AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these res...AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids.Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.展开更多
It has been emphasized that the assessment of residual liver function is of paramount importance to determine the following: severity of acute or chronic liver diseases independent of etiology; long-term prognosis; s...It has been emphasized that the assessment of residual liver function is of paramount importance to determine the following: severity of acute or chronic liver diseases independent of etiology; long-term prognosis; step-bystep disease progression; surgical risk; and efficacy of antiviral treatment. The most frequently used tools are the galactose elimination capacity to asses hepatocyte cytosol activity, plasma clearance of indocyanine green to assess excretory function, and antipyrine clearance to estimate microsomal activity. However, a widely accepted liver test (not necessarily a laboratory one) to assess quantitative functional hepatic reserve still needs to be established, although there have been various proposals. Furthermore, who are the operators that should order these tests? Advances in analytic methods are expected to allow quantitative liver function tests to be used in clinical practice.展开更多
Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated an...Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors(pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.展开更多
Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxi...Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function, its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.展开更多
AIM To evaluate the potential benefits and risks of the use of epidural anaesthesia within an enhanced recovery protocol in this specific subpopulation.METHODS A retrospective review was conducted, including all cirrh...AIM To evaluate the potential benefits and risks of the use of epidural anaesthesia within an enhanced recovery protocol in this specific subpopulation.METHODS A retrospective review was conducted, including all cirrhotic patients who underwent open liver resection between January 2013 and December 2015 at Bologna University Hospital. Patients with an abnormal coagulation profile contraindicating the placement of an epidural catheter were excluded from the analysis. The control group was composed by patients refusing epidural anaesthesia. RESULTS Of the 183 cirrhotic patients undergoing open liver resections, 57 had contraindications to the placement of an epidural catheter; of the remaining 126, 86 patients received general anaesthesia and 40 combined anaesthesia. The two groups presented homogeneous characteristics. Intraoperatively the metabolic data did not differ between the two groups, whilst the epidural group had a lower mean arterial pressure(P = 0.041) and received more colloid infusions(P = 0.007). Postoperative liver and kidney function did not differ significantly.Length of mechanical ventilation(P = 0.003) and hospital stay(P = 0.032) were significantly lower in the epidural group. No complications related to the epidural catheter placement or removal was recorded.CONCLUSION The use of Epidural Anaesthesia within a fast track protocol for cirrhotic patients undergoing liver resections had a positive impact on the patient's outcomes and comfort as demonstrated by a significantly lower length of mechanical ventilation and hospital stay in the epidural group. The technique appears to be safely manageable in this fragile population even though these results need confirmation in larger studies.展开更多
AIM: To evaluate the effects of combined treatment of glutamine (Gln) and recombinant human growth hormone(rhGH) on intestinal barrier function following portal hypertension surgery. METHODS: This study was desi...AIM: To evaluate the effects of combined treatment of glutamine (Gln) and recombinant human growth hormone(rhGH) on intestinal barrier function following portal hypertension surgery. METHODS: This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups: control group (n = 20) and supplemental group (adding Gin and rhGH, n = 22). Every patient received isocaloric and isonitrogenous standard total parenteral nutrition (TPN) starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein (CRP) levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively. RESULTS: On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group (33.7±5.5 vs 31.0 ± 5.4, P 〈 0.05, (1.17±0.32 vs 1.05 ± 0.15, P 〈 0.05, 13.94±1.09 vs 12.33±1.33, P 〈 0.05, and 368.12 ± 59.25 vs 318.12 ± 45.65, P 〈 0.05, respectively), whereas the increase in serum TNF-α concentration was significantly reduced (41.02 ± 27.56 vs 160.09 ± 35.17, P 〈 0.05). The increase in L/M ratio was significantly lower in the supplemental group than in the control group (0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P 〈 0.05). Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION: Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.展开更多
BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene...BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%) and (ii) hepatocellular carcinoma (HCC) 2 (28.6%), 5(71.4%) and 0 (0.0%) respectively revealed a marked association of C genotype with liver disease; however, the association was statistically insignificant (P >0.05). Differences in positive rate of HBeAg for the three genotypes B, 16(30.8%), C, 27(51.9%), and mixed B/C, 9(17.3%) were significant (P < 0. 05 ) , with genotype C showing predominance. CONCLUSIONS : These findings show an interesting distribution of HBV A-D genotypes in Zhejiang Province. Furthermore, our results indicate a novel and markedly high prevalence of mixed B/C genotype infections in subjects with severe CH and LC, and a possible association of mixed B/C infections with the severity of liver diseases in this region of China's Mainland.展开更多
More than five years ago,the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral(DAA)drugs.They proved highly efficient in curing patients with chronic...More than five years ago,the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral(DAA)drugs.They proved highly efficient in curing patients with chronic hepatitis C(CHC),including patients with cirrhosis.The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis,but the exact cause of the expected benefit was unclear.Further,little was known about how the underlying liver disease would be affected during and after viral clearance.In this review,we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects,such as macrophage activation,and the time-dependent effects of therapy,with specific emphasis on inflammation,structural liver changes,and liver function,as these factors are all related to morbidity and mortality in CHC patients.It seems clear that antiviral therapy,especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis.There seems to be a timedependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions.These improvements lead to favorable effects on liver function,followed by an improvement in cognitive dysfunction and portal hypertension.Overall,the data provide knowledge on the several beneficial effects of DAA therapy on liverrelated parameters in CHC patients suggesting short-and long-term improvements in the underlying disease with the promise of an improved longterm prognosis.展开更多
^13C-methacetin breath test was used for the evaluation of liver function, as for quantitative data could be achieved using this method, it had the characteristics of safety, quantification, and repetition and got rec...^13C-methacetin breath test was used for the evaluation of liver function, as for quantitative data could be achieved using this method, it had the characteristics of safety, quantification, and repetition and got recognition gradually through the world. We began this ^13C- methacetin test to assess liver function of patients with cirrhosis from January 2002. The aim of this study was to explore the characteristic of this test for liver function evaluation and explore the correlation of this method with some clinical liver biochemical parameters and Child-Pugh score.展开更多
BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define...BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a higher risk of splenomegaly associated with leukopenia and thrombocytopenia, although revealing milder liver dysfunction and portal hypertension symptoms, which recommends WD patients to be monitored for associated complications.展开更多
BACKGROUND As a country with a high burden of hepatitis B,China has about 86 million cases of hepatitis B virus infection,ranking the first in the world.Currently,there are about 390000 deaths due to hepatitis B-relat...BACKGROUND As a country with a high burden of hepatitis B,China has about 86 million cases of hepatitis B virus infection,ranking the first in the world.Currently,there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year.Consequently,how to control portal hypertension,improve liver functional reserve,and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention.Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt(TIPS),the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcoholinduced and immune cirrhosis,which may be related to the effective etiological treatment.AIM To investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China(2019)in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODS The clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively.According to different anti-viral drugs,the patients were divided into entecavir(ETV)(n=70),tenofovir alafenamide fumarate(TAF)(n=32),and tenofovir disoproxil fumarate(TDF)(n=35)groups.The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma,survival,and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTS At 24 mo after surgery,the Child-Pugh score in the TAF group(6.97±0.86)was lower than that in the TDF(7.49±0.82;t=-2.52,P=0.014)and ETV groups(7.64±1.17;t=-2.92,P=0.004).The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72±1.5,which was lower than that in the TDF(10.74±2.33;t=-2.09,P=0.040)and ETV groups(10.97±2.17;t=-2.93,P=0.004).At 24 mo after surgery,the estimated glomerular filtration rate(eGFR)in the TAF group(104.41±12.54)was higher than that in the TDF(93.54±8.97)and ETV groups(89.96±9.86)(F=21.57,P<0.001).CONCLUSION At 24 mo after surgery,compared with TDF and ETV,TAF has significant advantages in the improvement of liver functional reserve and eGFR.展开更多
Non-alcoholic fatty liver disease(NAFLD),is a disease spectrum characterized by fat accumulation in hepatocytes presenting as hepatic steatosis to advance disease with active hepatic inflammation,known as nonalcoholic...Non-alcoholic fatty liver disease(NAFLD),is a disease spectrum characterized by fat accumulation in hepatocytes presenting as hepatic steatosis to advance disease with active hepatic inflammation,known as nonalcoholic steatohepatitis.Chronic steatohepatitis will lead to progressive hepatic fibrosis causing cirrhosis and increased risk for developing hepatocellular carcinoma(HCC).Fatty liver disease prevalence has increased at alarming rates alongside obesity,diabetes and metabolic syndrome to become the second most common cause of cirrhosis after alcohol related liver disease worldwide.Given this rise in prevalence,it is becoming increasingly more important to find non-invasive methods to diagnose disease early and stage hepatic fibrosis.Providing clinicians with the tools to diagnose and treat the full spectrum of NAFLD will help prevent known complications such as cirrhosis and HCC and improve quality of life for the patients suffering from this disease.This article discusses the utility of current noninvasive liver function testing in the clinical progression of fatty liver disease along with the imaging modalities that are available.Additionally,we summarize available treatment options including targeted medical therapy through four different pathways,surgical or endoscopic intervention.展开更多
Background and aims:Due to the invasiveness of upper gastrointestinal endoscopy,non-invasive diagnostic tests for varices in liver cirrhosis have been widely established by numerous studies.A questionnaire survey,whic...Background and aims:Due to the invasiveness of upper gastrointestinal endoscopy,non-invasive diagnostic tests for varices in liver cirrhosis have been widely established by numerous studies.A questionnaire survey,which was aimed at understanding the current knowledge about non-invasive diagnostic tests for varices in liver cirrhosis,was distributed among the members of Gastroenterology Branch of the Liaoning Medical Association.Methods:A questionnaire assessing the knowledge about non-invasive diagnostic tests for varices was sent to 42 members who participated in the entire ninth committee.They were from 33 hospitals in 13 cities of Liaoning Province,China.Results:Overall,97.6%(41/42)of participants responded to the questionnaire.A majority of participants were chief physicians(85.4%),had>20 years of experience in clinical work of digestive diseases(80.5%)and worked at tertiary hospitals(97.6%).In 46.3%of participants’departments,there were>200 patients with liver cirrhosis and gastroesophageal varices admitted every year.In 90.2%of participants’departments,upper gastrointestinal endoscopy was regularly employed for the diagnosis of gastroesophageal varices.Only six(15%)participants often used non-invasive diagnostic tests for varices in clinical practice.Thirty(75%)participants knew at least one non-invasive diagnostic test for varices.The knowledge of at least one non-invasive diagnostic test was significantly associated with the number of cirrhotic patients with varices(P¼0.038)or the regular use of gastrointestinal endoscopy to diagnose varices(P¼0.022).Conclusions:This questionnaire survey suggested that non-invasive diagnostic tests for varices in liver cirrhosis were rarely or never used in clinical practices in Liaoning Province,China.Reliable,non-invasive indexes should be further explored in a well-designed multi-center observational study.展开更多
In the present study we observed dynamically and systemically the changes of plasma somatostatin and glucagon in the peripheral and portal vein, and the changes of pancreatic immunopathology in the course of developme...In the present study we observed dynamically and systemically the changes of plasma somatostatin and glucagon in the peripheral and portal vein, and the changes of pancreatic immunopathology in the course of development of cirrhosis induced by CCl<sub>4</sub> and after portacaval shunt (PCS) in the cirrhotic rats as well as investigated their causes and correlationship. The results showed that hyperglucagonemia was caused by spontaneous portosystemic shunting and surgically induced portacaval anastomosis. Moreover, there was much higher level of glucagon in the portal vein with corresponding increase of A cells in PCS rats than those in the controls, indicating that another cause for elevation of glucagon was hypersecretion of pancreatic A cells. Our data demonstrated that both deterioration of liver function and portosystemic shunting might not be responsible for the elevated level of somatostatin in the cirrhotic rats with PCS. However, there was a closed positive correlation between plasma glucagon and somatostatin. Thus it was concluded that hyperglucagonemia stimulated the release of somatostatin. In view of the fact the elevated level of glucagon was much higher than that of somatostatin, there was probably a relative lack of somatostatin in cirrhosis with portal hypertension.展开更多
Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce h...Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden.Breath is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease moni-toring.Having previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use.Methods:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from controls.Collection and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOCs)levels.Results:A set of 29 breath VOCs differed significantly between cirrhosis and controls.A classification model based on these VOCs had an area under the curve(AUC)of 0.95±0.04 in cross-validated test sets.The seven best performing VOCs were sufficient to maximize classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component analysis.Conclusions:A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.展开更多
文摘AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids.Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.
文摘It has been emphasized that the assessment of residual liver function is of paramount importance to determine the following: severity of acute or chronic liver diseases independent of etiology; long-term prognosis; step-bystep disease progression; surgical risk; and efficacy of antiviral treatment. The most frequently used tools are the galactose elimination capacity to asses hepatocyte cytosol activity, plasma clearance of indocyanine green to assess excretory function, and antipyrine clearance to estimate microsomal activity. However, a widely accepted liver test (not necessarily a laboratory one) to assess quantitative functional hepatic reserve still needs to be established, although there have been various proposals. Furthermore, who are the operators that should order these tests? Advances in analytic methods are expected to allow quantitative liver function tests to be used in clinical practice.
文摘Indocyanine green(ICG) kinetics(PDR/R15) used to quantitatively assess hepatic function in the perioperative period of major resective surgery and liver transplantation have been the object of an extensive, updated and critical review. New, non invasive bedside monitors(pulse dye densitometry technology) make this opportunity widely available in clinical practice. After having reviewed basic concepts of hepatic clearance, we analysed the most common indications ICG kinetic parameters have nowadays in clinical practice, focusing in particular on the diagnostic and prognostic role of PDR and R15 in the perioperative period of major liver surgery and liver transplantation. As recently pointed out, even if of extreme interest, ICG clearance parameters have still some limitations, to be considered when using these tests.
基金Supported by Fondo de Investigación Sanitaria,FIS 00/0232,02/0430, 05/1607the Instituto de Salud Carlos Ⅲ, C03/02,C03/08,G03/015the Generalitat de Catalunya,FI 05/00068
文摘Paraoxonase-1 (PON1) is an esterase and lactonase synthesized by the liver and found in the circulation associated with high-density lipoproteins. The physiological function of PON1 seems to be to degrade specific oxidized cholesteryl esters and oxidized phospholipids in lipoproteins and cell membranes. PON1 is, therefore, an antioxidant enzyme. Alterations in circulating PON1 levels have been reported in a variety of diseases involving oxidative stress including chronic liver diseases. Measurement of serum PON1 activity has been proposed as a potential test for the evaluation of liver function. However, this measurement is still restricted to research and has not been extensively applied in routine clinical chemistry laboratories. The reason for this restriction is due to the problem that the substrate commonly used for PON1 measurement, paraoxon, is toxic and unstable. The recent development of new assays with non-toxic substrates makes this proposal closer to a practical development. The present editorial summarizes PON1 biochemistry and function, its involvement with chronic liver impairment, and some aspects related to the measurement of PON1 activity in circulation.
文摘AIM To evaluate the potential benefits and risks of the use of epidural anaesthesia within an enhanced recovery protocol in this specific subpopulation.METHODS A retrospective review was conducted, including all cirrhotic patients who underwent open liver resection between January 2013 and December 2015 at Bologna University Hospital. Patients with an abnormal coagulation profile contraindicating the placement of an epidural catheter were excluded from the analysis. The control group was composed by patients refusing epidural anaesthesia. RESULTS Of the 183 cirrhotic patients undergoing open liver resections, 57 had contraindications to the placement of an epidural catheter; of the remaining 126, 86 patients received general anaesthesia and 40 combined anaesthesia. The two groups presented homogeneous characteristics. Intraoperatively the metabolic data did not differ between the two groups, whilst the epidural group had a lower mean arterial pressure(P = 0.041) and received more colloid infusions(P = 0.007). Postoperative liver and kidney function did not differ significantly.Length of mechanical ventilation(P = 0.003) and hospital stay(P = 0.032) were significantly lower in the epidural group. No complications related to the epidural catheter placement or removal was recorded.CONCLUSION The use of Epidural Anaesthesia within a fast track protocol for cirrhotic patients undergoing liver resections had a positive impact on the patient's outcomes and comfort as demonstrated by a significantly lower length of mechanical ventilation and hospital stay in the epidural group. The technique appears to be safely manageable in this fragile population even though these results need confirmation in larger studies.
文摘AIM: To evaluate the effects of combined treatment of glutamine (Gln) and recombinant human growth hormone(rhGH) on intestinal barrier function following portal hypertension surgery. METHODS: This study was designed as a prospective, randomized and controlled clinical trial. Forty two patients after portal hypertension surgery were randomly assigned into 2 groups: control group (n = 20) and supplemental group (adding Gin and rhGH, n = 22). Every patient received isocaloric and isonitrogenous standard total parenteral nutrition (TPN) starting 3 d after surgery for 7 d. Blood samples were obtained before surgery and at the 3rd and 10th day postoperatively. Host immunity was evaluated by measuring levels of CD4, CD8, CD4/CD8, IgG, IgM and IgA, and the inflammatory responses were determined by assessing IL-2, TNF-α and C-reactive protein (CRP) levels. Intestinal permeability and integrity was evaluated by L/M test and histological examination, respectively. RESULTS: On postoperative d 10, CD4, CD4/CD8, IgG and IL-2 levels in supplemental group were significantly higher than those in control group (33.7±5.5 vs 31.0 ± 5.4, P 〈 0.05, (1.17±0.32 vs 1.05 ± 0.15, P 〈 0.05, 13.94±1.09 vs 12.33±1.33, P 〈 0.05, and 368.12 ± 59.25 vs 318.12 ± 45.65, P 〈 0.05, respectively), whereas the increase in serum TNF-α concentration was significantly reduced (41.02 ± 27.56 vs 160.09 ± 35.17, P 〈 0.05). The increase in L/M ratio was significantly lower in the supplemental group than in the control group (0.0166 ± 0.0017 vs 0.0339 ± 0.0028, P 〈 0.05). Moreover, mucosal integrity in the supplemental group was better than in the control group.CONCLUSION: Postoperative administration of TPN supplemented with Gin and rhGH in patients after portal hypertension surgery improves immune function, modulates inflammatory response, prevents the intestinal mucous membrane from atrophy and preserves intestinal integrity.
文摘BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%) and (ii) hepatocellular carcinoma (HCC) 2 (28.6%), 5(71.4%) and 0 (0.0%) respectively revealed a marked association of C genotype with liver disease; however, the association was statistically insignificant (P >0.05). Differences in positive rate of HBeAg for the three genotypes B, 16(30.8%), C, 27(51.9%), and mixed B/C, 9(17.3%) were significant (P < 0. 05 ) , with genotype C showing predominance. CONCLUSIONS : These findings show an interesting distribution of HBV A-D genotypes in Zhejiang Province. Furthermore, our results indicate a novel and markedly high prevalence of mixed B/C genotype infections in subjects with severe CH and LC, and a possible association of mixed B/C infections with the severity of liver diseases in this region of China's Mainland.
文摘More than five years ago,the treatment of hepatitis C virus infection was revolutionized with the introduction of all-oral direct-acting antiviral(DAA)drugs.They proved highly efficient in curing patients with chronic hepatitis C(CHC),including patients with cirrhosis.The new DAA treatments were alleged to induce significant improvements in clinical outcome and prognosis,but the exact cause of the expected benefit was unclear.Further,little was known about how the underlying liver disease would be affected during and after viral clearance.In this review,we describe and discuss the liver-related effects of the new treatments in regards to both pathophysiological aspects,such as macrophage activation,and the time-dependent effects of therapy,with specific emphasis on inflammation,structural liver changes,and liver function,as these factors are all related to morbidity and mortality in CHC patients.It seems clear that antiviral therapy,especially the achievement of a sustained virologic response has several beneficial effects on liver-related parameters in CHC patients with advanced liver fibrosis or cirrhosis.There seems to be a timedependent effect of DAA therapy with viral clearance and the resolution of liver inflammation followed by more discrete changes in structural liver lesions.These improvements lead to favorable effects on liver function,followed by an improvement in cognitive dysfunction and portal hypertension.Overall,the data provide knowledge on the several beneficial effects of DAA therapy on liverrelated parameters in CHC patients suggesting short-and long-term improvements in the underlying disease with the promise of an improved longterm prognosis.
文摘^13C-methacetin breath test was used for the evaluation of liver function, as for quantitative data could be achieved using this method, it had the characteristics of safety, quantification, and repetition and got recognition gradually through the world. We began this ^13C- methacetin test to assess liver function of patients with cirrhosis from January 2002. The aim of this study was to explore the characteristic of this test for liver function evaluation and explore the correlation of this method with some clinical liver biochemical parameters and Child-Pugh score.
基金Supported by the Science and Technology Planning Project of Guangdong Province,No.2015A030302085 and No.2016A020212022
文摘BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a higher risk of splenomegaly associated with leukopenia and thrombocytopenia, although revealing milder liver dysfunction and portal hypertension symptoms, which recommends WD patients to be monitored for associated complications.
文摘BACKGROUND As a country with a high burden of hepatitis B,China has about 86 million cases of hepatitis B virus infection,ranking the first in the world.Currently,there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year.Consequently,how to control portal hypertension,improve liver functional reserve,and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention.Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt(TIPS),the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcoholinduced and immune cirrhosis,which may be related to the effective etiological treatment.AIM To investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China(2019)in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODS The clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively.According to different anti-viral drugs,the patients were divided into entecavir(ETV)(n=70),tenofovir alafenamide fumarate(TAF)(n=32),and tenofovir disoproxil fumarate(TDF)(n=35)groups.The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma,survival,and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTS At 24 mo after surgery,the Child-Pugh score in the TAF group(6.97±0.86)was lower than that in the TDF(7.49±0.82;t=-2.52,P=0.014)and ETV groups(7.64±1.17;t=-2.92,P=0.004).The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72±1.5,which was lower than that in the TDF(10.74±2.33;t=-2.09,P=0.040)and ETV groups(10.97±2.17;t=-2.93,P=0.004).At 24 mo after surgery,the estimated glomerular filtration rate(eGFR)in the TAF group(104.41±12.54)was higher than that in the TDF(93.54±8.97)and ETV groups(89.96±9.86)(F=21.57,P<0.001).CONCLUSION At 24 mo after surgery,compared with TDF and ETV,TAF has significant advantages in the improvement of liver functional reserve and eGFR.
文摘Non-alcoholic fatty liver disease(NAFLD),is a disease spectrum characterized by fat accumulation in hepatocytes presenting as hepatic steatosis to advance disease with active hepatic inflammation,known as nonalcoholic steatohepatitis.Chronic steatohepatitis will lead to progressive hepatic fibrosis causing cirrhosis and increased risk for developing hepatocellular carcinoma(HCC).Fatty liver disease prevalence has increased at alarming rates alongside obesity,diabetes and metabolic syndrome to become the second most common cause of cirrhosis after alcohol related liver disease worldwide.Given this rise in prevalence,it is becoming increasingly more important to find non-invasive methods to diagnose disease early and stage hepatic fibrosis.Providing clinicians with the tools to diagnose and treat the full spectrum of NAFLD will help prevent known complications such as cirrhosis and HCC and improve quality of life for the patients suffering from this disease.This article discusses the utility of current noninvasive liver function testing in the clinical progression of fatty liver disease along with the imaging modalities that are available.Additionally,we summarize available treatment options including targeted medical therapy through four different pathways,surgical or endoscopic intervention.
文摘Background and aims:Due to the invasiveness of upper gastrointestinal endoscopy,non-invasive diagnostic tests for varices in liver cirrhosis have been widely established by numerous studies.A questionnaire survey,which was aimed at understanding the current knowledge about non-invasive diagnostic tests for varices in liver cirrhosis,was distributed among the members of Gastroenterology Branch of the Liaoning Medical Association.Methods:A questionnaire assessing the knowledge about non-invasive diagnostic tests for varices was sent to 42 members who participated in the entire ninth committee.They were from 33 hospitals in 13 cities of Liaoning Province,China.Results:Overall,97.6%(41/42)of participants responded to the questionnaire.A majority of participants were chief physicians(85.4%),had>20 years of experience in clinical work of digestive diseases(80.5%)and worked at tertiary hospitals(97.6%).In 46.3%of participants’departments,there were>200 patients with liver cirrhosis and gastroesophageal varices admitted every year.In 90.2%of participants’departments,upper gastrointestinal endoscopy was regularly employed for the diagnosis of gastroesophageal varices.Only six(15%)participants often used non-invasive diagnostic tests for varices in clinical practice.Thirty(75%)participants knew at least one non-invasive diagnostic test for varices.The knowledge of at least one non-invasive diagnostic test was significantly associated with the number of cirrhotic patients with varices(P¼0.038)or the regular use of gastrointestinal endoscopy to diagnose varices(P¼0.022).Conclusions:This questionnaire survey suggested that non-invasive diagnostic tests for varices in liver cirrhosis were rarely or never used in clinical practices in Liaoning Province,China.Reliable,non-invasive indexes should be further explored in a well-designed multi-center observational study.
文摘In the present study we observed dynamically and systemically the changes of plasma somatostatin and glucagon in the peripheral and portal vein, and the changes of pancreatic immunopathology in the course of development of cirrhosis induced by CCl<sub>4</sub> and after portacaval shunt (PCS) in the cirrhotic rats as well as investigated their causes and correlationship. The results showed that hyperglucagonemia was caused by spontaneous portosystemic shunting and surgically induced portacaval anastomosis. Moreover, there was much higher level of glucagon in the portal vein with corresponding increase of A cells in PCS rats than those in the controls, indicating that another cause for elevation of glucagon was hypersecretion of pancreatic A cells. Our data demonstrated that both deterioration of liver function and portosystemic shunting might not be responsible for the elevated level of somatostatin in the cirrhotic rats with PCS. However, there was a closed positive correlation between plasma glucagon and somatostatin. Thus it was concluded that hyperglucagonemia stimulated the release of somatostatin. In view of the fact the elevated level of glucagon was much higher than that of somatostatin, there was probably a relative lack of somatostatin in cirrhosis with portal hypertension.
基金funding from the Cancer Re-search UK for the CRUK Cambridge Centre Early Detection Program and International Alliance for Cancer Early Detection(CRUK grant refs:A25117 and RG97677)the NIHR Cambridge Biomedical Research Centre(BRC-1215-20014)。
文摘Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare burden.Breath is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease moni-toring.Having previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical use.Methods:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from controls.Collection and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(GC-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOCs)levels.Results:A set of 29 breath VOCs differed significantly between cirrhosis and controls.A classification model based on these VOCs had an area under the curve(AUC)of 0.95±0.04 in cross-validated test sets.The seven best performing VOCs were sufficient to maximize classifica-tion performance.A subset of 11 VOCs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component analysis.Conclusions:A set of seven VOCs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.