Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhos...Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.展开更多
Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained incre...Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of medicine.After the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical application.Specific VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing scores.Preliminary results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver disease.However,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained results.Given the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.展开更多
Hepatocellular carcinoma(HCC)is the most frequent liver neoplasm,and its incidence rates are constantly increasing.Despite the availability of potentially curative treatments(liver transplantation,surgical resection,t...Hepatocellular carcinoma(HCC)is the most frequent liver neoplasm,and its incidence rates are constantly increasing.Despite the availability of potentially curative treatments(liver transplantation,surgical resection,thermal ablation),long-term outcomes are affected by a high recurrence rate(up to 70%of cases 5 years after treatment).HCC recurrence within 2 years of treatment is defined as“early”and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden.A recurrence that occurs after 2 years of treatment is defined as“late”and is related to de novo HCC,independent of the primary neoplasm.Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence.Different pathogenesis corresponds to different predictors of the risk of early or late recurrence.An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance.Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens.This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.展开更多
The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine.Nowadays several researches demonstrated an important role of biliary epithelia(i.e.cholangiocy...The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine.Nowadays several researches demonstrated an important role of biliary epithelia(i.e.cholangiocytes)in bile formation.The study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases,such as primary biliary cholangitis or primary sclerosing cholangitis.Bile acids(BAs),produced by the liver,are the most represented organic molecules in bile.The physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling molecules.In this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary(deriving by bacterial manipulation of primary molecules)ones.This class of BAs is demonstrated to have relevant biological effects,ranging from toxic to therapeutic ones.In this family ursodeoxycholic and lithocholic acid present the most interesting features.The molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic damage.These findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders.展开更多
Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease that is observed more frequently in middle-aged women.This disorder is considered an autoimmune disease,since liver injury is sustained by the pre...Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease that is observed more frequently in middle-aged women.This disorder is considered an autoimmune disease,since liver injury is sustained by the presence of selfdirected antimitochondrial antibodies targeting the bile duct cells.The prognosis may vary depending on an early diagnosis and response to therapy.However,nearly a third of patients can progress to liver cirrhosis,thus requiring a liver transplant.Traditional immunosuppressive therapies,commonly employed for other autoimmune diseases,have limited effects on PBC.In fact,dramatic functional changes that occur in the biliary epithelium in the course of inflammation play a major role in perpetuating the injury.In this minireview,after a background on the disease and possible predisposing factors,the sequential cooperation of cellular/molecular events leading to end-stage PBC is discussed in detail.The rise and maintenance of the autoimmune process,as well as the response of the biliary epithelia during inflammatory injury,are key factors in the progression of the disease.The so-called“ductular reaction(DR)”,intended as a reactive expansion of cells with biliary phenotype,is a process frequently observed in PBC and partially understood.However,recent findings suggest a strict relationship between this pathological picture and the progression to liver fibrosis,cell senescence,and loss of biliary ducts.All these issues(onset of chronic inflammation,changes in secretive and proliferative biliary functions,DR,and its relationship with other pathological events)are discussed in this manuscript in an attempt to provide a snapshot,for clinicians and researchers,of the most relevant and sequential contributors to the progression of this human cholestatic disease.We believe that interpreting this disorder as a multistep process may help identify possible therapeutic targets to prevent evolution to severe disease.展开更多
Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,it has represented a dramatic global public health concern.Though affectin...Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,it has represented a dramatic global public health concern.Though affecting mainly the respiratory system,SARS-CoV-2 disease,defined as coronavirus disease 2019(COVID-19),may have a systemic involvement leading to multiple organ dysfunction.Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2.On the other side,patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19.In particular,patients with liver cirrhosis appear extremely vulnerable to infection.Moreover,the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes.This review analyzes the impact of the disease stage and the related causes on morbidity and mortality,clinical outcomes during SARS-CoV-2 infection,as well as the efficacy of vaccination in patients with chronic liver disease.展开更多
BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis(UC).However,the knowledge of histology guidelines and the attitudes towards their use in clini...BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis(UC).However,the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown.AIM To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists.METHODS A prospective,cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted.The survey consisted of 34 questions to assess gastroenterologists’and pathologists’knowledge(score out of 19)and attitudes towards histological assessment in UC.Survey questions were formulated using the European Crohn’s and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines.It included knowledge of histological assessment of disease activity and dysplasia,knowledge of histological scoring systems for ulcerative colitis,uptake of histology scoring systems in routine practice,attitudes towards the role of histological activity,and the use of histological activity in clinical scenarios.RESULTS Of 89 responders(77 gastroenterologists,12 pathologists),there was almost universal acceptance that histological assessment should form part of UC evaluation[95%gastroenterologists,92%pathologists].However,gastroenterologists reported that 92%of their pathologists do not use a histological scoring system.Utilisation of a formal histological scoring system was preferred by 77%of gastroenterologists and 58%of pathologists.Both groups lacked awareness of the Geboes Score,Nancy Index and Robarts Histopathological Index scoring systems with 91%,87%,and 92%of gastroenterologists respectively;and 83%,83%,and 92%pathologists respectively,being uncertain of scoring systems’remission definitions.Histology knowledge score was not significantly different between gastroenterologists and pathologists[9/19(IQR:8-11)vs 8/19(IQR:7-10),P=0.54].Higher knowledge scores were predicted by hospital attending gastroenterologists(P=0.004),participation in inflammatory bowel disease(IBD)multidisciplinary teams(P=0.009),and self-declared IBD sub-specialist(P=0.03).CONCLUSION Histological remission is a recognised target for both gastroenterologists and pathologists.Despite this,knowledge of histological scoring systems and their utilisation is poor.展开更多
Patients with cirrhosis have an increased risk of infection and differently from other complications,that over the years are improving in their outcomes,infections in cirrhotic patients are still a major cause of hosp...Patients with cirrhosis have an increased risk of infection and differently from other complications,that over the years are improving in their outcomes,infections in cirrhotic patients are still a major cause of hospitalization and death(up to 50%in-hospital mortality).Infections by multidrug-resistant organisms(MDRO)have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact.About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years.MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution.An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects,such as the type of infection(spontaneous bacterial peritonitis,pneumonia,urinary tract infection and spontaneous bacteremia),bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition(community acquired,healthcare associated or nosocomial).Furthermore,regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology.Antibiotic treatment is the most effective measure to treat infections caused by MDRO.Therefore,optimizing antibiotic prescribing is critical to effectively treat these infections.Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality.On the other hand,the supply of new agents to treat these infections is very limited.Thus,specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.展开更多
Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or co...Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or complicated biliary cysts,atypical hemangiomas,hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography(CT) and magnetic resonance imaging(MRI) are often not diagnostic and in these cases fine needle aspiration(FNA) is used to confirm the presence of atypical biliary cells. FNA,however,lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma,it is important to exclude liver metastasis,of which colonic cancer is the most common primary site. Multiple biliary hamartomas(von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic,but occasionally a percutaneous biopsy may be required.展开更多
Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgical treat...Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgical treatment alternative,thanks to their minimal invasiveness,excellent tolerability and safety profile,proven efficacy in local disease control,virtually unlimited repeatability and cost-effectiveness.Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules.Among them,radiofrequency(RF) currents are the most used,while microwave ablations(MWA) are becoming increasingly popular.Starting from the 90s',RF ablation(RFA) rapidly became the standard of care in ablation,especially in the treatment of small HCC nodules;however,RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks.MWA,first introduced in the Far Eastern clinical practice in the 80s',showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors,resulting in a poor coagulative performance and a relatively high complication rate,nowadays shows better results both in terms of treatment controllability and of overall coagulative performance,thanks to the improvement of technology.In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems,and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications,both in absolute terms and in comparison with RFA.展开更多
Hepatocellular carcinoma(HCC), chronic hepatitis B(CHB) and chronic hepatitis C(CHC) are characterized by exhaustion of the specific CD8^+ T cell response. This process involves enhancement of negative costimulatory m...Hepatocellular carcinoma(HCC), chronic hepatitis B(CHB) and chronic hepatitis C(CHC) are characterized by exhaustion of the specific CD8^+ T cell response. This process involves enhancement of negative costimulatory molecules, such as programmed cell death protein-1(PD-1), cytotoxic T-lymphocyte antigen-4(CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8^+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4(tremelimumab and ipilimumab) and PD-1(nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.展开更多
Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increa...Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.展开更多
Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the...Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.展开更多
About 130-170 million people, is estimated to be infected with the hepatitis C virus(HCV). Chronic HCV infection is one of the leading causes of liverrelated death and in many countries it is the primaryreason for hav...About 130-170 million people, is estimated to be infected with the hepatitis C virus(HCV). Chronic HCV infection is one of the leading causes of liverrelated death and in many countries it is the primaryreason for having a liver transplant. The main aim of antiviral treatment is to eradicate the virus. Until a few years ago the only treatment strategy was based on the combination of pegylated interferon and ribavirin(PEG/RBV). However, in genotypes 1 and 4 the rates of viral response did not surpass 50%, reaching up to 80% in the rest. In 2011 approval was given for the first direct acting antiviral agents(DAA), boceprevir and telaprevir, for treatment of genotype 1, in combination with traditional dual therapy. This strategy managed to increase the rates of sustained viral response(SVR) in both naive patients and in retreated patients, but with greater toxicity, interactions and cost, as well as being less safe in patients with advanced disease, in whom this treatment can trigger decompensation or even death. The recent, accelerated incorporation since 2013 of new more effective DAA, with pan-genomic properties and excellent tolerance, besides increasing the rates of SVR(even up to 100%), has also created a new scenario: shorter therapies, less toxicity and regimens free of PEG/RBV. This has enabled their almost generalised applicability in all patients. However, it should be noted that most of the scientific evidence available is based on expert opinion, case-control series, cohort studies and phase 2 and 3 trials, some with a reduced number of patients and select groups. Few data are currently available about the use of these drugs in daily clinical practice, particularly in relation to the appearance of side effects and interactions with other drugs, or their use in special populations or persons with the less common genotypes. This situation suggests the need for the generalised implementation of registries of patients receiving antiviral therapy. The main inconvenience of these new drugs is their high cost. This necessitates selection and prioritization of candidate patients to receive them, via strategies established by the various national organs, in accordance with the recommendations of scientific societies.展开更多
Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver dis...Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist's clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac展开更多
AIM:To investigate the prevalence of the clinical parameters of insulin resistance and diabetes in patients affected by chronic hepatitis C(CHC) or chronic hepatitis B(CHB) . METHODS:We retrospectively evaluated 852 c...AIM:To investigate the prevalence of the clinical parameters of insulin resistance and diabetes in patients affected by chronic hepatitis C(CHC) or chronic hepatitis B(CHB) . METHODS:We retrospectively evaluated 852 consecutive patients(726 CHC and 126 CHB) who had undergone liver biopsy.We recorded age,sex,ALT,type 2 diabetes and/or metabolic syndrome(MS) ,body mass index(BMI) ,and apparent disease duration(ADD) . RESULTS:Age,ADD,BMI,prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC.However,the degree of steatosis and liver fibrosis evaluated in liver biopsies did not differ between CHC and CHB patients.At multivariate analysis,age,sex,BMI,ALT and diabetes were independent risk factors for liver fibrosis in CHC,whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis(>30%) and age,sex,BMI,diabetes,MS and liver fibrosis.Diabetes,BMI and liver fibrosis were associated with steatosis>30%in CHC,whereas only age and BMI were related to steatosis in CHB. CONCLUSION:These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.展开更多
Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic...Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.展开更多
AIM To analyse cumulative loss of heterozygosity (LOH) of chromosomal regions and tumor suppressor genes in hepatocellular carcinomas (HCCs) from 20 southern African blacks. METHODS p53, RB1, BRCA1, BRCA2, WT1 and E c...AIM To analyse cumulative loss of heterozygosity (LOH) of chromosomal regions and tumor suppressor genes in hepatocellular carcinomas (HCCs) from 20 southern African blacks. METHODS p53, RB1, BRCA1, BRCA2, WT1 and E cadherin genes were analysed for LOH, and p53 gene was also analysed for the codon 249 mutation, in tumor and adjacent non tumorous liver tissues using molecular techniques and 10 polymorphic microsatellite markers. RESULTS p53 codon 249 mutation was found in 25% of the subjects, as was expected, because many patients were from Mozambique, a country with high aflatoxin B 1 exposure. LOH was found at the RB1, BRCA2 and WT1 loci in 20%(4/*!20) of the HCCs, supporting a possible role of these genes in HCC. No LOH was evident in any of the remaining genes. Reports of mutations of p53 and RB1 genes in combination, described in other populations, were not confirmed in this study. Change in microsatellite repeat number was noted at 9/*!10 microsatellite loci in different HCCs, and changes at two or more loci were detected in 15%(3/*!20) of subjects. CONCLUSION We propose that microsatellite/genomic instability may play a role in the pathogenesis of a subset of HCCs in black Africans.展开更多
Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunom...Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.展开更多
Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the ini...Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound(US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography(CT) and contrast-enhanced magnetic resonance(MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography(PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound(CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement(wash in- wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is avery reliable technique with a high intrinsic sensitivity for portal vein patency assessment. More expensive and sophisticated techniques(i.e., CT, MRI, PET, and PET-CT) should only be indicated in undetermined cases at CEUS.展开更多
文摘Approximately 12-72 million people worldwide are co-infected with hepatitis B virus(HBV)and hepatitis delta virus(HDV).This concurrent infection can lead to several severe outcomes with hepatic disease,such as cirrhosis,fulminant hepatitis,and hepatocellular carcinoma,being the most common.Over the past few decades,a correlation between viral hepatitis and autoimmune diseases has been reported.Furthermore,autoantibodies have been detected in the serum of patients co-infected with HBV/HDV,and autoimmune features have been reported.However,to date,very few cases of clinically significant autoimmune hepatitis(AIH)have been reported in patients with HDV infection,mainly in those who have received treatment with pegylated interferon.Interestingly,there are some patients with HBV infection and AIH in whom HDV infection is unearthed after receiving treatment with immunosuppressants.Consequently,several questions remain unanswered with the challenge to distinguish whether it is autoimmune or“autoimmune-like”hepatitis being the most crucial.Second,it remains uncertain whether autoimmunity is induced by HBV or delta virus.Finally,we investigated whether the cause of AIH lies in the previous treatment of HDV with pegylated interferon.These pressing issues should be elucidated to clarify whether new antiviral treatments for HDV,such as Bulevirtide or immu-nosuppressive drugs,are more appropriate for the management of patients with HDV and AIH.
文摘Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of medicine.After the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical application.Specific VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing scores.Preliminary results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver disease.However,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained results.Given the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.
文摘Hepatocellular carcinoma(HCC)is the most frequent liver neoplasm,and its incidence rates are constantly increasing.Despite the availability of potentially curative treatments(liver transplantation,surgical resection,thermal ablation),long-term outcomes are affected by a high recurrence rate(up to 70%of cases 5 years after treatment).HCC recurrence within 2 years of treatment is defined as“early”and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden.A recurrence that occurs after 2 years of treatment is defined as“late”and is related to de novo HCC,independent of the primary neoplasm.Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence.Different pathogenesis corresponds to different predictors of the risk of early or late recurrence.An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance.Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens.This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.
文摘The biliary tract has been considered for several decades a passive system just leading the hepatic bile to the intestine.Nowadays several researches demonstrated an important role of biliary epithelia(i.e.cholangiocytes)in bile formation.The study of biliary processes therefore maintains a continuous interest since the possible important implications regarding chronic cholestatic human diseases,such as primary biliary cholangitis or primary sclerosing cholangitis.Bile acids(BAs),produced by the liver,are the most represented organic molecules in bile.The physiologic importance of BAs was initially attributed to their behavior as natural detergents but several studies now demonstrate they are also important signaling molecules.In this minireview the effect of BAs on the biliary epithelia are reported focusing in particular on secondary(deriving by bacterial manipulation of primary molecules)ones.This class of BAs is demonstrated to have relevant biological effects,ranging from toxic to therapeutic ones.In this family ursodeoxycholic and lithocholic acid present the most interesting features.The molecular mechanisms linking ursodeoxycholic acid to its beneficial effects on the biliary tract are discussed in details as well as data on the processes leading to lithocholic damage.These findings suggest that expansion of research in the field of BAs/cholangiocytes interaction may increase our understanding of cholestatic diseases and should be helpful in designing more effective therapies for biliary disorders.
文摘Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease that is observed more frequently in middle-aged women.This disorder is considered an autoimmune disease,since liver injury is sustained by the presence of selfdirected antimitochondrial antibodies targeting the bile duct cells.The prognosis may vary depending on an early diagnosis and response to therapy.However,nearly a third of patients can progress to liver cirrhosis,thus requiring a liver transplant.Traditional immunosuppressive therapies,commonly employed for other autoimmune diseases,have limited effects on PBC.In fact,dramatic functional changes that occur in the biliary epithelium in the course of inflammation play a major role in perpetuating the injury.In this minireview,after a background on the disease and possible predisposing factors,the sequential cooperation of cellular/molecular events leading to end-stage PBC is discussed in detail.The rise and maintenance of the autoimmune process,as well as the response of the biliary epithelia during inflammatory injury,are key factors in the progression of the disease.The so-called“ductular reaction(DR)”,intended as a reactive expansion of cells with biliary phenotype,is a process frequently observed in PBC and partially understood.However,recent findings suggest a strict relationship between this pathological picture and the progression to liver fibrosis,cell senescence,and loss of biliary ducts.All these issues(onset of chronic inflammation,changes in secretive and proliferative biliary functions,DR,and its relationship with other pathological events)are discussed in this manuscript in an attempt to provide a snapshot,for clinicians and researchers,of the most relevant and sequential contributors to the progression of this human cholestatic disease.We believe that interpreting this disorder as a multistep process may help identify possible therapeutic targets to prevent evolution to severe disease.
文摘Since the first identification in December of 2019 and the fast spread of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,it has represented a dramatic global public health concern.Though affecting mainly the respiratory system,SARS-CoV-2 disease,defined as coronavirus disease 2019(COVID-19),may have a systemic involvement leading to multiple organ dysfunction.Experimental evidence about the SARS-CoV-2 tropism for the liver and the increasing of hepatic cytolysis enzymes during infection support the presence of a pathophysiological relationship between liver and SARS-CoV-2.On the other side,patients with chronic liver disease have been demonstrated to have a poor prognosis with COVID-19.In particular,patients with liver cirrhosis appear extremely vulnerable to infection.Moreover,the etiology of liver disease and the vaccination status could affect the COVID-19 outcomes.This review analyzes the impact of the disease stage and the related causes on morbidity and mortality,clinical outcomes during SARS-CoV-2 infection,as well as the efficacy of vaccination in patients with chronic liver disease.
基金The study was approved by the Sydney Local Health District Human Research Ethics Committee(HREC CH62/6/2021-055).
文摘BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis(UC).However,the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown.AIM To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists.METHODS A prospective,cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted.The survey consisted of 34 questions to assess gastroenterologists’and pathologists’knowledge(score out of 19)and attitudes towards histological assessment in UC.Survey questions were formulated using the European Crohn’s and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines.It included knowledge of histological assessment of disease activity and dysplasia,knowledge of histological scoring systems for ulcerative colitis,uptake of histology scoring systems in routine practice,attitudes towards the role of histological activity,and the use of histological activity in clinical scenarios.RESULTS Of 89 responders(77 gastroenterologists,12 pathologists),there was almost universal acceptance that histological assessment should form part of UC evaluation[95%gastroenterologists,92%pathologists].However,gastroenterologists reported that 92%of their pathologists do not use a histological scoring system.Utilisation of a formal histological scoring system was preferred by 77%of gastroenterologists and 58%of pathologists.Both groups lacked awareness of the Geboes Score,Nancy Index and Robarts Histopathological Index scoring systems with 91%,87%,and 92%of gastroenterologists respectively;and 83%,83%,and 92%pathologists respectively,being uncertain of scoring systems’remission definitions.Histology knowledge score was not significantly different between gastroenterologists and pathologists[9/19(IQR:8-11)vs 8/19(IQR:7-10),P=0.54].Higher knowledge scores were predicted by hospital attending gastroenterologists(P=0.004),participation in inflammatory bowel disease(IBD)multidisciplinary teams(P=0.009),and self-declared IBD sub-specialist(P=0.03).CONCLUSION Histological remission is a recognised target for both gastroenterologists and pathologists.Despite this,knowledge of histological scoring systems and their utilisation is poor.
文摘Patients with cirrhosis have an increased risk of infection and differently from other complications,that over the years are improving in their outcomes,infections in cirrhotic patients are still a major cause of hospitalization and death(up to 50%in-hospital mortality).Infections by multidrug-resistant organisms(MDRO)have become a major challenge in the management of cirrhotic patients with significant prognostic and cost-related impact.About one third of cirrhotic patients with bacterial infections is infected with MDR bacteria and their prevalence has increased in recent years.MDR infections have a worse prognosis compared to infections by non-resistant bacteria because they are associated with lower rate of infection resolution.An adequate management of cirrhotic patients with infections caused by MDR bacteria depends on the knowledge of some epidemiological aspects,such as the type of infection(spontaneous bacterial peritonitis,pneumonia,urinary tract infection and spontaneous bacteremia),bacteriological profile of antibiotic resistance at each health care unit and site of infection acquisition(community acquired,healthcare associated or nosocomial).Furthermore,regional variations in the prevalence of MDR infections determine that the choice of empirical antibiotic therapy must be adapted to the local microbiological epidemiology.Antibiotic treatment is the most effective measure to treat infections caused by MDRO.Therefore,optimizing antibiotic prescribing is critical to effectively treat these infections.Identification of risk factors for multidrug resistance is essential to define the best antibiotic treatment strategy in each case and the choice of an effective empirical antibiotic therapy and its early administration is cardinal to reduce mortality.On the other hand,the supply of new agents to treat these infections is very limited.Thus,specific protocols that include preventive measures must be implemented in order to limit the negative impact of this severe complication in cirrhotic patients.
文摘Biliary cyst tumors(cystadenoma and cystadeno-carcinoma) are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver,but differential diagnosis with multiloculated or complicated biliary cysts,atypical hemangiomas,hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography(CT) and magnetic resonance imaging(MRI) are often not diagnostic and in these cases fine needle aspiration(FNA) is used to confirm the presence of atypical biliary cells. FNA,however,lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma,it is important to exclude liver metastasis,of which colonic cancer is the most common primary site. Multiple biliary hamartomas(von Meyenburg complex) can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic,but occasionally a percutaneous biopsy may be required.
文摘Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgical treatment alternative,thanks to their minimal invasiveness,excellent tolerability and safety profile,proven efficacy in local disease control,virtually unlimited repeatability and cost-effectiveness.Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules.Among them,radiofrequency(RF) currents are the most used,while microwave ablations(MWA) are becoming increasingly popular.Starting from the 90s',RF ablation(RFA) rapidly became the standard of care in ablation,especially in the treatment of small HCC nodules;however,RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks.MWA,first introduced in the Far Eastern clinical practice in the 80s',showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors,resulting in a poor coagulative performance and a relatively high complication rate,nowadays shows better results both in terms of treatment controllability and of overall coagulative performance,thanks to the improvement of technology.In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems,and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications,both in absolute terms and in comparison with RFA.
基金Supported by "Instituto de Salud Carlos Ⅲ",Spain& "European Regional Development Fund(ERDF)a way of making Europe",No.PI12/00130 and No.PI15/00074and"Gilead Spain&Instituto de Salud Carlos Ⅲ",No.GLD14_00217
文摘Hepatocellular carcinoma(HCC), chronic hepatitis B(CHB) and chronic hepatitis C(CHC) are characterized by exhaustion of the specific CD8^+ T cell response. This process involves enhancement of negative costimulatory molecules, such as programmed cell death protein-1(PD-1), cytotoxic T-lymphocyte antigen-4(CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8^+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4(tremelimumab and ipilimumab) and PD-1(nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.
文摘Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.
文摘Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.
文摘About 130-170 million people, is estimated to be infected with the hepatitis C virus(HCV). Chronic HCV infection is one of the leading causes of liverrelated death and in many countries it is the primaryreason for having a liver transplant. The main aim of antiviral treatment is to eradicate the virus. Until a few years ago the only treatment strategy was based on the combination of pegylated interferon and ribavirin(PEG/RBV). However, in genotypes 1 and 4 the rates of viral response did not surpass 50%, reaching up to 80% in the rest. In 2011 approval was given for the first direct acting antiviral agents(DAA), boceprevir and telaprevir, for treatment of genotype 1, in combination with traditional dual therapy. This strategy managed to increase the rates of sustained viral response(SVR) in both naive patients and in retreated patients, but with greater toxicity, interactions and cost, as well as being less safe in patients with advanced disease, in whom this treatment can trigger decompensation or even death. The recent, accelerated incorporation since 2013 of new more effective DAA, with pan-genomic properties and excellent tolerance, besides increasing the rates of SVR(even up to 100%), has also created a new scenario: shorter therapies, less toxicity and regimens free of PEG/RBV. This has enabled their almost generalised applicability in all patients. However, it should be noted that most of the scientific evidence available is based on expert opinion, case-control series, cohort studies and phase 2 and 3 trials, some with a reduced number of patients and select groups. Few data are currently available about the use of these drugs in daily clinical practice, particularly in relation to the appearance of side effects and interactions with other drugs, or their use in special populations or persons with the less common genotypes. This situation suggests the need for the generalised implementation of registries of patients receiving antiviral therapy. The main inconvenience of these new drugs is their high cost. This necessitates selection and prioritization of candidate patients to receive them, via strategies established by the various national organs, in accordance with the recommendations of scientific societies.
文摘Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist's clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac
文摘AIM:To investigate the prevalence of the clinical parameters of insulin resistance and diabetes in patients affected by chronic hepatitis C(CHC) or chronic hepatitis B(CHB) . METHODS:We retrospectively evaluated 852 consecutive patients(726 CHC and 126 CHB) who had undergone liver biopsy.We recorded age,sex,ALT,type 2 diabetes and/or metabolic syndrome(MS) ,body mass index(BMI) ,and apparent disease duration(ADD) . RESULTS:Age,ADD,BMI,prevalence of MS and diabetes in patients with mild/moderate liver fibrosis were significantly higher in CHC.However,the degree of steatosis and liver fibrosis evaluated in liver biopsies did not differ between CHC and CHB patients.At multivariate analysis,age,sex,BMI,ALT and diabetes were independent risk factors for liver fibrosis in CHC,whereas only age was related to liver fibrosis in CHB. We also evaluated the association between significant steatosis(>30%) and age,sex,BMI,diabetes,MS and liver fibrosis.Diabetes,BMI and liver fibrosis were associated with steatosis>30%in CHC,whereas only age and BMI were related to steatosis in CHB. CONCLUSION:These data may indicate that hepatitis C virus infection is a risk factor for insulin resistance.
文摘Alcoholic liver disease(ALD) is the commonest cause of cirrhosis in many Western countries and it has a high rate of morbidity and mortality. The pathogenesis is characterized by complex interactions between metabolic intermediates of alcohol. Bacterial intestinal flora is itself responsible for production of endogenous ethanol through the fermentation of carbohydrates. The intestinal metabolism of alcohol produces a high concentration of toxic acetaldehyde that modifies gut permeability and microbiota equilibrium. Furthermore it causes direct hepatocyte damage. In patients who consume alcohol over a long period, there is a modification of gut microbiota and, in particular, an increment of Gram negative bacteria. This causes endotoxemia and hyperactivation of the immune system. Endotoxin is a constituent of Gram negative bacteria cell walls. Two types of receptors, cluster of differentiation 14 and Toll-like receptors-4, present on Kupffer cells, recognize endotoxins. Several studies have demonstrated the importance of gut-liver axis and new treatments have been studied in recent years to reduce progression of ALD modifying gut microbiota. It has focused attention on antibiotics, prebiotics, probiotics and synbiotics.
文摘AIM To analyse cumulative loss of heterozygosity (LOH) of chromosomal regions and tumor suppressor genes in hepatocellular carcinomas (HCCs) from 20 southern African blacks. METHODS p53, RB1, BRCA1, BRCA2, WT1 and E cadherin genes were analysed for LOH, and p53 gene was also analysed for the codon 249 mutation, in tumor and adjacent non tumorous liver tissues using molecular techniques and 10 polymorphic microsatellite markers. RESULTS p53 codon 249 mutation was found in 25% of the subjects, as was expected, because many patients were from Mozambique, a country with high aflatoxin B 1 exposure. LOH was found at the RB1, BRCA2 and WT1 loci in 20%(4/*!20) of the HCCs, supporting a possible role of these genes in HCC. No LOH was evident in any of the remaining genes. Reports of mutations of p53 and RB1 genes in combination, described in other populations, were not confirmed in this study. Change in microsatellite repeat number was noted at 9/*!10 microsatellite loci in different HCCs, and changes at two or more loci were detected in 15%(3/*!20) of subjects. CONCLUSION We propose that microsatellite/genomic instability may play a role in the pathogenesis of a subset of HCCs in black Africans.
文摘Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis,but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation,has immunomodulatory and anti-inflammatory properties.Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease(NAFLD)and chronic hepatitis C(CHC)virus infection.The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known,but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases.Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease.Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.
文摘Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound(US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography(CT) and contrast-enhanced magnetic resonance(MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography(PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound(CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement(wash in- wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is avery reliable technique with a high intrinsic sensitivity for portal vein patency assessment. More expensive and sophisticated techniques(i.e., CT, MRI, PET, and PET-CT) should only be indicated in undetermined cases at CEUS.
