Background & Aims: Inadequate data are available about retreatment of nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the efficacy and tolerability of a 48-week therapy ...with pegylated IFN-α-2b plus high-dose ribavirin in patients who have failed to respond to the combination. Treatment up to 48 weeks also in patients who have failed to clear hepatitis C virus (HCV) RNA by week 24 was also evaluated. Methods: One hundred forty-one patients who previously did not respond to IFN and ribavirin, 86% with genotype 1 or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis, were retreated with pegylated IFN-α-2b 1.5 μg/kg per week and ribavirin 1000–1200 mg/day for 48 weeks and followed up for 24 weeks. Results: By intent-to-treat analysis, 20% of patients achieved a sustained virologic response (SVR). SVR of genotype 1 patients was 19%. Independent predictors of SVR were low γ-glutamyltransferase levels (OR, 22.9; 95% CI: 6.6–79.6) and low viral load (OR, 3.8; 95% CI: 1.1–12.6). Twelve (23%) out of 51 patients who were HCV RNA positive after 24 weeks of therapy achieved a late virologic response (after week 24) and 5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not associated with response (P = .2) or with early response (P = .3). Conclusions: Retreatment with pegylated IFN-α-2b and ribavirin of multiexperienced and “difficult to treat” nonresponder patients produced a very promising SVR. Accurate selection of patients, such as those with low viral load and low γ-glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in HCV RNA-positive patients may further increase the rate of SVR.
Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC) associated with cirrhosis is rising in some developed countries, whereas mortality from non-HCC complications of ...cirrhosis is decreasing or is stable. Cohort studies indicate that HCC is currently the major cause of liver-related death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection is associated with the highest HCC incidence in persons with cirrhosis, occurring twice as commonly in Japan than in the West (5-year cumulative incidence, 30% and 17%, respectively), followed by hereditary hemochromatosis (5-year cumulative incidence, 21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the absence of HCV and HBV infection, the HCC incidence is lower in alcoholic cirrhotics (5-year cumulative risk, 8%) and subjects with advanced biliary cirrhosis (5-year cumulative risk, 4%). There are limited data on HCC risk in cirrhosis of other causes. Older age, male sex, severity of compensated cirrhosis at presentation, and sustained activity of liver disease are important predictors of HCC, independent of etiology of cirrhosis. In viral-related cirrhosis, HBV/HCV and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol abstinence). Sustained reduction of HBV replication lowers the risk of HCC in HBV-related cirrhosis. Further studies are needed to investigate other viral factors (eg, HBV genotype/mutant, occult HBV, HIV coinfection) and preventable or treatable comorbidities (eg, obesity, diabetes) in the HCC risk in cirrhosis.
The impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been ...extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin.
For 48 weeks, 388 "naïve"genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000-1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR).
The rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.
Dual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance.
ClinicalTrials.gov Identifier: NCT01342003.
AbstractBackground and rationale of the study. Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has ...not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. Results. HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). Conclusions. Liver cirrhosis and age > 60 years are the stronger risk factors for HCC in genotype D HBeAnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.
The aim of this study was to evaluate whether the transmission of hepatitis C virus (HCV) between spouses occurs through sexual contact or through other types of exposure.
We consecutively enrolled ...311 chronic HCV carriers and their spouses. The spouses underwent HCV blood testing. Exposure to parenteral risk factors was compared between couples of which both partners were HCV positive and couples with one positive partner. In couples with both partners positive, qualitative detection of serum HCV RNA and genotyping were performed.
The prevalence among spouses was 10.3% (32/311). The mean age was higher for HCV-positive spouses (57.7 vs 49.6 yr for HCV-negative spouses; p < 0.01). The prevalence among spouses increased with the duration of marriage, whereas no difference was found in relation to the clinical status of the index case. The 32 HCV-positive spouses reported parenteral exposure (blood transfusion, drug use, and use of multiple-use glass syringes inside or outside the family) more often than the 279 HCV-negative spouses (84.4% vs 26.2%; odds ratio OR, adjusted for age by multiple logistic regression analysis, 12.4; 95% CI = 4.5-34.0). The percentage of couples sharing glass syringes was significantly higher among those with both partners infected (65.6% vs 12.9%; OR = 12.9; 95% CI = 5.4-31.4). Qualitative serum HCV RNA was determined in 22 couples with both partners infected; in 13 of them, both partners were HCV RNA positive, whereas in the remaining nine, only one partner was positive. In eight of the 13 couples with both partners HCV RNA positive, the same genotype was found for both partners.
The findings that the same genotype was detected for both partners in relatively few couples, and that a history of parenteral exposure was an independent predictor of HCV positivity, suggest that the risk of sexual transmission is low. The sharing of glass syringes may have played an important role in transmission between spouses.
The effect of achieving a sustained virological response (SVR) following interferon‐α (IFNα) treatment on the clinical outcomes of patients with HCV‐related cirrhosis is unknown. In an attempt to ...assess the risk of liver‐related complications, HCC and liver‐related mortality in patients with cirrhosis according to the response to IFNα treatment, a retrospective database was developed including all consecutive patients with HCV‐related, histologically proven cirrhosis treated with IFNα monotherapy between January 1992 and December 1997. SVR was an undetectable serum HCV‐RNA by PCR 24 weeks after IFNα discontinuation. HCC was assessed by ultrasound every 6 months. Independent predictors of all outcomes were assessed by Cox regression analysis. Of 920 patients, 124 (13.5%) were classified as achieving a SVR. During a mean follow‐up of 96.1 months (range: 6‐167) the incidence rates per 100 person‐years of liver‐related complications, HCC and liver‐related death were 0, 0.66, and 0.19 among SVR and 1.88, 2.10, and 1.44 among non‐SVR (P < 0.001 by log‐rank test). Multivariate analyses found that non‐SVR was associated with a higher risk of liver‐related complications (hazard ratio, HR, not applicable), HCC (HR 2.59; 95% CI 1.13‐5.97) and liver‐related mortality (HR 6.97; 95% CI 1.71‐28.42) as compared to SVR. Conclusion: Thus, in patients with HCV‐related, histologically proven cirrhosis, achievement of a SVR after IFNα therapy was associated with a reduction of liver‐related mortality lowering both the risk of complications and HCC development. Irrespective of SVR achievement, all patients should continue surveillance because the risk of occurrence of HCC was not entirely avoided. (HEPATOLOGY 2007;45:579–587.)
Data on the prevalence of hepatitis C virus (HCV) infection in Italy are outdated and usually derived from studying residents in small towns.
To assess prevalence of and risk factors for HCV ...infection among Italian residents in 5 metropolitan areas, subjects ≥20 years of age were randomly selected from the list of the general practitioners' registers in 2015. Anti-HCV was tested by a salivary test; HCV-RNA, HCV genotypes, and ALT were determined in positive individuals. Logistic regression analysis evaluated independent risk factors for HCV.
Of the 4907 enrolled subjects, 112 (2.3%) tested anti-HCV positive. The prevalence of HCV increased with age, from 0.2% in subjects born after the year 1984, to 4.2% in those born before the year 1935 (P < 0.01). The birth-cohort prevalence peaked (7.0%) in elderly. Serum HCV-RNA was detected in 1.7% of the whole population. Nearly 80% of anti-HCV subjects were aware of their status. Age > 70 years, low education level, past use of glass syringes, blood transfusion, intravenous drug use, and cohabitation with an anti-HCV positive subject predicted the HCV positivity.
In metropolitan areas in Italy, HCV is prevalent in elderly, reflecting a cohort effect determined by modalities of viral transmission no longer operative. The impact of the infection will further diminish in the years to come due to the natural depletion of the reservoir of the virus. This age pattern and the high proportion of subjects aware of their status do not warrant a policy of screening.
•In Italy the seroprevalence for anti-HCV among the general population is outdated.•We evaluated 4907 subjects in 5 metropolitan areas.•The birth-cohort prevalence peaked in elderly.•Nearly 80% of the anti-HCV subjects were aware of their status.•This epidemiological pattern does not warrant a policy of screening in Italy.
To evaluate the long-term eradication of hepatitis C virus (HCV) infection and liver-related complications in chronically infected patients that have achieved sustained virological response.
One ...hundred and fifty subjects with chronic hepatitis C (CHC) or cirrhosis and sustained virological response (SVR) between the years of 1989 and 2008 were enrolled in a long-term clinical follow-up study at the Gastrointestinal and Liver Unit of the University Hospital of Naples "Federico II". At the beginning of the study, the diagnosis of HCV infection was made on the basis of serum positivity for antibodies to HCV and detection of HCV RNA transcripts, while a diagnosis of chronic hepatitis was formulated using imaging techniques and/or a liver biopsy. SVR was achieved by interferon-based therapy, both conventional and pegylated, with and without ribavirin treatment. The patients were evaluated for follow-up at a median length of 8.6 years, but ranged from 2-19.9 years. Among them, 137 patients had pre-treatment CHC and 13 had cirrhosis. The patients were followed with clinical, biochemical, virological, and ultrasound assessments on a given schedule. Finally, a group of 27 patients underwent a liver biopsy at the beginning of the study and transient elastography at their final visit to evaluate changes in liver fibrosis.
The median follow-up was 8.6 years (range 2-19.9 years). HCV RNA remained undetectable in all patients, even in patients who eventually developed liver-related complications, indicating no risk of HCV recurrence. Three liver-related complications were observed: two cases of hepatocellular carcinoma and one case of bleeding from esophageal varices resulting in an incidence rate of 0.23%/person per year. Further, all three complications took place in patients diagnosed with cirrhosis before treatment began. Only one death due to liver-related causes occurred, resulting in a mortality rate of 0.077% person per year. This amounts to a 99.33% survival rate in our cohort of patients after therapy for HCV infection. Finally, of the 27 patients who underwent a liver biopsy at the beginning of the study, a reduction in liver fibrosis was observed in 70.3% of the cases; only three cases registering values of liver stiffness indicative of significant fibrosis.
Patients with CHC and SVR show an excellent prognosis with no risk of recurrence and a very low rate of mortality. Our data indicate that virus-eradication following interferon treatment can last up to 20 years.
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