Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase

BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.

The rat eustachian tube:Anatomical, histological, and radiological features

Purpose: This study investigated the anatomical and histological characteristics of the rat Eustachian tube(E-tube)and the feasibility of Eustachian tubography in a rat model.Materials and methods: Fifteen male Wistar rats were used in this study, and the bilateral E-tubes of each rat were examined. Ten E-tubes were used for anatomical studies, another ten for histological analysis, and the other ten for Eustachian tubography. Five rats were euthanized and decapitated, and ten E-tubes were dissected to describe the anatomy of the E-tube. Ten E-tube specimens obtained from five other rats were sectioned to investigate Etube histology. Eustachian tubography was performed on the bilateral E-tubes of the other five rats using the trans-tympanic approach.Results: The rat E-tubes consisted of bony and membranous parts. Cartilage and bone tissue covered only the bony part. The E-tubes’ mean diameter and overall length were 2.97 mm and 4.96 mm, respectively. The tympanic orifices’ mean diameter was 1.21 mm. The epithelium of E-tubes was mainly composed of pseudostratified ciliated and goblet cells. Eustachian tubography was successfully performed on both sides of the E-tube for each rat.The technical success rate was 100%, the average running time was 4.9 min, and no procedure-related complications occurred. On tubography images, the E-tube, tympanic cavity, and nasopharynx could be identified because of the visualization of bony landmarks.Conclusion: In this study, we described the anatomical and histological features of rat E-tubes. With the aid of these findings, E-tube angiography was successfully performed using a transtympanic approach. These results will facilitate further investigation of E-tube dysfunction.

Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease

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 non-alcoholic 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 &#x000b1; 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-&#x003b1; levels were associated independently with steatosis grade of more than 33% [&#x003b2; = 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 &#x0003c; 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [&#x003b2; = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P &#x0003c; 0.05]. Similarly, higher TNF-&#x003b1;, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [&#x003b2; = 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 &#x0003c; 0.05]. Serum IL-8 and TNF-&#x003b1; values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [&#x003b2; = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P &#x0003c; 0.05].CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.

Shear wave elastography results correlate with liver fibrosis histology and liver function reserve

AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to 1/2 of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P = 0.037) and F3 (P = 0.032) as compared to F0 and significantly lower with F4 as compared to F2 (P = 0.032). CONCLUSION: SWE LSM shows a good correlation with histologic fibrosis grading and pharmacologic quantitative liver function reserve in experimental severe fibrosis and cirrhosis.

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA more than 10^5 copies/mL.Compared to HBeAg positive patients, HBeAg negative patients are older and have a lower HBV DNA level and a longer HBV infection history. There is no significant difference in sex ratio, ALT and AST levels and liver histology between the two groups.

Liver histology according to the presence of metabolic syndrome in nonalcoholic fatty liver disease cases

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.

Life style modification improves insulin resistance and liver histology in patients with non-alcoholic fatty liver disease

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.

Liver histology in ICU patients dying from sepsis:A clinico-pathological study

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.

Pediatric nonalcoholic fatty liver disease:Overview with emphasis on histology

Nonalcoholic fatty liver disease(NAFLD) is a disease in which excessive fat accumulates in the liver of a patient without a history of alcohol abuse.This disease includes simple steatosis and nonalcoholic steatohepatitis(NASH).NAFLD/NASH is recognized as a hepatic manifestation of metabolic syndrome.In recent years,pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity.The estimated prevalence of pediatric NAFLD is 2.6%-9.6%,and it is associated with sex,age,and ethnicity.With regard to the pathogenesis of NAFLD,the "two-hit" hypothesis is widely accepted and oxidative stress is thought to play an important role in the second hit.Although clinical symptoms,laboratory data,and imaging findings are important,liver biopsy is regarded as the gold standard for the diagnosis of NAFLD/NASH.In addition,liver biopsy is essential for assessing the degree of necro-inflammatory change and fibrosis in NASH.Two different types of steatohepatitis(type 1 and type 2 NASH) have been reported,with type 2 NASH being present in as many as 51% of pediatric NAFLD patients.However,we and others have observed that type 1 and 2 patterns commonly overlap.Although pharmacotherapy has been studied in clinical trials,lifestyle modification by diet and exercise remains the mainstay of treatment for NAFLD/NASH.

Normal liver stiffness: a study in living donors with normal liver histology

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.

A Study of Prevalence of Diabetes and Prediabetes in Patients of Non-Alcoholic Fatty Liver Disease and the Impact of Diabetes on Liver Histology in Coastal Eastern India

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.

Liver surface depressions in the presence of diaphragmatic muscular bands on trans-illumination

Traditional descriptions of liver anatomy refer to a smooth,convex surface contacting the diaphragm.Surface depressions are recognized anatomic variants.There are many theories to explain the cause of the depressions.We discuss the theory that these are caused by hypertrophic muscular bands in the diaphragm.

Comprehensive Review of Thyroid Embryology,Anatomy,Histology,and Physiology for Surgeons

Emil Theodor Kocher and Theodor Billroth pioneered the surgical management of thyroid disease. Their surgical techniques, knowledge of thyroid anatomy, embryology, histology, physiology, and antisepsis practices transitioned a life-threatening operation to one with acceptable morbidity. The modern head and neck surgeon should have a meticulous surgical technique, combined with a thorough understanding of thyroid embryology and anatomy that is central to the understanding and treatment of the different disease processes of the thyroid gland and the consequences of thyroid gland surgery. In this manuscript we will be examining thyroid gland embryology, anatomy, histology, and physiology that is essential to the practicing thyroid surgeon.

Histologic features and genomic alterations of primary colorectal adenocarcinoma predict growth patterns of liver metastasis

BACKGROUND Different histological growth patterns(HGPs)of colorectal carcinoma(CRC)liver metastasis are associated with patients’prognosis and response to antiangiogenic therapy.However,the relationship between HGPs of liver metastasis and clinicopathological and genomic characteristics of primary cancer has not been well established.AIM To assess whether certain clinicopathological and genomic features of primary CRC could predict the HGPs of liver metastasis.METHODS A total of 29 patients with paired resections of both primary CRC and liver metastasis were divided into two groups:A(15 cases with desmoplastic liver metastasis)and B(14 cases with replacement liver metastasis).Clinical information was obtained from patients’charts.Mismatch repair proteins,BRAFV600E,and PD-L1 were evaluated by immunohistochemistry.Five cases were selected randomly from each group for whole exome sequencing(WES)analysis.RESULTS In the primary tumor,expanding growth pattern,low tumor budding score(TBS),and Crohn’s disease-like response(CDR)were associated with desmoplastic liver metastasis and better overall survival,whereas infiltrating growth pattern alone of primary carcinoma could predict the replacement liver metastasis and worse overall survival(P<0.05).On WES analysis,primary carcinoma with desmoplastic liver metastasis showed mutations in APC(4/5);TP53(3/5);KRAS,PIK3CA,and FAT4(2/5);BRCA-1,BRCA2,BRAF,and DNAH5(1/5),whereas primary carcinoma with replacement liver metastasis showed mutations in APC and TP53(3/5);KRAS,FAT4,DNH5,SMAD,ERBB2,ERBB3,LRP1,and SDK1(1/5).CONCLUSION The HGPs,TBS,and CDR of primary CRC as well as the presence of specific genetic mutations such as those in PIK3CA could be used to predict the HGPs of liver metastasis,response to therapy,and patients’prognosis.

Serum hyaluronic acid, procollagen type Ⅲ and Ⅳ in histological diagnosis of liver fibrosis

OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.

Predictive factors of histological response of colorectal liver metastases after neoadjuvant chemotherapy

BACKGROUND Colorectal cancer is the third most common cancer in men and the second most common in women worldwide. Almost a third of the patients has or will develop liver metastases. Neoadjuvant chemotherapy(NAC) has recently become nearly systematic prior to surgery of colorectal livers metastases(CRLMs). The response to NAC is evaluated by radiological imaging according to morphological criteria.More recently, the response to NAC has been evaluated based on histological criteria of the resected specimen. The most often used score is the tumor regression grade(TRG), which considers the necrosis, fibrosis, and number of viable tumor cells.AIM To analyze the predictive factors of the histological response, according to the TRG, on CRLM surgery performed after NAC.METHODSFrom January 2006 to December 2013, 150 patients who had underwent surgery for CRLMs after NAC were included. The patients were separated into two groups based on their histological response, according to Rubbia-Brandt TRG.Based on their TRG, each patient was either assigned to the responder(R) group(TRG 1, 2, and 3) or to the non-responder(NR) group(TRG 4 and 5). All of the histology slides were re-evaluated in a blind manner by the same specialized pathologist. Univariate and multivariate analyses were performed.RESULTS Seventy-four patients were classified as responders and 76 as non-responders.The postoperative mortality rate was 0.7%, with a complication rate of 38%.Multivariate analysis identified five predictive factors of histological response.Three were predictive of non-response: More than seven NAC sessions, the absence of a radiological response after NAC, and a repeat hepatectomy(P <0.005). Two were predictive of a good response: A rectal origin of the primary tumor and a liver-first strategy(P < 0.005). The overall survival was 57% at 3 yr and 36% at 5 yr. The disease-free survival rates were 14% at 3 yr and 11% at 5 yr.The factors contributing to a poor prognosis for disease-free survival were: No histological response after NAC, largest metastasis > 3 cm, more than three preoperative metastases, R1 resection, and the use of a targeted therapy with NAC(P < 0.005).CONCLUSION A non-radiological response and a number of NAC sessions > 7 are the two most pertinent predictive factors of non-histological response(TRG 4 or 5).

Usefulness of a scoring system in the interpretation of histology in neonatal cholestasis

AIM:To ascertain the usefulness of a histological scoring system devised to assist in the interpretation of liver histology in neonatal cholestasis(NC) .METHODS:Liver biopsy specimens obtained from infants with NC referred to a tertiary pediatric unit in Malaysia were prospectively studied.The first author,blinded to the final diagnosis,devised the histological diagnosis based on a 7-feature(portal ductal proliferation,bile plugs in portal ductules,portoportal bridging,lymphocytic infiltration in portal region,multinucleated hepatocytes,neutrophilic infiltration,hepatocellular swelling) ,15-point(0 to 15) scoring system.The author classified the histological diagnosis as either biliary atresia(BA) or neonatal hepatitis(NH,all other diagnoses) ,and subsequently compared the author's diagnosis with the final diagnosis.RESULTS:Eighty-four biopsy specimens obtained from 78 patients were reviewed.Without the scoring system,BA was correctly diagnosed by the author histologically in 30 cases,labelled as NH in 3.For other diagnoses,BA was excluded correctly in 33 cases and mislabeled as BA in 2 cases.The overall sensitivity for BA was 91%,specificity 86% and accuracy 88%.With the scoring system,a score of ≥ 7 had the best diagnostic utility to differentiate BA from other intrahepatic cholestasis histologically(sensitivity 88%,specificity 94%,accuracy 92%) .Four patients with a score < 7 had BA,and 3 patients with a score ≥ 7 had NH.CONCLUSION:A 7-feature,15-point histological scoring system had good diagnostic accuracy in the interpretation of liver histology in neonatal cholestasis.

Live donor liver transplantation in adults: graft size, related anatomical anomaly and imaging evaluation of donor

The shortage of cadaveric livers has sparked aninterest in adult live donor liver transplantation. Rightlobe donor hepatectomy is frequently required to ob-tain a graft of adequate size for adult recipients. Thisprocedure requires not only a precise understanding ofliver anatomy and anatomic anomaly, but also themeans of assessing them. This review focuses on thekey points in adult live donor liver transplantation us-ing the right lobe combined with our own experiencein 81 cases including graft size, related anatomicalanomaly and imaging evaluation of donor.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease

BACKGROUND Recently,nonalcoholic fatty liver disease(NAFLD)has been renamed metabolicassociated fatty liver disease(MAFLD).Based on the definition for MAFLD,a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature.AIM To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD.METHODS Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups.The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction.The histologic features were compared according to different metabolic disorders and liver enzyme levels.RESULTS MAFLD individuals had a higher NAFLD activity score(P=0.002)and higher severity of hepatic steatosis(42.6%Grade 1,42.6%Grade 2,and 14.8%Grade 3 in MAFLD;81.8%Grade 1,13.6%Grade 2,and 4.5%Grade 3 in non-MAFLD;P=0.007)than the non-MAFLD group.Lobular and portal inflammation,hepatic ballooning,fibrosis grade,and the presence of nonalcoholic steatohepatitis(NASH)and significant fibrosis were comparable between the two groups.The higher the liver enzyme levels,the more severe the grades of hepatic steatosis(75.0%Grade 1 and 25.0%Grade 2 in normal liver function;56.6%Grade 1,39.6%Grade 2,and 3.8%Grade 3 in increased liver enzyme levels;27.8%Grade 1,27.8%Grade 2,and 44.4%Grade 3 in liver injury;P<0.001).Patients with liver injury(alanine aminotransferase>3×upper limit of normal)presented a higher severity of hepatocellular ballooning(P=0.021).Moreover,the grade of steatosis correlated significantly with hepatocellular ballooning degree(r=0.338,P=0.002)and the presence of NASH(r=0.466,P<0.001).CONCLUSION Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD.Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

Chronic effect of olive oil on some neurotransmitter contents in different brain regions and physiological, histological structure of liver and kidney of male albino rats

Olive oil is an important source of mono-unsaturated fat and a prime component of the Mediterranean diet. The beneficial health effects of olive oil are due to both its high content of mono-unsaturated fatty acids and its high content of anti-oxidative substances. The objective of this study was to investigate the basis for the epidemiological information relating to the health benefits associated with the consumption of ex-tra-virgin olive oil (EVOO). The effect of olive oil on norepinephrine (NE), dopamine (DA), serotonin (5-HT) and gamm-aminobutyric acid (GABA) con-tents in different brain regions and histological structure of liver and kindey of male albino rats was studied. The chronic administration of olive oil (7.5 mg/kg body wt.) caused a significant increase in norepinephrine (NE), dopamine (DA) , serotonin (5-HT) and gamm-aminobutyric acid (GABA) con-tent in different brain regions (Cerebellum, striatum, cerebral cortex, hypothalamus, brain steam and hip-pocampus) of male albino rats. The increase in NE, DA, 5-HT, and GABA content in the different CNS areas of male albino rat may be due to the inhibition of Ca2+/calmodulin binding which plays an important role in the release of these neurotransmitters. The results, also, revealed that urea and creatinne con-centrations in rats with oral administration with olive oil were decreased. Meanwhile, the activities of the enzymes AsT, AlT and ALP were elevated. The pre-sent results indicated that there is no change in tis-sues of kidney after treated with virgin olive oil. Olive oil may potentially be safe for use as a sedative drug. improvement also led to the reductions in risk of Alzheimer’s and Parkinson’s diseases.