Diagnosis, Management, and Treatment of Hepatitis C: An Update

Department of Health and Human Services, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Hepatology (Impact Factor: 11.06). 04/2009; 49(4):1335-74. DOI: 10.1002/hep.22759
Source: PubMed


At least five groups have evaluated treatment for patients with decompensated cirrhosis preliminary to liver transplantation.330–334 In the earliest reported study, 32 patients awaiting liver transplantation were considered for antiviral treatment, but over one-half were found ineligible because of cytopenias.330 Among those treated with standard or low doses of interferon alfa-2b or low doses of both interferon alfa-2b and ribavirin, 33% became HCV RNA negative. Almost all developed adverse effects, most of which was graded as severe. In a second study, 30 patients with HCV-related cirrhosis destined for liver transplantation (half graded as CTP class A) were treated with interferon alfa-2b, 3 mU daily and ribavirin, 800 mg/day if their presumed time to liver transplantion was less than 4 months.331 After a median treatment duration of 12 weeks, 30% responded to treatment and then underwent liver transplantation, 2/3 of whom remained HCV RNA negative over a median follow-up period of 46 weeks. Sixty percent developed neutropenia. Reported in the same year was a study of 20 patients, most with genotype 1 infection, who were treated before transplantation for a mean of 14 months with interferon alfa-2b in a dose of 5 mU daily.332 At transplantation, 60% were HCV RNA negative, but only 20% remained negative after transplantation. A fourth study involved 124 patients with advanced cirrhosis (CTP classes A, B and C) treated mainly with interferon alfa-2b plus ribavirin, and less frequently, with pegylated interferon plus ribavirin.333 Treatment began with half doses that were increased incrementally as tolerated at 2 week intervals (referred to as a low accelerating dose regimen), and growth factors were used as needed. An SVR developed in 13% of patients with genotype 1 and in 50% with non-genotype 1 infections. Adverse events were frequent, requiring dose reductions or treatment termination, but among those who did become HCV RNA negative before transplantation, 80% remained negative 6 or more months after transplantation. The most recent study is the only one to include non-treated controls but these consisted of patients unwilling to participate in the study.334 The treatment administered was peginterferon alfa-2b, 1.0 μg/kg body weight given weekly and ribavirin, 800 to 1000 mg daily for 24 weeks. An SVR developed in 44% of the patients with HCV genotypes 2 or 3, and in 7% of those with genotypes 1 or 4. Treatment had to be discontinued in 20%, was reduced in 39%, and was tolerated in 41%. Over a 30-month follow-up period, decompensated events occurred in 83% of the controls, 62% of the non-responders, and in 23% of the patients who had developed an SVR. The conclusion of this study was that antiviral therapy can be life-saving, improves hepatic function, and that treatment seems appropriate for persons with genotype 2 and 3 infections particularly in those with cirrhosis, CTP classes A and B.

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    • "It is widely accepted that patients without HF or with early HF have a low risk of liver failure, while those in stages higher than F2 (i.e. significant HF) have a higher risk of liver failure, along with a higher risk of cirrhosis in the future[10]. Therefore, the early and accurate diagnosis of HF in patients with chronic hepatic disease is critical and necessary. "
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    ABSTRACT: Objectives: To determine the potential of intravoxel incoherent motion (IVIM) MR imaging for staging of hepatic fibrosis (HF). Methods: We searched PubMed and EMBASE from their inception to 31 July 2015 to select studies reporting IVIM MR imaging and HF staging. We defined F1-2 as non-advanced HF, F3-4 as advanced HF, F0 as normal liver, F1 as very early HF, and F2-4 as significant HF. Then we compared stage F0 with F1, F0-1 with F2-3, and F1-2 with F3-4 using IVIM-derived parameters (pseudo-diffusion coefficient D*, perfusion fraction f, and pure molecular diffusion parameter D). The effect estimate was expressed as a pooled weighted mean difference (WMD) with 95% confidence interval (CI), using the fixed-effects model. Results: Overall, we included six papers (406 patients) in this study. Significant differences in D* were observed between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 2.46, 95% CI 0.83-4.09, P = 0.006; WMD 13.10, 95% CI 9.53-16.67, P < 0.001; WMD 14.34, 95% CI 10.26-18.42, P < 0.001, respectively). Significant differences in f were also found between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 1.62, 95% CI 0.06-3.18, P = 0.027; WMD 5.63, 95% CI 2.74-8.52, P < 0.001; WMD 3.30, 95% CI 2.10-4.50, P < 0.001, respectively). However, D showed no differences between F0 and F1, F0-1 and F2-3, and F1-2 and F3-4 (WMD 0.05, 95% CI -0.01─0.11, P = 0.105; WMD 0.04, 95% CI -0.01─0.10, P = 0.230; WMD 0.02, 95% CI -0.02─0.06, P = 0.378, respectively). Conclusions: IVIM MR imaging provides an effective method of staging HF and can distinguish early HF from normal liver, significant HF from normal liver or very early HF, and advanced HF from non-advanced HF.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "The duration of therapy for those who completed the course was 48 weeks. Virological responses of therapy were defined as reported by Ghany et al. [6]. Thirty-six (72%) children attained ETR and SVR with no relapses, while 14 (28%) children were nonre- sponders. "
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    ABSTRACT: Background & Aims.The currently available treatment for chronic hepatitis C (CHC) in children is costly and with much toxicity. So, predicting the likelihood of response before starting therapy is important. Methods. Serum adiponectin, vitamin D, and alphafetoprotein (AFP) were measured before starting pegylated-interferon/ribavirin therapy for 50 children with CHC. Another 21 healthy children were recruited as controls. Results. Serum adiponectin, vitamin D, and AFP were higher in the CHC group than healthy controls (𝑝 < 0.0001, 𝑝 = 0.071, and 𝑝 = 0.87, resp.). In univariate analysis, serum adiponectin was significantly higher in responders than nonresponders (𝑝 < 0.0001) and at a cutoff value ≥8.04 ng/mL it can predict treatment response by 77.8%sensitivity and 92.9% specificity, while both AFP and viremia were significantly lower in responders than nonresponders, 𝑝 < 0.0001 and 𝑝 = 0.0003, respectively, and at cutoff values ≤3.265 ng/mL and ≤235,384 IU/mL, respectively, they can predict treatment response with a sensitivity of 83.3% for both and specificity of 85.7% and 78.6%, respectively. Inmultivariate analysis, adiponectin was found to be the only independent predictor of treatment response (𝑝 = 0.044). Conclusions.The pretreatment serum level of adiponectin can predict the likelihood of treatment response, thus avoiding toxicities for those unlikely to respond to therapy.
    Full-text · Article · Nov 2015
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    • "Around 20% of people chronically infected with HCV develop cirrhosis over 30 years. Once cirrhosis is established, patients have a 20-fold greater risk of developing HCC, at a rate of ∼3% per year (Ghany et al., 2009). Thus, 27% of the liver cirrhosis and 25% of HCC worldwide are caused by a primary infection with HCV. "
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    ABSTRACT: HCV is an ideal model to study how the infected cell is altered to allow the establishment of a chronic infection. After infection, the transcriptome of the cell changes in response to the virus or to the antiviral pathways induced by infection. The cell has evolved to sense HCV soon after infection and to activate antiviral pathways. In turn, HCV has evolved to block the antiviral pathways induced by the cell and, at the same time, to use some for its own benefit. In this review, we summarize the proviral and antiviral factors induced in HCV infected cells. These factors can be proteins and microRNAs, but also long noncoding RNAs (lncRNAs) that are induced by infection. Interestingly, several of the lncRNAs upregulated after HCV infection have oncogenic functions, suggesting that upregulation of lncRNAs could explain, at least in part, the increased rate of liver tumors observed in HCV-infected patients. Other lncRNAs induced by HCV infection may regulate the expression of coding genes required for replication or control genes involved in the cellular antiviral response. Given the evolutionary pressure imposed by viral infections and that lncRNAs are specially targeted by evolution, we believe that the study of proviral and antiviral lncRNAs may lead to unexpected discoveries that may have a strong impact on basic science and translational research.
    Full-text · Article · Oct 2015 · Virus Research
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