Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent...Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review,we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The Pub Med and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeS H terms: metformin and mammalian target of rapamycin, hepatitis B virus(HBV), hepatitis B virus(HCV), nonalcoholic fatty liver disease(NAFLD), hepatocellular carcinoma(HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level Ⅲ evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.展开更多
AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathol...AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathology data underwent 3.0T 1H MRS, andthe results of MRS and pathological analysis werecompared.RESULTS： This group of patients included 26 peoplewith mild fatty liver （28.89%）, 16 people withmoderate fatty liver （17.78%）, 18 people with severefatty liver （20.0%）, and 30 people without fatty liver（33.33%）. The water peak was near 4.7 parts permillion （ppm）, and the lipid peak was near 1.3 ppm.Analysis of variance revealed that differences in thelipid peak, the area under the lipid peak, ratio of thelipid peak to the water peak, and ratio of the areaunder the lipid peak to the area under the waterpeak were statistically significant among the groups.Specifically, as the severity of fatty liver increased, thevalue of each index increased correspondingly. In thepairwise comparisons, the mean lipid peak, area underthe lipid peak, ratio of the lipid peak to the waterpeak, and ratio of the area under the lipid peak to thearea under the water peak were significantly differentbetween the no fatty liver and moderate fatty liver groups, whereas no differences were noted betweenthe severe fatty liver group and the mild or moderatefatty liver group. Area under the ROC curve （AUC） ofarea ratio in lipid and water and ratio in lipid and waterin the no fatty liver group to mild fatty liver group, mildfatty liver group to moderate fatty liver group, andmoderate fatty liver disease group to severe fatty livergroup, were 0.705, 0.900, and 0.975, respectively.CONCLUSION： 1H MRS is a noninvasive techniquethat can be used to provide information on the effectof liver steatosis on hepatic metabolic processes. Thisstudy indicates that the 1H MRS can be used as anindicator of steatosis in patients with chronic hepatitis C.展开更多
Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin....Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.展开更多
Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in ap...Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.展开更多
Liver diseases are an increasingly common cause of morbidity and mortality; new approaches for investigation of mechanisms of liver diseases and identification of therapeutic targets are emergent. Lipid rafts (LRs) ar...Liver diseases are an increasingly common cause of morbidity and mortality; new approaches for investigation of mechanisms of liver diseases and identification of therapeutic targets are emergent. Lipid rafts (LRs) are specialized domains of cellular membranes that are enriched in saturated lipids; they are small, mobile, and are key components of cellular architecture, protein partition to cellular membranes, and signaling events. LRs have been identified in the membranes of all liver cells, parenchymal and non-parenchymal; more importantly, LRs are active participants in multiple physiological and pathological conditions in individual types of liver cells. This article aims to review experimental-based evidence with regard to LRs in the liver, from the perspective of the liver as a whole organ composed of a multitude of cell types. We have gathered up-to-date information related to the role of LRs in individual types of liver cells, in liver health and diseases, and identified the possibilities of LR-dependent therapeutic targets in liver diseases.展开更多
Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of ...Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex （MHC） class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability ＇of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 （IL-10） and transforming growth factor beta （TGFβ） predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.展开更多
Chronic hepatitis C infection is the leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma as well as the primary indication for liver transplantation in the United States. Despite recent advance...Chronic hepatitis C infection is the leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma as well as the primary indication for liver transplantation in the United States. Despite recent advances in drugs for the treatment of hepatitis C, predictive models estimate the incidence of cirrhosis due to hepatitis C infection will to continue to rise for the next two decades. There is currently an immense interest in the treatment of patients with fibrosis and early-stage cirrhosis as treatment can lead to decrease in the rates of decompensated cirrhosis, hepatocellular carcinoma and need for liver transplantation in these patients. The goal of this paper is to provide clinicians and health care professionals further information about the treatment of patients with hepatitis C infection and cirrhosis. Additionally, the paper focuses on the disease burden, epidemiology, diagnosis and the disease course from infection to treatment. We provide an overview of multiple studies for the treatment of chronic hepatitis C infection that have included patients with cirrhosis. We also discuss the advantages and disadvantages of treatment in cirrhotic patients and focus on the most up to date guidelines available for treatment.展开更多
A substantial proportion of individuals with chronic hepatitis C virus(HCV) are co-infected with human immunodeficiency virus(HIV). Co-infected individuals are traditionally considered as one of the "special popu...A substantial proportion of individuals with chronic hepatitis C virus(HCV) are co-infected with human immunodeficiency virus(HIV). Co-infected individuals are traditionally considered as one of the "special populations" amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals(DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the "special population" designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users.展开更多
AIM: To characterize management of telaprevir(TVR)-based triple therapy of hepatitis C virus(HCV) reinfection after liver transplantation(LT).METHODS: We retrospectively analyzed safety and efficacy of telaprevir- bas...AIM: To characterize management of telaprevir(TVR)-based triple therapy of hepatitis C virus(HCV) reinfection after liver transplantation(LT).METHODS: We retrospectively analyzed safety and efficacy of telaprevir- based triple therapy in a single center cohort of 19 patients with HCV genotype(GT) 1 recurrence after LT, with respect to factors possibly predicting sustained viral response(SVR) or non-SVR. All patients were treated with TVR, pegylated(PEG) and ribavirine(RBV) for 12 wk followed by a dual phase with PEG/RBV for 12 wk in 7 patients and for 36 wk in 5 patients. RESULTS: In total 11/19(58%) of patients achieved a sustained response. All(11/11) SVR patients showed a rapid viral response at treatment weeks 4 and 11/14 rapid virological response(RVR) patients achieved SVR. Notably, all(7/7) patients who completed 48 wk of therapy and 80%(4/5) patients who completed 24 wk of therapy achieved SVR24. Treatment failure was significantly(P > 0.049) more frequent in GT1 a infection(5/7) compared to GT1b(3/12) infection and was associated with emergence of resistance-associated mutations in the NS3 protease domain. Bilirubin level at baseline is also related to SVR(P > 0.030). None of the patients had to discontinue treatment due to side effects. CONCLUSION: RVR, GT and bilirubin are clearly related to achievement of SVR. Providing a thorough patient selection and monitoring, a full course of TVR-based triple therapy in LT patients is feasible and achieves high SVR rates.展开更多
文摘Metformin, a biguanide derivative, is the most commonly prescribed medication in the treatment of type 2 diabetes mellitus. More recently, the use of metformin has shown potential as a preventive and therapeutic agent for a broad spectrum of conditions, including liver disease and hepatic malignancies. In this systematic review,we critically analyze the literature behind the potential use of metformin across the spectrum of liver disease and malignancies. The Pub Med and Ovid MEDLINE databases were searched from 2000 to March 2015, using a combination of relevant text words and MeS H terms: metformin and mammalian target of rapamycin, hepatitis B virus(HBV), hepatitis B virus(HCV), nonalcoholic fatty liver disease(NAFLD), hepatocellular carcinoma(HCC) or cholangiocarcinoma. The search results were evaluated for pertinence to the issue of metformin in liver disease as well as for quality of study design. Metformin has a number of biochemical effects that would suggest a benefit in treating chronic liver diseases, particularly in the context of insulin resistance and inflammation. However, the literature thus far does not support any independent therapeutic role in NAFLD or HCV. Nonetheless, there is Level Ⅲ evidence for a chemopreventive role in patients with diabetes and chronic liver disease, with decreased incidence of HCC and cholangiocarcinoma. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. In conclusion, there is insufficient evidence to recommend use of metformin in the adjunctive treatment of chronic liver diseases, including NAFLD and HCV. However, there is good evidence for a chemopreventive role against HCC among patients with diabetes and chronic liver disease, and metformin should be continued in patients even with cirrhosis to provide this benefit.
基金Supported by National Natural Science Foundation of China,No.30970415
文摘AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathology data underwent 3.0T 1H MRS, andthe results of MRS and pathological analysis werecompared.RESULTS： This group of patients included 26 peoplewith mild fatty liver （28.89%）, 16 people withmoderate fatty liver （17.78%）, 18 people with severefatty liver （20.0%）, and 30 people without fatty liver（33.33%）. The water peak was near 4.7 parts permillion （ppm）, and the lipid peak was near 1.3 ppm.Analysis of variance revealed that differences in thelipid peak, the area under the lipid peak, ratio of thelipid peak to the water peak, and ratio of the areaunder the lipid peak to the area under the waterpeak were statistically significant among the groups.Specifically, as the severity of fatty liver increased, thevalue of each index increased correspondingly. In thepairwise comparisons, the mean lipid peak, area underthe lipid peak, ratio of the lipid peak to the waterpeak, and ratio of the area under the lipid peak to thearea under the water peak were significantly differentbetween the no fatty liver and moderate fatty liver groups, whereas no differences were noted betweenthe severe fatty liver group and the mild or moderatefatty liver group. Area under the ROC curve （AUC） ofarea ratio in lipid and water and ratio in lipid and waterin the no fatty liver group to mild fatty liver group, mildfatty liver group to moderate fatty liver group, andmoderate fatty liver disease group to severe fatty livergroup, were 0.705, 0.900, and 0.975, respectively.CONCLUSION： 1H MRS is a noninvasive techniquethat can be used to provide information on the effectof liver steatosis on hepatic metabolic processes. Thisstudy indicates that the 1H MRS can be used as anindicator of steatosis in patients with chronic hepatitis C.
文摘Hepatitis C virus (HCV) infects approximately 170 million individuals worldwide. Prevention of HCV infection complications is based on antiviral therapy with the combination of pegylated interferon alfa and ribavirin. The use of serological and virological tests has become essential in the management of HCV infection in order to diagnose infection, guide treatment decisions and assess the virological response to antiviral therapy. Anti- HCV antibody testing and HCV RNA testing are used to diagnose acute and chronic hepatitis C. The HCV genotype should be systematically determined before treatment, as it determines the indication, the duration of treatment, the dose of ribavirin and the virological monitoring procedure. HCV RNA monitoring during therapy is used to tailor treatment duration in HCV genotype 1 infection, and molecular assays are used to assess the end-of-treatment and, most importantly the sustained virological response, i.e. the endpoint of therapy.
文摘Over the last years it has started a real revolution in the treatment of chronic hepatitis C. This occurred for the availability of direct-acting antiviral agents that allow to reach sustained virologic response in approximately 90% of cases. In the near future further progress will be achieved with the use of pan-genotypic drugs with high efficacy but without side effects.
文摘Liver diseases are an increasingly common cause of morbidity and mortality; new approaches for investigation of mechanisms of liver diseases and identification of therapeutic targets are emergent. Lipid rafts (LRs) are specialized domains of cellular membranes that are enriched in saturated lipids; they are small, mobile, and are key components of cellular architecture, protein partition to cellular membranes, and signaling events. LRs have been identified in the membranes of all liver cells, parenchymal and non-parenchymal; more importantly, LRs are active participants in multiple physiological and pathological conditions in individual types of liver cells. This article aims to review experimental-based evidence with regard to LRs in the liver, from the perspective of the liver as a whole organ composed of a multitude of cell types. We have gathered up-to-date information related to the role of LRs in individual types of liver cells, in liver health and diseases, and identified the possibilities of LR-dependent therapeutic targets in liver diseases.
基金Supported by Development funds from Section of Gastroenterology/Hepatology, Internal Medicine, University of Nebraska Medical Center
文摘Alcoholic patients have a high incidence of hepatitis C virus （HCV） infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV- induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex （MHC） class Ⅰ- and class Ⅱ-restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class ~I in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability ＇of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 （IL-10） and transforming growth factor beta （TGFβ） predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class Ⅱ-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I -restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.
文摘Chronic hepatitis C infection is the leading cause of chronic liver disease, cirrhosis, hepatocellular carcinoma as well as the primary indication for liver transplantation in the United States. Despite recent advances in drugs for the treatment of hepatitis C, predictive models estimate the incidence of cirrhosis due to hepatitis C infection will to continue to rise for the next two decades. There is currently an immense interest in the treatment of patients with fibrosis and early-stage cirrhosis as treatment can lead to decrease in the rates of decompensated cirrhosis, hepatocellular carcinoma and need for liver transplantation in these patients. The goal of this paper is to provide clinicians and health care professionals further information about the treatment of patients with hepatitis C infection and cirrhosis. Additionally, the paper focuses on the disease burden, epidemiology, diagnosis and the disease course from infection to treatment. We provide an overview of multiple studies for the treatment of chronic hepatitis C infection that have included patients with cirrhosis. We also discuss the advantages and disadvantages of treatment in cirrhotic patients and focus on the most up to date guidelines available for treatment.
文摘A substantial proportion of individuals with chronic hepatitis C virus(HCV) are co-infected with human immunodeficiency virus(HIV). Co-infected individuals are traditionally considered as one of the "special populations" amongst those with chronic HCV, mainly because of faster progression to end-stage liver disease and suboptimal responses to treatment with pegylated interferon alpha and ribavirin, the benefits of which are often outweighed by toxicity. The advent of the newer direct acting antivirals(DAAs) has given hope that the majority of co-infected individuals can clear HCV. However the "special population" designation may prove an obstacle for those with co-infection to gain access to the new agents, in terms of requirement for separate pre-licensing clinical trials and extensive drug-drug interaction studies. We review the global epidemiology, natural history and pathogenesis of chronic hepatitis C in HIV co-infection. The accelerated course of chronic hepatitis C in HIV co-infection is not adequately offset by successful combination antiretroviral therapy. We also review the treatment trials of chronic hepatitis C in HIV co-infected individuals with DAAs and compare them to trials in the HCV mono-infected. There is convincing evidence that HIV co-infection no longer diminishes the response to treatment against HCV in the new era of DAA-based therapy. The management of HCV co-infection should therefore become a priority in the care of HIV infected individuals, along with public health efforts to prevent new HCV infections, focusing particularly on specific patient groups at risk, such as men who have sex with men and injecting drug users.
基金The Federal funds for the National Reference Centre for Hepatitis C,Herzer K has received grant support from Astellas,Biotest and Novartis and been a consultant/speaker for Abb Vie,Biotest,Bristol-Myers Squibb,Gilead Sciences,Janssen Pharmaceuticals,Novartis,and RocheGerken G has been a consultant/speaker for Abb Vie,Bristol-Myers Squibb,Gilead Sciences,Janssen Pharmaceuticals and Roche
文摘AIM: To characterize management of telaprevir(TVR)-based triple therapy of hepatitis C virus(HCV) reinfection after liver transplantation(LT).METHODS: We retrospectively analyzed safety and efficacy of telaprevir- based triple therapy in a single center cohort of 19 patients with HCV genotype(GT) 1 recurrence after LT, with respect to factors possibly predicting sustained viral response(SVR) or non-SVR. All patients were treated with TVR, pegylated(PEG) and ribavirine(RBV) for 12 wk followed by a dual phase with PEG/RBV for 12 wk in 7 patients and for 36 wk in 5 patients. RESULTS: In total 11/19(58%) of patients achieved a sustained response. All(11/11) SVR patients showed a rapid viral response at treatment weeks 4 and 11/14 rapid virological response(RVR) patients achieved SVR. Notably, all(7/7) patients who completed 48 wk of therapy and 80%(4/5) patients who completed 24 wk of therapy achieved SVR24. Treatment failure was significantly(P > 0.049) more frequent in GT1 a infection(5/7) compared to GT1b(3/12) infection and was associated with emergence of resistance-associated mutations in the NS3 protease domain. Bilirubin level at baseline is also related to SVR(P > 0.030). None of the patients had to discontinue treatment due to side effects. CONCLUSION: RVR, GT and bilirubin are clearly related to achievement of SVR. Providing a thorough patient selection and monitoring, a full course of TVR-based triple therapy in LT patients is feasible and achieves high SVR rates.
