AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir(0.5 mg) in Chinese nucleosidenaive patients with cirrhosis.METHODS: A total of 204 nucleoside-naive patients with compensated(n = 96) or decomp...AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir(0.5 mg) in Chinese nucleosidenaive patients with cirrhosis.METHODS: A total of 204 nucleoside-naive patients with compensated(n = 96) or decompensated(n = 108) hepatitis B virus(HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital(Jilin University, Changchun, China) who were treated with entecavir(0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment(baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/m L, the association of interleukin-28 B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ2 test.RESULTS: At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/m L. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype(CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pughclass A disease was significantly increased at week 240(68%) from the baseline(47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240(25%) from the baseline(39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points(7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points(5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01).CONCLUSION: Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.展开更多
AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined...AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm nonalcoholic liver disease(NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score(NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic(ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis,lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08(95%CI: 1.03-1.14), 1.04(95%CI: 1.008-1.07), 1.04(95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4(95%CI: 1.09-1.8), 1.07(95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06(95%CI: 1.002-1.12), 19.86(95%CI: 2.79-141.19), 560.72(95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05(95%CI: 1.01-1.1), 1.13(95%CI: 1.04-1.22), P < 0.05]. CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.展开更多
AIM: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Sixty (mean age 40.0 ± 8.5 yea...AIM: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m 2 ). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. RESULTS: Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m 2 to 25.0 ± 3.3 kg/m 2 , WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r s = 0.90) and liver histology (P = 0.03, r s = 0.73). CONCLUSION: Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients.展开更多
AIM: To define the normal range of liver stiffness(LS) values using transient elastography in living-related liver transplantation candidate donors with normal liver histology. METHODS: LS was measured using Fibroscan...AIM: To define the normal range of liver stiffness(LS) values using transient elastography in living-related liver transplantation candidate donors with normal liver histology. METHODS: LS was measured using Fibroscan in 50(16 women, 34 men) healthy potential donors(mean age 28.4 ± 5.9 years) who were being evaluated for liver donation for their relatives at the National Liver Institute, Menoufeya University, Egypt. All potential donors had normal liver tests and were negative for hepatitis B or C virus infection. Abdominal ultrasounds showed normal findings. None of the subjects had diabetes, hypertension, renal impairment, heart disease, or body mass index > 30 kg/m2. All subjects had normal liver histology upon liver biopsy. They all donated the right lobe of their liver with successful outcomes.RESULTS: The mean LS was 4.3 ± 1.2 k Pa(range: 1.8-7.1 k Pa). The 5th and 95 th percentiles of normal LS were 2.6 k Pa and 6.8 k Pa, respectively, with a median of 4 k Pa; the interquartile range was 0.6 ± 0.4. LS measurements were not significantly different between men and women(4.4 ± 1.1 k Pa vs 3.9 ± 1.3 k Pa) and did not correlate with age. However, stiffness values were significantly lower in subjects with a body mass index < 26 kg/m2 compared to those with an index ≥ 26 kg/m2(4.0 ± 1.1 k Pa vs 4.6 ± 1.2 k Pa; P <0.05). There were no differences in hospital stay or postoperative bilirubin, albumin,alanine and aspartate transaminases, or creatinine levels(at discharge) between donors with livers stiffness ≤ 4 k Pa and those with stiffness > 4 k Pa. CONCLUSION: Healthy donors with normal liver histology have a median LS of 4 k Pa. Stiffness values are elevated relative to increase in body mass index.展开更多
Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is more common in diabetic patients. There are limited studies on clinical, biochemical and histological features of NAFLD patients who are diabetic...Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is more common in diabetic patients. There are limited studies on clinical, biochemical and histological features of NAFLD patients who are diabetic. The aim of the study was to determine the prevalence of diabetes and prediabetes in a cohort of NAFLD patients and to compare anthropometry, biochemical and metabolic parameters and hepatic histology of diabetic NAFLD patients with non-diabetic NAFLD patients. Methods: 515 consecutive NAFLD patients diagnosed by abdominal ultrasound and 100 healthy controls were subjected to detailed anthropometric measurements and biochemical assays including blood sugars, LFT, lipid profile and HOMA. Diabetes and prediabetes were defined according to WHO criteria. Patients were categorized and compared according to the presence or absence of diabetes. Liver biopsy was performed in 240 NAFLD patients and the liver histology was also compared between the two groups. Statistical analysis was performed on SPSS 16. Results: 124 out of the 515 (24.08%) NAFLD patients were diabetics, 118 out of 515 (22.9%) were pre-diabetics, while only 3 out of 100 controls had impaired glucose tolerance. Diabetic patients were older. NAFLD patients with diabetes had significantly higher waist circumference [98.02 ± 12.01 vs 93.89 ± 8.8, p = 0.000] as compared to the NAFLD patients without diabetes. Fasting blood sugar [124 ± 46.3 vs 90.8 ± 10.2, p = 0.000], triglyceride level [218.4 ± 17.6 vs 192 ± 9, p = 0.03] and HOMA-IR [2.6 ± 0.36 vs 1.84 ± 0.2, p < 0.001] were significantly higher in NAFLD-diabetes group. Hypertension [35% vs 11.7%, p = 0.000] was commoner in diabetic NAFLD patients. Histopathology in the diabetic patients revealed steatosis alone in 34.2% cases, borderline NASH in 31.4% and definite NASH in 34.2%. Fatty change alone was noted in 16.5% cases, borderline NASH in 34.1%, while 49% had definite NASH on liver biopsy of NAFLD patients without diabetes. Fibrosis was noted in 31.4% in diabetic and 27% in non-diabetic patients. IR alone had a linear correlation with necroinflammatory activity. Conclusion: The prevalence of diabetes and prediabetes is six times more in NAFLD patients than in healthy controls. NAFLD patients with diabetes have higher metabolic risk factors such as large waistline, hypertension, high triglyceride levels and increased insulin resistance. Diabetes or pre diabetes patients per se do not have histologically severe disease, rather insulin resistance play an important role in increasing the severity of the disease.展开更多
AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (...AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (40 male,41 fe-male) who were diagnosed with fatty liver by ultraso-nographic scan and fulfi lled the inclusion criteria. First anamnesis,anthropometric,clinical,laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification. RESULTS:Sixty-nine of the 81 patients had nonalco-holic steatohepatitis (NASH),11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation. Comparisons were made between two groups of NASH patients,those with and without metabolic syndrome. We did not detect statistically significant differences in liver histology between NASH patients with and wit-hout metabolic syndrome. CONCLUSION:NASH can progress without metabolic risk factors or the presence of metabolic syndrome.展开更多
AIM:To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis ...AIM:To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver bi- opsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholan- gitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was ob- served in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was as- sociated with increased hospitalization in the ICU prior death (P = 0.026). CONCLUSION: Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.展开更多
BACKGROUND Exposure to high sustained +Gz(head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the prec...BACKGROUND Exposure to high sustained +Gz(head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined.AIM To investigate rat liver function changes in response to repeated +Gz exposure.METHODS Ninety male Wistar rats were randomly divided into a blank control group(BC group, n = 30), a +6 Gz/5 min stress group(6 GS group, n = 30), and a +10 Gz/5 min stress group(10 GS group, n = 30). The 6 GS and 10 GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure(for 5 exposures, and 5-min intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury bymeasuring the portal venous flow volume, serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST), liver tissue malondialdehyde(MDA), Na+-K+-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures.RESULTS After repeated +Gz exposures in the 6 GS and the 10 GS groups, the velocity and flow signal in the portal vein(PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6 GS group had a much higher portal venous flow volume than the 10 GS group at 0 h after exposure. The 6 GS group had significantly lower ALT, AST, and MDA values than the 10 GS group 0 h and 6 h post exposure. The Na^+-K^+-ATPase activity in the 6 GS group was significantly higher than that in the 10 GS group 0 h and 6 h post exposure.Hepatocyte injury, determined pathologically, was significantly lower in the 6 GS group than in the 10 GS group.CONCLUSION Repeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.展开更多
Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary man...Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil(cholesterol free diet) and 1% HC containing 12% olive oil(HC+OO) enriched with MUFA and 12% sunflower oil(HC+SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results: Comparatively, rats treated with HC+OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC+SO diet(P<0.05). Otherwise, HC+OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions: HC+OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC+SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC+OO diet can be caused by the delay in the FA release to the blood.展开更多
To examine the effect of Gankang Suppository on duck hepatitis B virus (DHBV), the serum biochemistry and hepatic histology in an animal model of DHBV infection, a model of DHBV infection was established by infecting ...To examine the effect of Gankang Suppository on duck hepatitis B virus (DHBV), the serum biochemistry and hepatic histology in an animal model of DHBV infection, a model of DHBV infection was established by infecting 1-day-old Yingtaogu ducklings with DHBV-positive serum. The successful model was confirmed by PCR assay and 48 ducklings infected with DHBV were randomly divided into 3 groups: a Gankang Suppository treatment group, an acyclovir (ACV) group and a DHBV model group (control), with each group having 16 animals. All the animals were given the medicines for 4 weeks in a row. The serum of the animals was taken 14 and 28 days after the medica- tion and 7 days after drug discontinuation. Real-time PCR was performed to detect the copy numbers of DHBV DNA in the serum. ALT and AST were dynamically monitored. The ducklings were sacrificed on the 7th day after the discontinuation of the treatment and livers were harvested and examined for inflammation and degeneration of liver cells by using HE staining. The results showed that on day 14, 28 after the treatment and day 7 after the withdrawal, the logarithmic values (log) of DHBV DNA copy numbers in ducklings of Gankang Suppository treatment group were significantly lower than that before the treatment (P=0.0092, P=0.0070, P=0.0080, respectively). Compared with DHBV model control group, the ALT level was significantly decreased (P=0.0020, P=0.0019, respectively) on day 28 after the treatment and on day 7 after the withdrawal. The AST level was also reduced on day 14 after the treatment (P=0.0298). Compared with the ACV control group, the level of ALT was lower on day 7 after the withdrawal (P=0.0016). Histologically, the hepatocyte swelling, vacuolous degeneration and acidophilic degeneration in Gankang Suppository treatment group were alleviated 7 days after the withdrawal as compared with model control group (P=0.0282, P=0.0084, P=0.0195, respectively). It is concluded that Gankang Suppository can effectively suppress DHBV replication, reduce the levels of serum ALT and AST and improve hepatic histology.展开更多
AIM To evaluate the relationship between serum adenosine deaminase(ADA) levels and histological features in patients with autoimmune hepatitis(AIH).METHODS A total of 80 subjects(52 AIH cases and 28 healthy controls) ...AIM To evaluate the relationship between serum adenosine deaminase(ADA) levels and histological features in patients with autoimmune hepatitis(AIH).METHODS A total of 80 subjects(52 AIH cases and 28 healthy controls) were included in the study. Patients were diagnosed according to the simplified criteria suggested by the International Autoimmune Hepatitis Group. All of the cases had been diagnosed with AIH between 2010-2015 at Hacettepe University, Department of Gastroenterology. Serum blood samples were collected and stored at-80 ℃ until the biochemical estimation of ADA activity. The diagnosis of patients was confirmed by liver biopsy. Serum ADA > 20 U/L was considered to be high level.RESULTS Mean serum ADA levels were significantly higher in AIH patients than those in healthy controls(25.4 ± 9.6 U/L vs 12.8 ± 2.2 U/L, P < 0.001). Serum ADA levels > 20 U/L were found in 63.5% AIH patients and in 0% healthy controls(P < 0.001). Mean serum ADA levels were significantly increased in each stage of histological activity: 15.2 ± 3.5 U/L for patients with mild interface hepatitis, 23.1 ± 10.0 U/L for patients with moderate interface hepatitis and 30.9 ± 7.0 U/L for patients with severe interface hepatitis(P < 0.001). Correlation analysis showed that there was a positive association between serum ADA levels and histological activity(r = 0.71, P < 0.001). Receiver operating characteristic analysis suggested that 24.5 U/L was the optimum cut-off point of ADA level for severe interface hepatitis(sensitivity 88%, specificity 85.2%, area under thecurve: 0.88).CONCLUSION Because of the positive correlation with inflammatory activity, serum ADA level may be a potential biomarker for predicting or monitoring histological activity in patients with AIH.展开更多
AIM To determine incidence and clinical biomarkers of marked necroinflammation and fibrosis characteristics among chronic hepatitis B(CHB) patients with persistently normal alanine aminotransferase(PNALT).METHODS Live...AIM To determine incidence and clinical biomarkers of marked necroinflammation and fibrosis characteristics among chronic hepatitis B(CHB) patients with persistently normal alanine aminotransferase(PNALT).METHODS Liver biopsy was performed on 115 CHB patients with PNALT. Necroinflammation and fibrosis were graded by the Knodell histologic activity index and the Ishak fibrosis score, respectively. Correlations between the available clinical parameters and necroinflammation and fibrosis were analysed.RESULTS Marked necroinflammation(Knodell activity index ≥ 7) and fibrosis(Ishak fibrosis score ≥ 3) were found in 36.5% and 15.5% of CHB patients with PNALT, respectively. Following a univariate logistic regression analysis, multiple logistic regression analysis indicated that aspartate transaminase(AST)(AUROC = 0.852, cut-off value = 22.5 U/L) serves as an independent predictor of notable liver inflammation, while platelet(PLT) count(AUROC = 0.905, cut-off value = 171.5 ×109/m L) and gamma-glutamyl transpeptidase(GGT)(AUROC = 0.909, cut-off value = 21.5 U/L) level serve as independent predictors of notable liver fibrosis.CONCLUSION A considerable proportion of marked histological abnormalities existed in our cohort, who will benefit from optimal therapeutic strategies administered according to predictive indication by AST, PLT and GGT levels.展开更多
The present study was conducted to determine the effects of dietary phosphorus(P)levels on growth performance,body composition,liver histology and enzymatic activity,and expression of lipid metabolism-related genes in...The present study was conducted to determine the effects of dietary phosphorus(P)levels on growth performance,body composition,liver histology and enzymatic activity,and expression of lipid metabolism-related genes in spotted seabass(Lateolabrax maculatus).Seven diets were prepared to contain available P levels of 0.48%(the control group),0.69%,0.89%,1.10%,1.28%,1.51%and 1.77%and feed fish(4.26±0.03 g)to satiety twice daily for 10 weeks.Significantly higher weight gain and specific growth rate were recorded at P levels of 0.69%-1.51%compared to the control group.Feed conversion ratio decreased with increasing P levels up to 0.89%and increased thereafter.The lowest liver lipid content,viscerosomatic index and lipid content of whole-body were obtained in the 0.89%-P group among dietary treatments.P and calcium(Ca)contents in whole body were increased,while liver triglyceride and cholesterol contents were decreased with increasing dietary P levels from 0.48%to 1.77%.The highest activity of hepatic lipase was recorded in the 1.10%-P group among dietary treatments.Compared to the control group,1.10%P enhanced the proportion of HUFA and reduced the proportion of SFA and MUFA.The histological observations showed that P deficiency(0.48%)led to the vacuolization of hepatocytes and increased number of lipid droplets.Meanwhile,overall liver tissue structure was improved when P level increased to 1.28%.Compared to the control group,expression of lipid metabolism-related genes such as FAS,ACC-2 and SREBP-1 was decreased at 0.89%-1.10%P group while an opposite trend was observed in the expression of PPARa2 and CPT-1 genes.The current study showed that 0.89%dietary P levels could promote growth performance of spotted seabass and reduce lipid accumulation in the liver.A broken-line regression analysis based on weight gain showed that the optimum dietary P level(available P)for juvenile spotted seabass reared in freshwater was 0.72%.展开更多
Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which ...Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.展开更多
BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are p...BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.展开更多
Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Stud-ies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is...Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Stud-ies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.展开更多
Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the r...Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver re-section and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic pa-tients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.展开更多
The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary chola...The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.展开更多
基金Supported by Grant from the Youth scientific research fund,No.2013207059
文摘AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir(0.5 mg) in Chinese nucleosidenaive patients with cirrhosis.METHODS: A total of 204 nucleoside-naive patients with compensated(n = 96) or decompensated(n = 108) hepatitis B virus(HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital(Jilin University, Changchun, China) who were treated with entecavir(0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment(baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/m L, the association of interleukin-28 B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ2 test.RESULTS: At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/m L. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype(CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pughclass A disease was significantly increased at week 240(68%) from the baseline(47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240(25%) from the baseline(39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points(7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points(5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01).CONCLUSION: Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.
文摘AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm nonalcoholic liver disease(NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score(NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic(ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis,lobular inflammation and fibrosis. RESULTS: Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08(95%CI: 1.03-1.14), 1.04(95%CI: 1.008-1.07), 1.04(95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4(95%CI: 1.09-1.8), 1.07(95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06(95%CI: 1.002-1.12), 19.86(95%CI: 2.79-141.19), 560.72(95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05(95%CI: 1.01-1.1), 1.13(95%CI: 1.04-1.22), P < 0.05]. CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.
文摘AIM: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m 2 ). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. RESULTS: Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m 2 to 25.0 ± 3.3 kg/m 2 , WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r s = 0.90) and liver histology (P = 0.03, r s = 0.73). CONCLUSION: Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients.
文摘AIM: To define the normal range of liver stiffness(LS) values using transient elastography in living-related liver transplantation candidate donors with normal liver histology. METHODS: LS was measured using Fibroscan in 50(16 women, 34 men) healthy potential donors(mean age 28.4 ± 5.9 years) who were being evaluated for liver donation for their relatives at the National Liver Institute, Menoufeya University, Egypt. All potential donors had normal liver tests and were negative for hepatitis B or C virus infection. Abdominal ultrasounds showed normal findings. None of the subjects had diabetes, hypertension, renal impairment, heart disease, or body mass index > 30 kg/m2. All subjects had normal liver histology upon liver biopsy. They all donated the right lobe of their liver with successful outcomes.RESULTS: The mean LS was 4.3 ± 1.2 k Pa(range: 1.8-7.1 k Pa). The 5th and 95 th percentiles of normal LS were 2.6 k Pa and 6.8 k Pa, respectively, with a median of 4 k Pa; the interquartile range was 0.6 ± 0.4. LS measurements were not significantly different between men and women(4.4 ± 1.1 k Pa vs 3.9 ± 1.3 k Pa) and did not correlate with age. However, stiffness values were significantly lower in subjects with a body mass index < 26 kg/m2 compared to those with an index ≥ 26 kg/m2(4.0 ± 1.1 k Pa vs 4.6 ± 1.2 k Pa; P <0.05). There were no differences in hospital stay or postoperative bilirubin, albumin,alanine and aspartate transaminases, or creatinine levels(at discharge) between donors with livers stiffness ≤ 4 k Pa and those with stiffness > 4 k Pa. CONCLUSION: Healthy donors with normal liver histology have a median LS of 4 k Pa. Stiffness values are elevated relative to increase in body mass index.
文摘Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is more common in diabetic patients. There are limited studies on clinical, biochemical and histological features of NAFLD patients who are diabetic. The aim of the study was to determine the prevalence of diabetes and prediabetes in a cohort of NAFLD patients and to compare anthropometry, biochemical and metabolic parameters and hepatic histology of diabetic NAFLD patients with non-diabetic NAFLD patients. Methods: 515 consecutive NAFLD patients diagnosed by abdominal ultrasound and 100 healthy controls were subjected to detailed anthropometric measurements and biochemical assays including blood sugars, LFT, lipid profile and HOMA. Diabetes and prediabetes were defined according to WHO criteria. Patients were categorized and compared according to the presence or absence of diabetes. Liver biopsy was performed in 240 NAFLD patients and the liver histology was also compared between the two groups. Statistical analysis was performed on SPSS 16. Results: 124 out of the 515 (24.08%) NAFLD patients were diabetics, 118 out of 515 (22.9%) were pre-diabetics, while only 3 out of 100 controls had impaired glucose tolerance. Diabetic patients were older. NAFLD patients with diabetes had significantly higher waist circumference [98.02 ± 12.01 vs 93.89 ± 8.8, p = 0.000] as compared to the NAFLD patients without diabetes. Fasting blood sugar [124 ± 46.3 vs 90.8 ± 10.2, p = 0.000], triglyceride level [218.4 ± 17.6 vs 192 ± 9, p = 0.03] and HOMA-IR [2.6 ± 0.36 vs 1.84 ± 0.2, p < 0.001] were significantly higher in NAFLD-diabetes group. Hypertension [35% vs 11.7%, p = 0.000] was commoner in diabetic NAFLD patients. Histopathology in the diabetic patients revealed steatosis alone in 34.2% cases, borderline NASH in 31.4% and definite NASH in 34.2%. Fatty change alone was noted in 16.5% cases, borderline NASH in 34.1%, while 49% had definite NASH on liver biopsy of NAFLD patients without diabetes. Fibrosis was noted in 31.4% in diabetic and 27% in non-diabetic patients. IR alone had a linear correlation with necroinflammatory activity. Conclusion: The prevalence of diabetes and prediabetes is six times more in NAFLD patients than in healthy controls. NAFLD patients with diabetes have higher metabolic risk factors such as large waistline, hypertension, high triglyceride levels and increased insulin resistance. Diabetes or pre diabetes patients per se do not have histologically severe disease, rather insulin resistance play an important role in increasing the severity of the disease.
基金Supported by Uludag University Scientific Project Grant
文摘AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (40 male,41 fe-male) who were diagnosed with fatty liver by ultraso-nographic scan and fulfi lled the inclusion criteria. First anamnesis,anthropometric,clinical,laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification. RESULTS:Sixty-nine of the 81 patients had nonalco-holic steatohepatitis (NASH),11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation. Comparisons were made between two groups of NASH patients,those with and without metabolic syndrome. We did not detect statistically significant differences in liver histology between NASH patients with and wit-hout metabolic syndrome. CONCLUSION:NASH can progress without metabolic risk factors or the presence of metabolic syndrome.
文摘AIM:To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver bi- opsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholan- gitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was ob- served in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was as- sociated with increased hospitalization in the ICU prior death (P = 0.026). CONCLUSION: Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.
文摘BACKGROUND Exposure to high sustained +Gz(head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined.AIM To investigate rat liver function changes in response to repeated +Gz exposure.METHODS Ninety male Wistar rats were randomly divided into a blank control group(BC group, n = 30), a +6 Gz/5 min stress group(6 GS group, n = 30), and a +10 Gz/5 min stress group(10 GS group, n = 30). The 6 GS and 10 GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure(for 5 exposures, and 5-min intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury bymeasuring the portal venous flow volume, serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST), liver tissue malondialdehyde(MDA), Na+-K+-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures.RESULTS After repeated +Gz exposures in the 6 GS and the 10 GS groups, the velocity and flow signal in the portal vein(PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6 GS group had a much higher portal venous flow volume than the 10 GS group at 0 h after exposure. The 6 GS group had significantly lower ALT, AST, and MDA values than the 10 GS group 0 h and 6 h post exposure. The Na^+-K^+-ATPase activity in the 6 GS group was significantly higher than that in the 10 GS group 0 h and 6 h post exposure.Hepatocyte injury, determined pathologically, was significantly lower in the 6 GS group than in the 10 GS group.CONCLUSION Repeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.
文摘Objective: To compare the effects of high-monounsaturated(MUFA) and polyunsaturated fatty acids(PUFA) against the metabolic disorders elicited by a high-cholesterol diet(HC) in rats. Methods: Using in vivo dietary manipulation, rats were fed with different diets containing 4% soybean oil(cholesterol free diet) and 1% HC containing 12% olive oil(HC+OO) enriched with MUFA and 12% sunflower oil(HC+SO) enriched with PUFA for 60 d. Serum lipid levels and hepatic steatosis were evaluated after the treatment period. Results: Comparatively, rats treated with HC+OO diet experienced a decrease in the serum LDL-C, VLDL-C and CT levels compared to those fed with HC+SO diet(P<0.05). Otherwise, HC+OO provoked significant microvesicular steatosis situated in the hepatic acinar zone 1. Conclusions: HC+OO diet has high absorption velocity in the acinar zone 1 of liver compared to the HC+SO diet. Based on this, the reduction of the LDL-C, VLDL-C and CT serum levels in the animals treated with HC+OO diet can be caused by the delay in the FA release to the blood.
基金the National Natural Science Foundation of China (No. 30471533)
文摘To examine the effect of Gankang Suppository on duck hepatitis B virus (DHBV), the serum biochemistry and hepatic histology in an animal model of DHBV infection, a model of DHBV infection was established by infecting 1-day-old Yingtaogu ducklings with DHBV-positive serum. The successful model was confirmed by PCR assay and 48 ducklings infected with DHBV were randomly divided into 3 groups: a Gankang Suppository treatment group, an acyclovir (ACV) group and a DHBV model group (control), with each group having 16 animals. All the animals were given the medicines for 4 weeks in a row. The serum of the animals was taken 14 and 28 days after the medica- tion and 7 days after drug discontinuation. Real-time PCR was performed to detect the copy numbers of DHBV DNA in the serum. ALT and AST were dynamically monitored. The ducklings were sacrificed on the 7th day after the discontinuation of the treatment and livers were harvested and examined for inflammation and degeneration of liver cells by using HE staining. The results showed that on day 14, 28 after the treatment and day 7 after the withdrawal, the logarithmic values (log) of DHBV DNA copy numbers in ducklings of Gankang Suppository treatment group were significantly lower than that before the treatment (P=0.0092, P=0.0070, P=0.0080, respectively). Compared with DHBV model control group, the ALT level was significantly decreased (P=0.0020, P=0.0019, respectively) on day 28 after the treatment and on day 7 after the withdrawal. The AST level was also reduced on day 14 after the treatment (P=0.0298). Compared with the ACV control group, the level of ALT was lower on day 7 after the withdrawal (P=0.0016). Histologically, the hepatocyte swelling, vacuolous degeneration and acidophilic degeneration in Gankang Suppository treatment group were alleviated 7 days after the withdrawal as compared with model control group (P=0.0282, P=0.0084, P=0.0195, respectively). It is concluded that Gankang Suppository can effectively suppress DHBV replication, reduce the levels of serum ALT and AST and improve hepatic histology.
文摘AIM To evaluate the relationship between serum adenosine deaminase(ADA) levels and histological features in patients with autoimmune hepatitis(AIH).METHODS A total of 80 subjects(52 AIH cases and 28 healthy controls) were included in the study. Patients were diagnosed according to the simplified criteria suggested by the International Autoimmune Hepatitis Group. All of the cases had been diagnosed with AIH between 2010-2015 at Hacettepe University, Department of Gastroenterology. Serum blood samples were collected and stored at-80 ℃ until the biochemical estimation of ADA activity. The diagnosis of patients was confirmed by liver biopsy. Serum ADA > 20 U/L was considered to be high level.RESULTS Mean serum ADA levels were significantly higher in AIH patients than those in healthy controls(25.4 ± 9.6 U/L vs 12.8 ± 2.2 U/L, P < 0.001). Serum ADA levels > 20 U/L were found in 63.5% AIH patients and in 0% healthy controls(P < 0.001). Mean serum ADA levels were significantly increased in each stage of histological activity: 15.2 ± 3.5 U/L for patients with mild interface hepatitis, 23.1 ± 10.0 U/L for patients with moderate interface hepatitis and 30.9 ± 7.0 U/L for patients with severe interface hepatitis(P < 0.001). Correlation analysis showed that there was a positive association between serum ADA levels and histological activity(r = 0.71, P < 0.001). Receiver operating characteristic analysis suggested that 24.5 U/L was the optimum cut-off point of ADA level for severe interface hepatitis(sensitivity 88%, specificity 85.2%, area under thecurve: 0.88).CONCLUSION Because of the positive correlation with inflammatory activity, serum ADA level may be a potential biomarker for predicting or monitoring histological activity in patients with AIH.
基金Supported by the National Science and Technology Major Project of China,No.2012ZX10002004-001
文摘AIM To determine incidence and clinical biomarkers of marked necroinflammation and fibrosis characteristics among chronic hepatitis B(CHB) patients with persistently normal alanine aminotransferase(PNALT).METHODS Liver biopsy was performed on 115 CHB patients with PNALT. Necroinflammation and fibrosis were graded by the Knodell histologic activity index and the Ishak fibrosis score, respectively. Correlations between the available clinical parameters and necroinflammation and fibrosis were analysed.RESULTS Marked necroinflammation(Knodell activity index ≥ 7) and fibrosis(Ishak fibrosis score ≥ 3) were found in 36.5% and 15.5% of CHB patients with PNALT, respectively. Following a univariate logistic regression analysis, multiple logistic regression analysis indicated that aspartate transaminase(AST)(AUROC = 0.852, cut-off value = 22.5 U/L) serves as an independent predictor of notable liver inflammation, while platelet(PLT) count(AUROC = 0.905, cut-off value = 171.5 ×109/m L) and gamma-glutamyl transpeptidase(GGT)(AUROC = 0.909, cut-off value = 21.5 U/L) level serve as independent predictors of notable liver fibrosis.CONCLUSION A considerable proportion of marked histological abnormalities existed in our cohort, who will benefit from optimal therapeutic strategies administered according to predictive indication by AST, PLT and GGT levels.
基金This study was supported by National Natural Science Foundation of China(grant number:31972804)the China Agricultural Research System(grant number:CARS47-14).
文摘The present study was conducted to determine the effects of dietary phosphorus(P)levels on growth performance,body composition,liver histology and enzymatic activity,and expression of lipid metabolism-related genes in spotted seabass(Lateolabrax maculatus).Seven diets were prepared to contain available P levels of 0.48%(the control group),0.69%,0.89%,1.10%,1.28%,1.51%and 1.77%and feed fish(4.26±0.03 g)to satiety twice daily for 10 weeks.Significantly higher weight gain and specific growth rate were recorded at P levels of 0.69%-1.51%compared to the control group.Feed conversion ratio decreased with increasing P levels up to 0.89%and increased thereafter.The lowest liver lipid content,viscerosomatic index and lipid content of whole-body were obtained in the 0.89%-P group among dietary treatments.P and calcium(Ca)contents in whole body were increased,while liver triglyceride and cholesterol contents were decreased with increasing dietary P levels from 0.48%to 1.77%.The highest activity of hepatic lipase was recorded in the 1.10%-P group among dietary treatments.Compared to the control group,1.10%P enhanced the proportion of HUFA and reduced the proportion of SFA and MUFA.The histological observations showed that P deficiency(0.48%)led to the vacuolization of hepatocytes and increased number of lipid droplets.Meanwhile,overall liver tissue structure was improved when P level increased to 1.28%.Compared to the control group,expression of lipid metabolism-related genes such as FAS,ACC-2 and SREBP-1 was decreased at 0.89%-1.10%P group while an opposite trend was observed in the expression of PPARa2 and CPT-1 genes.The current study showed that 0.89%dietary P levels could promote growth performance of spotted seabass and reduce lipid accumulation in the liver.A broken-line regression analysis based on weight gain showed that the optimum dietary P level(available P)for juvenile spotted seabass reared in freshwater was 0.72%.
基金supported by the grant from the National Natural Science Foundation of China (82070609)
文摘Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical illness.The pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ failure.Methods:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+AGK2.Cultured L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA groups.The liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also measured.Mitochondriaassociated endoplasmic reticulum membranes(MAMs)were measured by immunofluorescence.Results:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 pre-treatment.In comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 pre-treatment.The levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 pretreatment.Compared with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA group.AGK2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 cell.Immunofluorescence observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced group in both mice and L02 cells.Conclusions:The data suggested that AGK2 pre-treatment had hepatoprotective role in TAA-induced ALF via upregulating the expression of MFN2 and then inhibiting PERK and ferroptosis pathway in ALF.
文摘BACKGROUND Liver transplantation(LT)is a life-saving intervention for patients with end-stage liver disease.However,the equitable allocation of scarce donor organs remains a formidable challenge.Prognostic tools are pivotal in identifying the most suitable transplant candidates.Traditionally,scoring systems like the model for end-stage liver disease have been instrumental in this process.Nevertheless,the landscape of prognostication is undergoing a transformation with the integration of machine learning(ML)and artificial intelligence models.AIM To assess the utility of ML models in prognostication for LT,comparing their performance and reliability to established traditional scoring systems.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines,we conducted a thorough and standardized literature search using the PubMed/MEDLINE database.Our search imposed no restrictions on publication year,age,or gender.Exclusion criteria encompassed non-English studies,review articles,case reports,conference papers,studies with missing data,or those exhibiting evident methodological flaws.RESULTS Our search yielded a total of 64 articles,with 23 meeting the inclusion criteria.Among the selected studies,60.8%originated from the United States and China combined.Only one pediatric study met the criteria.Notably,91%of the studies were published within the past five years.ML models consistently demonstrated satisfactory to excellent area under the receiver operating characteristic curve values(ranging from 0.6 to 1)across all studies,surpassing the performance of traditional scoring systems.Random forest exhibited superior predictive capabilities for 90-d mortality following LT,sepsis,and acute kidney injury(AKI).In contrast,gradient boosting excelled in predicting the risk of graft-versus-host disease,pneumonia,and AKI.CONCLUSION This study underscores the potential of ML models in guiding decisions related to allograft allocation and LT,marking a significant evolution in the field of prognostication.
文摘Background:Liver transplantation(LT)for neuroendocrine liver metastases(NELM)is still in debate.Stud-ies comparing LT with liver resection(LR)for NELM are scarce,as patient selection is heterogeneous and experience is limited.The goal of this review was to provide a critical analysis of the evidence on LT versus LR in the treatment of NELM.Data sources:A scoping literature search on LT and LR for NELM was performed with PubMed,including English articles up to March 2023.Results:International guidelines recommend LR for NELM in resectable,well-differentiated tumors in the absence of extrahepatic metastatic disease with superior results of LR compared to systemic or liver-directed therapies.Advanced liver surgery has extended resectability criteria whilst entailing increased perioperative risk and short disease-free survival.In highly selected patients(based on the Milan criteria)with unresectable NELM,oncologic results of LT are promising.Prognostic factors include tumor biology(G1/G2)and burden,waiting time for LT,patient age and extrahepatic spread.Based on low-level evi-dence,LT for low-grade NELM within the Milan criteria resulted in improved disease-free survival and overall survival compared to LR.The benefits of LT were lost in patients beyond the Milan NELM-criteria.Conclusions:With adherence to strict selection criteria especially tumor biology,LT for NELM is becoming a valuable option providing oncologic benefits compared to LR.Recent evidence suggests even stricter selection criteria with regard to tumor biology.
文摘Hepatectomy is still the major curative treatment for patients with liver malignancies.However,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic veins.Ex vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation.Due to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver re-section and liver transplantation.The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar echinococcosis.Recently,the application of ELRA for liver malignances has gained more attention.However,standardization of clinical practice norms and international consensus are still lacking.The prognostic impact in these oncologic pa-tients also needs further evaluation.In this review,we summarized the principles and recent progresses on ELRA.
文摘The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver injury.The ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction models.It is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection indicators.An increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation events.This article presents a review of the application of ALBI scores in various non-malignant liver diseases.
