Hepatic lidocaine metabolism in chronic hepatitis C virus hepatitis with or without steatosis

Taliani, Gloria; Duca, F.; Lecce, R.; Livoli, D.; Pasquazzi, C.; Bac, Carlo De; Fabbri, Andrea; Bianchi, Giampaolo; Marchesini, G.

doi:10.1002/hep.1840210646

Cited by 23 publications

(8 citation statements)

References 4 publications

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“…It has therefore been suggested that hepatic steatosis decreases the contact area between drug and hepatocyte membranes, leading to a reduction in anti-viral drug efficacy [30,31] and therefore, in SVR rates. However, patients with genotype 3 have an excellent response to treatment, despite their greater extent of hepatic steatosis, rendering this an unlikely explanation [32].…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3

Poustchi¹,

Negro²,

Hui³

et al. 2008

Journal of Hepatology

165

122

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Section: Discussionmentioning

confidence: 99%

Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3

Poustchi¹,

Negro²,

Hui³

et al. 2008

Journal of Hepatology

165

122

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“…Therefore, this study firstly reported the negative effect of hepatic steatosis on Entecavir treatment failure in CHB patients. Such effect is biologically possible, as cellular fat accumulation may decrease the contact area between drugs and hepatocytes, causing reduced bioavailability of Entecavir [22]. Besides, diminished activity of hepatic cytochromes in steatotic hepatocytes may also hamper drug metabolism [23].…”

Section: Discussionmentioning

confidence: 99%

Association between Hepatic Steatosis and Entecavir Treatment Failure in Chinese Patients with Chronic Hepatitis B

et al. 2012

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BackgroundThe coexistence of HBV infection and nonalcoholic fatty liver disease (NAFLD) becomes characteristic of liver disease in China, with unknown bilateral influence. We aimed to investigate the effect of hepatic steatosis, a common hepatocyte change in NAFLD, on antiviral therapy in patients with chronic hepatitis B (CHB).Methods and FindingsWe carried out a prospective nested case control study in CHB patients receiving Entecavir for initial antiviral therapy, by recording demographic, anthropometric and clinical data at baseline, 24wk, 48wk and 96wk. Univariate analysis and multivariate logistic regression were applied to find out independent factors of hepatic steatosis and Entecavir treatment failure. The rates of HBV-DNA clearance, HBeAg seroconversion and ALT normalization were compared between CHB patients with and without steatosis by post hoc analysis. A total of 267 Chinese patients with CHB entered final analysis, with overall percentages of hepatic steatosis and HBeAg positive as 30.5% and 62.4%. Multivariate analysis showed waist circumference, serum TG and uric acid levels were independent factors of hepatic steatosis. The response rates to Entecavir were 54.9%, 63.8%, 74.2% at 24wk, 48wk and 96wk. Hepatic steatosis was revealed as an independent factor of Entecavir treatment failure by multivariate logistic regression at 24wk, 48wk and 96wk. In CHB patients with hepatic steatosis, HBV-DNA clearance and HBeAg seroconversion were both lower throughout the follow-up, but only the former reached statistical significance. Besides, ALT normalization was also significantly lower at 24wk and 48wk.ConclusionHepatic steatosis is significantly associated with Entecavir treatment failure and metabolic factors are independent factors of hepatic steatosis in CHB patients, which called for a specified antiviral strategy in CHB patients with NAFLD.

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“…Previous studies showed that liver fibrosis correlates with steatosis and obesity [Hourigan et al, 1999;Clouston et al, 2001;Hwang et al, 2001]. Thus, lipid deposits within hepatocytes might cause functional disturbances by increasing the architectural distortion of the hepatic lobule caused by fibrosis and decrease in the contact area between drugs and hepatocytes [Taliani et al, 1995;Giannini , 1999]. Another study reported a close correlation between the level of intrahepatic HCV-RNA and severity of steatosis [Rubbia-Brandt et al, 2000].…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: Virological features of IFN‐resistant cases with hepatocyte steatosis

Akuta

Suzuki

et al. 2005

Journal of Medical Virology

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The role of hepatocyte steatosis in interferon (IFN) resistance is still unclear, especially in patients infected with hepatitis C virus (HCV) genotype 2a. The present study was conducted in 364 consecutive non-cirrhotic naive patients infected with genotype 2a, who were evaluated for the severity of steatosis and response to IFN monotherapy after a 24-week median duration of therapy. The patients were examined for factors associated with steatosis and treatment efficacy according to the grade of steatosis. Early viral kinetics was also evaluated in 64 patients for predictors of response to therapy. Nine IFN-resistant patients were assessed for the relationship between amino acid sequence of HCV core region/NS5A and severity of steatosis. Multivariate analysis identified two independent factors associated with steatosis; serum ferritin > or =200 microg/l and body mass index > or =25.0 kg/m(2). The sustained virological response rate in patients with high-grade steatosis was significantly lower than in the low-grade group. Study of early viral kinetics showed a significantly lower cumulative HCV-RNA negative rate for the high-grade than low-grade steatosis group. Sequence analysis of HCV core region/NS5A in IFN-resistant patients with or without steatosis failed to identify steatosis-specific amino acid substitutions associated with resistance. This study of HCV genotype 2a suggested that steatosis is associated with excess iron storage, and that it is an important predictor of efficacy of IFN monotherapy. Further large-scale studies are warranted to examine the role of amino acid substitutions on IFN resistance specific for steatosis.

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Hepatic lidocaine metabolism in chronic hepatitis C virus hepatitis with or without steatosis

Cited by 23 publications

References 4 publications

Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3

Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3

Association between Hepatic Steatosis and Entecavir Treatment Failure in Chinese Patients with Chronic Hepatitis B

Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: Virological features of IFN‐resistant cases with hepatocyte steatosis

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