Disturbance of hepatic and intestinal microcirculation in experimental liver cirrhosis

AIM: To analyze hepatic, mesenteric and mucosal microcirculation and leukocyte-endothelium interaction (LEI) in a rat model with liver cirrhosis.METHODS: Hepatic cirrhosis was induced in Wistar rats by gavage with carbon tetrachloride, and intravital videomicroscopy was performed in liver, mesentery and small intestine mucosa. Special emphasis is given on microcirculatory and morphometric changes during cirrhotic portal hypertension.RESULTS: LEI was influenced significantly in the cirrhotic liver but not in the gut. Blood flow measurement showed significant differences among liver, main mesenteric vessels and the mucosa. The results of our study indicate that liver cirrhosis leads to alterations in hepatic and mesenteric blood flow but not in mucosal blood flow.CONCLUSION: The enhanced inflammatory response in hepatic microvessels may be caused by a decrease of antithrombin Ⅲ levels and could be responsible for disturbances of organ pathology.

EVALUATION OF CIRRHOTIC LIVER WITH PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING:A PRELIMINARY EXPERIMENTAL STUDY IN ANIMAL MODELS WITH HALF-LIVER CIRRHOSIS

Objective To investigate the role of peffusion-weighted magnetic resonance imaging （MRI） in evaluation of cirrhotic fiver. Methods With a 4F catheter, 1% diluted carbon tetrachloride （ 1 ml/kg） was selectively injected into fight or left hepatic artery of 12 dogs fortnightly. The half fiver into which carbon tetrachloride was injected was called as study side （SS）, while the other half fiver without carbon tetrachloride injection was called as study control side （SCS）. Conventional and peffusion-weighted MRI were performed in every 4 weeks. Via a 4F catheter, 5ml gadolinium diethylentriamine pentaaceti acid （Gd-DTPA） dilution was injected into superior mesenteric artery at the 5th scan. The signal intensity-thne curves of SS, SCS, and portal vein were completed in MR workstation. The maximal relative signal increase （ MRSI）, peak time （ tp）, and slope of the curves were measured. Results On conventional MR images, no abnormalities of externality and signal intensity were observed in both SS and SCS of fiver at each stage. The mean tp, MP, SI, and slope of intensity-time curves in normal fiver were 10. 56 seconds, 1.01, and 10. 23 arbitrary unit （au）/s, respectively. Three parameters of curves didn＇t show obvious change in SCS of fiver at every stage. Abnormal perfusion curves occurred in SS of fiver at the 12th week after the 1st injection. The abnormality of perfusion curve in SS was more and more serious as the times of injection increased. The mean tp, IVlRSI, and slope intensity-time curves in SS of fiver were 19.45 seconds, 0. 43, and 3. 60 au/s respectively at the 24th week. Conclusion Perfusion-weighted imaging can potentially provide information about portal peffusion of hepatic parenchyma, and to some degree, reflect the severity of cirrhosis.

Dynamical influence of Cordyceps sinensis on the activity of hepatic insulinase of experimental liver cirrhosis

BACKGROUND: Cordeceps sinensis (CS) is a herb which can inhibit the liver fibrosis. Hyperinsulinemia is common in liver cirrhosis patients. The activity of insulin degrading enzyme could reflect the metabolism of insulin. This study was to detect the dynamical effects and mechanisms of CS on the activity of hepatic insulinase in CCl4 induced liver cirrhosis in rats. METHODS: Rats were randomly allocated into three groups: normal group, model group and CS group. The rats in the normal group were sacrificed at the beginning of experi- ment, and the other two groups were sacrificed randomly at the end of the third, sixth and ninth weeks. Blood and tissue specimens were taken. Biochemical assays were used to determine the changes of alanine transaminase (ALT), albumin levels in serum. And radioimmunological assays were used to determine the changes of hyaluronic acid ( HA), insulin levels in serum and the activity of hepatic in- sulinase. RESULTS: No significant differences were seen in the se- rum levels of ALT, albumin, HA between the CS group and the model group at the third and sixth weeks (P > 0.05). The serum levels of ALT, HA in the CS group were lower than those in the model group at the ninth week (P <0.05), but the serum level of albumin in the CS group was higher than that in the model group at the ninth week (P<0.05). No significant differences were observed in the serum levels of insulin and the activity of hepatic insulinase between the CS and model groups at the third week and the normal group (P >0.05). The serum levels of insulin in the CS and model groups at the sixth and ninth weeks were higher than those in the normal group (P<0.05). But the activity of hepatic insulinase was lower than that in the nor- mal group ( P < 0. 05 or P < 0. 01). No significant diffe- rences were found in the serum levels of insulin and the ac- tivity of hepatic insulinase between the CS and model groups at the third, sixth and ninth weeks (P >0.05). CONCLUSIONS: CS may decrease the damage to hepato- cyte by CCl4 , and inhibit hepatic fibrogenesis. Six weeks after CCl4 administration, the activity of hepatic insulinase began decreasing. CS could not inhibit the decrease of the activity of hepatic insulinase.

Impact of antithrombin Ⅲ on hepatic and intestinal microcirculation in experimental liver cirrhosis and bowel inflammation: An in vivo analysis

AIM： To analyze the hepatic and intestinal microcirculation in an animal model of liver cirrhosis and inflammatory bowel disease （IBD） and to characterize bhe anti-inflammatory action of antithrombin Ⅲ （ATⅢ） on leukocyte kinetics and liver damage. METHODS： Hepatic and intestinal microcirculation was investigated by intravital videomicroscopy. Standardized models of experimental chronic liver cirrhosis and bowel inflammation were employed. Animals were divided into four groups （n = 6/group）： controls, animals with cirrhosis, animals with cirrhosis and IBD, animals with cirrhosis and IBD treated with ATIII. RESULTS： Cirrhosis facilitated leukocyte rolling and sticking in hepatic sinusoids （1.91±0.28 sticker/μm vs 0.5±0.5 sticker/μm in controls, P〈0.05）. The effect enhanced in animals with cirrhosis and IBD （5.4±1.65 sticker/μm）, but reversed after ATIII application （3.97±1.04 sticker/μm, P〈0.05）. Mucosal blood flow showed no differences in cirrhotic animals and controls （5.3±0.31 nL/min vs5.4±0.25 nL/min） and was attenuated in animals wibh cirrhosis and IBD significantly （3.49±0.6 nL/min）. This effect was normalized in the treatment group （5.13±0.4 nL/min, P〈0.05）. Enzyme values rose during development of cirrhosis and bowel inflammation, and reduced after ATIII application （P〈0.05）. CONCLUSION： Liver cirrhosis in the presence of IBD leads to a significant reduction in mucosal blood flow and an increase in hepatic leukocyte adherence with consecutive liver injury, which can be prevented by administration of ATⅢ.

DYNAMIC CHANGES OF ITO CELLS IN EXPERIMENTAL LIVER CIRRHOSIS OF RAT

That Ho cells in rat liver express desmin was confirmed by immunohistochemical technique. Consequently, changes of desmin-positive cells, lysozyme-positive cells and fibronectin were further studied in experimental cirrhosis of rat. It was found that desmln- positive cells, with the transitional feature between Ito cells and myofibroblasts or fibrobiasts under electron microscope, increased in number and expression of desmin in the necrotic areas as well as in the cellular fibrous septa, but decreased in number in the fibrous septa except those areas closed to the edges of the septa. These results suggested that Ito cells, myofibroblasts and fibroblasts might belong to the same cellular system and play an important role in the pathogenesis of cirrhosis. Meanwhile, it was also noted that changes of both fibronectin and lysozymepositive cells were correlated with those of desmin-positive cells. These provide evidence in vivo that flbronectin and Kupffer cells might exert certain effects on the migration and proliferation of Ito cells in liver cirrhosis.

Action mechanism of Yiqi Hexue Formula in the treatment of liver cirrhosis based on network pharmacology and experimental verification

Objective:To study the mechanism of Yiqi Hexue Formula in the treatment of liver cirrhosis based on network pharmacology and experimental verification.Methods:Firstly,the effective components and action targets of various traditional Chinese medicines in Yiqi Hexue Formula were searched from TCMSP and BATMAN-TCM databases.The disease target genes were obtained by using GeneCard,PharmGkb,OMIM,DrugBank and TTD databases.The potential target genes of drugs and disease target genes were intersected,and the Venn diagram was drawn.The"active ingredient-core target"network was constructed by Cytoscape software,and the KEGG pathway of the intersection genes was analyzed by R software.Animal experiments were conducted to observe the effect of Yiqi Hexue Formula on histopathology of CCl4-induced liver cirrhosis model rats,determine the expression levels of JAK2 and STAT3 mRNA in liver tissue,and preliminarily explore the mechanism of Yiqi Hexue Formula in the treatment of liver cirrhosis.Results:A total of 43 active components and 648 targets of Yiqi Hexue Formula for the treatment of liver cirrhosis were screened through the database.KEGG pathway analysis showed that Yiqi Hexue Formula mainly affected PI3K/Akt,MAPK,IL-17 and JAK/STAT signaling pathway.Animal experimental research showed that compared with the model group,the degree of inflammation and fibrosis in liver tissue of rats treated with Yiqi Hexue Formula was significantly improved;The expression of JAK2 and STAT3 mRNA decreased significantly in the treatment group of Yiqi Hexue Formula(P<0.05).Conclusion:Yiqi Hexue Formula can treat liver cirrhosis through multiple components,multiple targets and multiple pathways.JAK2/STAT3 signaling pathway is involved in the formation of liver cirrhosis.Yiqi Hexue Formula can improve the pathological manifestations of cirrhotic rats.Its mechanism may be related to inhibiting the transmission of JAK2/STAT3 signaling pathway.

Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension

AIM To investigate the potential effect of inhibitors of phosphodiesterase-5(PDE-5) for therapy of portal hypertension in liver cirrhosis.METHODS In the rat model of thioacetamide-induced liver fibrosis/cirrhosis the nitric oxide-cyclic guanosine monophosphate(NO-cGMP) pathway was investigated. Expression and localization of PDE-5, the enzyme that converts vasodilating cGMP into inactive 5'-GMP, was in the focus of the study. Hepatic gene expression of key components of the NO-cGMP pathway was determined by qRT-PCR: Endothelial NO synthase(eNOS), inducible NO synthase(iNOS), soluble guanylate cyclase subunits α1 and β1(sGCa1, sGCb1), and PDE-5. Hepatic PDE-5 protein expression and localization were detected by immunohistochemistry. Serum cGMP concentrations were measured using ELISA. Acute effects of the PDE-5 inhibitor Sildenafil(0.1 mg/kg or 1.0 mg/kg) on portal and systemic hemodynamics were investigated using pressure transducers.RESULTS Hepatic gene expression of eNOS(2.2-fold; P = 0.003), sGCa1(1.7-fold; P = 0.003), sGCb1(3.0-fold; P = 0.003), and PDE-5(11-fold; P = 0.003) was increased in cirrhotic livers compared to healthy livers. Overexpression of PDE-5(7.7-fold; P = 0.006) was less pronounced in fibrotic livers. iNOS expression was only detected in fibrotic and cirrhotic livers. In healthy liver, PDE-5 protein was localized primarily in zone 3 hepatocytes and to a lesser extent in perisinusoidal cells. This zonation was disturbed in cirrhosis: PDE-5 protein expression in perisinusoidal cells was induced approximately 8-fold. In addition, PDE-5-expressing cells were also found in fibrous septa. Serum cGMP concentrations were reduced in rats with cirrhotic livers by approximately 40%. Inhibition of PDE-5 by Sildenafil caused a significant increase in serum cGMP concentrations [+ 64% in healthy rats(P = 0.024), + 85% in cirrhotic rats(P = 0.018)]. Concomitantly, the portal venous pressure was reduced by 19% in rats with liver cirrhosis. CONCLUSION Overexpression and abrogated zonation of PDE-5 likely contribute to the pathogenesis of cirrhotic portal hypertension. PDE-5 inhibition may therefore be a reasonable therapeutic approach for portal hypertension.

Clinical study on the relationship between liver cirrhosis,ascites,and hyponatremia

BACKGROUND Cirrhosis is a common liver disease,and ascites is one of the common clinical conditions.However,the clinical manifestations of ascites combined with hyponatremia as a high-risk condition and its relationship to patient prognosis have not been fully studied.AIM To explore the clinical manifestations,prognostic factors,and relationships of ascites with hyponatremia in patients with cirrhosis to provide better diagnostic and treatment strategies.METHODS In this study,we retrospectively analyzed the clinical data of 150 patients diagnosed with cirrhosis and ascites between 2017 and 2022.Patients were divided into two groups:ascites combined with hyponatremia group and ascites group.We compared the general characteristics,degree of hyponatremia,complications,treatment,and prognosis between the two groups.RESULTS In the study results,patients in the ascites combined with hyponatremia group showed an older average age(58.2±8.9 years),64.4%were male,and had a significantly longer hospitalization time(12.7±5.3 d).Hyponatremia was more severe in this group,with a mean serum sodium concentration of 128.5±4.3 mmol/L,which was significantly different from the ascites group of 137.6±2.1 mmol/L.Patients with ascites and hyponatremia were more likely to develop hepatic encephalopathy(56.2%vs 39.0%),renal impairment(45.2%vs 28.6%)and infection(37.0%vs 23.4%).Regarding treatment,this group more frequently used diuretics(80.8%vs 62.3%)and salt supplements(60.3%vs 38.9%).Multiple logistic regression analysis identified older age[Odds ratio(OR)=1.06,P=0.025]and male gender(OR=1.72,P=0.020)as risk factors for hyponatremia combined with ascites.Overall,patients with ascites and hyponatremia present a clear high-risk status,accompanied by severe complications and poor prognosis.CONCLUSION In patients with cirrhosis,ascites with hyponatremia is a high-risk condition that is often associated with severe complications.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis

BACKGROUND Liver cirrhosis patients admitted to intensive care unit(ICU)have a high mortality rate.AIM To establish and validate a nomogram for predicting in-hospital mortality of ICU patients with liver cirrhosis.METHODS We extracted demographic,etiological,vital sign,laboratory test,comorbidity,complication,treatment,and severity score data of liver cirrhosis patients from the Medical Information Mart for Intensive Care IV(MIMIC-IV)and electronic ICU(eICU)collaborative research database(eICU-CRD).Predictor selection and model building were based on the MIMIC-IV dataset.The variables selected through least absolute shrinkage and selection operator analysis were further screened through multivariate regression analysis to obtain final predictors.The final predictors were included in the multivariate logistic regression model,which was used to construct a nomogram.Finally,we conducted external validation using the eICU-CRD.The area under the receiver operating characteristic curve(AUC),decision curve,and calibration curve were used to assess the efficacy of the models.RESULTS Risk factors,including the mean respiratory rate,mean systolic blood pressure,mean heart rate,white blood cells,international normalized ratio,total bilirubin,age,invasive ventilation,vasopressor use,maximum stage of acute kidney injury,and sequential organ failure assessment score,were included in the multivariate logistic regression.The model achieved AUCs of 0.864 and 0.808 in the MIMIC-IV and eICU-CRD databases,respectively.The calibration curve also confirmed the predictive ability of the model,while the decision curve confirmed its clinical value.CONCLUSION The nomogram has high accuracy in predicting in-hospital mortality.Improving the included predictors may help improve the prognosis of patients.

Contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis patients

This editorial describes the contemporary concepts of prevention and management of gastroesophageal variceal bleeding in liver cirrhosis(LC)patients according to the current guidelines.Gastroesophageal variceal bleeding is the most dangerous complication of portal hypertension in LC patients.Risk stratification and determination of an individual approach to the choice of therapeutic measures aimed at their prevention and management has emerged as one of the top concerns in modern hepatology.According to the current guidelines,in the absence of clinically significant portal hypertension,etiological and nonetiological therapies of LC is advisable for the primary preventing gastroesophageal variceal bleeding,whereas its presence serves as an indication for the administration of non-selectiveβ-blockers,among which carvedilol is the drug of choice.Non-selectiveβ-blockers,as well as endoscopic variceal ligation and transjugular intrahepatic portosystemic shunt can be used to prevent recurrence of gastroesophageal variceal bleeding.Pharmacotherapy with vasoactive drugs(terlipressin,somatostatin,octreotide),endoscopic variceal ligation,endovascular techniques and transjugular intrahepatic portosystemic shunt are recommended for the treatment of acute gastroesophageal variceal bleeding.Objective and accurate risk stratification of gastroesophageal variceal bleeding will allow developing individual strategies for their prevention and management,avoiding the first and further decompensation in LC,which will improve the prognosis and survival of patients suffering from it.

Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian randomization analysis

BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.

Pituitary stalk interruption syndrome complicated with liver cirrhosis:A case report

BACKGROUND Pituitary stalk interruption syndrome(PSIS)is a rare disorder,often characterized by delayed growth and development,short stature,and hypogonadism as the main clinical manifestations.It is not clear whether PSIS can lead to liver cirrhosis.CASE SUMMARY This paper reported a case of liver cirrhosis of unknown origin.The patient was admitted to Beijing Ditan Hospital Affiliated to Capital Medical University in November 2023.The diagnosis of PSIS complicated with liver cirrhosis was established after a series of blood tests and pituitary magnetic resonance imaging examination.CONCLUSION We also reviewed the literature from both domestic and international sources to deepen the clinical understanding of PSIS in conjunction with liver cirrhosis among medical practitioners.

Fat necrosis of liver in a patient with mixed type liver cirrhosis

To the Editor: Fatty liver diseases, including nonalcoholic fatty liver disease and alcohol related fatty liver disease, have become a major public health concern [ 1, 2 ]. Fatty liver diseases have been shown to progress through various stages, from steatosis or necrosis with inflammation and hepatocyte damage to the development of fibrosis and eventual cirrhosis with an increased risk of carcinoma [ 2, 3 ].

Dapagliflozin as an oral antihyperglycemic agent in the management of diabetes mellitus in patients with liver cirrhosis

BACKGROUND The use of dapagliflozin in patients with cirrhosis has been relatively restricted due to concerns regarding its overall safety and pharmacological profile in this population.AIM To determine the safety and effectiveness of dapagliflozin in the co-management of diabetes mellitus and cirrhosis with or without ascites.METHODS The patients studied were divided into two groups:100 patients in the control group received insulin,while 200 patients received dapagliflozin.These patients were classified as Child A,B,or C based on the Child–Pugh classification.Child A or B and Child C were administered doses of 10 mg and 5 mg of dapagliflozin,respectively.RESULTS The rate of increased diuretics dose was markedly elevated in the group that received insulin compared to the group that received dapagliflozin.In addition,dapagliflozin treatment substantially reduced weight,body mass index,and fasting blood glucose compared to the insulin group during follow-up.However,there were no significant differences in hemoglobin A1c,liver function,or laboratory investigations between both groups during the follow-up period.The incidence of hypoglycemia,hepatic encephalopathy,variceal bleeding,and urinary tract infection was significantly higher in the insulin group compared to the dapagliflozin group.In contrast,the dapagliflozin group experienced significantly higher rates of frequent urination and dizziness.In addition,the insulin group exhibited a marked worsening of ascites compared to the dapagliflozin group.CONCLUSION Dapagliflozin demonstrated safety and efficacy in the treatment of diabetic patients who have cirrhosis with or without ascites.This resulted in an improvement of ascites,as well as a decrease in diuretic dose and Child–Pugh score.

Immunohistochemical study on expression of epidermal growth factor receptor at hepatocyte nuclei in experimental rat liver cirrhosis

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Determination of IL-2/IL-2R system in patients with liver cirrhosis.and carcinoma

AIMS To.determine the interleuking-2 and interleukin- 2 receptor (IL-2/IL-2R) system in patients with liver cirrhosis and carcinoma and compare their immune functions. The clinical significance is also discussed. METHODS Fifty patients with Liver cirrhosis (LC), 50 patients with hepatocellular carcinoma (HCC) and 30 normal controls were studied. The expression of mlL-2R was examined by immunofluorescence. IL-2's activity and serum level of soluble interleukin-2 recep- tor (sIL-2R) were measured by enzyme linked im- munosorbent assay. RESULTS IL-2's activity and the percentage of mIL- 2R expression in carcinoma were significantly lower than those in cirrhosis (P<0.01) and controls (P< 0.01),while the IL-2's activity and the expression of mlL-2R in cirrhosis were also lower than normal controls (P<0.05). The serum level of sIL-2R in carcinoma was significantly higher than that in cirrhosis (P<0.05) and controls (P<0.01),and the level in cirrhosis was higher than in controls (P<0.05). CONCLUSIONS Patients with liver cirhosis and car- cinoma share the decreased immune function of similar nature,but the latter has a more profound degree. Such resemblance in immune disturbances may be the important factor affecting the carcinogenesis of cirrhotic liver.

Study of liver cirrhosis over ten consecutive years in Southern China

AIM: To investigate the etiology and complications of liver cirrhosis (LC) in Southern China.

Contrast-enhanced ultrasound in the diagnosis of nodules in liver cirrhosis

Contrast-enhanced ultrasound(CEUS)using microbubble contrast agents are useful for the diagnosis of the nodules in liver cirrhosis.CEUS can be used as a problem-solving method for indeterminate nodules on computed tomography(CT)or magnetic resonance imaging(MRI)or as an initial diagnostic test for small newly detected liver nodules.CEUS has unique advantages over CT and MRI including no renal excretion of contrast,real-time imaging capability,and purely intravascular contrast.Hepatocellular carcinoma(HCC)is characterized by arterial-phase hypervascularity and later washout(negative enhancement).Benign nodules such as regenerative nodules or dysplastic nodules are usually isoechoic or slightly hypoechoic in the arterial phase and isoechoic in the late phase.However,there are occasional HCC lesions with atypical enhancement including hypovascular HCC and hypervascular HCC without washout.Cholangiocarcinomas are infrequently detected during HCC surveillance and mostly show rimlike or diffuse hypervascularity followed by rapid washout.Hemangiomas are often found at HCC surveillance and are easily diagnosed by CEUS.CEUS can be effectively used in the diagnostic work-up of small nodules detected at HCC surveillance.CEUS is also useful to differentiate malignant and benign venous thrombosis and to guide and monitor the local ablation therapy for HCC.

Gallstones in patients with liver cirrhosis:Incidence,etiology,clinical and therapeutical aspects

Gallstones occur in about one third of the patients having liver cirrhosis.Pigment gallstones are the most frequent type,while cholesterol stones represent about15%of all stones in cirrhotics.Increased secretion of unconjugated bilirubin,increased hydrolysis of conjugated bilirubin in the bile,reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics.Gallbladder hypomotility also contributes to lithogenesis.The most recent data regarding risk factors for gallstones are presented.Gallstone prevalence increases with age,with a ratio male/female higher than in the general population.Chronic alcoholism,viral C cirrhosis,and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones.Gallstones are often asymptomatic,and discovered incidentally.If asymptomatic,expectant management is recommended,as for asymptomatic gallstones in the general population.However,a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications.For symptomatic stones,laparoscopic cholecystectomy has become the therapy of choice.Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy.Patients with severe liver disease are at highest surgical risk,therefore gallstone complications should be treated using noninvasive or minimally invasive procedures,until stabilization of the patient condition.