Measurement of hepatic functional mass by means of ^(13)C-methacetin and ^(13)C-phenylalanine breath tests in chronic liver disease: Comparison with Child-Pugh score and serum bile acid levels

AIM: To evaluate and compare the clinical usefulness of 13C-phenylalanine and 13C-methacetin breath tests in quantitating functional hepatic mass in patients with chronic liver disease and to further compare these results with those of conventional tests, Child-Pugh score and serum bile acid levels.METHODS: One hundred and forty patients (50 HCV-related chronic hepatitis, 90 liver cirrhosis patients) and 40 matched healthy controls were studied. Both breath test and routine liver test, serum levels of cholic and chenodeoxycholic acid conjugates were evaluated.RESULTS: Methacetin breath test, expressed as 60 min cumulative percent of oxidation, discriminated the hepatic functional capacity not only between controls and liver disease patients, but also between different categories of chronic liver disease patients. Methacetin breath test was correlated with liver function tests and serum bile acids.Furthermore, methacetin breath test, as well as serum bile acids, were highly predictive of Child-Pugh scores. The diagnostic power of phenylalanine breath test was always less than that of methacetin breath test.CONCLUSION: Methacetin breath test represents a safe and accurate diagnostic tool in the evaluation of hepatic functional mass in chronic liver disease patients.

Assessment of hepatic functional reserve by cirrhosis grading and liver volume measurement using CT

AIM： To explore a method for quantitative assessment of hepatic functional reserve by combining computed tomography （CT） volumetry with CT grading of liver cirrhosis before liver resection in patients with hepatocellular carcinoma. METHODS： CT images of 55 patients undergoing liver resection were studied prospectively. The degree of liver cirrhosis was referred as ＂CT grade＂ and the percentage of remnant liver volume （PRLV） [PRLV = predicted RLV/predicted total liver volume （PTLV） × 100%; PTLV （mL） = 121.75 ＋ 16.49 × body mass （kg）] were calculated by adding slice by slice of CT liver images. The postoperative RLV, pathologic stages of liver fibrosis in non-tumor area and survival time in these cases were analyzed. RESULTS： There was a significant difference in survival time between the group with PRLV ≤ 50% and the group with PRLV 〉 50% （X^2= 4.988, P = 0.026）, and between the group with CT grade 0/1 and the group with CT grade 2/3 （X^2= 5.429, P = 0.026）. With combination of the both parameters, an oblique line was identified according to the distribution of 32 survivors versus 23 deceased subjects. The mortality rate above the line was 7.1% （1/14）, and that below the line was 53.7% （22/41）, indicating a significant difference between the two rates （X^2 = 9.281, P = 0.002, P 〈 0.05）. CONCLUSION： PRLV and CT grades are significantly correlated with hepatic functional reserve. The predicted line using these two parameters is useful in candidates undergoing liver resection for judging hepatic functional reserve.

The Influence of Enteral Nutrition on Gut Barrier in the Post-operative Patients with Damaged Hepatic Function

The safty, rationality and the practicality of enteral nutrition (EN) support in the postoperative patients with damaged hepatic function were investigated and the protective effect of EN on the gut barrier and the clinical implication studied. Seventy six adult patients whose hepatic function were in Child B or C grade were randomly assigned in EN group (30 cases), total parenteral nutrition (TPN) group (26 cases) and control group (CON, 20 cases). The patients received different nutritional sopport. The signs of nutritional condition and hepatic function were massured at 1 day before, 5 days and 10 days after the surgical operation respectively. The changes in the urine lactulose (L) and mannitol (M) contents and L/M ratio were observed by using pulsed electrochemical detection (HPLC PED) to acquire the defferent effects among the different nutritional support performence. The results showed that the patients in the EN group and TPN group had no worse hepatic function damage after operation. The patients in the EN group reached the positive nitrogen balance earlier, had a less weight loss than in the TPN group with the difference being significant ( P <0 05). There was no obvious change in L/M ratio in the postoperative patients in the EN group ( P >0.05), but there was significant difference in L/M between TPN group and CON group ( P <0.05). It was concluded that EN was a rational, safe, effective and practical nutrition support mathod in the patients with damaged hepatic function patients after surgical operation and EN can effectively protect the structure and function of gut barrier from sever infection.

Clinical efficacy of total laparoscopic splenectomy for portal hypertension and its influence on hepatic hemodynamics and liver function

BACKGROUND The liver hemodynamic changes caused by portal hypertension(PH)are closely related to various complications such as gastroesophageal varices and portosystemic shunts,which may lead to adverse clinical outcomes in these patients,so it is of great clinical significance to find treatment strategies with favorable clinical efficacy and low risk of complications.AIM To study the clinical efficacy of total laparoscopic splenectomy(TLS)for PH and its influence on hepatic hemodynamics and liver function.METHODS Among the 199 PH patients selected from October 2016 to October 2020,100 patients[observation group(OG)]were treated with TLS,while the remaining 99[reference group(RG)]were treated with open splenectomy(OS).We observed and compared the clinical efficacy,operation indexes[operative time(OT)and intraoperative bleeding volume],safety(intraperitoneal hemorrhage,ascitic fluid infection,eating disorders,liver insufficiency,and perioperative death),hepatic hemodynamics(diameter,velocity,and flow volume of the portal vein system),and liver function[serum alanine aminotransferase(ALT),serum aspartate aminotransferase(AST),and serum total bilirubin(TBil)]of the two groups.RESULTS The OT was significantly longer and intraoperative bleeding volume was significantly lesser in the OG than in the RG.Additionally,the overall response rate,postoperative complications rate,and liver function indexes(ALT,AST,and TBil)did not differ significantly between the OG and RG.The hepatic hemodynamics statistics showed that the pre-and postoperative blood vessel diameters in the two cohorts did not differ statistically.Although the postoperative blood velocity and flow volume reduced significantly when compared with the preoperative values,there were no significant inter-group differences.CONCLUSION TLS contributes to comparable clinical efficacy,safety,hepatic hemodynamics,and liver function as those of OS in treating PH,with a longer OT but lesser intraoperative blood loss.

Effect of hepatic function on the EC_(50) of midazolam and the BIS_(50) at the time of loss of consciousness

Objective： To explore the effect of hepatic function on loss of consciousness （LOC） and bispectral index （BIS） during sedation with midazolam （MDZ）. Methods： Forty-five patients were assigned to three groups according to their liver function. Thirty of these patients with diagnoses of cholelithiasis were scheduled laparoscopic cholecys- tectomy, including 15 patients with normal liver function （normal group）, and 15 patients with moderately abnormal liver function based on the results of ultrasonic diagnosis of a moderately fatty liver and elevated alanine transaminase levels of less than three times normal （moderate group）. The other 15 patients with end-stage liver disease （severe group） underwent liver transplantation. Each patient was administered MDZ by way of target-controlled infusion to increase the concentration gradually. At the time of LOC, the BIS was recorded and a blood sample was withdrawn for measurement of the concentration of MDZ. The concentration of MDZ （EC50） and the BIS value （BIS50） at which 50% of patients lose consciousness were calculated using logistic regression. Results： At the time of LOC, the EC50 of MDZ and the BIS50 were similar in the normal and moderate groups （P〉0.05）. LOC occurred at a lower EC50 of MDZ and at a higher BIS50 in the severe group, compared with the normal and moderate groups （P〈0.01）. Conclusions： Patients with end-stage liver disease were more sensitive to MDZ and this affected the prediction of their time of LOC following MDZ administration. There were no changes in response in patients with moderately abnormal hepatic function.

Significance of functional hepatic resection rate calculated using 3D CT/^(99m)Tc-galactosyl human serum albumin singlephoton emission computed tomography fusion imaging

AIM: To evaluate the usefulness of the functional hepatic resection rate (FHRR) calculated using 3D computed tomography (CT)/99mTc-galactosyl-human serum albumin (GSA) single-photon emission computed tomography (SPECT) fusion imaging for surgical decision making.METHODS: We enrolled 57 patients who underwent bi- or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and 99mTc-GSA scintigraphy. We compared the parenchymal hepatic resection rate (PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/99mTc-GSA SPECT fusion images.RESULTS: In total, 50 patients underwent bisectionectomy and seven underwent trisectionectomy. Biliary reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 ± 19.9 and 44.5 ± 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16 (P < 0.0001). The ratio of FHRR to PHRR for patients with preoperative therapies (transcatheter arterial chemoembolization, radiation, radiofrequency ablation, etc.), large tumors with a volume of > 1000 mL, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors (0.73 ± 0.19 vs 0.82 ± 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities (Clavien-Dindo grade ≥ 3) occurred in 17 patients (29.8%). There was no case of surgery-related death.CONCLUSION: Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, macroscopic vascular invasion, and/or a tumor volume of > 1000 mL.

Gum resin extract of Boswellia serrata attenuates lipopolysaccharide-induced inflammation and oxidative damage in hepatic and renal tissues of rats

Objective:To explore the effect of ethyl acetate gum resin extract of Boswellia serrata on lipopolysaccharide(LPS)induced inflammation and oxidative damage in hepatic and renal tissues of rats.Methods:The rats were divided into four groups:control,LPS,LPS+Boswellia serrata extracts(100 mg/kg and 200 mg/kg).LPS(1 mg/kg)and the extract(100 and 200 mg/kg,30 min before LPS)were administered intraperitoneally for 3 weeks.The levels of liver enzymes,albumin,total protein,creatinine,blood urea nitrogen(BUN),interleukin(IL)-6,malondialdehyde(MDA),and total thiol groups and superoxide dismutase(SOD)and catalase(CAT)activities were measured.Results:The levels of liver enzymes,creatinine,and BUN,IL-6,MDA in the LPS group were markedly increased(P<0.001)while albumin,total protein,and total thiol concentration,as well as SOD and CAT activities,were decreased compared with the control group(P<0.05 or 0.01).Boswellia serrata extracts diminished the levels of liver enzymes,creatinine,BUN,IL-6,and MDA(P<0.01 and P<0.001),and elevated the concentration of total protein and total thiol and SOD and CAT activities(P<0.05 or 0.01).Conclusions:The ethyl acetate gum resin extract of Boswellia serrata reduces LPS-induced inflammatory reactions and oxidative damage,thus ameliorating hepatic and renal function.

Framework nucleic Acid-MicroRNA mediated hepatic differentiation and functional hepatic spheroid development for treating acute liver failure

The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.

Liver Dysfunction in Sternness Burn Injury in Association to Age Estimate: A Conceivable Role of Antioxidant Biomarker and Tumor Necrosis Factor Alpha

Background: Burn injuries represent one of the greatest public health problems that induce significant patient morbidity and mortality. Scalds are the most common cause of burn injuries which is known to have long term grave consequences on general health. Aim: The current study was performed to identify the age of scald burn from histopathological changes and TNF-α immunoexpression. As well, study the probable relation between the scald age and the hepatic function impairment. Materials and Methods: A total number of 40 adult male albino rats were used in the study. Eight kept as control group I. Thirty-two rats were exposed to scald injury involving 20% of total body surface area (TBSA). Histopathological examination for the scald area, liver, and skin TNF-α immunohistochemistry was performed. Liver function tests and liver tissue malondialdehyde (MDA) were also determined. The study was carried out after 2, 7 days, 1 and 3 months of scald incidence. Results: Progressive histopathological changes and elevated liver enzymes were observed in the early scald ages while manifestations of healing and improvement in liver parameters, started to occur after 1 and 3 months of scald infliction in comparison with the other periods. There was a highly significant (P Conclusion: Overall, the results showed the ability to identify the age of scald injury using routine histopathological examination. Also, scald injury involving 20% of TBSA may cause long term impairment of hepatic function. Moreover, the proinflammatory results revealed that TNF-α may consider as mediators in the post-burn pathophysiological process. Furthermore, our results declare a significant correlation between MDA levels and the degree of burn complications, including shock and remote organ damage.

OPTIMIZATION OF TETRANDRINE TREATMENT IN RAT HEPATIC FIBROSIS MODEL

Objective To optimize the therapeutic dosage of tetrandrine （Tet） in rat hepatic fibrosis roodel. Methods 50 Wistar rats were divided into 5 groups at random including normal control, model control, Tettreated model groups of 10mg· kg^ - 1· d^ - 1, 5mg· kg^ - 1· d^ - 1 and 2.5mg· kg^ - 1· d^ - 1（ n = 10 in each group ）. All rats, except for the normal controls, were injected with axenic porcine serum （0. 5ml each time, twice a week） intraperitoneally for 8 weeks to establish hepatic fibrosis. After the 8th week, rats of Tet-treated model groups were given by gavage once a day with different doses of Tet for another 8 weeks. Then the liver function, serum levels of hyaluronic acid （ HA ）, laminin （ LM）, and procollagen type Ⅲ （PCⅢ） were tested. Collagen type 1 and Ⅲ, pathological changes in liver tissue were also assessed. Results Most indices of liver function including alanine minotransferase （ALT）, aspartate aminotransferase （AST）, albumin （ ALB）, albumin/globulin ratio （ A/G） and alkaline phosphatase （ALP） improved significantly in Tet-treated groups with the exception of γ-glutamyl transpeptidase （γ- GT） and total bilirubin （TBIL）. Secondly, markedly lowered levels of HA, LM and collagen type I, III were also detected by radioimmunology and immunohistochemistry in the 5 mg· kg^ - 1· d^ - 1 Tet-treated model group. Moreover, pathologi- cal findings confirmed the statistically significant improvement in hepatofibrotic degree resulted from the treatment of 5mg· kg^ - 1· d^ - 1 rather than other doses of Tet. Conclusion For experimental Wistar rats, Tet exhibited an anti-hepatofibrotic action in doses within the range of 2.5mg· kg^ - 1· d^ - 1 to 10mg· kg^ - 1· d^ - 1 and 5mg· kg^ - 1· d^ - 1 may be the optimum one among all doses.

Professor Zhang Ning's experience in treating hyperthyroidism from liver

In recent years,due to the increasingly accelerated pace of life,the incidence of hyperthyroidism is increasing year by year,which has a serious impact on the quality of life of patients.Traditional Chinese Medicine has a unique effect on hyperthyroidism,Professor Zhang Ning,my tutor,who has been devoting to the clinical study of traditional Chinese medicine in the prevention and treatment of thyroid diseases for a long time,has rich theoretical knowledge as well as clinical practice experience.She's also good at using classical prescriptions for syndrome differentiation treatment,and has achieved excellent clinical efficacy.Professor Zhang Ning summarized the diagnosis and treatment idea of"treating from the liver"and ran it throughout the whole treatment process.For the patients prone to abnormal liver function,it is advocated to focus on protecting the liver in terms of medication,increase the effect of anti-hyperthyroidism,and also obtain satisfactory efficacy.

Ypel5 regulates liver development and function in zebrafish

YPEL5 is a member of the Yippee-like(YPEL)gene family that is evolutionarily conserved in eukaryotic species.To date,the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models.Here,using CRISPR/Cas9-mediated genome editing,we generated a stable ypel5^(−/−)mutant zebrafish line.Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation.Meanwhile,hepatic metabolism and function are dysregulated in ypel5^(−/−)mutant zebrafish,as revealed by metabolomic and transcriptomic analyses.Mechanistically,Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5.Zebrafish hnf4a overexpression could largely rescue ypel5 deficiencyinduced hepatic defects.Furthermore,PPARαsignaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene.Herein,this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

Expectations for partial splenic arterial embolization simultaneous transcatheter arterial chemoembolization for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is frequently complicated by cirrhosis,and it is not unusual for treatment options to be limited as a result of pancytopenia due to hypersplenism.Partial splenic embolization(PSE)has been performed for thrombocytopenia resulting from hypersplenism.However,the safety and effi cacy of concurrent transcatheter arterial chemoembolization(TACE)with PSE for HCC remain unclear.Thrombocytopenia has been improved,and treatment continued using concurrent PSE.In addition,the hepatic functional reserve could be maintained even after treatment for HCC.Concurrent TACE and PSE for HCC with thrombocytopenia can be expected to help maintain a hepatic reserve,and it may contribute to improving the prognosis of HCC.Hence,PSE could lead to an asplenic state.The appearance of Howell-Jolly bodies on a peripheral blood smear is reported useful for assessing splenic function.The appearance of Howell-Jolly bodies is associated with an increased risk for post-splenectomy sepsis/overwhelming post-splenectomy infection in patients with reduced splenic function.These bodies are frequently observed in peripheral erythrocytes after PSE,and when they are present,it is appropriate to administer the pneumococcal vaccine to prevent severe infection.The expectations for PSE combined with TACE for the treatment of HCC associated with cirrhosis are reviewed.