liver biopsies
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Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3324
Author(s):  
Ikki Mitsui ◽  
Shigeaki Ohtsuki ◽  
Kazuyuki Uchida

(1) Background: Chronic cholecystitis of dogs has not been vigorously investigated histopathologically. In addition, the relationship between gallbladder and liver diseases is not known. (2) Methods: We aimed to provide a hallmark for canine chronic cholecystitis using clinical data, histopathology, histochemistry, immunohistochemistry, and statistical analysis. (3) Results: Our investigation of 219 ultrasonographically abnormal surgically resected canine gallbladders revealed 189 cases (86.3%) of mucosal lymphoplasmacytic infiltration (chronic cholecystitis). Sludge, a gravity-dependent or nondependent fine granular hyperechoic material, was more prevalent (105/219, 47.9%) than mucocele (51/219, 23.2%) in this cohort. Mucosal lymphoid follicles were detected in 68/219 cases (31%), suggesting the influence of long-standing antigenic stimulation. Bacteria were histochemically detected in 41/60 (68.3%) of heavily inflamed gallbladders, 18/129 (14%) of lightly inflamed, and 3/18 (16.7%) of uninflamed gallbladders, suggesting a possible relationship between bacteria and chronic cholecystitis. Simultaneous liver biopsies revealed mild or no inflammation, changes consistent with primary portal vein hypoplasia, and mild hepatocellular degeneration. (4) Conclusions: Based on the results of our statistical analysis, we conclude that canine chronic cholecystitis is a long-standing inflammatory process of unknown (but possibly bacterial) etiology and that liver pathology is unlikely the cause of chronic cholecystitis in dogs.


Author(s):  
Andrzej Chruscinski ◽  
Vanessa Rojas-Luengas ◽  
Sajad Moshkelgosha ◽  
Assaf Issachar ◽  
Jane Luo ◽  
...  

Abstract LITMUS was a single-centre, Phase 2a study designed to investigate whether the gene biomarker FGL2/IFNG previously reported for the identification of tolerance in murine models could identify operationally tolerant liver transplant recipients. Multiplex RT-PCR was used to amplify eight immunoregulatory genes in peripheral blood mononuclear cells (PBMC) from 69 adult liver transplant recipients. Patients with PBMC FGL2/IFNG ≥ 1 and a normal liver biopsy underwent immunosuppression (IS) withdrawal. The primary endpoint was the development of operational tolerance. Secondary endpoints included correlation of tolerance with allograft gene expression and immune cell markers. Twenty-eight of 69 patients (38%) were positive for the PBMC tolerance biomarker and 23 proceeded to IS withdrawal. Nine of the 23 patients had abnormal baseline liver biopsies and were excluded. Of the14 patients with normal biopsies, eight (57%) have achieved operational tolerance and are off IS (range 12-57 months). Additional studies revealed that all of the tolerant patients and only one non-tolerant patient had a liver gene ratio of FOXP3/IFNG ≥1 prior to IS withdrawal. Increased CD4 + T regulatory T cells were detected both in PBMC and livers of tolerant patients following IS withdrawal. Higher expression of SELE (gene for E-selectin) and lower expression of genes associated with inflammatory responses (GZMB, CIITA, UBD, LSP1 and CXCL9) were observed in the pre-withdrawal liver biopsies of tolerant patients by RNA sequencing. These results suggest that measurement of PBMC FGL2/IFNG may enrich for the identification of operationally tolerant liver transplant patients, especially when combined with intragraft measurement of FOXP3/IFNG.


Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Norio Akuta ◽  
Yusuke Kawamura ◽  
Fumitaka Suzuki ◽  
Satoshi Saitoh ◽  
Yasuji Arase ◽  
...  

<b><i>Introduction:</i></b> It is unclear whether the relationships between changes in fibrosis and circulating microRNA-122 (miR-122) dynamics might influence the prognosis of nonalcoholic fatty liver disease (NAFLD). <b><i>Methods:</i></b> This study investigates the impact of serum miR-122 dynamics and histological changes on the incidence of liver cancer and mortality in 81 Japanese NAFLD patients who underwent serial liver biopsies. The median interval between the first and second liver biopsies was 2.9 years. <b><i>Results:</i></b> The fibrosis stage scores indicated progression, no change, and improvement (a decrease of one point or more) in 21.0%, 56.8%, and 22.2% of the patients, respectively. There were 64 patients in the high-risk group who had no improvement in stage scores. Among these, the miR-122 levels were significantly lower in 7 patients with liver cancer than those of the 54 patients who had no liver cancer at the second liver biopsy. The cumulative rates of liver cancer were significantly higher in cases with miR-122 ratios &#x3c;0.5 (serum miR-122 level at second biopsy to that at first biopsy) than those with ratios ≥0.5. The cumulative survival rates in cases with miR-122 ratios &#x3c;0.5 tended to be lower than those with ratios ≥0.5. Of the 64 high-risk patients, 39 indicated stage 2 or greater (severe fibrosis stage) at the first liver biopsy and also showed similar results of cumulative liver cancer and survival rates. <b><i>Conclusions:</i></b> Longitudinal examination of serial liver biopsies indicated that the circulating miR-122 dynamics might be useful in predicting the prognosis for NAFLD patients with severe fibrosis stage and no improvement of the stage scores.


Author(s):  
Vandana Baloda ◽  
Abhinav Anand ◽  
Rajni Yadav ◽  
Lalita Mehra ◽  
Madhu Rajeshwari ◽  
...  

Context.— The histologic features in patients with acute-on-chronic liver failure (ACLF) are evolving and histologic indicators of patients' poor prognosis are not yet fully established. Objective.— To evaluate the independent histologic predictors of 28-day mortality in ACLF patients on core-needle liver biopsies. Design.— Core-needle biopsies from patients with a diagnosis of ACLF (n = 152) as per the European Association for the Study of the Liver criteria were included during 8 years. Liver biopsies from 98 patients with compensated chronic liver disease were included as disease controls for histologic comparison. Features of ongoing changes, such as hepatic necrosis, hepatic apoptosis, cholestasis, hepatocyte degeneration, bile ductular proliferation, Mallory Denk bodies, steatosis, and extent of liver fibrosis, were analyzed for predicting short-term mortality (28 days). A P value of &lt;.05 was considered significant. Results.— In our cohort of ACLF patients, the following etiologies for acute decompensation were identified: alcohol, 47 of 152 (30.9%); sepsis, 24 of 152 (15.7%); hepatotropic viruses, 20 of 152 (13.1%); drug-induced liver injury, 11 of 152 (7.2%); autoimmune flare, 9 of 152 (5.9%); mixed etiologies, 5 of 152 (3.2%); and cryptogenic, 36 of 152 (23.6%). On histologic examination, hepatic necrosis (P &lt; .001), dense lobular inflammation (P = .03), cholestasis (P &lt; .001), ductular reaction (P = .001), hepatocyte degeneration (P &lt; .001), and absence of advanced fibrosis stages (P &lt; .001) were identified significantly more in ACLF patients than in disease controls on univariate analysis. On multivariate Cox regression analysis, the absence of advanced Ishak histologic activity index fibrosis stages (P = .02) and the presence of dense lobular inflammation (P = .04) were associated with increased 28-day mortality in ACLF patients. After adjusting the clinical causes of acute decompensation, only dense lobular inflammation was found as an independent predictor of short-term mortality (P = .04) in ACLF patients. Conclusions.— Dense lobular necroinflammatory activity is a clinically independent histologic predictor of 28-day short-term mortality in patients with ACLF.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Martin Leníček ◽  
Václav Šmíd ◽  
Petr Pajer ◽  
Anna Nazarova ◽  
Karel Dvořák ◽  
...  

AbstractThe patatin-like phospholipase domain containing 3 (PNPLA3) gene (viz. its I148M variant) is one of the key players in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We have identified a novel insertion/deletion variant of 1114 bp, localized in the second intron of the PNPLA3 gene, which corresponds to the 3′ terminal sequence of the long-interspersed element (LINE-1). DNA analysis of 122 NAFLD patients and 167 control subjects as well as RNA analysis of 19 liver biopsies revealed that the novel variant is very common (frequency = 0.41), fully linked to the clinically important I148M variant, and clinically silent. Although the LINE-1 insertion does not seem to have any biological effect, it can impede genotyping of the I148M variant. If insertion prevents the attachment of the diagnostic primer, then the non-insertion allele will be selectively amplified; and thus the frequency of the 148M "risk" allele will be significantly overestimated due to the complete linkage of the LINE-1 insertion and the 148I allele of the PNPLA3 gene. Therefore, our findings underline the importance of careful design and consistent documentation of the methodology, including primer sequences. Critical revisions of the results of some studies that have already been reported may therefore be needed.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 432-433
Author(s):  
Kelsey Harvey ◽  
Reinaldo F Cooke ◽  
Eduardo Colombo ◽  
Bruna Rett ◽  
Osvaldo Sousa ◽  
...  

Abstract Pregnant, non-lactating beef cows (n = 190; 117 ± 2.2 d of gestation; d 0) were assigned to receive: 1) sulfate sources of Cu, Co, Mn, and Zn (INR; n = 95) or 2) an organic complexed source of Cu, Mn, Co, and Zn (AAC; Availa®4, Zinpro; n = 95). From d 0 to calving, cows were maintained in a single pasture and individually offered treatments three times weekly. Cow BW and BCS were recorded on d -30, d 97, upon calving, and at weaning and liver biopsies performed in 30 cows/treatment. Milk production was estimated at 42 ± 0.5 d postpartum via weigh-suckle-weigh (WSW). Liver and longissimus muscle (LM) biopsies were performed in 30 calves/treatment upon calving and 24 h later, at WSW, and at weaning. No treatment effects were detected (P ≥ 0.49) for cow BCS, despite AAC cows having greater (P = 0.04) BW on d 97. Liver Co (P &lt; 0.01) concentrations were greater for AAC compared to INR cows, and liver concentrations of Cu were greater (P = 0.02) for INR compared to AAC cows on d 97. Upon calving, INR cows had greater (P ≤ 0.01) liver Cu and Zn concentrations compared to AAC cows. Cows receiving AAC had greater (P = 0.04) hepatic mRNA expression of metallothionein 1A at calving, and their calves had greater (P = 0.04) hepatic mRNA expression of superoxide dismutase at weaning. Milk production did not differ between AAC and INR cows (P = 0.70). No treatment effects were detected (P ≥ 0.29) for mRNA expression of LM genes in calves at birth and weaning. Calf birth and weaning BW were similar (P ≥ 0.19) between treatments. Hence, supplementing AAC or INR to beef cows during the last 5 mo of gestation yielded similar cow-calf productive responses until weaning.


Author(s):  
Felix Zhou ◽  
Ashley Stueck ◽  
Magnus McLeod

BACKGROUND: With new treatments for non-alcoholic fatty liver disease (NAFLD) on the horizon, it will be important to risk-stratify patients based on degree of fibrosis to allocate treatment to those at highest risk. No studies have examined the complication rates of liver biopsies in patients with NAFLD in the outpatient setting. METHODS: We conducted a retrospective chart review of all outpatient elective liver biopsies for NAFLD at a tertiary care centre over a 10-year period. Demographic variables and stage of fibrosis were recorded. Complications up to 1-week post-procedure were recorded. We used univariate logistic regression models to estimate the odds of major complications by fibrosis stage, age, sex, platelets, and international normalized ratio (INR). RESULTS: There were 582 biopsies reviewed in total. The mean age was 53 years. There was an even proportion of males to females. The mean fibrosis stage was 1.9; platelet count was 223.9, INR was 1, and partial thromboplastin time (PTT) was 31. Major complications occurred in 8 out of 582 biopsies (1.4%). Bleeding accounted for 6 of the major complications observed, while infection and pneumoperitoneum each occurred once. There were no statistically significant associations between age (odds ratio [OR] 0.97, 95% CI 0.92–1.03), female sex (OR 1.00, 95% CI 0.25–4.04), platelet count <150 (OR 0.59, 95% CI [-inf.], 3.86), INR >1.3 (OR 0.47, 95% CI 0.057–3.85), fibrosis stage, and complication rate. CONCLUSIONS: Our results are consistent with previous studies examining complication rates in other patient populations and clinical settings and support the overall safety of liver biopsies.


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