AIM： To investigate the usefulness of transient elastography by Fibroscan （FS）, a rapid non-invasive technique to evaluate liver fibrosis, in the management of chronic hepatitis B virus （HBV） carriers. METHODS： ...AIM： To investigate the usefulness of transient elastography by Fibroscan （FS）, a rapid non-invasive technique to evaluate liver fibrosis, in the management of chronic hepatitis B virus （HBV） carriers. METHODS： In 297 consecutive HBV carriers, we studied the correlation between liver stiffness （LS）, stage of liver disease and other factors potentially influencing FS measurements. In 87 chronic hepatitis B （CriB） patients, we monitored the FS variations according to the spontaneous or treatment-induced variations of biochemical activity during follow-up. RESULTS： FS values were 12.3 ± 3.3 kPa in acute hepatitis, 10.3 ± 8.8 kPa in chronic hepatitis, 4.3 ± 1.0 kPa in inactive carriers and 4.6 ± 1.2 kPa in blood donors. We identified the cut-offs of 7.5 and 11.8 kPa for the diagnosis of fibrosis ≥S3 and cirrhosis respectively, showing 93.9% and 86.5% sensitivity, 88.5% and 96.3% specificity, 76.7% and 86.7% positive predictive value （PPV）, 97.3% and 96.3% negative predictive value （NPV） and 90.1% and 94.2% diagnostic accuracy. At multivariate analysis in 171 untreated carriers, fibrosis stage （t = 13.187,P 〈 0.001）, active vs inactive HBV infection （t = 6.437, P 〈 0.001）, alanine aminotransferase （ALT） （t = 4.740, P 〈 0.001） and HBV-DNA levels （t = -2.046, P = 0.042） were independently associated with FS. Necroinflammation score （t = 2.158, 〉 10/18 vs ≤ 10/18, P = 0.035） and ALT levels （t = 3.566, P =0.001） were independently associated with LS in 83 untreated patients without cirrhosis and long-term biochemical remission （t = 4.662, P 〈 0.001） in 80 treated patients. During FS monitoring （mean followup 19.9 ± 7.1 mo） FS values paralleled those of ALT in patients with hepatitis exacerbation （with 1.2 to 4.4-fold increases in Crib patients） and showed a progressive decrease during antiviral therapy. CONCLUSION： FS is a non-invasive tool to monitor liver disease in chronic HBV carriers, provided that the pattern of biochemical activity is taken into account. In the inactive carrier, it identifies non-HBV-related causes of liver damage and transient reactivations. In CHB patients, it may warrant a more appropriate timing of control liver biopsies.展开更多
Metabolic associated fatty liver disease(MAFLD),formerly named“nonalcoholic fatty liver disease”occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity a...Metabolic associated fatty liver disease(MAFLD),formerly named“nonalcoholic fatty liver disease”occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death,such as cardio-vascular,digestive,metabolic,neoplastic and neuro-degenerative diseases.However,progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation,which acts as disease accelerator.Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver,where insulin resistance has been assumed to play an important role.Special emphasis has been given to digital imaging studies and in particular to positron emission tomography,as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism.An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver,dysregulated endogenous glucose production and insulin resistance.展开更多
AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional co...AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.展开更多
Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma(HCC),includi...Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma(HCC),including those with cirrhosis,advanced fibrosis and special subgroups of chronic hepatitis B(CHB).Application of the standard surveillance strategy to all patients with chronic liver disease(CLD)with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems.Thus,a number of HCC risk scores were constructed,mainly from Asian cohorts,to stratify the HCC prediction in patients with CHB.Similarly,even if less than for CHB,a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies.Recently,a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters.Overall,the HCC risk stratification appears at hand by several validated multiple score systems,but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic,epidemiologic,etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice.A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics,epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future,with the possibility to achieve a real and cost/effective personalization of surveillance.展开更多
The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe...The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the f irst 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.展开更多
基金Educational grants from the Italian Ministry of Health,"ERASMO" 2005
文摘AIM： To investigate the usefulness of transient elastography by Fibroscan （FS）, a rapid non-invasive technique to evaluate liver fibrosis, in the management of chronic hepatitis B virus （HBV） carriers. METHODS： In 297 consecutive HBV carriers, we studied the correlation between liver stiffness （LS）, stage of liver disease and other factors potentially influencing FS measurements. In 87 chronic hepatitis B （CriB） patients, we monitored the FS variations according to the spontaneous or treatment-induced variations of biochemical activity during follow-up. RESULTS： FS values were 12.3 ± 3.3 kPa in acute hepatitis, 10.3 ± 8.8 kPa in chronic hepatitis, 4.3 ± 1.0 kPa in inactive carriers and 4.6 ± 1.2 kPa in blood donors. We identified the cut-offs of 7.5 and 11.8 kPa for the diagnosis of fibrosis ≥S3 and cirrhosis respectively, showing 93.9% and 86.5% sensitivity, 88.5% and 96.3% specificity, 76.7% and 86.7% positive predictive value （PPV）, 97.3% and 96.3% negative predictive value （NPV） and 90.1% and 94.2% diagnostic accuracy. At multivariate analysis in 171 untreated carriers, fibrosis stage （t = 13.187,P 〈 0.001）, active vs inactive HBV infection （t = 6.437, P 〈 0.001）, alanine aminotransferase （ALT） （t = 4.740, P 〈 0.001） and HBV-DNA levels （t = -2.046, P = 0.042） were independently associated with FS. Necroinflammation score （t = 2.158, 〉 10/18 vs ≤ 10/18, P = 0.035） and ALT levels （t = 3.566, P =0.001） were independently associated with LS in 83 untreated patients without cirrhosis and long-term biochemical remission （t = 4.662, P 〈 0.001） in 80 treated patients. During FS monitoring （mean followup 19.9 ± 7.1 mo） FS values paralleled those of ALT in patients with hepatitis exacerbation （with 1.2 to 4.4-fold increases in Crib patients） and showed a progressive decrease during antiviral therapy. CONCLUSION： FS is a non-invasive tool to monitor liver disease in chronic HBV carriers, provided that the pattern of biochemical activity is taken into account. In the inactive carrier, it identifies non-HBV-related causes of liver damage and transient reactivations. In CHB patients, it may warrant a more appropriate timing of control liver biopsies.
文摘Metabolic associated fatty liver disease(MAFLD),formerly named“nonalcoholic fatty liver disease”occurs in about one-third of the general population of developed countries worldwide and behaves as a major morbidity and mortality risk factor for major causes of death,such as cardio-vascular,digestive,metabolic,neoplastic and neuro-degenerative diseases.However,progression of MAFLD and its associated systemic complications occur almost invariably in patients who experience the additional burden of intrahepatic and/or systemic inflammation,which acts as disease accelerator.Our review is focused on the new knowledge about the brain-gut-liver axis in the context of metabolic dysregulations associated with fatty liver,where insulin resistance has been assumed to play an important role.Special emphasis has been given to digital imaging studies and in particular to positron emission tomography,as it represents a unique opportunity for the noninvasive in vivo study of tissue metabolism.An exhaustive revision of targeted animal models is also provided in order to clarify what the available preclinical evidence suggests for the causal interactions between fatty liver,dysregulated endogenous glucose production and insulin resistance.
文摘AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.
文摘Surveillance with abdominal ultrasound with or without alpha-fetoprotein is recommended by clinical practice guidelines for patients who are considered to be at risk of developing hepatocellular carcinoma(HCC),including those with cirrhosis,advanced fibrosis and special subgroups of chronic hepatitis B(CHB).Application of the standard surveillance strategy to all patients with chronic liver disease(CLD)with or without cirrhosis imposes major sustainability and economic burdens on healthcare systems.Thus,a number of HCC risk scores were constructed,mainly from Asian cohorts,to stratify the HCC prediction in patients with CHB.Similarly,even if less than for CHB,a few scoring systems were developed for chronic hepatitis C patients or cirrhotic patients with CLD of different etiologies.Recently,a few newsworthy HCC-risk algorithms were developed for patients with cirrhosis using the combination of serologic HCC markers and clinical parameters.Overall,the HCC risk stratification appears at hand by several validated multiple score systems,but their optimal performance is obtained only in populations who show highly homogenous clinic-pathologic,epidemiologic,etiologic and therapeutic characteristics and this limitation poses a major drawback to their sustainable use in clinical practice.A better understanding of the dynamic process driving the progression from CLD to HCC derived from studies based on molecular approaches and genetics,epigenetics and liquid biopsy will enable the identification of new biomarkers to define the individual risk of HCC in the near future,with the possibility to achieve a real and cost/effective personalization of surveillance.
文摘The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the f irst 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.
