Hepatitis C-related Liver Cirrhosis Research Articles

Prediction of hepatic decompensation and hepatocellular carcinoma after direct-acting antiviral therapy in patients with hepatitis C-related liver cirrhosis: a cohort study

AimThis study aimed to evaluate the rate of hepatic decompensation and de novo HCC and identify their independent factors in HCV genotype 4-infected patients with compensated liver cirrhosis following successful direct-acting antiviral (DAA) therapy.MethodsThis prospective cohort study included 1789 patients with HCV genotype 4-related compensated liver cirrhosis who achieved viral eradication after DAAs. Baseline and follow-up clinical, laboratory, albumin-bilirubin score (ALBI), and abdominal ultrasound were recorded to detect hepatic decompensation and de novo HCC. Logistic regression was performed to evaluate the variables associated with decompensation and HCC.ResultsDuring the 24-month period of follow-up, 184 (10.28%) patients developed hepatic decompensation. Ascites was the commonest presentation. Baseline serum albumin, bilirubin, and platelet count were the independent factors associated with hepatic decompensation (P-values 0.022, 0.03, and < 0.001, respectively). A formula was developed for the prediction of decompensation using these 3 factors (AUC: 0.641 at cutoff 0.1098969 with a sensitivity of 59.9% and specificity of 61.7%). Pre-treatment ALBI score could predict decompensation at cutoff value − 2.5184, AUC 0.609, sensitivity 58.3%, and specificity 59.7%. Post-treatment ALBI score could predict hepatic decompensation after DAA therapy at cutoff value − 2.9521, AUC 0.597, sensitivity 48.1%, and specificity 75.5%. Sixteen (0.9%) patients developed de novo HCC. Age (odds ratio: 1.061, 95%, confidence interval: 1–1.126) and male gender (OR 3.450, 95% CI 1.105–10.769) were the independent factors associated with the development of de novo HCC but not the ALBI score.ConclusionBaseline demographic and laboratory data could predict hepatic decompensation and HCC in patients with compensated liver cirrhosis after successful DAA therapy

Three cases of immune-related hypopituitarism after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

We herein report three cases of immune-related hypopituitarism after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1 was a man in his 60s with hepatitis C-related liver cirrhosis. He had been diagnosed with HCC and undergone surgical resection. However, HCC recurred 17months after surgery. After 13 cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. The plasma levels of adrenocorticotropic hormone (ACTH) and cortisol were decreased. He was diagnosed with central adrenal insufficiency associated with hypopituitarism. Glucocorticoid therapy rapidly improved his symptoms. Case 2 was a man in his 70s with HCC associated with non-alcoholic steatohepatitis (NASH). After eight cycles of atezolizumab-bevacizumab therapy, general fatigue, appetite loss, and muscle weakness appeared. Hyponatremia and eosinophilia were observed. He was also diagnosed with hypopituitarism, and glucocorticoid therapy rapidly improved his symptoms. Case 3 was a man in his 60s with HCC associated with alcoholic liver cirrhosis. After 10 cycles of atezolizumab-bevacizumab therapy, hypopituitarism developed. In these cases, the presence of hyponatremia and/or eosinophilia was useful for making a diagnosis. Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody is reported to be likely to induce hypophysitis two to three months after its administration. In contrast, anti-programmed cell death 1 (PD-1) antibody is likely to induce hypopituitarism six to seven months after its administration. These three patients treated with anti-programmed death ligand 1 (PD-L1) antibody developed hypopituitarism six to nine months later, close to the condition with anti-PD-1 antibody administration. Although immune-related hypopituitarism after atezolizumab-bevacizumab treatment is rare, we should be alert for hypopituitarism developing during atezolizumab-bevacizumab treatment.

The role of serum visfatin and vaspin in hepatocellular carcinoma in hepatitis C-related liver cirrhosis.

To investigate the role of the novel adipokines visfatin and vaspin in hepatitis C virus (HCV)-cirrhotic patients with and without hepatocellular carcinoma (HCC) and their association with tumour characteristics and liver dysfunction. This case-control study was carried out between March 2021 and September 2021. Serum visfatin and vaspin were measured in 67 HCV-cirrhotic patients (37 had HCC, and 30 did not) and 20 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Serum visfatin and vaspin were substantially elevated in HCC patients compared to those without HCC and healthy controls (p = 0.001, < 0.0001, respectively) and significantly associated with hepatic dysfunction. At a cut-off value of 12.1 ng/ml, the sensitivity and specificity of the serum visfatin in detecting HCC were 67.6% and 83.3%, respectively. Serum vaspin at a cut-off value of 321 ng/dl had a sensitivity of 94.6% and specificity of 66.7%. In multivariate regression analysis, serum vaspin and albumin were independent risk factors for HCC development. Patients with Barcelona Clinic Liver Cancer (BCLC) stage D had significantly the highest serum levels of visfatin and vaspin (p = 0.03, 0.008, respectively). Serum visfatin and vaspin were substantially higher in HCC patients, associated with tumour stage, and might be considered as potential biomarkers of HCC, but this should be confirmed in larger independent cohorts of patients with liver cirrhosis. Serum vaspin and albumin were independent risk factors for HCC development. There was a substantial association between visfatin, vaspin, and the severity of the underlying liver dysfunction.

Classification and survival prediction in early-stage cirrhosis by gene expression profiling.

Liver cirrhosis has been increasingly diagnosed at an early stage owing to the non-invasive diagnostic techniques. However, it is difficult to identify patients at high risk of disease progression. Screening cirrhotic patients with poor prognosis who are most in need of surveillance is still challenging. Gene expression data GSE15654 and GSE14520 were downloaded for performing unsupervised clustering analysis. The prognostic differences between the different clusters were explored by Cox regression. Integrative analysis of gene expression signature, immune cell enrichments and clinical characterization was performed for different clusters. Two distinctive subclasses were identified in HCV-related GSE15654, and Kaplan-Meier analysis indicated that subtype 2 had lower survival rates than subtype 1 (p=0.0399). Further analysis revealed subtype 2 had a higher density of follicular T helper cells, resting natural killer cells and M0, M2 macrophages while subtype 1 with a higher fraction of naive B cells, memory B cells, resting memory CD 4T cells, activated natural killer cells and monocytes. 226 differentially expressed genes were identified between the two subtypes, and Reactome analysis showed the mainly enriched pathways were biological oxidations and fatty acid metabolism. Five hub genes (AKT1, RPS16, CDC42, CCND1 and PCBP2) and three significant modules were extracted from the PPI network. The results were validated in HBV-related GSE14520 cohort. We identified two subtypes of patients with different prognosis for hepatitis C-related early-stage liver cirrhosis. Bioinformatics analysis of the gene expression and immune cell profile may provide fresh insight into understanding the prognosis difference.

Necrotic lesions of the hands

An 82-year-old man with a history of end-stage renal disease due to glomerulonephritis requiring haemodialysis, hepatitis C-related liver cirrhosis and hypertensive cardiomyopathy presented with painful and necrotic lesions of both his hands. He had no other symptoms. [...]

Two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma.

We report two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral. He was diagnosed with HCC 8years previously. He had undergone surgical resection 4 times, radio-frequency ablation (RFA) several times, and transcatheter arterial chemoembolization (TACE). However, HCC progressed and could not be controlled by locoregional treatment. Systemic chemotherapy was, therefore, selected. Atezolizumab-bevacizumab was administered after lenvatinib and sorafenib failure. Before starting treatment, his liver function was preserved (Child-Pugh score 5 and class A). His alpha fetoprotein and des-gamma-carboxyprothrombin levels were 3.6ng/mL and 443 mAU/mL, respectively. Esophagogastroduodenoscopy showed no remarkable esophageal varices before atezolizumab-bevacizumab treatment. Nine months after the initiation of atezolizumab-bevacizumab, the patient was admitted for hematemesis from esophageal varices. The disease control of HCC was classified as stable disease (SD) for the liver and lung metastases, and partial response for the lymph node metastases. Neither AST nor ALT was markedly elevated in the clinical course. Endoscopic variceal ligation (EVL) for the spurting point of large esophageal varices with red wale signs was able to successfully achieve hemostasis. Atezolizumab-bevacizumab was stopped and additional EVL eradicated the esophageal varices. However, the post-banding ulcer was prolonged in comparison to usual cases. Case 2: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral therapy. He was diagnosed with HCC 6years previously. He had received RFA 2 times and TACE 7 times. Atezolizumab-bevacizumab was administered after lenvatinib failure. The disease control of HCC was classified as SD; however, the esophageal varices ruptured after 15 courses of atezolizumab-bevacizumab. Neither AST nor ALT were markedly elevated in the clinical course. The esophageal varices of these patients did not require treatment before atezolizumab-bevacizumab; however, they rapidly worsened and ruptured during atezolizumab-bevacizumab treatment. Although rare, similar cases with rapid progression of portal hypertension after atezolizumab-bevacizumab have been reported. We should pay attention to the worsening of esophageal varices during atezolizumab-bevacizumab treatment and poor wound healing after EVL.

Laboratory Profile of COVID-19 Patients with Hepatitis C-Related Liver Cirrhosis.

Patients with cirrhosis are known to have multiple comorbidities and impaired organ system functioning due to alterations caused by chronic liver failure. In the past two years, since the COVID-19 pandemic started, several studies have described the affinity of SARS-CoV-2 with the liver and biliary cells. Considering hepatitis C as a significant independent factor for cirrhosis in Romania, this research was built on the premises that this certain group of patients is susceptible to alterations of their serum parameters that are yet to be described, which might be useful in the management of COVID-19 in these individuals. A retrospective cohort study was developed at a tertiary hospital for infectious disease in Romania, which included a total of 242 patients with hepatitis C cirrhosis across two years, out of which 46 patients were infected with SARS-CoV-2. Stratification by patient weight and COVID-19 status identified several important laboratory serum tests as predictors for acute-on-chronic liver failure and risk for intensive care unit admission. Thus, white blood cell count, lymphocyte count, ferritin, hypoglycemia, prothrombin time, and HCV viral load were independent risk factors for ACLF in patients with COVID-19. High PT, creatinine, BUN, and HCV viral load were the strongest predictors for ICU admission. Inflammatory markers and parameters of gas exchange were also observed as risk factors for ACLF and ICU admission, including procalcitonin, CRP, IL-6, and D-dimers. Our study questions and confirms the health impact of COVID-19 on patients with cirrhosis and whether their laboratory profile significantly changes due to SARS-CoV-2 infection.

Survival benefits of adding simvastatin to standard therapy for secondary prevention of bleeding esophageal varices in patients with hepatitis C-related liver cirrhosis

BackgroundThe combination of endoscopic band ligation and beta-blockers is the standard of care treatment for secondary prevention of variceal bleeding; however, rebleeding still occurs with associated high mortality. Simvastatin (a lipid-lowering agent) was found to reduce portal hypertension and decrease hepatic fibrosis. This study aimed to assess the effect of adding simvastatin to the standard therapy to prevent variceal rebleeding and its impact on survival in patients with liver cirrhosis.ResultsThis single-center randomized controlled clinical trial included 80 patients with cirrhosis receiving the standard secondary prophylaxis for variceal bleeding composed of endoscopic variceal ligation and non-selective β-blockers (either propranolol or carvedilol). Two weeks after the first attack of hematemesis, patients were randomized into two groups: group I who received the standard therapy (40 patients) and group II who administered simvastatin (20 mg daily for 2 weeks and 40 mg daily after that). Patients were followed up for 1 year. The primary endpoints were rebleeding and overall survival. Thirty patients of group I completed the study while ten patients died during the follow-up period. The simvastatin group showed a significantly better overall 1-year survival (3 deaths during follow-up) compared to the control group (37/40, 92.5% vs. 30/40; 75%) (p-value 0.034); however, this was lacking in Child C patients. No similar difference was present in rebleeding rates between the two groups (5/40, 12.5% vs. 3/40, 7.5%) (p-value 0.456) in groups I and II, respectively.ConclusionsAdding simvastatin to the standard therapy in secondary prevention of variceal bleeding could be associated with survival benefits in patients with Child A and B cirrhosis, while was incapable of reducing rebleeding.

The expression of microRNA-331-3p and microRNA-23b3 in Egyptian patients with early-stage hepatocellular carcinoma in hepatitis C-related liver cirrhosis

BackgroundHepatocellular carcinoma and hepatitis C are strongly associated. The current work aimed to study the expression levels of microRNA-331-3p and microRNA-23b-3p as propable biomarkers for detecting liver cancer (HCC) at its early stages in patients with HCV-related liver cirrhosis. The current prospective study included two hundred participants, divided into three groups: group I, 100 patients with HCV-related liver cirrhosis; group II, 50 HCC patients at early stages; and group III, 50 apparentlyhealthy controls. All patients had routine laboratory workup and ultrasound hepatic assessment. Values of microRNA-331-3p and microRNA-23b-3p were measured by real-time quantitative PCR.ResultsLevels of miR-331-3p were significantly higher in HCC patients than in cirrhotic patients and controls (p < 0.001), while levels of miR-23b-3p were significantly lower in HCC patients compared to cirrhotics and controls (p < 0.001). ROC curve revealed that miR-23b-3p had 80% sensitivity and 74% specificity, miR-331-3p had 66% sensitivity and 61% specificity, and AFP had 64% sensitivity and 61% specificity of 61% in discrimination between HCC patients from controls.ConclusionSerum miR-23b-3p is a more effective predictor than miR-331-3p and AFP for the development of hepatocellular carcinoma in hepatitis C (HCV)-related cirrhotic patients.

Evaluation Transplantation of Bone-Derived Mesenchymal Stem Cell in the Patients with Hepatitis C-Related Liver Cirrhosis (Pi lot Study)

Introduction. Liver cirrhosis (LC) is the final stage in the progression of chronic diffuse diseases. As common, late stages of LC do not respond to conservative treatment methods, so liver transplantation is the most effective method at this stage. Widespread use of transplantation in clinical practice is due to serious obstacles: a shortage of donor organs, transplant rejection, complications during the operation and the postoperative period, as well as the high cost of such an intervention. We consider bone marrow stem cell transplantation as a potential treatment for liver cirrhosis and additional clinical trials for efficacy and safety.The aim of the study was to assess the efficacy and safety of intraparenchymal transplantation of autologous MSCs from the bone marrow for the treatment of patients with cirrhosis of the liver caused by the hepatitis C virus (HCV-LC).Materials and methods. A pilot open-label non-randomized prospective study with the inclusion of 6 patients with HCV-LP. Autologous MSCs were transplanted intraparenchymally into the liver tissue at the rate of 1x106/kg body weight — 1 ml at 5 points.Results. By 6 months after transplantation, there has been a decrease in the level of bilirubin (from 36,4 μmol/L to 27 μmol/L, p=0.03), MELD scores (from 11,5 to 8, p=0.035), and an increase in platelet levels by 3 months (from 83x109 / l to 124,6x109/l, p=0,031) and 6 months (up to 119,5x109/l, p=0,031). By 6 months after transplantation, there has been no statistically significant result in changing on points on the Child-Pugh scale (p=0,181), cytolysis indicators (maintaining elevated levels of ALT (p=0,062) and AST (p=0,844)), replicative activity of the virus (рreservation of HCV RNA in the blood) (p=0,219 ). Moreover, introduction of MSCs by 6 months after transplantation did not lead to resolution of liver cirrhosis and inflammatory infiltration according to light microscopy data, as well as to resolution of sinusoidal capillarization (p=0,586) and PCI transdifferentiation into myofibroblasts (p&gt;0,99) according to immunohistochemical studies. None of the procedures after the transplantation had an increase in body temperature, an increase in laboratory parameters, or changes in vital functions. One patient was admitted to hospital after 6 months. after MSC transplantation, deep vein thrombosis of the right leg was diagnosed.Conclusion. The positive effect of MSCs on the improvement of liver function was noted. There was no effect on the replicative activity of the virus. The continuing activity of the inflammatory process was observed. The used MSC transplantation technique is a safe procedure for patients with HCV-LC severity classes A and B and can be applied in clinical practice.

Vitamin D receptor gene polymorphisms and risk of hepatocellular carcinoma in hepatitis C-related liver cirrhosis

BackgroundHCV is a major risk factor for HCC; however, the exact mechanism of hepatocarcinogenesis is still not fully understood. Host genetic factors have been reported to play a significant role. Experimental studies support the tumor inhibitory effect of vitamin D on HCC cells. Several single nucleotide polymorphisms (SNPs) have been depicted in the vitamin D receptor (VDR) gene. We aimed to assess whether any of these polymorphisms could be significantly associated with increased risk of HCC.ResultsThis study was conducted on 76 patients with HCV-related liver cirrhosis (48 patients had HCC on top of cirrhosis, and the other 28 had liver cirrhosis only). All patients underwent full medical history assessment, clinical examination, laboratory investigations, abdominal ultrasonography, and genotyping of the VDR gene. HCC patients had a significantly higher frequency of ApaI CC genotype compared with those patients without HCC. There is no statistically significant difference between the studied groups at any TaqI genotypes, but the carriage of the ApaI CC genotype had a significant association with liver disease severity in both patients groups compared with ApaI CA/AA genotypes. The carriage of the ApaI CC genotype was an independent predictor for HCC in HCV-related liver cirrhosis.ConclusionsVDR ApaI polymorphism is significantly associated with the development of HCC; thus, ApaI CC genotype could be used as an important molecular marker to predict the risk of HCC in patients with HCV-related liver cirrhosis.

A case of hepatitis C-related liver cirrhosis treated with lusutrombopag before coil embolization for splenic artery aneurysm

A case of hepatitis C-related liver cirrhosis treated with lusutrombopag before coil embolization for splenic artery aneurysm

Study of Dickkopf-1 (DKK-1) in patients with chronic viral hepatitis C-related liver cirrhosis with and without hepatocellular carcinoma

Aim of the studyDickkopf-1 (DKK-1) is a secreted protein which acts as an inhibitor of Wnt/β-catenin signaling. DKK-1 was found to be a helpful biomarker for many cancers including hepatocellular carcinoma (HCC). HCC is multifactorial in origin and its main etiology in Egypt is attributed to chronic hepatitis C virus (HCV) infection. Objectives: To assess the serum level and diagnostic performance of DKK-1 and α-fetoprotein (AFP) in Egyptian patients with chronic HCV-related liver cirrhosis with and without HCC.Material and methods80 subjects were divided into: a control group (group I, 20 healthy volunteers) and two patient groups: group II (HCV with liver cirrhosis, 30 patients), and group III, (HCV-related liver cirrhosis with HCC, 30 patients). Thorough physical examination, triphasic computed tomography, calculation of Child-Pugh score, laboratory investigations (complete blood picture, liver profile, hepatitis B surface antigen, anti-HCV antibodies, AFP (chemiluminometry) and DKK-1 (ELISA) were performed.ResultsThere was a significant decrease in DKK-1 level in HCV patients with liver cirrhosis (group II) and HCV patients with HCC (group III) compared to the control group (group I) (p < 0.001). However, there was a significant increase in DKK-1 level in HCV patients with HCC (group III) compared to HCV patients with liver cirrhosis (group II) (p < 0.033). The ROC curve showed that DKK-1 has less sensitivity but higher specificity in HCV patients with HCC (group III) compared with HCV patients with liver cirrhosis (group II).ConclusionsThe combination of DKK-1 and AFP could further improve the diagnostic accuracy of HCV-related cirrhosis with or without HCC.

MicroRNA-10a Impairs Liver Metabolism in Hepatitis C Virus-Related Cirrhosis Through Deregulation of the Circadian Clock Gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocator-Like 1.

The circadian rhythm of the liver plays an important role in maintaining its metabolic homeostasis. We performed comprehensive expression analysis of microRNAs (miRNAs) using TaqMan polymerase chain reaction of liver biopsy tissues to identify the miRNAs that are significantly up‐regulated in advanced chronic hepatitis C (CHC). We found miR‐10a regulated various liver metabolism genes and was markedly up‐regulated by hepatitis C virus infection and poor nutritional conditions. The expression of miR‐10a was rhythmic and down‐regulated the expression of the circadian rhythm gene brain and muscle aryl hydrocarbon receptor nuclear translocator‐like 1 (Bmal1) by directly suppressing the expression of RA receptor‐related orphan receptor alpha (RORA). Overexpression of miR‐10a in hepatocytes blunted circadian rhythm of Bmal1 and inhibited the expression of lipid synthesis genes (sterol regulatory element binding protein [SREBP]1, fatty acid synthase [FASN], and SREBP2), gluconeogenesis (peroxisome proliferator‐activated receptor gamma coactivator 1 alpha [PGC1α]), protein synthesis (mammalian target of rapamycin [mTOR] and ribosomal protein S6 kinase [S6K]) and bile acid synthesis (liver receptor homolog 1 [LRH1]). The expression of Bmal1 was significantly correlated with the expression of mitochondrial biogenesis‐related genes and reduced Bmal1 was associated with increased serum alanine aminotransferase levels and progression of liver fibrosis in CHC. Thus, impaired circadian rhythm expression of Bmal1 by miR‐10a disturbs metabolic adaptations, leading to liver damage, and is closely associated with the exacerbation of abnormal liver metabolism in patients with advanced CHC. In patients with hepatitis C‐related liver cirrhosis, liver tissue miR‐10a levels were significantly associated with hepatic reserve, fibrosis markers, esophageal varix complications, and hepatitis C‐related hepatocellular carcinoma recurrence. Conclusion: MiRNA‐10a is involved in abnormal liver metabolism in cirrhotic liver through down‐regulation of the expression of the circadian rhythm gene Bmal1. Therefore, miR‐10a is a possible useful biomarker for estimating the prognosis of liver cirrhosis.

Genetic variations in death receptor domain 4 gene and the susceptibility to hepatitis C related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide, particularly in Egypt. The role of apoptosis in tumorigenesis has been well-documented and resistance to apoptosis is a hallmark of cancer. Several studies discussed the association between death receptor 4 (DR4) genetic variants and HCC risk. To study the possible link between DR4 gene polymorphisms and the susceptibility to HCC. Genotyping of DR4-C626G, -A683C, and DR4-A1322G single nucleotide polymorphisms (SNP) was determined by polymerase chain reaction assay for 100 de novo HCV-related HCC patients, 100 chronic hepatitis C-related liver cirrhosis patients, and 150 healthy controls. DR4-A1322G polymorphic genotypes (AG and GG) were significantly higher in HCC and cirrhotic patients than controls. The AG genotype conferred two-fold increased risk of HCC (odds ratio [OR],2.34; 95% confidence interval [CI], 1.56-3.51) and the risk increased to three-fold for the GG genotype (OR,3.51; 95%CI, 2.33-5.28). The frequency of DR4-C626G and -A683C SNPs in HCC and cirrhotic patients were not significantly different from the controls. Combined genotype analysis showed that coinheritance of the polymorphic genotypes of DR4-C626G and -A1322G conferred nine-fold increased risk of HCC (OR,9.34; 95%CI, 3.76-23.12). The risk increased to be 12-fold when DR4-A683C and -A1322G variants were coinherited (OR,11.9; 95%CI,4.82-29.39). Coexistence of the variant genotypes of the three SNPs conferred almost 10-foldincreased risk of HCC (OR,9.75; 95%CI, 1.86-51.19). The G allele of DR4 -A1322G could be considered as a novel independent molecular predictor for HCV-related HCC in the Egyptian population.

Role of the von Willebrand factor and the VITRO score as predictors for variceal bleeding in patients with hepatitis C-related cirrhosis

Noninvasive methods have been established to detect clinically significant portal hypertension in liver cirrhosis with variable limitations. The von Willebrand factor (vEF) has been found to increase in liver cirrhosis. The aim of this study was to explore the vEF and VITRO (von Willebrand factor antigen/platelet ratio) score in the prediction of variceal bleeding in patients with portal hypertension. Fifty patients with hepatitis C-related liver cirrhosis (25 patients with variceal bleeding and 25 without variceal bleeding) as well as 80 healthy controls were included. Laboratory investigations and upper gastrointestinal endoscopy were performed in all patients. Serum vEF was measured in the patient and the control group. The VITRO score was calculated. The mean levels of the vEF antigen and the VITRO score were higher in patients with variceal bleeding compared with patients without variceal bleeding and controls (P<0.001). At levels of at least 100.1 ng/ml and at least 0.732, the vEF and the VITRO score could predict variceal bleeding with a sensitivity and a specificity of 92 and 99.9% for the vEF and 80 and 68% for the VITRO score (area under the curve=0.982 and 0.843), respectively. Levels of vEF were correlated positively with esophageal varices grade. Serum vEF level and the VITRO score are potential noninvasive biomarkers for the prediction and risk stratification of variceal bleeding in hepatitis C-related liver cirrhosis.

Profiling of plasma metabolomics in patients with hepatitis C-related liver cirrhosis and hepatocellular carcinoma.

Aim of the studyThe diagnosis of hepatocellular carcinoma (HCC) is usually late, due to the lack of early detection of biomarkers for HCC. Metabolomics analysis has emerged as a useful tool for studying human diseases. The objective of the study was to investigate the differences in plasma metabolites between hepatitis C virus (HCV)-induced cirrhosis and HCC.Material and methods22 subjects with HCV-related liver cirrhosis and 22 subjects with HCC were enrolled. Clinical, routine laboratory and imaging studies were done. Gas chromatography/mass spectrometry (GC/MS) was used for metabolomics analysis of patients’ plasma samples.Results34 known metabolites were detected, of which five metabolites were identified to have the strongest discriminatory power for separation between HCC and cirrhosis groups: octanoic acid (caprylic acid), decanoic (capric acid), oleic acid, oxalic acid and glycine. These are 3 fatty acids (FA), a dicarboxylic acid and a glucogenic amino acid, respectively. No significant correlation was found between the relative intensities of the five metabolites and any of the patient or tumor characteristics (Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, number of focal lesions and size of largest focal lesion). ROC curve analysis was performed and area under the curve (AUC) was calculated, revealing that oleic acid, octanoic (caprylic) acid and glycine had higher positive predictive value than α-fetoprotein.ConclusionsThe study of metabolomics (particularly involving FA) may help define distinct metabolic patterns to distinguish HCV-induced liver cirrhosis from HCC patients. Future research in this field is still needed, particularly concerning HCC treatment strategies which target fatty acid-related metabolic pathways.

Sofosbuvir plus daclatasvir with or without ribavirin in 551 patients with hepatitis C-related cirrhosis, genotype 4.

The Daclatasvir and Sofosbuvir combination therapy (SOF/DCV) has shown efficacy in patients with chronic hepatitis C in clinical trials. To investigate the efficacy and safety of SOF/DCV for treatment of patients with hepatitis C-related liver cirrhosis genotype 4. Multicentre study involving 551 patients with liver cirrhosis genotype 4; 432 naïve patients and 119 treatment-experienced patients. All patients received SOF (400mg) and DCV (60mg) daily in addition to weight-based ribavirin (RBV) for 12weeks and when RBV is contraindicated the treatment duration was extended to 24weeks. Sustained virological response at 12weeks after end of treatment (SVR12) rate was 92% in naïve cirrhotic patients and 87% in previous treated patients (by ITT analysis). Virological failure was infrequent, occurring in 42 patients (8%) overall. Thirty-two (6%) were non responders; and 10 (2%) cases were relapsers, 31 patients (7%) were CTP-A and 11 (13.3%) patients were CTP-B (by ITT analysis). The most common adverse events were anaemia, fatigue, headache, pruritus. Serious side effects were recorded mainly in CTP-B cirrhotic patients including HCC and hepatic encephalopathy. The SOF/DCV combination therapy has proven efficacy and safety in treating patients with hepatitis C-related liver cirrhosis genotype 4 in a large cohort of patients in the real world.

Assessment of serum betatrophin concentrations in patients with chronic hepatitis C-related liver cirrhosis

Objective The aim of this study was to evaluate serum betatrophin concentrations in patients with chronic hepatitis C-related liver cirrhosis and to explore its potential relations with liver cirrhosis progression and insulin resistance (IR). Background Hepatitis C virus infection is a serious clinical condition that usually progresses to liver cirrhosis. Betatrophin is a newly discovered hormone that has been considered as important regulator of pancreatic β-cell proliferation. Patients and methods We analyzed 70 patients who were diagnosed with chronic hepatitis C-related liver cirrhosis. Patients were assorted into three groups according to Child–Pugh score. In addition, a control group was included and consisted of 20 healthy volunteers. Serum betatrophin and IR were evaluated for all patients and controls. Results Patients with cirrhosis showed significantly higher circulating betatrophin levels in comparison with healthy controls ( P r = 0.66; P P r = 0.96; P Conclusion Serum betatrophin was significantly increased in patients with chronic hepatitis C-related liver cirrhosis and its level positively associated with liver cirrhosis severity and IR.

Accuracy of transient elastography in the assessment of chronic hepatitis C-related liver cirrhosis.

Staging liver cirrhosis is essential for the management of chronic hepatitis C (CHC). The current meta-analysis evaluated the accuracy of transient elastography for detecting liver cirrhosis in patients with CHC. Either prospective or retrospective studies, including cohort and cross sectional studies, in patients diagnosed with chronic hepatitis C, as assessed by transient elastography, were searched from Medline, Cochrane, EMBASE, and Google Scholar databases until March 3, 2015, using the terms "transient elastography, chronic hepatitis C and liver cirrhosis". The primary outcome analyzed was the diagnostic performance, which included sensitivity, specificity, diagnostic odds ratio and area under the receiver-operating characteristic (ROC) curve. Data from 24 articles included in the meta-analysis demonstrated high sensitivity (84%) and specificity (90%) of transient elastography (TE) for assessing liver cirrhosis patients with HCV. Subgroup analysis of patients by underlying diseases revealed a sensitivity and specificity of 91% and 92% (HCV alone), 100% and 75% (HCV-liver transplant), 83.6% and 89.7% (HIV/HCV co-infection) and 97.1% and 90.7% (recurrent CHC after liver transplantation). The pooled diagnostic odds ratio was 61.57 (95% CI, 39.5 - 96.00) and the area under the summary ROC curves was 0.952 ± 0.008, suggesting high diagnostic accuracy of TE. Transient elastography can accurately predict liver cirrhosis in patients with hepatitis C, with a sensitivity and specificity of 84% and 90%, respectively. The present results further validate the utility of TE in staging liver cirrhosis in chronic HCV infections.