Hepatitis C Research Articles

Direct-acting antivirals for chronic hepatitis C treatment: The experience of two tertiary university centers in Brazil.

BACKGROUNDHepatitis C virus (HCV) treatment has undergone major changes in recent years. Previous interferon-based therapies have been replaced by oral direct-acting antivirals (DAA) regimens, with high sustained virologic response (SVR) rates, and a lower incidence of adverse events (AEs). AIMTo evaluate the efficacy and safety of DAAs for HCV treatment in subjects from two tertiary university centers in Brazil.METHODSThis is a multicenter retrospective cohort study of 532 patients with chronic hepatitis C (CHC), undergoing treatment with interferon-free regimens from November 2015 to November 2019. The therapeutic regimen was defined by the current Brazilian guidelines for HCV management at the time of treatment. Demographic, anthropometric, clinical, and laboratory variables were evaluated. SVRs were assessed at 12 to 24 wk after therapy by intention-to-treat (ITT), and modified ITT (m-ITT) analysis. AEs and serious adverse events (SAEs) were registered. In the statistical analysis, a P value of < 0.05 was considered significant.RESULTSThe mean age was 56.88 years, with 415 (78.5%) being HCV genotype 1, followed by genotype 3 (20.1%). Moreover, 306 (57.5%) subjects had cirrhosis, and a third of them had decompensated cirrhosis. Sofosbuvir (SOF) plus daclatasvir ± ribavirin was the most frequently used treatment (66.9%), followed by SOF plus simeprevir (21.2%). The overall ITT SVR was 92.6% (493/532), while the m-ITT SVR was 96.8% (493/509). Variables associated with treatment failure via ITT evaluation were hepatic encephalopathy (OR: 4.320; 95%CI: 1.920-9.721, P = 0.0004), presence of esophageal varices (OR: 2.381; 95%CI: 1.137-4.988, P = 0.0215), previous portal hypertensive bleeding (OR: 2.756; 95%CI: 1.173-6.471, P = 0.02), higher model for end-stage liver disease scores (OR: 1.143, 95%CI: 1.060–1.233, P = 0.0005), lower serum albumin levels (OR: 0.528, 95%CI: 0.322-0.867, P = 0.0115), higher serum creatinine (OR: 1.117, 95%CI: 1.056-1.312, P = 0.0033), and international normalized ratio (INR) levels (OR: 5.542, 95%CI: 2.023-15.182, P = 0.0009). AEs were reported in 41.1% (211/514) of patients, and SAEs in 3.7%. The female gender, higher body mass index, esophageal varices, higher INR values, and longer treatment duration were independently associated with AE occurrence.CONCLUSIONTreatment with oral DAAs attains a high SVR rate, with fewer SAEs in a real-life cohort of subjects with CHC, from two tertiary university centers in Brazil.

Prevalence of Helicobacter pylori infection in patients with chronic hepatitis C

BackgroundAssociation between Helicobacter pylori (H. pylori) and chronic hepatitis C (CHC) still remains controversial. This work is concerned with assessing the potential role of H. pylori in the progression of hepatitis C virus (HCV)-related chronic liver disease. ResultsA total of 449 individuals constituted this study (200 individuals were used to validate the assay while 249 individuals were used to assess the correlation between H. pylori infection and CHC). H. pylori antigen was quantified in serum samples using ELISA. As a consequence, our findings showed that H. pylori positivity was increased significantly (P = 0.021) with liver fibrosis progression as it was found in 44.45% of fibrotic patients and 71.88% of cirrhotic patients. We demonstrated that patients with F4 were accompanied by a significant (P < 0.05) increase in the concentration of H. pylori antigen displaying 16.52-fold and 1.34-fold increase in its level over F0 and F1-F3, respectively. Patients co-infected with H. pylori and HCV are 3.19 times (219%) more likely to experience cirrhosis than those who are mono-infected with HCV. This suggests that the risk for developing F4 was found to increase upon H. pylori co-infection when compared to CHC mono-infected patients. ConclusionThe elevated levels of H. pylori-antigen in HCV/H. pylori co-infection suggest increased susceptibility of co-infected patients for promoting hepatic fibrosis progression.

Statins for the Treatment of Liver Fibrosis in Chronic Hepatitis-C Patients

Background: Hepatitis C virus (HCV) is one of the most common causes of chronic liver disease and the leading indication for liver transplantation worldwide. Chronic hepatitis C (CHC) leads to cirrhosis and hepatocellular carcinoma (HCC). Statins have gained attention for their pleiotropic effects. There is mounting evidence that statins offer chemoprevention against many malignancies. The aim of this was to determine the efficacy of the statin for the treatment of liver fibrosis in chronic hepatitis C patients.&#x0D; Methodology: A randomized control trial was conducted at Hepatitis Clinic, People Medical College Hospital, Nawabshah from August 20, 2020, to February 20, 2021. Non-probability, consecutive sampling was adapted. Patients with chronic hepatitis C infection and liver fibrosis were included. Group-A was administered statins in addition to antiviral treatment while Group-B was given anti-viral medications only. Stages of fibrosis were determined by shear wave elastography at the start of the study and after 6 months. All the data were entered and analyzed in Statistical Packages for Social Sciences (SPSS) v25.0.&#x0D; Results: There were 73 patients in each group. Fibrosis progression occurred in 7(9.6%) patients in group-A and 23(31.5%) in group-A. The link between the efficacy of the treatment given with the group-A and group-B was significant with a p-value of 0.001.&#x0D; Conclusion: Findings demonstrate a significant reduction in the risk of fibrosis progression among statin users with advanced chronic hepatitis C. These results support a possible role for statins in the prevention of liver disease progression.

Enhanced Liver Fibrosis Score: Is It Useful for Evaluation of Fibrosis Severity in Chronic Hepatitis C Infection?

Introduction: The assessment of liver fibrosis is important in patients with chronic hepatitis C (CHC). In recent years, non-invasive tests like enhanced liver fibrosis (ELF) have been developed as an alternative to liver biopsy for estimating the severity of liver fibrosis. Therefore, we aimed to assess whether the ELF score can be used for fibrosis severity estimation using liver biopsy as the gold standard.Materials and methods: Forty-nine patients with CHC were enrolled in this study. Liver biopsy, ELF assessment, and transient elastography (TE) were performed in all patients, and severity of fibrosis on histopathology was assessed by meta-analysis of histological data in viral hepatitis (METAVIR) score. In addition, the diagnostic performance of ELF was evaluated by receiver operator characteristic curve (ROC) analyses, and liver biopsy histopathology was taken as the gold standard for the severity of liver fibrosis.Results: The area under receiver operator characteristic curve (AUROC) for significant fibrosis of ELF score was 0.64 (95% confidence interval {CI}, 0.48-0.79) and of TE was 0.85 (95% CI, 0.73-0.96). The AUROC for advance fibrosis of ELF was 0.77 (95% CI, 0.57-0.97) and TE was 0.98 (95% CI, 0.94-1.0). The calculated cut-offs of ELF overestimated fibrosis in 53.06% (26/49) of patients and underestimated fibrosis in 6.12% (3/49) patients. AUROC of TE was significantly better than ELF for diagnosis of significant fibrosis (p=0.004) and advanced fibrosis (p=0.034).Conclusion: The ELF score can be used for estimating the severity of fibrosis but it is inferior to TE in estimating liver fibrosis severity.

Are There Still Difficult-to-Treat Patients with Chronic Hepatitis C in the Era of Direct-Acting Antivirals?

Difficult-to-treat populations with chronic hepatitis C (CHC), in the era of interferon treatment, included patients with liver cirrhosis, kidney impairment, treatment-experienced individuals, and those coinfected with the human immunodeficiency virus. The current study aimed to determine whether, in the era of direct-acting antivirals (DAA), there are still patients that are difficult-to-treat. The study included all consecutive patients chronically infected with hepatitis C virus (HCV) who started interferon-free therapy between July 2015 and December 2020 in the Department of Infectious Diseases in Kielce. The analyzed real-world population consisted of 963 patients, and most of them were infected with genotype 1 (87.6%) with the predominance of subtype 1b and were treatment-naïve (78.8%). Liver cirrhosis was determined in 207 individuals (21.5%), of whom 82.6% were compensated. The overall sustained virologic response, after exclusion of non-virologic failures, was achieved in 98.4%. The univariable analysis demonstrated the significantly lower response rates in males, patients with liver cirrhosis, decompensation of hepatic function at baseline, documented esophageal varices, concomitant diabetes, body mass index ≥25, and previous ineffective antiviral treatment. Despite an overall very high effectiveness, some unfavorable factors, including male gender, genotype 3 infection, liver cirrhosis, and treatment experience, significantly reduce the chances for a virologic response were identified.

Elevated Levels of IL-33, IL-17 and IL-25 Indicate the Progression from Chronicity to Hepatocellular Carcinoma in Hepatitis C Virus Patients.

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma.

COMPARISON OF CXCL-8 and IFN-γ PRODUCTION IN ACUTE AND CHRONIC STAGES OF LIVER DISEASE

Hepatitis C virus and alcoholism are the main causes of Chronic Liver Disease. (1) The increase of CXCL-8 has been correlated with mortality in alcoholic hepatitis (AH), while in Chronic Hepatitis C (CHC) with the disease severity. (2) The IFN-γ has an anti-viral and anti-fibrotic function. There are few comparative studies in patients regarding the production of these mediators and their possible implication in liver damage. The objective is to evaluate the concentrations of CXCL-8 and IFN-γ in the serum of AH, alcoholic cirrhosis (CiOH) and CHC patients. A multicenter cross-sectional study was carried out. Four participant groups were included: AH, CiOH, CHC and control group (CT). For the quantification of CXCL-8 and IFN-γ a multiple suspension array assay (Milliplex®-MERCK©) was used. Statistical analysis was performed by the SPSS V.22 software using Mann-Whitney-U-test. A p-value<0.05 was considered statistically significant. Values were expressed as median (Q3, Q1). 110 individuals were included: AH (10), CiOH (25), CHC (25) and CT (50). In CXCL-8 quantification, significant differences were detected in AH vs. CT, CiOH vs. CT, CHC vs. CT, CiOH vs. AH and CHC vs. AH (p≤0.001). While in IFN-γ, the differences were detected in AH vs. CT, CiOH vs. CT, CHC vs. CT, CiOH vs. AH and CHC vs. AH (p≤0.001). Differences were detected in both molecules when comparing the chronic stages (CiOH and CHC) with the acute stage (HA), while no differences were found when comparing both chronic stages. The highest CXCL-8 concentration corresponds to AH, reflecting its importance in prognosis and mortality. (2) The increase of IFN-γ in CiOH and CHC may have a role in the regulation of fibrogenesis because of its anti-fibrotic function. The deregulation of mediators such as IL-8 and IFN-γ promotes systemic inflammation in both acute and chronic stages, being greater in AH. This may indicate an association with the susceptibility to persistent respiratory and gastrointestinal diseases. The authors declare that there is no conflict of interest. This work was partially financed by CONACyT SALUD-2016-272579 (GRG) and PAPIIT- UNAM TA200515 (GRG).

The importance and impact of recognizing metabolic dysfunction-associated fatty liver disease in patients with chronic hepatitis C.

Metabolic dysfunction-associated fatty liver disease (MAFLD) can develop in any patient, including those with chronic hepatitis C (CHC). The recently proposed diagnostic criteria for MAFLD provide a unique opportunity to investigate the impact of concomitant fatty liver in patients with another established cause for their liver disease. The objective of our study was to assess the characteristics and outcomes of patients with a dual etiology liver disease. We evaluated 1181 patients including 744 with CHC and 437 with MAFLD. All patients in both cohorts underwent liver biopsy indicating disease activity and fibrosis stage. Nearly half (43.1%) the patients with CHC had concomitant MAFLD. Comparing patients with CHC alone with those with a dual etiology disease, we found that the latter had more severe liver injury, hepatic inflammation and fibrosis (all P< 0.001). Interestingly, lean or normal-weight patients with CHC and MAFLD had a similar fibrosis stage compared to the two other subgroups of MAFLD (obesity and/or diabetes mellitus). There was no statistical significance in hepatic steatosis and fibrosis between genotype 3 CHC and MAFLD group compared to other genotypes. Patients with CHC and concomitant MAFLD had more severe liver disease than those with viral hepatitis alone. Recognizing coexisting MAFLD in patients with CHC is important for the delivery of holistic care.

IL-10 Y TNF-α IN SERUM OF PATIENTS WITH CHRONIC HEPATITIS C AND HEPATIC DAMAGE CHRONIC AND ACUTE FOR ALCOHOL CONSUMPTION

The virus of hepatitis C (HCV) and alcoholic liver disease (ALD), are of the main causes of liver disease mortality. There is a need to determine biomarkers, serum cytokines are candidates since they participate in the immunopathogenesis of these diseases by activating the inflammatory process. Increased serum levels of IL-10 and TNF-α have been reported in cirrhosis and have been associated with progression to hepatocellular carcinoma. While TNF-α has become a key factor in the inflammatory process with high circulating levels in alcoholic hepatitis (HA). The objective of this work is to evaluate the serum levels of IL-10 and TNF-α in patients with chronic hepatitis C and ALD. A cross-sectional and multicenter study. Patients with chronic Hepatitis C (CHC) and CiOH (cirrhotic by alcohol) and alcoholic hepatitis (HA) with criteria for alcoholism (WHO) were included, personalized survey, clinical and biochemical evidence of ALD was recorder. The groups were compared with subjects with a negative viral panel obtained from the CT blood bank (controls). IL-10 and TNF-α from serum was quantified using the multiple suspension arrangement method (Milliplex®-MERCK ©). Statistical analysis was performed using SPSS software version 22 using Mann Whitney U test. It was considered statistically significant p <0.05; values ​​expressed as median (Q3, Q1). A total of 110 subjects were included, 25 for CHC, 25 CiOH, 10 HA and 50 CT. We observed a significant increase on bilirubin, mainly in HA vs CT (p≤0.001), also AST and GGT was overproduced in CHC, CiOH and HA vs CT (p≤0.001). IL-10 was found elevated in CHC vs CT (p≤0.0001) and in CiOH vs CT (p≤0.05), which confirms that this anti-inflammatory cytokine increases in accordance with liver disease progresses. TNF-α was found to be increased in CiOH vs CHC (p≤0.05), increased levels in HA vs three study groups CHC, CiOH and CT (p≤0.001). Overproduction of IL-10 in CHC and CiOH support that this anti-inflammatory cytokine increases as liver disease progresses, possibly due to its role as a regulator in inflammation. Has been reported the increment of IL-10 and TNF-α in patients with HA, it is related to the severity of HA and mortality 1 . Also, there are reports about high levels of TNF-α in patients with CHC 2 , that contrast with our data, this may be because TNF-α acts differently in a chronic stage. The low concentration of TNF-α in HCc may reflect the regulatory mechanisms of the virus. This study confirms the participation of IL-10 as a cytokine present in stages of chronic liver damage, elevated serum levels of TNF-α in HA compared to CiOH indicates that the inflammatory process actively participates in the acute damage induced by excessive alcohol consumption. The authors declare that there is no conflict of interest. This work was partially financed by CONACyT SALUD-2016-272579 (GRG) and PAPIIT- UNAM TA200515 (GRG)

DYNAMICS OF FIBROTIC CHANGES IN THE LIVER AFTER THE SUCCESSFUL ERADICATION OF HEPATITIS C VIRUS IN PATIENTS WITH NAFLD.

The aim: To assess the dynamics of serum levels of angiopoietin-2 and transforming growth factor-β1 in patients with chronic hepatitis C (CHC) with concomitant nonalcoholic fatty liver disease (NAFLD) after successful DAAs. Materials and methods: 82 patients with CHC were examined, of which 56 were diagnosed with NAFLD and increased body weight. Ang-2, TGF-β1, leptin, adiponectin, and the degree of liver fibrosis were determined for all participants. The patients were divided into groups: 1 gr. (n=23) - CHС + increased body weight + hepatic steatosis, 2 gr. (n=33) - СНС + increased body weight + nonalcoholic steatohepatitis, 3rd gr. (n=26) - CHC. All patients received DAAs for 12 weeks. Results: From 82 patients F3-4 had 31 people, F1-2 - 25, F0-1 - 11, F0 -15 patients. F3-4 and steatosis S2-3 (p<0.05) was more common in patients of 2 gr.. Serum Ang-2 levels were higher (p<0.05) in patients of 2 gr. with F3-4, than in patients with F0-2. Fibrosis regression occurred more often in patients with 1 and 3 gr. with F1-2 than in patients 2 gr. and F3-4 and was accompanied by a decrease in Ang-2 and TGF-β1 levels. Conclusions: High levels of Ang-2 and TGF-β1 are registered in patients with CHC+NAFLD, which correlate with the degree of liver fibrosis and significantly decrease after successful DAAs in patients with low initial stages of liver fibrosis and normal body weight.

Changes in hepatic fibrosis and incidence of HCC following direct-acting antiviral treatment of F3 chronic hepatitis c patients: a prospective observational study

Aim: Studies of clinical outcomes in chronic hepatitis C (CHC) patients with pretreatment advanced liver fibrosis (F3) after sustained virologic response (SVR) are scarce, and most studies are of small cohorts and retrospective in nature. Our aim was to assess the clinical outcomes following direct acting antiviral (DAA) treatment among hepatitis C F3 patients after SVR. Methods: This study included 1517 chronic hepatitis C patients with F3 fibrosis receiving DAAs in the out-patient clinics at the Egyptian Liver Research Institute and Hospital (ELRIAH). We included patients 18 years or older with HCV who received DAAs, have F3 by transient elastography, and have no history of hepatocellular carcinoma (HCC). Patients were followed up every six months after end of treatment using ultrasonography and AFP. Results: Significant improvement of fibrosis occurred with decreases in LSM, FIB-4, APRI, and FIB-6. When changes in LSM were categorized depending on delta LSM, 873 patients (57.5%) showed regression, 454 (29.9%) were stable, and 190 patients (12.5%) showed progression of fibrosis. Overall, 33 cases developed HCC during follow-up with incidence rate of 0.915/100 py (95%CI: 0.64-1.27). Incidence was high with progression of liver fibrosis (6.17/100 py) compared to patients with stable fibrosis (1.09/100 py) and regression of liver fibrosis (0.75/100 py). There were no significant differences as regards fibrosis indicators at baseline (LSM, FIB-4, APRI, and FIB-6) between those who developed HCC and those who did not. Conclusion: CHC Patients with F3 fibrosis showed a high rate of regression of fibrosis and decreased HCC incidence after achieving SVR following DAAs.

The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection.

BackgroundVitamin D and its receptor (VDR) exert important immunoregulatory functions that contribute to liver homeostasis. The aim of this study was to investigate the influence of FokI, ApaI, BsmI and TaqI VDR polymorphisms on cirrhosis development and laboratory variables in patients with chronic hepatitis C (CHC).MethodsA total of 48 patients were enrolled in this retrospective, observational study and underwent genotype analysis; their medical records were examined to obtain relevant data.ResultsThe cumulative rate of progression to cirrhosis during the course of CHC was 31.3% after a median period of 11 years from diagnosis. Importantly, in multivariate analysis, FokI ff (adjusted hazard ratio [aHR] 13.6, 95% confidence interval [CI] 2.51-73.73; P=0.002) and ApaI aa (aHR 4.69, 95%CI 1.13-19.43; P=0.033) genotypes were independently associated with progression to cirrhosis. The presence of the aa genotype was also associated with higher liver stiffness measurements measured by transient elastography compared to the AA/Aa genotype (12.3kPa interquartile range [IQR] 9.6-17.3 vs. 7.1kPa IQR 5.6-11.1; P=0.012). In addition, higher HCV RNA and lower serum albumin levels were observed in patients with the tt genotype of the TaqI polymorphism compared to TT/Tt carriers, and in patients with the aa genotype compared to AA/Aa carriers. In haplotype analysis, no association was found between any haplotype and disease progression.ConclusionsIn patients with CHC, laboratory parameters are influenced by VDR polymorphisms and the development of cirrhosis is related to homozygosity for the dominant trait of ApaI and FokI variants.

RASSF1A and p16 promoter methylation and treatment response in chronic hepatitis C genotype 1b patients treated with pegylated interferon/ribavirin

Prevention of chronic hepatitis C (CHC) and its complications is based on antiviral therapy and early detection of reliable molecular markers in persons under risk. We investigated whether the methylation status of RASSF1A and p16 genes, alone or in combination with host and viral factors, affects the response to therapy with pegylated interferon/ribavirin (PEG-IFN/RBV). Methylation-specific polymerase chain reaction (MSP) was used to determine the methylation status of the target promoter sequences of RASSF1A and p16 in circulating-free DNA from the peripheral blood of 49 patients with CHC genotype 1b. The methylation status of the examined genes did not affect the response to therapy. However, the simultaneous presence of either RASSF1A or p16 methylation and the CC genotype of IL28B was significantly related to a sustained virologic response (P=0.009 and P=0.032, respectively). After Bonferroni correction, only the result concerning the RASSF1A gene remained significant (P&lt;0.0125). Methylation of RASSF1A was associated with the CC genotype of the IL28B gene (P=0.024) and a higher viral load (?400 000 IU/mL, P=0.009). Our results suggest that combined analysis of RASSF1A gene methylation and IL28B rs12979860 polymorphism could potentially help in the prediction of therapy response in CHC genotype 1b patients.

Three regimens for re-treatment failure of Sofosbuvir-based therapy for chronic hepatitis-C genotype-4: a cohort study.

ABSTRACTDespite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.

Long-term surveillance of liver histological changes in chronic hepatitis C patients completing pegylated interferon-α plus ribavirin therapy: an observational cohort study.

Background:For chronic hepatitis C (CHC) patients completing pegylated interferon (PegIFN)-α/ribavirin therapy, long-term liver histological changes remain largely unexplored.Methods:This observational cohort study included 85 CHC patients completing PegIFN-α/ribavirin therapy with liver biopsies performed at baseline and the end of surveillance (EOS). Median years between paired biopsies were 6.75 (interquartile range: 5.63–7.54).Results:In patients with baseline METAVIR fibrosis stages (F) <4 (able to undergo fibrosis progression; n = 77), cases achieving sustained virological response (SVR) (n = 52) had a significantly lower rate of fibrosis progression than non-SVR cases (n = 25) (3.8% versus 24.0%, p = 0.012). Among the entire cohort (n = 85), the rate of activity response [METAVIR activity grades (A) decreasing or maintaining at A0] in SVR cases (n = 59) was significantly higher than that in non-SVR cases (n = 26) (94.9% versus 65.4%, p = 0.001). For SVR cases among the entire cohort, independent predictors of fibrosis clearance included baseline F <2 [odds ratio (OR) = 7.877, p = 0.042] and aspartate transaminase (AST) levels declining by >70% at EOS compared with baseline (OR = 9.013, p = 0.038). For non-SVR cases among the entire cohort, baseline AST levels >80 U/l and glucose levels ⩽ 105 mg/dl independently predicted significant fibrosis (F2/F3/F4) at EOS (OR = 12.558, p = 0.049) and activity response (OR = 17.741, p = 0.047), respectively.Conclusions:Among CHC patients completing PegIFN-α/ribavirin therapy, SVR lowers the risk of liver histological progression but does not guarantee fibrosis clearance. For SVR cases, those with baseline F ⩾ 2 or without significantly declined follow-up AST levels should be specifically monitored. As for non-SVR cases, those with a higher baseline AST or glucose level should preferentially receive retreatment.

Клінічні та біохімічні аспекти хронічного гепатиту С за умови дисбіозу кишківника

Prolonged intestinal dysbiosis (DB) increases the risk of developing metabolic liver diseases, such as nonalcoholic fatty liver disease (NAFLD), cholestasis, hepatocellular dysfunction and dyskinetic disorders of the biliary tract. According to various studies, hepatic steatosis is observed in almost 50% of patients with chronic hepatitis C (HCV). The presence of NAFLD in patients with CHC contributes to the onset and further progression of fibrosis from the initial stages to cirrhosis of the liver within a short time. The purpose of the research is to study the clinical and biochemical features of the course of chronic HCV in the conditions of intestinal dysbiosis. Materials and methods. There were 142 patients with chronic HCV under observation. The control group consisted of 20 healthy people. The diagnosis of chronic HCV was made according to the International Classification of Diseases of the 10th revision and confirmed by the detection of total IgG antibodies to HCV by enzyme-linked immunoassay, as well as the detection of RNA-HCV in the blood by polymerase chain reaction. All patients were determined the functional state of the liver by the level of activity of alanine and asparagine aminotransferases (ALT, AST), alkaline phosphatase (AP), conjugated bilirubin, gammaglutamyl transpeptidase (GGTP), trophological status was assessed and a microbiological study of feces was performed. To determine the degree of steatosis and fibrosis of the liver, a noninvasive diagnostic method – FibroMax was used. The obtained results allowed to divide all patients into two groups: 1 group (n = 84) of patients with chronic HCV + dysbiosis DB and 2 group (n = 58) of patients with chronic HCV without dysbiosis of the intestine. The analysis and processing of the patients’ examination results were carried out using the Statisticsfor Windows v.7.0 computer program (StatSoftInc, USA). Results and Discussion. It was found that the intestinal dysbiosis had 59.2% (84 out of 142) of patients with chronic HCV, and 52 of them had increased body weight, which was 61.9%. Clinical manifestations of intestinal microbiocenosis disorders in 58 patients were predominant constipation (69%) and minimization of typical diarrheal syndrome in 26 people (31%). A large number of patients with chronic HCV with the intestinal dysbiosis (82.1%) complained of decreased ability to work, headaches, depressed mood and sleep disorders, which confirmed the presence of asthenovegetative syndrome. Analysis of biochemical indicators demonstrated that cholestasis syndrome prevails in patients with chronic HCV in the conditions of intestinal dysbiosis, proving significantly higher levels of total bilirubin, AP and GGTP, compared with patients without dysbiosis (p &lt; 0.05). Also, in patients with chronic HCV, in conditions of intestinal dysbiosis in 3.5 times (p &lt; 0.001) were more often detected increased levels of liver enzyme activity (ALT, AST, GGTP), compared to patients without dysbiosis, which characterizes the cytolysis syndrome. In patients with chronic HCV with intestinal dysbiosis, in 1.6 times more often than in patients without dysbiosis, steatosis of the S1-2 degree was registered, and in 2.4 times more often S2-3. Inflammation in different degrees of hepatic steatosis in 2 times more common in patients with chronic HCV with dysbiosis than in patients without dysbiosis. It was found that in patients with chronic HCV combined with intestinal dysbiosis deep stages of liver fibrosis (F2-3 and F3-4) are registered in 3.6 times more often compared to patients only with chronic HCV (53.6% vs. 24.1% and 11, 9% vs. 3.4% p &lt; 0.05). Conclusions. Intestinal dysbiosis is more often recorded in patients with chronic HC with increased body weight and is characterized by an atypical course, in the predominance of constipation (in 69% of patients). In patients with chronic HCV in the conditions of intestinal dysbiosis dyspeptic, asthenovegetative and cholestatic syndrome, as well as high activity of ALT and AST are more often observed, compared to patients without dysbiosis. According to Fibromax, patients with CHC with intestinal dysbiosis are in 2.4 times more likely to have hepatic steatosis of 2–3 degree (S2-3) and steatohepatitis (N2,) which characterizes the existing metabolic disorders.

Evaluation of Regulatory T Cells in Chronic Hepatitis C Patients

Hepatitis C virus (HCV), defined as a non-A non-B hepatitis agent in 1989, is a hepatotropic, noncytopathic, positive-stranded ribonucleic acid (RNA) virus from the family Flaviviridae. HCV infection is an acute or chronic necroinflammatory (...)

Intercellular interactions and their role in fibrogenesis in chronic hepatitis C

Introduction. The development of life-threatening complications in chronic hepatitis C (CHC) is based on progressive fibrogenesis. The developing of liver fibrosis is provided by intercellular interactions, first of all, of lymphocytes, macrophages and stellate cells (SC), the patterns of mutual influences of which have not been sufficiently studied at the moment.The objective was to study the features of intercellular interplay of nonparenchymal liver cells at different histological activity, at different stages of CHC fibrosis, and at different genotypes of the hepatitis C virus (HCV).Methods and materials. The object of the study was 64 liver biopsies of adult patients with natural course of CHC. Нistological, immunohistochemical and immunohistomorphometric methods were used.Results. The increasing histological activity is accompanied by an increase in the number and size (area) of CD68 + macrophages and SMA-alfa + SC. Correlation relationships of intercellular interactions at low and moderate histological activity had significant differences. In mild fibrosis, a relationship was found between the number of CD8 + lymphocytes, the number and area of CD68 + macrophages and SMA-alfa + SC. HCV genotype 1 is characterized by a predominance of the interactions between the number of CD8 + lymphocytes, the number and area of CD68 + macrophages in the liver, for genotype 3 – between the number of CD8 + lymphocytes, the number and area of SMA + SC.Conclusions. The maximum activation of SC and macrophages occurs even with moderate histological activity and persists with an increase. The consolidation of the immunopathological nature of the intercellular interplay between lymphocytes, macrophages and SC occurs at the stage of mild fibrosis. Intercellular interactions have significant differences depending on the HCV genotype, which can determine a poor prognosis of the disease.

ХРОНИЧЕСКИЙ ВИРУСНЫЙ ГЕПАТИТ И ВОСПАЛИТЕЛЬНЫЕ ЗАБОЛЕВАНИЯ КИШЕЧНИКА

The article presents the results of a literature review devoted to the study of the problems of the concurrent course of inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), as well as chronic viral hepatitis (CVH) - chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The prevalence of CHB and CHC in IBD in different countries ranges from 1% to 9%. The clinical course of these concurrent diseases, the possibility of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation during immunosuppressive therapy are described. Recommendations on the peculiarities of examination and management of patients with concurrent pathology of IBD and CVH are presented. The combined pathology of IBD and CVH is a significant public health problem worldwide that requires further largescale study. The use of immunosuppressive therapy for IBD can be accompanied by the activation of HBV and HCV infection, therefore, the management of such patients should occur on an individual basis.

Clinical and economic impact of an alert system in primary care for the detection of patients with chronic hepatitis C

IntroductionPrevalence of chronic hepatitis C (CHC) is higher in patients born between 1955–1975. The aim was to perform an economic evaluation of an age-based electronic health record (EHR) alert in primary care to detect patients with undiagnosed CHC and its treatment in comparison with non-use of the alert system, in Valencian Community, Spain.Materials and methodsDecision trees and Markov model were used to evaluate the diagnosis and progression of the disease, respectively. CHC was diagnosed by serology and viral load in seropositive subjects. Epidemiological data and diagnostic costs were extracted from public sources of the Valencian Community. Probabilities, utilities and costs of model states were obtained from the literature. The impact on mortality and hepatic complications avoided by the implementation of the alert were estimated, and efficiency was measured as an incremental cost-utility ratio (ICUR) based on quality-adjusted life years (QALYs) and the costs of both alternatives.ResultsThe EHR alert detected 269,548 patients, of whom 1,331 had CHC (vs. 23 patients with non-alert). Over the patients’ lifetime, the alert would prevent 93% of decompensated cirrhosis cases, 87% of hepatocellular carcinomas, 90% of liver transplants, and 89% of liver related deaths compared to non-use of the alert system. In addition, it would obtain an additional 3.3 QALY per patient, with an incremental cost of €10,880 and an ICUR of €3,321.ConclusionsThe implementation of an age-based EHR alert in primary care to detect patients with CHC reduces hepatic complications and mortality and is an efficient strategy.