Porto-Sinusoidal Vascular Disease and Focal Nodular Hyperplasia-like Nodules in a Patient with Neurofibromatosis and Non-Cirrhotic Portal Hypertension

Introduction/Objective Non-cirrhotic portal hypertension (NCPH) is uncommon. The underlying pathophysiology appears to lie at the level of intrahepatic portal veins and sinusoids, hence the term “porto-sinusoidal vascular disease” (PSVD). We report a rare case of PSVD with focal nodular hyperplasia (FNH)-like nodules in a patient with neurofibromatosis type 2 (NF2). Methods/Case Report A 57-year-old male with NF2 and type 2 diabetes, presented with a large variceal bleed requiring blood transfusion and subsequent transjugular intrahepatic portosystemic shunt (TIPS). Imaging showed a nodular liver, presumed to be cirrhosis due to non-alcoholic liver disease. Liver biopsy was not done. Thereafter, he had several episodes of hepatic encephalopathy and TIPS was downsized to prevent recurrences. The patient required liver transplantation for intractable portal hypertension and severe hepatic encephalopathy; his liver synthetic function was near normal and MELD was 11. Portal vein was patent. The explanted liver was micronodular, soft and weighed 946 grams. Unencapsulated nodules, a few mm to 1 cm in size, were present. Microscopically, there was diffuse nodularity in the absence of bridging fibrosis. Thin, incomplete curvilinear fibrous septa were present. There were aberrant veins, hypervascular portal tracts, herniated portal veins and rare occluded portal veins. Trichrome and reticulin stains confirmed architectural abnormalities including nodularity, lack of bridging fibrosis and approximation of portal tracts. Immunohistochemistry for glutamine synthetase accentuated architectural distortion and revealed nodules with FNH-like geographic areas of staining. Results (if a Case Study enter NA) NA Conclusion This is a rare case of NCPH due to PSVD in a patient with NF2. Microscopy suggested incomplete septal cirrhosis (ISC), a pattern associated with both PSVD and regression of fibrosis in a cirrhotic liver. Isolated portal hypertension without loss of synthetic function favors primary PSVD over regression of fibrosis. FNH-like nodules are consistent with regenerative changes caused by localized abnormalities of blood flow.

Histological Appearance Of The Liver In Experimental Injury

In this work, the morphofunctional state has been studied at various times after the simulation of experimental syphilis. It is noted that discirculatory and dystrophic changes develop in the early stages of the study. The appearance of focal and massive necrosis of hepatocytes is accompanied by the development of an inflammatory process in the form of lymphoid infiltration around necrosis and hypertrophy of Kupffer cells. Subsequently, lymphohistiocytic infiltration spreads along the portal tracts, in which plasma cells and eosinophils appear, which are characteristic of syphilitic inflammation.

Liver transplantation for post-COVID-19 sclerosing cholangitis

Since identified in December 2019, COVID-19 has remained a pandemic across the globe. Although primarily a respiratory illness, the impact of COVID-19 on other end organs has been increasingly identified. The effect of COVID-19 on the liver has yet to be completely understood. We describe a case of COVID-19 leading to end-stage cholangiopathy and deceased donor liver transplantation (LT). A 64-year-old man with no underlying respiratory or liver disease presented with acute respiratory distress secondary to COVID-19 pneumonia requiring intubation. Several months after resolution of his respiratory symptoms, he developed transaminitis, worsening jaundice, abdominal pain and dark-coloured urine. Hepatic function remained severely impaired warranting LT 259 days following his initial COVID-19 diagnosis. Explant pathology demonstrated diffuse hepatic injury, onion skinning of the bile ducts and bile duct loss in scattered portal tracts. As more patients develop COVID-19-related complications, we suggest LT as an option for COVID-19-related end-stage liver disease.

A real-world study evaluating ultrasound guided percutaneous non-targeted liver biopsy needle failures and pathology sample quality assessment in both end-cut and side-notch needles

Objectives: To determine biopsy device failures, causative factors, complications and sample quality of the 16G end-cut Biopince™ and side-notch Bard™ needles. Methods: All ultrasound-guided non-targeted liver biopsies between 01/01/2016 to 31/12/2018 were included. Operator, device, number of failures, complications and repeat biopsies were recorded. Histopathology samples were reviewed for all cases of needle failure and a group with no failures, and graded “yes/no” for presence of steatosis, inflammation and fibrosis. The pathology slides from these cases were reviewed to assess biopsy sample quality (length and portal tract number). The failure and no-failure groups were compared in terms of device type/ histology and sample quality was compared between the needle types. Results: 1004 patients were included. 93.8% (n = 942) required one needle pass to obtain a sample and 6.2% (n = 62) required >1 pass due to needle failure. Total of 76 needle failures, more with end-cut than side-notch needles (8.7% vs 2.9%) (p < 0.001). No needle failures resulted in complication. The presence of liver fibrosis was associated with fewer needle failures (p = 0.036). The major complication rate was 0.4% (4/1044). A biopsy with >10 portal tracts was obtained in 90.2% of specimens > 20 mm long, compared with 66% of 16–20 mm biopsies and 21% of <16 mm biopsies. The target of >10 portal tracts was achieved in 10/26 (38.5%) of side-notch biopsies and 64/90 (71.1%) of end-cut biopsies (p = 0.004). Conclusion: Ultrasound-guided liver biopsy is safe and sample quality is consistently good when a core >20 mm long is obtained. The end-cut biopsy device generated reliably good quality biopsy samples, however the needle failure rate was significantly higher than the side-cut needle. Advances in knowledge: Ultrasound guided liver biopsy specimen quality is consistently good when a core >20 mm long is obtained which can be achieved with a single pass using the 16G BiopinceTM end-cut needle, although the needle failure rate is significantly higher than the 16G Max-Core™ Bard™ side-notch needle.

MORPHOLOGICAL CHANGES IN THE LIVER VASCULAR SYSTEM OF RATS UNDER THE INFLUENCE OF THIOACETAMIDE

Background. Angiogenesis plays a key role in the progression of liver fibrosis. However, the available data on morphological changes in the liver vascular system are insufficient and contradictory. Objective. The aim of the work is to study the morphological changes in the liver vascular system of rats under the influence of thioacetamide. Material and methods. Fibrosis and cirrhosis of the liver in Wistar rats were induced with thioacetamide given at a dose of 200 mg/kg of animal weight for 17 weeks. To study morphological changes, we used classical and immunohistochemical staining methods. Microscopic analysis was performed using OLYMPUS BX51 microscope and image analysis software ImageScope Color and cellSens Standard. Results. The introduction of a solution of thioacetamide through the stomach leads to a gradual increase in the progression of pathological changes. In addition, it permits to track all stages of cirrhosis development and morphological restructuring of the liver vascular system. Throughout the experiment there was intensive capillarization of the parenchyma sinusoids and neoangiogenesis in the portal tracts and connective tissue septa manifested by the formation of many venules and small veins. We also observed an increase in the area of interlobular veins, which in some places had reached gigantic proportions. Three morphological phenotypes of CD34-positive cells were revealed. In the interlobular arteries as well as interlobular, central and sublobular veins, these cells had an elongated shape and a rod-shaped dark-colored nucleus. During the transformation of liver fibrosis into cirrhosis CD34-positive cells of an elongated shape with light roundedelongated nuclei were observed in the sinusoids closer to the periphery of individual false nodules. Rounded cells with dark-colored nuclei were present in the connective tissue near the hepatic triads, in the connective tissue septa among the cells of the infiltrate and between the sharply increased number of bile ducts. Conclusions. The established complex phenotypic changes in sinusoidal endothelial cells prove a close connection between fibrogenesis and neoangiogenesis. They probably play a leading role in the development of fibrosis and restructuring of the venous system of the portal vein.

Diagnostic Yield of Endoscopic Ultrasound-Guided Liver Biopsy in Comparison to Percutaneous Liver Biopsy: A Two-Center Experience

There is scarce and conflicting evidence on the comparison between endoscopic ultrasound (EUS) and percutaneous (PC)-guided liver biopsy (LB). The aim of this study was to compare the two approaches in a series of patients with parenchymal and focal liver lesions. Fifty-four patients undergoing EUS-LB in two high-volume centers between 2017 and 2021 were compared to 62 patients who underwent PC-LB. The primary outcome was diagnostic adequacy rate. The secondary outcomes were diagnostic accuracy, total sample length (TSL), number of complete portal tracts (CPTs), procedural duration, and adverse events. Variables were compared using the Chi-square and Mann–Whitney test. Median age was 56 years (interquartile range 48–69) in the EUS-LB group and 54 years (45–67) in the PC-LB group with most patients being male. Indication for LB was due to parenchymal disease in 50% of patients, whereas the other patients underwent LB due to focal liver lesions. Diagnostic adequacy was 100% in PC-LB and 94.4% in the EUS-LB group (p = 0.74), whereas diagnostic accuracy was 88.8% in the EUS-LB group and 100% in the PC-LB group (p = 0.82). Median TSL was significantly greater in the PC-LB group (27.4 mm, IQR 21–29) when compared to the EUS-LB group (18.5 mm, 10.1–22.4; p = 0.02). The number of complete portal tracts was 21 (11–24) in the PC-LB group and 18.5 (10–23.2) in EUS-LB group (p = 0.09). EUS-LB was a significantly longer procedure (7 min, 5–11 versus 1 min, 1–3 of PC-LB; p < 0.001) and no evidence of adverse events was observed in any of the study groups. These results were confirmed in the subgroup analysis performed according to an indication for LB (parenchymal disease versus focal lesion). Although PC-LB yielded specimens with greater TSL, diagnostic adequacy and accuracy were similar between the two procedures.

Audit of medical (non-targeted) liver biopsy specimen quality, pathology reporting and effect on patient management

AimsTo evaluate our medical liver pathology practice and its influence on patient management, using audit templates published by the UK Royal College of Pathologists (RCPath).MethodsWe audited medical liver biopsies reported in our centre in 2019 using RCPath proformas. Data were collected from pathology reports and corresponding electronic patient record.Results60 cases were selected for audit from 135 eligible biopsies reported in 2019. 58/60 cases were core biopsies and 2/60 were laparoscopic wedge biopsies. 53/57 (93%) core biopsies with available data met RCPath adequacy criteria (length >15 mm and/or ≥6 portal tracts). Most reports (57/60; 95%) were judged to have helped patient management. 25/60 (42%) biopsy reports helped to clarify the clinical diagnosis and 48/60 (80%) led to altered management.ConclusionsWe demonstrate the utility of the RCPath audit templates, highlighting the clinical value of medical liver biopsies in the diagnostic work-up and management of patients with liver disease.

MORPHOLOGICAL CHANGES IN THE LIVER AT DIFFERENT INVASIVE DOSES OF OPHISTORCHIS FELINEUS (RIVOLTA, 1884) IN RODENTS (ORYCTOLAGUS CUNICULUS)

A morphometric study of liver changes at different invasive doses was conducted in rodents (Oryctolagus cuniculus). In a comparative aspect, the thickness of connective tissue formed around the portal tracts and the thickness of cellular infiltrates in the same area were studied at an invasive dose of 100, 50 and 10 metacercariae of Ophistorchis felineus (Rivolta, 1884). The experiment was conducted on sexually mature male rabbits at the age of 6 months, in each observation group of 10 individuals. Clinically healthy animals were infested with Ophistorchis felineus per os metacercariae once. The intermediate stage of the parasite was isolated from a dead fish (ide, Leuciscus idus (Linnaeus, 1758) and dace fish, Leuciscus leuciscus) obtained from the Tom River in Tomsk. The invasion that took place after 1 month was confirmed by a positive analysis of feces for parasite eggs by the Ragaser and KatoMiura methods. The animals were sacrificed after 5 weeks from the period of infestation. Histological preparations of the liver were made, stained with hematoxylin and eosin, according to Van Gieson. Histological preparations were studied by light microscopy with morphometry. The results obtained characterize a twofold change in the morphometric parameters of connective tissue thickness and cellular infiltration around the portal tracts of the liver lobes with an increase in the invasive dose.

Hepatoportal Sclerosis in patient with Systemic Sclerosis and Sjögren’s Syndrome: a rare association

We present the case of a 51 years-old woman who was referred to our Liver Unit for suspected dysmetabolic liver disease. She had a previous diagnosis of Systemic Sclerosis and Sjögren’s Syndrome and had altered hepatic enzymes with a positive anti-Nuclear Antibodies centromeric pattern, anti-Cardiolipin Antibodies and anti b2 Glycoprotein I Antibodies. Despite complete liver assessment and disease staging was negative, the clinical course was complicated by the development of anemia, due to esophageal varices bleeding associated with worsening splenomegaly. Liver biopsy was key for reaching the diagnosis as it showed portal tracts with fibrous expansion, ductular proliferation and focal lympho-granulocytic infiltrate, reduced caliber of portal vessels, hypoplastic portal tracts, focal herniation, aberrant microvasculature and positive endothelial CD34 staining. Having ruled out any other cause of portal hypertension such as cirrhosis, blood diseases, occlusion of the hepatic and portal veins, etc., we finally concluded that the portal hypertension was due to hepatoportal sclerosis associated with Systemic Sclerosis and Sjögren’s Syndrome. Keywords: Idiopathic Non-Cirrhotic Portal Hypertension (INCPH; Hepatoportal Sclerosis (HPS); Systemic sclerosis (SSc); Sjögren’s Syndrome (SS).

Primary biliary cholangitis

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is an organ-specific autoimmune disease predominantly affecting middle-aged women. It does not occur in children. PBC prevalence varies depending on the geographic location of the country. Over the past 30 years, there has been an increased incidence of PBC, while significant progress has been made in understanding the pathogenesis of PBC due to the development of innovative technologies in molecular biology, immunology and genetics. The presence of antimitochondrial antibodies and cholestasis on biochemical analysis is sufficient to make a diagnosis, without the need for liver biopsy. Small- and medium-sized bile ducts are the targets of PBC. In the first stage of the disease, granulomatous destruction of the bile ducts occurs; in the second stage, loss of bile ducts, their proliferation, increased size of the portal tracts with chronic inflammation; in the third stage - fibrosis with septal formation, loss of bile ducts and cholestasis; in the fourth stage - liver cirrhosis. Previously, the survival rate of PBC patients ranged from 7.5 to 16 years. However, it has improved significantly with ursodeoxycholic acid and obeticholic acid treatment. If there is no effect from treatment and end-stage liver failure sets in, liver transplantation is performed.