCV patients, significant down regulation of miR-182 and miR-150 compared to non-cirrhotic HCV (p = 0.003, p = 0.024 respectively). On the other hand, significant upregulation of miR-182 was observed in non-cirrhotic HCV compared to controls (p = 0.036). Alpha-fetoprotein (AFP) showed sensitivity 15% for HCC diagnosis at the cut-off value of 400 ng/ml, while combining AFP with miR-182 and miR-150, resulted in improving sensitivity to (90%) and diagnostic accuracy to (80%).miR-182 and miR-150 can be used as non invasive biomarkers for HCC and combination of these miRNAs and AFP markedly improve the diagnosis of HCC. Both miR-182 and miR-150 can also be used as predictive markers for detection of cirrhosis progression in HCV infected patients.

The Role of Fibroscan as a Non-Invasive Predictor for Oesophageal Varices in Post HCV Cirrhotic Egyptian Patients With or Without Bilhariziasis

Background: Development of oesophageal varices is a major complication that may occur in up to 90% of cirrhotic patients. The endoscopic screening is an invasive procedure. This is why the selection of patients with large oesophageal varices at high risk for bleeding has become an issue of growing importance. In this respect, several clinical, biochemical, ultrasonographic and elastrogarphic (transient elastography-TE) methods have been proposed (and some of them validated) as noninvasive alternatives to endoscopy. Objectives: It was to evaluate transient elastography by fibroscan in the prediction and determination of the grade of esophageal varices in cirrhotic patients due to chronic hepatitis c virus (HCV) infection with or without bilharziasis. Patients and Methods: Sixty Egyptian patients with body mass index (BMI) <35, no history of: upper gastro-intestinal tract (GIT) bleeding, hepatocellular carcinoma, moderate and tense ascites or any other cause of liver cirrhosis. The patients were divided into two groups: Group I included thirty patients with liver cirrhosis due to HCV infection only. Group II included thirty patients with liver cirrhosis due to HCV infection associated with bilharziasis. The patients were subjected to: 1) Thorough history taking. 2) Detailed clinical examination. 3) Laboratory tests. 4) Abdominal ultrasound. 5) Rectal snip for diagnosis of bilharziasis. 6) Upper gastrointestinal endoscopy. 7) fibroscan. Results: Regarding fibroscan in both groups, the mean values of fibroscan were lower in patients without esophageal varices than patients with esophageal varices or with large esophageal varices with statistically high significant differences (p 0.05). In both groups, the mean values of fibroscan were lower in patients with small esophageal varices than patients with large esophageal varices with statistically non significant differences (p > 0.05). Conclusion: fibroscan is valuable in predicting the presence of esophageal varices and large esophageal varices in patients with post HCV liver cirrhosis with or without bilharziasis but couldnot predict the grade of esophageal varices.

English

This study aimed to investigate the incidence of bacterial infection in chronic hepatitis C virus (HCV) patients with cirrhosis and association between toll-like receptor 4 D299G gene polymorphism and Gram-negative bacterial infections in the patients. 100 HCV cirrhotic patients with ascites and 20 age- and sex-matched healthy subjects as control were included. Conventional culture methods were used to identify the causative organism of infection. Toll-like receptor 4 D299G polymorphism was detected by PCR- RFLP (polymerase chain reaction &ndash; restriction fragment length polymorphism). Patients were divided into: Group I: 100 HCV cirrhotic patients with ascites. They were subdivided into: Group I (a): Patients with Toll-like receptor 4 D299G polymorphism, Group I (b): Patients without polymorphism. Group II (control): 20 healthy subjects. This study showed significant higher incidence of infections in cirrhotic patients with Toll-like receptor 4 D299G polymorphism which play a role in the development of bacterial infection in cirrhotic patients that makes down-regulation of TLR4 response one of the immune mechanisms predisposed to Gram negative bacterial infection in cirrhotic patients. &nbsp; Key words: TLR-4 gene polymorphism, cirrhosis, bacterial infection.&nbsp

SVR is the strongest predictor of occurrence and recurrence of hepatocellular carcinoma in HCV cirrhotic patients after treatment with direct acting antivirals: A prospective multicenter Italian study

Patients with hepatitis C virus (HCV) related cirrhosis have an expected high rate of progression to liver decompensation and hepatocellular carcinoma (HCC); dramatic improvement in viral eradication rates has been reached with direct antiviral agents (DAAs). Nevertheless, the real benefit of viral eradication after DAAs on disease progression, including HCC development, are still limited and controversial. We aim to prospectively assess the risk of HCC occurrence and early recurrence in a large prospective cohort of DAA-treated HCV-cirrhotic patients.

Analysis of Plasma Tenascin-C in Post-HCV Cirrhosis: A Prospective Study.

Hepatitis C virus (HCV)-related cirrhosis, one of the most common etiologies of liver cirrhosis in the Western world, is a risk factor for hepatocellular carcinoma. To confirm and improve current effectiveness of screening and prognosis of patients with established cirrhosis, a credible, simple plasma biomarker is needed. Hepatic stellate cell activation, a pivotal event in cirrhosis development, results in increased secretion of extracellular matrix proteins, including tenascin-C (TnC). Herein, we tested TnC as a simple biomarker to identify cirrhotic patients with active HCV infection from those with HCV eradication. A prospective study of subjects with HCV-related cirrhosis, stratified into two groups, HCV or virologic cure, was conducted. Plasma TnC expression was measured by ELISA and Western blots. TnC values were correlated with markers of liver injury and ROC analyses performed between groups. The HCV cirrhotic cohort, consisting mostly of men (56%), Caucasians (76%), and genotype 1a or 1b (84%), was compared to healthy controls (HCs). Plasma TnC was significantly higher in HCV cirrhotic patients with active infection compared to HCs (P<0.0001) and virologic cure (P<0.0001). TnC concentrations in virologic cure subjects were not statistically different from HCs. TnC levels correlated with AST, platelets, MELD, APRI, FIB-4, and Child-Pugh score. TnC and AST together were significantly better indicators of cirrhosis in patients with active HCV infection than other markers tested. TnC and AST provided the best model for discriminating HCV cirrhotics with active infection from HC and virologic cure cohorts over current liver injury markers, suggesting TnC as a potential indicator of ongoing hepatic injury and inflammation.

Associations between CD133, CK19 and G2/M in cirrhotic HCV (genotype-4) patients with or without accompanying tumor

Hepatitis C virus (HCV)-cirrhotic patients have the highest threat of developing hepatocellular carcinoma (HCC) and may be at risk of extra hepatic cancer. The present study was designed to investigate CD133 and CK19 in HCV (genotype-4)-cirrhotic patients with/without HCC or extra hepatic cancer, to assess the degree of their correlation with cell cycle abnormalities and finally to assess the role of their combination as diagnostic tool for discrimination of cirrhotic patients with HCC from those with extra hepatic cancer. The study included 77 HCV-cirrhotic patients and 20 healthy non-disease control group. Patients were categorized histo-pathologically into: 24 have only liver cirrhosis, 26 with HCC, and 27 patients with extra hepatic cancer. Cell cycle abnormalities, CD133 and CK19 were determined by flow cytometry technique. CD133 and CK19 showed marked elevation in HCC and extra hepatic cancer compared with liver cirrhosis and control subjects (p<0.0001). Positive associations were noted between CK19, CD133 and G2/M. They were gradually increased with progression from liver cirrhosis to HCC. Combination of the three showed the best AUC (0.978) and accuracy (92.5%) for discrimination of HCC from extra hepatic cancer. Combined CD133 with G2/M and CK19 comprises an excellent diagnostic panel for discrimination of HCV-cirrhotic patients with HCC from those with extra hepatic cancer.

Interferon‐free therapy of chronic hepatitis C with direct‐acting antivirals does not change the short‐term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis

Hepatitis C virus (HCV) clearance with IFN-based therapies reduces the incidence of hepatocellular carcinoma (HCC). There has been some debate if IFN-free therapy with direct-acting antivirals alters the risk for HCC. To investigate the HCC incidence in cirrhotic HCV patients who cleared HCV with direct-acting antivirals vs untreated controls. We prospectively monitored 373 patients with chronic hepatitis C who received IFN-free therapies with direct-acting antiviral after January 2014. A retrospective control cohort of untreated cirrhotic patients was recruited out of 3715 HCV patients who were followed at our centre between 2007 and 2013, with similar HCC screening protocols. 158 direct-acting antiviral-treated and 184 control patients with liver cirrhosis were included in this analysis. The groups did not differ in gender and genotype distribution, severity of liver disease and prevalence of diabetes mellitus. Patients were followed up for a median of 440 (range 91-908) and 592 (range 90-1000)days. HCCs developed in 6 and 14 patients during follow-up, resulting in an incidence of 2.90 vs 4.48 HCCs per 100 person-years. In the direct-acting antiviral-treated group, there was no new case of HCC later than 450 days after treatment initiation. In multivariate analysis, higher MELD-Scores and AFP-levels were independently associated with HCC development. Transplant-free patient survival was similar in both groups. IFN-free direct-acting antiviral therapy of chronic hepatitis C does not alter the short-term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5years of follow-up.

High Dose of Silymarin in Patients with Decompensated Liver Disease: A Randomized Controlled Trial.

Hepatitis C virus (HCV) is a major public health problem being the most common cause of chronic liver disease in Egypt. HCV-induced decompensated liver cirrhosis patients have a median survival of 2 years even with currently used new treatments. Silymarin is the most commonly used herbal product in chronic liver disease for its anti-inflammatory, antiviral, antioxidant, and antifibrotic effects. The aim of this study was to assess the effects of silymarin in high dose on the clinical and biochemical status of chronic HCV-associated decompensated liver cirrhosis. The study was conducted on 62 chronic HCV-decompensated cirrhotic patients. Patients were randomized according to treatment plans: group A, included 31 patients who received silymarin in dose of 1,050 mg/day, and group B, included 31 patients who received silymarin in dose of 420 mg/day. Patients were subjected to baseline history taking, laboratory evaluation, abdominal ultrasound, Child scoring, and quality-of-life (QoL) questionnaire. Follow-up was done every 2 weeks for 12 weeks. Silymarin in high dose had an effect on reducing alanine transaminase, aspartate aminotransferase levels (P ≤ 0.01), as well as improving albumin (P = 0.04), bilirubin (P = 0.02), and international normalized ratio (P = 0.03), thus resulted in improvement in Child score (P = 0.048), however, regular silymarin regimen (420 mg/day) failed to achieve the previous biochemical changes. High-dose regimen of silymarin also had a positive impact on improving QoL. No serious adverse events were reported. Silymarin in high dose is a good choice for improvement of liver biochemical profile and QoL in chronic HCV cirrhotic patients.

Hepatitis C Virus as risk factor for development of hepatocellular carcinoma in Egypt: II-Enhancement role of matrix metalloproteinases-2 in dissemination of HCC

Hepatitis C virus (HCV) infection is a major public health problem all over the world. Egypt has the highest prevalence of HCV worldwide (17-26%) with subsequent high morbidity from chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC). Matrix metalloproteinase are proteolytic enzymes that play a role in the degradation of extracellular matrix (ECM) which is necessary for invasion and metastasis of tumor cells. The present work was designed to study the relationship between HCV infection and circulating MMP-2 level in chronic HCV patients (either without or with hepatic complication) and compared to that of non- HCV cirrhotic patients as well as healthy controls, in order to clarify the role of HCV in changing microenvironment and underlying mechanisms associated with dissemination of malignancy. The level of MMP-2 was estimated in sera collected at different stages of HCV infections as well as in ascetic fluids collected from those developing either HCC or cirrhosis. Statistical analysis of their results revealed that MMP-2 levels were significantly elevated in all patient groups as compared to healthy controls. The level of MMP-2 in HCV patients with HCC was significantly elevated when compared to other HCV patients. Meanwhile MMP-2 in ascetic fluids of cirrhotic patients were similar to that detected in their sera, while in HCC patients there were 2.4 times elevations in serum level of MMP-2 as compared to that in ascetic fluids. These results revealed that HCV infection is not only responsible for biochemical and hematological abnormalities recorded at chronic stages of infection but also creating a microenvironmental change by enhancing MMP-2 release, which effect on infected cell by obliging them to modify their phenotype in order to survive, thus increasing the invasion potential and facilitate tumor progression.

Evaluation of Ledipasvir plus Sofosbuvir for Treatment of Compensated and Decompensated HCV Cirrhotic Patients

Background:unlike human immunodeficiency virus (HIV) and hepatitis B virus (HBV), hepatitis C virus (HCV) infection is a curable disease. Current direct acting antiviral agent (DAA) targets are focused on HCV NS3/4A protein (protease), NS5B protein (polymerase) and NS5A protein. The first generation of DAAs includes boceprevir and telaprevir, which are protease inhibitors and were approved for clinical use in 2011. The cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/ribavirin. More effective and less toxic second generation DAAs supplanted these drugs by 2013. The second generation of DAAs includes sofosbuvir, simeprevir and fixed combination medicines containing ledipasvir plus sofosbuvir and Viekira Pak. These drugs increase cure rates to over 90% without the need for interferon and effectively treat all HCV genotypes. With these drugs the “cure HCV” goal has become a reality. The aim of this study was to assess of ledipasvir plus sofosbuvir as treatment of HCV infection in patients with advanced liver disease including cirrhotic patients with child B and C. Patients and methods:in this prospective study, seventy five HCV PCR positive patients were classified into three groups according to child score. Each group included twenty five patients. All patients received ledipasvir plus sofosbuvir for six months. For all patients thorough medical history, clinical examination, kidney function tests, liver function tests, complete blood count, pelvi-abdominal ultrasound, HCVantibodies, hepatitis C viral RNA, quantitative, HbsAg, alpha fetoprotein as baseline screening. HCV PCR done for all patients at end of treatment and three months later to detect sustained virological response (SVR12). Patients with combined HCV and HBV infection, hepatic or extrahepatic malignancies and late child C were excluded. Results: showed that no statistical significant difference were detected in patients of group A as regard liver function tests before and after treatment and SVR12 achieved by 96%. Patients of group B showed significant statistical difference as regard liver function tests before and after treatment with SVR12 achieved by 88%. In patients of group C there were significant statistical difference in liver function tests with SVR12 achieved by 80%. Also there were clinical improvement in patients of group B and C after end of treatment. Conclusion:it could be concluded that there will be a dramatic improvement in HCV therapy followed the introduction of oral medicines that directly inhibiting the replication cycle of HCV. The combination pill contains a fixed-dose of ledipasvir 90 mg and sofosbuvir 400 mg, two direct-acting antiviral agents against HCV. Ledipasvir is an inhibitor of the NS5A protein, which is required for HCV replication. Sofosbuvir inhibits the HCV NS5B RNA-dependent RNA polymerase, which is also required for viral replication. Sofosbuvir is a nucleotide prodrug that undergoes intracellular metabolism to form a pharmacologically active triphosphate that can incorporate into the HCV RNA. Ledipasvir plus sofosbuvir can be used safely in treatment of compensated and decompensated post hepatitis C liver cirrhosis. SVR12 can be achieved by 96% in patients with early cirrhosis (child A), 88% in patients with child B cirrhosis and 80% in patients with child C with subsequent improvement in liver functions.

Soluble fas levels as a marker in chronic hepatitis C

Objective The aim of the study was to investigate the effect of soluble Fas (sFas) on patients with chronic hepatitis C. Background Programmed cell death has been observed in leukocytes among patients with chronic Hepatitis C and hepatocellular carcinoma (HCC), and now there is a strong trend to use sFas as a predictive marker for chronic hepatitis C and tumorigenesis in HCC. Methods Seventy patients were divided into three groups. Group I included 30 patients with chronic hepatitis C infection due to hepatitis C virus (HCV) (cirrhotic and noncirrhotic). Group II included 20 patients with HCC with HCV infection. Group III included 20 healthy individuals without hepatitis C infection or any other disease, which served as the control group. Liver function tests, complete blood count, analysis of viral markers, analysis of HCV-RNA by PCR, and evaluation of serum sFas by enzyme-linked immunosorbent assay were carried out. Results Serum sFas level increases in chronic hepatitis C and HCC, with positive correlation between sFas and aspartate aminotransferase, alanine aminotransferase, total bilirubin, and direct bilirubin and negative correlation between sFas and Hb level, platelet count, serum albumin, prothrombin time, and viral load (PCR). sFas at cutoff of 6581.12 could predict patients with HCV with 83.3% sensitivity and 65% specificity. sFas at cutoff of 6960.91 could predict patients with HCC with 85% sensitivity and 30% specificity. sFas at cutoff of 9125.99 could discriminate between cirrhotic and noncirrhotic HCV patients with 80.0% sensitivity and 53.3% specificity. Conclusion sFas can be considered a predictive marker for chronic hepatitis C and tumorigenesis in HCC.

Serum Level of Thyroid Hormones in Patients with Chronic Hepatitis C Virus Infection

Objective: There are clinical and laboratory associations between thyroid and liver diseases. Hepatitis C virus (HCV) is known to be responsible for both hepatic and extrahepatic diseases. The most frequent and clinically important endocrine extrahepatic diseases are thyroid disorders and type 2 diabetes mellitus. We aim to study the relationship between the serum level of thyroid hormones (THs) and the severity of liver disease in patients with chronic hepatitis C virus (CHC) infection. Methods: 60 patients with CHC infection were selected for the study. They were divided into two groups: with or without liver cirrhosis. Those with liver cirrhosis were further subdivided according to the Child-Turcotte-Pugh scoring system. Serum levels of free T3 (FT3), free T4 (FT4) and TSH were measured to all patients. Results: There was decrease in the FT3 and FT4 levels and increase in the TSH levels in patients with CHC with cirrhosis when compared to patients with CHC without cirrhosis. Conclusion: Thyroid profile abnormalities were seen in cirrhotic HCV patients when compared to non-cirrhotic patients. The abnormalities in the serum level of THs (decreased FT3, FT4, and increased TSH) are strongly associated with the severity of liver damage and advancing of the child score.

Influence of sustained viral response on the regression of fibrosis and portal hypertension in cirrhotic HCV patients treated with antiviral triple therapy.

The regression of liver fibrosis and portal hypertension (PH) and their influence on the natural history of compensated hepatitis C virus (HCV)-related cirrhosis has not been studied previously. Our objective was to evaluate the influence of sustained virologic response (SVR) on the portal pressure gradient (HVPG) and non-invasive parameters of PH and prognostic factors of response. Sixteen patients with compensated HCV genotype 1-related cirrhosis with PH (HVPG > 6 mmHg) without beta-blocker therapy were considered as candidates for PEGα2a + RBV + BOC (48 weeks; lead-in and accepted stopping rules). A hemodynamic study and Fibroscan® were performed at baseline, at eight weeks and, in the case of SVR, 24 weeks after treatment. In each hemodynamic study, serum samples were analyzed for inflammatory biomarkers associated with PH. In eight cases, SVR was obtained; five patients relapsed, and treatment was stopped early for non-response to lead in (one case) and a decrease of < 3 log at week 8 (two patients). Compared to baseline, there was a significant decrease in HVPG and Fibroscan® at weeks 8 and 72 (10.31 ± 4.3 vs 9.4 ± 5.04 vs 6.1 ± 3.61 mmHg, p < 0.0001 and 21.3 ± 14.5 vs 16.2 ± 9.5 vs 6.4 ± 4.5 kPa, p < 0.0001, respectively). The average HVPG decrease in SVR was 40.8 ± 17.53%, achieving an HVPG < 6 mmHg in five patients (62.5%) and a Fibroscan® < 7.1 kPa in three patients (37.5%). Complete hemodynamic response (HVPG < 6 mmHg) and fibrosis regression (Fibroscan® < 7.1 kPa) occur in more than half and one-third of patients achieving SVR, respectively, and must be another target in cirrhotic patients with SVR.

Significance of hepatocyte growth factor concentrations in serum of patients with liver cirrhosis and patients with hepatocellular carcinoma

Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection worldwide with the development of cirrhosis and hepatocellular carcinoma (HCC). The hepatocyte growth factor (HGF)–cMET axis promotes cell survival, proliferation, migration, and invasion. This study aimed to evaluate the role of serum HGF as a noninvasive biomarker in the diagnosis of liver cirrhosis and HCC. This study included 80 individuals. They were divided into three groups: group 1 included 20 healthy volunteers as a control group, group 2 included 30 patients with liver cirrhosis, and group 3 included 30 patients with HCC. HGF was highly significantly elevated in the HCC group (median 3709 pg/ml) and the cirrhotic group (median 2843.5 pg/ml) compared with the control group (median 913 pg/ml). α-Fetoprotein (AFP) was highly significantly elevated in the HCC group (median 128.5 ng/ml) than both the cirrhotic (median 4.9 ng/ml) and the control (median 3.15 ng/ml) group. Results of aspartate aminotransferase/alanine aminotransferase, APRI, fibroindex, and model 3 in the cirrhotic group were highly significantly different from those in the control group. We found a positive significant correlation between HGF and AFP for all the participants studied. There were direct correlations between HGF and aspartate aminotransferase/platelet ratio index (APRI), fibroindex, and model 3. The sensitivity and specificity of HGF for selective detection of the HCC group over the non-HCC group (HCV group and healthy control group) were 93.3 and 46%, respectively, at a cut-off value of 1415 pg/ml, whereas that of AFP were 100 and 92%, respectively, at a cut-off value of 10 ng/ml, and area under the curve of HGF and AFP were 0.787 and 0.999, respectively. The sensitivity and specificity of both AFP and HGF together were 100 and 66%, respectively, at the same cut-off values. The odds ratio of occurrence of HCC in patients with elevated HGF levels was 11.926 and 95% confidence interval 2.56–55.55. We conclude from this study that both HGF and AFP can be used as noninvasive biomarkers for early detection of HCC in HCV cirrhotic patients, especially if their values match the cut-off levels detected in our study.

12 weeks of interferon-based therapy is feasible in patients with hepatitis C-related cirrhosis and thrombocytopenia: A post hoc analysis of eltrombopag studies

BackgroundA 24–48-week course of interferon-based therapy poorly tolerated in hepatitis C virus (HCV) cirrhosis patients with thrombocytopenia. Aim of the study was to identify patients at low-risk of liver-related complications over a 12-week course of interferon-based therapy. MethodsWe assessed the rate of complications and death during the first 12 weeks of interferon-based therapy in HCV cirrhotics with thrombocytopenia (platelets ≤75×109/L) enrolled in the ENABLE-1 and -2 phase 3 randomised controlled trials. ResultsOverall, among 1441 patients, 89 complications (6.9%) and 10 deaths (0.7%) were observed within the first 12 weeks of therapy. At univariate analysis baseline albumin levels and Model for End Stage Liver Disease (MELD) score (≤35g/L, p<0.001, and ≥10, p<0.001, respectively) were the only predictors associated with occurrence of complications and death. Of the 1026 patients with serum albumin >35g/L (71.2%), one patient died (0.1%) and 17 experienced liver-related complications (1.7%). Among 667 patients with serum albumin >35g/L and MELD score <10, no deaths occurred and 4 experienced liver-related complications (0.6%). ConclusionAmong HCV cirrhotic patients with thrombocytopenia, albumin levels and MELD score can identify patients who may safely receive a 12-week course of interferon-based therapy with a low risk of complications.

Long-term evaluation of partial splenic embolization followed by interferon therapy in patients with hepatitis C virus (HCV) cirrhosis and thrombocytopenia.

Patients with hepatitis C virus (HCV) cirrhosis and thrombocytopenia are often excluded from receiving interferon therapy because the treatment results in severe platelet depletion. Surgical splenectomy or partial splenic embolization (PSE) is a promising procedure for increasing the platelet count before interferon therapy. We performed PSE and evaluated the long-term clinical course in HCV cirrhotic patients. Patients with HCV cirrhosis and thrombocytopenia were included (n=108) in this study. The straight-coiled PSE procedure (Takatsuka method) was performed. The platelet count, hemodynamic changes, rate of a sustained virological response (SVR) and prevalence of hepatocellular carcinoma (HCC) were evaluated. PSE resulted in a significant increase in the platelet count (before PSE: 7.9±2.3×10(4)/μL, two weeks after PSE: 16.7±6.6×10(4)/μL (p<0.001). Therefore, all participants were started on regular-dose interferon therapy. The SVR rate was 24% for serotype 1 and 62% for serotype 2. In the biochemical responders (BR) with SVR, the overall survival rate was 94.6% over five years and 89.3% over 10 years. In the non-responders (NR), the overall survival rate was 78.7% over five years and 62.2% over 10 years. The overall survival rate of the patients with SVR+BR was significantly higher than that observed in the patients with NR (p=0.0082). There were no differences in the prevalence of HCC between the patients with SVR+BR and NR. PSE enabled the induction of regular-dose interferon therapy in patients with HCV cirrhosis and thrombocytopenia. Although the prevalence of HCC did not differ between the SVR+BR and NR patients, there was a significant survival benefit in the patients with SVR+BR.