(160) Predictors of responses to adefovir therapy in patients with lamivudine-resistant hepatitis B virus YMDD mutant before and after liver transplantation (original) (raw)
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The Egyptian Journal of Medical Microbiology, 2014
Hepatitis C virus (HCV) infection is a major problem affecting about 180 million people worldwide, or roughly 3% of the world's population is currently infected. The burden of disease is greatest in developing countries: the highest reported prevalence is in, Egypt (22%), Pakistan (4.8%) and China (3.2%). HCV infection is one of the major causes of end-stage liver disease and hepatocellular carcinoma (HCC) worldwide. Cirrhosis rates become significant after 20 years of HCV infection. About 20-30% of patients could develop a progressive liver disease leading to cirrhosis and HCC. HCC develops at about 1-7% per year. This study aims to determine the common prevalent HCV genotypes among chronic HCV patients in Sana'a-Yemen and to evaluate the rate of sustained virological response (SVR) with some factors that affecting it. The study population includes all the 500 patients with chronic HCV infection who were treated in different hospitals during the period February 2010-August 2013. Epi-Info 7 was used to calculate the sample size, it was decided to use a simple random sampling technique in this study and a random sample of 88 patients were selected with confidence level of 99%, the sample size was then increased to 120 to maximize accuracy of the study, later 20 patients dropped out of the study & data of only 100 patients was analyzed. Each specimen was determined for HCV genotyping and HCV RNA viral load was measured before, after 12 weeks, 48 weeks and 6 months after stopping the treatment. In our study, the most predominant genotype was genotype IV with 86 %, 9 % genotype I followed by 5 % genotype II, 86 patients were investigated, after 12 weeks of treatment, 39 of them (45.3%) were HCV-RNA-ve, after 48 weeks of the treatment, some remained HCV-RNA-ve and others turned into HCV-RNA +ve, but overall 39 patients (45.3%) were HCV-RNA-ve and after 6 months of stopping the treatment, 23 out of 39 (58.9 %) achieved SVR, i.e. 26.74 % of the total sample (n = 86) achieved SVR. Regarding the effect of SVR according to gender, in this study, it showed that 84.2% of females had a SVR compared to 35% of males only (p.value of 0.003) , our study also showed that there is no statistical difference between SVR and various age groups, as it showed that 100% of those >45 years old who had a +ve HCV-RNA after 6 months from stopping treatment while 68.4 % of the age groups 30-45 years old & 58.8% of the age group < 30 years old had a-ve HCVRNA after 6 months from stopping treatment.(p.value of 0.082). We found out that only 2.6 % of those who had +ve HCV RNA after 6 months from stopping the treatment were overweight, and there was no statistical difference in SVR between normal and overweight groups according to Body Mass Index (BMI) measuring , it showed that 60.5 % of those with normal BMI had a SVR.(p.value of 0.41), In our study, there is statistical difference in SVR between those who had low (66.6%) and high viral load (16.6%) (P. value 0.033) and also there was statistical significance between EVR after 12 weeks and SVR after 6 months of stopping treatment (P value = 0.0) , 23 out of 25 patients (92%) who had Early virological response (EVR) persist to have SVR. In our study, the most predominant genotype was genotype IV with 86 %. Of our HCV-treated patients, 58.9% had SVR. HCV genotype-4, EVR, and low baseline viral load were predictive of SVR.
Liver International, 2009
Background: Hepatic steatosis is common in patients infected with hepatitis C virus (HCV). The effect of steatosis on anti-HCV therapy efficacy is unclear. Methods: We studied host and viral factors associated with steatosis and the effect of steatosis on treatment efficacy using the database of a large prospective trial in patients with HCV genotypes 2 and 3. Results: Out of 885 patients assessed for steatosis, a total of 614 patients or 69% had steatosis. Patients with genotype 3 were more likely to have steatosis than those with genotype 2 (79 vs. 59%, P o 0.001). Using the logistic regression model, steatosis was associated with genotype 3 (P o 0.0001), older age (P = 0.0025), heavier weight (P o 0.0001), higher HCV RNA (P o 0.0001), and higher ALT levels (P = 0.015). By univariate analysis, steatosis was associated with lower sustained virological response (SVR) in patients with genotype 3, but not in patients with genotype 2. When all factors associated with steatosis and SVR were evaluated by logistic regression analysis; genotype, age, bodyweight, histological diagnosis, ALT quotient, baseline HCV RNA and treatment duration were associated with the probability of SVR, but gender, race and steatosis were not. Further analysis showed that steatosis remained a non-significant factor while baseline viral load was significantly associated with the probability of an SVR. Conclusions: Steatosis did not influence the efficacy of treatment in our study population. Baseline viral load is a confounding factor, particularly in patients infected with genotype 3 and once baseline viral load was accounted for, the association between steatosis and SVR was not relevant.
Hepatology, 2010
We read with great interest the article by Petta et al. 1 The compound 25-hydroxyvitamin D3 (25[OH]D3) was reported as an independent predictor of cardiovascular disease (by a decreased expression of profibrotic markers, and an increased expression of antifibrotic markers) despite the fact that its real pathological pathway is still not clear. 2 Incubation of the multipotent mesenchymal cell with 25(OH)D3 also resulted in antiproliferative and antiapoptotic processes. 2 Therefore, the lower levels of 25(OH)D3 in liver with greater fibrosis is understandable. Lower cholesterol and lower 25(OH)D3 levels, along with greater steatosis, were found to be risk factors affecting sustained virological response (SVR) as seen in recent studies. The stage of fibrosis was found to be a risk factor for SVR not only in hepatitis C virus (HCV) alone, but also in patients coinfected with human immunodeficiency virus and HCV, in contrast to the results of the current article. 3,4 Moreover, age, sex, and body mass index were also described as predictors for SVR in patients infected with HCV, 5 in contrast to the current study. These challenging results could be related in the methodologic differences between the present study and recent studies, or mistakes could have happened during the sampling and/or analyzing periods. For example, SVR was reached in the half the male patients, whereas it was reached in just one-third of the females, results which are also different from the recent data. The patients in the study may also be infected with an unknown subgroup of HCV, which could explain these patients' characteristics.
Viral Hepatit Dergisi
Objective: Chronic hepatitis C (CHC) virus infection is one of the leading causes of chronic liver disease in all over the world. The prevalence of CHC is almost 0.5-1% in Turkey. Until recently, pegylated-interferon (PEG IFN) alpha in combination with ribavirin was the main treatment of CHC. The aim of the study was to evaluate the real life data of CHC patients. Materials and Methods: We retrospectively evaluated the demographical data and treatment responses of patients with CHC who were followed and treated in our clinic between January 2008 and December 2015. Results: A total of 117 patients (67 female and 50 male) with a mean age of 48 (15-65) were included in the study. 105 patients were genotype 1, 3 were genotype 2 and 9 were with genotype 3. The patients were treated with PEG IFN alpha-2a (81/117) or alpha-2b (36/117) combined with ribavirin. We observed sustained virologic response (SVR) in 68% of all genotype 1 patients. While relapse was observed in only 1 patient among those with genotype 2 and 3, SVR was achieved in 11. The rate of SVR was only 42% among patients older than 60 years of age, whereas SVR was achieved in all young patients (range: 15-30). The overall SVR rate was 70%. Conclusion: As CHC can result in long-term complications (cirrhosis, terminal liver failure and hepatocellular carcinoma), patients without therapy remain at risk of developing progressive liver disease. Since advanced fibrosis is a predictor for poor prognosis and insufficient therapy outcome, early treatment is required to efficiently cope with this health problem, Although the rates of SVR with direct acting antivirals are very high, starting treatment in early stage could reduce the complications of CHC and transmission of the disease.
On the outcome of antiviral therapy for hepatitis C virus genotype 2 or 3 infection
2011
Approximately 80% of patients infected with HCV genotypes 2 or 3 achieve a sustained virological response, (SVR) following 24 weeks of therapy with ribavirin and pegylated interferon (peg-IFN), but in light of considerable side effects and cost, shortened treatment duration without impaired efficacy is desirable. Thus, 382 genotype 2/3 infected patients were randomized in an investigator-initiated phase III study (NORDynamIC) evaluating the efficacy of 12 (short-term) vs. 24 (standard-ofcare) weeks of treatment with peg-IFN α-2a 180 µg/week and ribavirin 800 mg/day. Overall, 12 weeks of therapy was inferior to 24 (SVR 59% vs. 78%, P<0.0001) regardless of fibrosis stage or HCV genotype. However, in a multivariate intention-totreat analysis, HCV RNA <1,000 IU/mL on day 7, age <40 years, and undetectable HCV RNA on day 29 were independent predictors of SVR following 12 weeks of therapy. Outcome of short-term treatment was similar to standard treatment in patients younger than 40 years, as well as in older patients provided that HCV RNA was <1,000 IU/mL on day 7 and undetectable on day 29. Patients achieving HCV core antigen (coreAg) levels in plasma <0.2 pg/mL on day 3 had similar sustained viral response (SVR) rates in both study arms (86% and 84% for 12 vs. 24 week arms respectively). Patients who never achieved undetectable HCV RNA (n=12), had significantly higher age, pretreatment viral load, and bod mass index (BMI) as well as lower interferon concentrations on days 7 and 29. Similarly, obesity (BMI ≥30 kg/m 2) was significantly associated with lower peg-IFN and ribavirin concentrations which entailed impaired outcome following 24 weeks of therapy (SVR 62% vs. 89%, for BMI ≥30 vs. <30; P=0.006). In a multivariate analysis among per-protocol patients in the 24 week arm, ribavirin and peg-IFN concentrations, as well as baseline HCV RNA levels were independent predictors of SVR, suggesting that reduced bioavailability of interferon and ribavirin in obese patients may affect treatment outcome. Pretreatment plasma levels of Interferon-γ Inducible Protein 10 kDa (IP-10) predicted the reduction of HCV RNA during day 1-3 (first phase) but not the decline between days 8-29 (second phase). In addition, a significant association was identified between expression of intrahepatic IP-10 mRNA and plasma IP-10, indicating that the liver is likely the primary source of systemic IP-10 in chronic HCV infection.
Hepatology, 2004
The aim of this study was to determine the efficacy of 14 weeks of treatment in patients infected with hepatitis C virus (HCV) genotype 2 or 3 who achieve early virological response (EVR). In a noncontrolled multicenter trial, 122 treatment-naive patients received 1.5 g/kg pegylated interferon alfa-2b subcutaneously once weekly and 800 to 1,400 mg/d ribavirin based on body weight. Treatment was stopped at week 14 in patients with EVR, defined as undetectable HCV RNA at weeks 4 and 8. Patients without EVR were assigned to 24 weeks of treatment. The primary end point was sustained virological response (SVR), defined as undetectable HCV RNA 24 weeks after end of treatment. Among the 122 patients, 95 (78%) had EVR and received 14 weeks of treatment. The remaining 27 (22%) were treated for 24 weeks. SVR was obtained in 85 (90%) of 95 patients in the 14-week treatment group and 15 of (56%) 27 in the 24-week treatment group. Altogether, SVR was obtained in 100 of 122 patients (82%; 95% CI, 75%-89%). SVR after 14 weeks of treatment was achieved more frequently among genotype 3a patients with low viral load compared with high viral load (98% vs. 79%; P ؍ .019). Logistic regression analysis showed that absence of bridging fibrosis/cirrhosis was the only independent predictor of SVR. In conclusion, patients with genotype 2 or 3 and EVR obtained a high SVR after 14 weeks of treatment. The results need to be confirmed in a randomized, controlled study before this treatment approach can be recommended, particularly for patients with genotype 3 and high viral load or severe fibrosis. (HEPATOLOGY 2004;40:1260 -1265