Course Of Chronic Hepatitis C Research Articles

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.

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.

The Role of Direct-acting Antivirals in the Treatment of Children with Chronic Hepatitis C.

In the United States, chronic infection with the hepatitis C virus (HCV) affects an estimated 0.1–2% of the pediatric population, who are consequently at risk for major complications, including cirrhosis, hepatocellular carcinoma, and death. The current standard of treatment for chronic hepatitis C (CHC) in children is pegylated-interferon-alpha (PEG-IFN) in combination with ribavirin. PEG-IFN/ribavirin therapy is approved for children ages 3 and older; however, it is often held from use until adulthood because of its extensive list of potential side effects and high likelihood of causing adverse symptoms. While CHC is usually indolent in children and adolescents, immediately treating and curbing the spread of HCV before adulthood is important, as there can be transmission to other individuals via sexual activity and infected females can later vertically transmit the infection during pregnancy, the latter representing the most common means of transmission for children in the United States. The recent development of direct-acting antivirals has shown promising results in clinical trials for use in children and has dramatically increased the rates of sustained virological response in adults while improving side effect profiles as compared to interferon-based treatments. Given the usually indolent course of CHC in children, significant side effects of the currently-approved PEG-IFN/ribavirin therapy, and likely availability of all-oral interferon-free regimens for children within a few years, deferring treatment in clinically-stable children with CHC in anticipation of upcoming superior treatment modalities may be justified.

Clinical and laboratory characteristics of chronic hepatitis C on the early stages of development

Aim of the research – to assess the clinical and laboratory parameters in patients with chronic hepatitis C (CHC) on the early stages of development and their comparison with the level of galectin3. The study included 78 patients with oligosymptomatic course of the disease and minimal liver fibrosis in the most cases. In the most patients with stages of the disease exceeding 8 years, viral load was over a million copies/ml. In 10 % of patients on the early stages of the disease, changes corresponding to severe liver fibrosis and cirrhosis F3 and F4 were detected. Moderate correlation of ALT activity, viral load and low severity with the duration of the disease was identified. There is a trend towards a higher level of galectin3 in a long course of CHC in comparison with earlier stages of its development, with significantly higher average level of galectin-3 in patients with minimal liver fibrosis (F0–F1) as compared to advanced stages, suggesting its importance in the launching and initial mechanisms of fibrogenesis.

Mathematic Model for Prediction of Liver Fibrosis Progression Rate in Patients with Chronic Hepatitis C Based on Combination of Genomic Markers

To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, N0S3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC). 118 patients with CHC were divided into "fast" and "slow" (fibrosis rate progression ≥ 0.13 and < 0.13 fibrosis units/yr; n = 64 and n = 54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10. A allele (p = 0.012) and genotype AA (p = 0.024) of AGT G-6T gene, as well as T allele (p = 0.013) and MT+TT genotypes (p = 0.005) of AGT 235 M/T gene were significantly more common in "fast fibrosers" than in "slow fibrosers". Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p = 0.02). Our analysis showed a protective effect of TTgenotype of ITGA2 807 C/T on fibrosis progression rate (p = 0.03). There was a trend (p < 0.15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI-675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical modelfor prediction of liverfibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R = 0.39, p = 0.000). Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.

Experience of Using Metformin in Patients Infected with HCV Genotype 3 with Concomitant Metabolic Disorders

Summary: The so-called “metabolic syndrome” is among the most significant factors that influence the natural course of Chronic Hepatitis C (CHC) and the effectiveness of specific Antiviral Therapy (AVT). Materials and methods: 34 patients with chronic hepatitis C (genotype 3) treated with standard AVT (PEGylated interferon in combination with ribavirin) were included in the study. The study group included 18 patients with chronic hepatitis C in combination with metabolic disorders, namely the Insulin Resistance (IR). They received metformin 20 mg/kg for 24 weeks. The control group included 16 patients with chronic hepatitis C and IR, who did not receive metformin. The patients’ age (35.7 ± 1.5) and sex prevalence were matched in both groups. The diagnosis criteria of CHC included: clinical and laboratory signs of the disease, the presence of RNA HCV determined by PCR, with a specific genotype 3. The presence of IR was assessed by HOMA-index (HOMA-IR), fasting insulin levels (IU/ml) × fasting glucose (mmol/L)/22.5. IR was diagnosed in case of HOMA index>2. Conclusion: IR frequently follows the course of CHC in patients with or without metabolic syndrome. Metformin administration leads to weight loss in overweight patients with chronic hepatitis C, reduces the severity of metabolic disorders, such as IR, in these patients, resulting in increased frequency of achieving rapid and early virological responce and biochemical remission. The administration of metformin had a positive effect on liver steatosis, resulting in a decrease of its severity according to ultrasonography.

Insulin resistance and its consequences in chronic hepatitis C.

Chronic hepatitis C (CHC) is generally a slowly progressive disease, but some factors associated with rapid progression have been identified. Hepatitis C virus (HCV) may contribute to a broad spectrum of metabolic disturbances – namely, steatosis, insulin resistance (IR), increased prevalence of impaired glucose tolerance, type 2 diabetes mellitus (T2DM), lipid metabolism abnormalities and atherosclerosis.HCV can directly or indirectly cause both IR and steatosis, but it is still not resolved whether this viral impact bears the same prognostic value as the metabolic counterparts. As the population exposed to HCV ages, the morbidity due to this disease is increasing. The rising epidemic of obesity contributes to higher prevalence of IR and T2DM. Our understanding of the mutual association between both disease states continues to grow, but is still far from complete. This review briefly discusses the most probable mechanisms involved in IR development in the course of CHC. Molecular mechanisms for the direct and indirect influence of HCV on intracellular insulin signaling are described. Subsequently, the consequences of IR/T2DM for disease progression and management are summarized.

Association of CYP2E1*6 polymorphism of gene CYP2E1 with the risk and severity of chronic hepatitis C

Aim. The effectiveness of treatment of chronic hepatitis C (CHC) depends on the genetic characteristics of the patients. The aim was to analyze the association of CYP2E1*6 polymorphism with the risk of development and severity of CHC.Methods and results. We determined the frequency of CYP2E1*6 polymorphism in 77 patients with CHC and 64 healthy donors using molecular genetic methods. Case histories were retrospectively analyzed. We did not find association between CYP2E1*6 polymorphism and the risk of CHC. The majority of patients with genotype CD had more frequently normal alanineaminotransferase levels than the patients with genotype DD (55,6 % vs 27,1 %, p = 0,026). Patients with genotype DD more often had different stages of liver fibrosis than the patients with genotype CD (34,5 % greater, p = 0,009, OR 4,24, 95% CI 1,37 – 12,93).Conclusion.This indicates that the genotype DD of the gene CYP2E1 was associated with more severe course of CHC.

The impact of chronic hepatitis C infection on the circadian clock and sleep

The impact of chronic hepatitis C infection on the circadian clock and sleep

Hepatic flares in chronic hepatitis C: spontaneous exacerbation vs hepatotropic viruses superinfection.

The hepatitis C virus (HCV) causes an acute infection that is frequently asymptomatic, but a spontaneous eradication of HCV infection occurs only in one-third of patients. The remaining two-thirds develop a chronic infection that, in most cases, shows an indolent course and a slow progression to the more advanced stages of the illness. Nearly a quarter of cases with chronic hepatitis C (CHC) develop liver cirrhosis with or without hepatocellular carcinoma. The indolent course of the illness may be troubled by the occurrence of a hepatic flare, i.e., a spontaneous acute exacerbation of CHC due to changes in the immune response, immunosuppression and subsequent restoration, and is characterized by an increase in serum aminotransferase values, a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment. A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses, namely hepatitis B virus (HBV), HBV plus hepatitis D virus, hepatitis E virus, cytomegalovirus, particularly in geographical areas with high endemicity levels. The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

Prevalence of Non Organ-Specific Auto Antibodies and its Effect on Response to Antiviral Therapy in Patients with Chronic Hepatitis C Virus Genotype 4

Background and study aim:: Immunological disorders have been frequently described in the course of hepatitis C virus (HCV)–related chronic hepatitis. Our aim was to determine the prevalence of non-organ-specific autoantibodies (NOSAs) and evaluate its impact on the response to combined antiviral therapy in patients with chronic HCV genotype-4 Patients and methods: A total of 134 adult patients with chronic HCV genotype-4 were investigated for the presence of serum Antinuclear antibody (ANA), anti–smooth muscle antibody (SMA), and anti liver/kidney microsomal antibody type 1 (LKM1). 109 out of 134 HCV patients were treated naive and received combined antiviral therapy (pegylated interferon–ribavirin). The presence of these autoantibodies was studied in relation to the patient’s characteristics and the outcome of antiviral therapy. Results :Thirty-six (26.9%) patients were positive for at least one autoantibody. Various autoantibodies were presented as follows: ANA in 29 (21.6%) patients, SMA in 9 (6.7%) and anti-LKM-1 in 2 (1.5%). In two patients, both ANA and anti-SMA were positive, and in other two cases both ANA anti-LKM-1 were positive. Female patients had a higher prevalence of positive autoantibodies (P=0.005). Chronic hepatitis C (CHC) patients with positive autoantibodies had higher serum ALT, AST and GGT levels. The rate of sustained virological response to combined antiviral therapy was similar between autoantibody-positive and -negative groups (46.9% vs. 53.2%). Conclusion : Autoantibodies can be induced in the course of CHC. Autoantibody-positive CHC patients are older and have higher disease activity and severity. However, the presence of these autoantibodies did not influence the response to combination antiviral therapy.

IL28B minor allele is associated with a younger age of onset of hepatocellular carcinoma in patients with chronic hepatitis C virus infection

IL28B polymorphisms were shown to be associated with a response to peg-interferon-based treatment in chronic hepatitis C (CHC) and spontaneous clearance. However, little is known about how this polymorphism affects the course of CHC, including the development of hepatocellular carcinoma (HCC). We evaluated the influence of IL28B polymorphisms on hepatocarcinogenesis in CHC patients. We genotyped the rs8099917 single-nucleotide polymorphism in 351 hepatitis C-associated HCC patients without history of IFN-based treatment, and correlated the age at onset of HCC in patients with each genotype. Frequencies of TT, TG, and GG genotypes were 74.3% (261/351), 24.8% (87/351), and 0.9% (3/351), respectively. The mean ages at onset of HCC for TT, TG, and GG genotypes were 69.9, 67.5 and 66.8, respectively. In multivariate analysis, IL28B minor allele (TG and GG genotypes) was an independent risk factor for younger age at onset of HCC (P=0.02) in males (P<0.001) with higher body mass index (BMI; P=0.009). The IL28B minor allele was also associated with a lower probability of having aspartate aminotransferase-to-platelet ratio index (APRI) >1.5 (minor vs. major, 46.7vs. 58.6%; P=0.01), lower AST (69.1 vs. 77.7IU/L, P=0.02), lower ALT (67.8 vs. 80.9IU/L, P=0.002), higher platelet count (12.8 vs. 11.2×10(4)/μL, P=0.002), and higher prothrombin time (79.3 vs. 75.4%, P=0.002). The IL28B minor allele was associated with lower inflammatory activity and less progressed fibrosis of the liver; however, it constituted a risk factor for younger-age onset of HCC in CHC patients.

Optimization of tactics of management of patients with chronic hepatitis C

The prognostic significance of characteristics of patients (gender, age, infectious dose, the presence of habitual intoxication) and of the virus (replicative activity, genotype, viral load, viral kinetics) in the natural course of HCV infection and the probability of achieving sustained virologic response (SVR) as a result of antiviral therapy (AVT ) were studied. The natural course of chronic hepatitis C (CHC) infection in 100 patients and the effectiveness of AVT in 68 CHC patients have been analyzed. The factors that determine the unfavorable course of CHC (male gender, age at the moment of infection older than 30 years, infection through a hemotransfusion or drug use, the presence of habitual intoxications, virus 3a genotype, and the presence of a/HCV NS3 and a/HCV NS5). The factors that determine a high probability of achieving SVR are detected. In this case the treatment by AVT, regardless of the prognosis of the natural course of HCV is recommended

Hepatitis C in patients with β-thalassemia major. A single-centre experience

Chronic hepatitis C (CHC) and iron overload are the main causes of liver disease in β-thalassemia major (βTM). There is limited data regarding the course of CHC in this population. All patients (n=144) from the thalassemia centre of the University Hospital of Patras were evaluated (January 1981 to June 2012). Patients were classified into group A (n=57), which consisted of patients with CHC, who either had received antiviral treatment (n=49) or not (n=8), and group B which included 87 patients without CHC. Nineteen patients died during follow-up (median: 257.5 months (1-355)). Survival rates were 84.2 % and 88.5 % for group A and B, respectively. The causes of death were heart failure (63.2 %), accident (10.5 %), sepsis (5.3 %), liver failure (5.3 %), hepatocellular carcinoma (HCC) (5.3 %), non-Hodgkin lymphoma (5.3 %) and multiorgan failure (5.3 %). There were no differences in total survival between the two groups (p=0.524). In the multivariate analysis, survival was neither correlated with CHC (p=ns), nor with anti-HCV treatment (p=ns), whereas independent negative predictors were presence of heart failure (p<0.001), presence of malignancy other than HCC (p=0.001) and non-adherence to chelation treatment (p=0.013). Predictive factors for the development of cirrhosis were: CHC (p<0.001), age>35 years (p=0.007), siderosis grade 3/4 (p=0.029) and splenectomy (p=0.001); however, multivariately, only siderosis grade 3/4 was found to be significant (p=0.049). In this study, survival of patients with βTM was mainly associated with heart failure, presence of malignancy other than HCC and non-adherence to chelation treatment, rather than with liver disease. Multicentre studies need to be designed to define more accurately the indications of antiviral treatment in this population.

Whole-body Insulin Resistance is Associated with Elevated Serum α-fetoprotein Levels in Patients with Chronic Hepatitis C

Little is known about the relationship between elevated serum α-fetoprotein (AFP) levels and insulin resistance, which adversely influence the clinical course of chronic hepatitis C (CHC). Therefore, we investigated the association between serum AFP and insulin resistance in patients with CHC. We retrospectively investigated 300 patients with CHC without hepatoma who underwent liver biopsies and oral glucose tolerance tests. Patients taking antidiabetic drugs were excluded. We analyzed factors associated with elevated AFP levels (≥ 10.0 ng/mL) in 265 eligible patients. Twenty patients with a homeostasis model assessment for insulin resistance value of ≥ 2.0 and a whole-body insulin sensitivity index of <5.0 received prospective lifestyle intervention. A univariate analysis showed that the body mass index, platelet count, levels of albumin, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transpeptidase, glucose metabolism, hepatic inflammation, fibrosis and steatosis were associated with elevated AFP levels. In a multivariate analysis, a platelet count of < 15 × 10(4) /μL, aspartate aminotransferase level of ≥ 50 IU/L, γ-glutamyl transpeptidase level of ≥ 35 IU/L, whole-body insulin sensitivity index of <5.0 and stage 3-4 fibrosis were independently associated with an elevated AFP level. A Bayesian Network analysis showed that the aspartate aminotransferase level, whole-body insulin sensitivity index and hepatic fibrosis were directly associated with an elevated AFP level. The lifestyle intervention significantly improved the serum AFP level, homeostasis model assessment for insulin resistance and whole-body insulin sensitivity index. Whole-body insulin resistance is associated with an elevated serum AFP level in patients with CHC. Lifestyle interventions targeting insulin resistance can reduce the serum AFP level and may ameliorate the clinical course of CHC.

Clinical Picture and Liver Histology of Chronic Hepatitis C in Children

Background and Aim Chronic hepatitis C (CHC) is still a significant clinical problem because of not only a large proportion of infected individuals, but also unclear remote consequences of the disease. The aim of the study was to analyze the clinical course and the liver histology of CHC in children searching for potential influencing factors. Methods Sixty-eight children were enrolled into the study (mean, 13.34 [SD, 3.27] years). Medical records and a current clinical status of children were analyzed considering clinical symptoms, liver function tests, and qualitative and quantitative hepatitis C virus–RNA assay with genotype and liver histology. Results A parenteral route of infection concerned 98% of children; mean length of infection was 7.34 (SD, 4.03) years. Genotype 1a was found in 78% and 1b in 16.2% children. The history of malignancy was present in 74% of patients. The symptoms of liver cirrhosis with abnormal vein circulation were found in 2 children (3%). An increased alanine aminotransferase activity was detected in 62% of patients, whereas viral load less than 6 × 105 IU/mL was found in 56 children (82%). Histological evaluation of biopsy specimens showed moderate inflammatory activity (G2) and fibrosis (S2; mean, 2.0). Progression of fibrosis was proportional to the age at infection. Conclusions The clinical course of CHC is usually mild but may result in the liver cirrhosis during childhood. Transient or constant increased alanine aminotransferase activity is observed in majority of children. Inflammatory activity and fibrosis have moderate progression in children and are proportional to the age at infection.

Natural course of treated and untreated chronic HCV infection: results of the nationwide Hepnet.Greece cohort study

Interferon (IFN-alpha)-based regimens have been used with varying success in the treatment of chronic hepatitis C (CHC) for over two decades. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results. To investigate the natural course of IFNalpha-based-treated and untreated patients with CHC by analysing data from the HEPNET.GREECE study. We retrospectively analysed 1738 patients from 25 Greek Centres (median age 40.1; males 57.6%; cirrhosis 9.2%), 734 untreated and 993 treated with IFNalpha-based regimens [44.7% sustained viral response (SVR)], followed-up for median 25.2 and 46.8 months, respectively. During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit. IFNalpha-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR.

Hepatitis C comorbidities affecting the course and response to therapy.

Several studies have demonstrated that the outcome of chronic hepatitis C (CHC) infection is profoundly influenced by a variety of comorbidities. Many of these comorbidities have a significant influence on the response to antiviral therapy. These comorbidities negatively affect the course and outcome of liver disease, often reducing the chance of achieving a sustained virological response with PEGylated interferon and ribavirin treatments. Comorbidities affecting response to antiviral therapy reduce compliance and adherence to inadequate doses of therapy. The most important comorbidities affecting the course of CHC include hepatitis B virus coinfection, metabolic syndrome, and intestinal bacterial overgrowth. Comorbidities affecting the course and response to therapy include schistosomiasis, iron overload, alcohol abuse, and excessive smoking. Comorbidities affecting response to antiviral therapy include depression, anemia, cardiovascular disease, and renal failure.

Long-Term Course of Chronic Hepatitis C in Children: From Viral Clearance to End-Stage Liver Disease

The natural course of chronic hepatitis C (CHC) in children is not well understood. The aim of this study was to assess the long-term course of CHC in a large sample of otherwise healthy children. From 1990 to 2005, 504 consecutive antihepatitis C virus (HCV)-positive children were enrolled at 12 centers of a national observatory and were followed up retrospectively/prospectively. Putative exposure was perinatal in 283 (56.2%) cases, parenteral in 158 (31.3%), and unknown in 63 (12.5%). At baseline, 477 (94.6%) cases were HCV RNA seropositive, 118 (24.7%) of which were treated with standard interferon alpha. Ten years after putative exposure, the outcome in 359 HCV RNA-positive, untreated patients was (1) undetectable viremia in 27 (7.5%) (by Cox regression analysis, spontaneous viral clearance was independently predicted by genotype 3 [hazard ratio 6.44; 95% confidence interval: 2.7-15.5]) and (2) persistent viremia in 332 (92%) cases. Six of these 332 cases (1.8%) progressed to decompensated cirrhosis (mean age, 9.6 years). This latter group included 5 Italian children perinatally infected with genotype 1a (4 of the mothers were drug users). Thirty-three (27.9%) treated patients achieved a sustained virologic response. Over the course of a decade, few children with chronic HCV infection cleared viremia spontaneously, and those who did were more likely to have genotype 3. Persistent viral replication led to end-stage liver disease in a small subgroup characterized by perinatal exposure, maternal drug use, and infection with HCV genotype 1a. Children with such features should be considered for early treatment.

Influence of the presence of HCV-RNA in peripheral blood mononuclear cells on the clinical course of chronic hepatitis C in children

The clinical course of chronic hepatitis C (CHC) is generally asymptomatic in children. The aim of this study was to examine the influence of HCV RNA in peripheral blood mononuclear cells (PBMCs) on the clinical course of CHC considering age at the time of infection, length of infection, hepatitis virus C (HCV) genotype, baseline viral load, ALT activity, the degree of liver fibrosis and oncologic history. The study group included forty children, aged 6-18 years with diagnosed CHC. Children were divided into two subgroups: group A (n = 28), with HCV-RNA found in PBMCs and group B (n = 12), with negative results of HCV-RNA in PBMCs. Chosen parameters were analyzed in both study groups according to the aim of the study. Similar age at the time of infection and the length of infection was found in both groups. The majority of the children were infected with genotype 1. Viral load, the stage of fibrosis and ALT activity were comparable in both groups. History of pediatric malignancy concerned the vast majority of children. Presence of HCV-RNA does not seem to influence the clinical course of HCV infection in children.