Sex, Genotype, and Liver Volume Progression as Risk of Hospitalization Determinants in Autosomal Dominant Polycystic Liver Disease.

BACKGROUND & AIMS: Autosomal dominant polycystic liver disease is a rare condition with a female preponderance, based mainly on pathogenic variants in 2 genes, PRKCSH and SEC63. Clinically, autosomal dominant polycystic liver disease is characterized by vast heterogeneity, ranging from asymptomatic to highly symptomatic hepatomegaly. To date, little is known about the prediction of disease progression at early stages, hindering clinical management, genetic counseling, and the design of randomized controlled trials. To improve disease prognostication, we built a consortium of European and US centers to recruit the largest cohort of patients with PRKCSH and SEC63 liver disease. METHODS: We analyzed an international multicenter cohort of 265 patients with autosomal dominant polycystic liver disease harboring pathogenic variants in PRKCSH or SEC63 for genotype-phenotype correlations, including normalized age-adjusted total liver volumes and polycystic liver disease-related hospitalization (liver event) as primary clinical end points. RESULTS: Classifying individual total liver volumes into predefined progression groups yielded predictive risk discrimination for future liver events independent of sex and underlying genetic defects. In addition, disease severity, defined by age at first liver event, was considerably more pronounced in female patients and patients with PRKCSH variants than in those with SEC63 variants. A newly developed sex-gene score was effective in distinguishing mild, moderate, and severe disease, in addition to imaging-based prognostication. CONCLUSIONS: Both imaging and clinical genetic scoring have the potential to inform patients about the risk of developing symptomatic disease throughout their lives. The combination of female sex, germline PRKCSH alteration, and rapid total liver volume progression is associated with the greatest odds of polycystic liver disease-related hospitalization.

Liver damage and hepatomegaly in COVID-19 patients.

INTRODUCTION: The aim of this study was to evaluate the patients with high liver function test results detected at admission to the hospital diagnosed with COVID-19. METHODOLOGY: Patients diagnosed with COVID-19 by a nasopharyngeal RT-PCR (+) test in the emergency department were included in the study. CRP, liver function tests, and abdominal ultrasonography (US) findings of the patients were recorded. RESULTS: A total of 367 COVID-19 patients, 254 (69.2%) males and 113 (30.8%) females, with a mean age of 60.39 (16.81) years, were included in the study. It was seen that 236 (68.7%) patients were treated without complications, 131 (35.7%) patients needed intensive care, and 81 (22.1%) patients died. The frequency of hepatomegaly was significantly higher in patients with severe course and mortality (p < 0.001). When COVID-19 patients who developed mortality were compared with other patients with a diagnosis of COVID-19, no additional risk factors affecting mortality were detected, except LDH [OR: 1.009, (1.006-1.012); p < 0.001] and high CK [OR: 1.001 CI: 95%, (1.000-1.001); p = 0.032]. CONCLUSIONS: Patients who need to be hospitalized with COVID-19 and who do not have acute and/or chronic liver disease, elevated liver function test results, and an increase in liver sizes at presentation, it was seen that these did not have an effect on the clinical outcome. However, in addition to the presence of advanced age and comorbidity, the presence of hepatomegaly measured by CT at admission, and high LDH and CK levels were associated with poor clinical outcomes.

Combined liver-kidney transplant in polycystic diseases: a case report.

Polycystic liver disease, a hereditary pathology, usually manifests as autosomal dominant polycystic kidney disease. The many cysts in the liver cause massive hepatomegaly, majorly affecting the patient's quality of life. In cases of refractory symptoms, liver transplantation is the only treatment choice. A 43-year-old woman was followed up as a hepatology outpatient in August 2020, with a progressive increase in abdominal volume, lower limb edema, and cachexia. The patient was diagnosed with polycystic renal and liver disease with massive hepatomegaly in March 2021, a combined kidney-liver transplant. Liver size represented 13% of the patient's corporal composition, weighing 8.6kg. The patient was discharged on the 7th postoperative day with no complications. Only 10-20% of patients with polycystic liver disease have clinical manifestations, most of which result from hepatomegaly. An increase in liver volume deteriorates liver function until the condition becomes end-stage liver disease, as kidney function is already compromised; liver-kidney transplantation remains the only treatment choice. The case described drew significant attention to the massive hepatomegaly presented in the patient, with the liver representing over 10% of the patient's body weight, approximately five to six times larger than a normal-sized liver.

Lóbulo hepático de Riedel, una falsa hepatomegalia / Riedel's lobe, a false impression of hepatomegaly

La hepatomegalia es un signo clínico relativamente frecuente en la exploración del paciente pediátrico. Esta puede ser la manifestación de una hepatopatía o de un trastorno sistémico con afectación hepática. Una variante de la normalidad del lóbulo hepático derecho es el llamado lóbulo de Riedel, que en ocasiones puede interpretarse como una hepatomegalia. Estas personas están asintomáticas y no presentan signos clínicos ni analíticos de hepatopatía. Se presenta el caso de un niño de 4 años en el que se encuentra, de forma casual, una hepatomegalia radiológica (AU)

Hepatomegaly is a relatively frequent clinical sign in the examination of the pediatric patient. This may be due to a hepatic disease or a generalized disease with hepatic involvement. A variant of the normal right hepatic lobe is the called Riedel´s lobe, which can sometimes be interpreted as hepatomegaly. These patients are asymptomatic and have no clinical or laboratory signs of the liver disease. We present the case of a 4-year-old boy in whom a radiological hepatomegaly was found by chance. (AU)

Metabolic assessment in children with neuromuscular disorders shows risk of liver enlargement, steatosis and fibrosis.

AIM: The aim of this study was to conduct a metabolic and nutritional assessment of children with neuromuscular disorders, including the investigation of the liver and bone mineral density. METHODS: In this observational study, we included 44 children with neuromuscular disorders. The nutritional status, bone health and liver were assessed by ultrasound, transient elastography, dual X-ray absorptiometry scan, blood samples, anthropometric measurements and 3-day diet registration. RESULTS: Liver involvement was found in 31.0%: liver enlargement in 7.1%, steatosis in 4.8%, fibrosis in 14.3% and liver enlargement together with steatosis or fibrosis was found in 4.8%. These changes were found in 9/23 patients with Duchenne muscular dystrophy, 4/9 patients with spinal muscular atrophy type II and 0/12 patients with other neuromuscular diagnoses. Low bone mineral density was found in 44.0% of the patients, though the majority used daily vitamin D and calcium supplements. Vitamin D insufficiency or deficiency was found in 22.6%. CONCLUSION: The metabolic assessment in children with neuromuscular disorders shows an increased risk of liver enlargement, steatosis and fibrosis. Possible causes are obesity, decreased mobility, low skeletal muscle mass and for a subgroup the use of glucocorticoids. The findings suggest that monitoring liver function should be part of the nutritional assessment in patients with neuromuscular disorders.

Diagnostic imaging findings in a referral population of dogs diagnosed with immune-mediated haemolytic anaemia: 50 cases (2015-2018).

OBJECTIVES: To describe and characterise changes documented on thoracic and abdominal imaging of dogs with confirmed immune-mediated haemolytic anaemia. MATERIALS AND METHODS: Medical records from a referral hospital were searched from 2015 to 2018 for all dogs diagnosed with immune-mediated haemolytic anaemia that underwent thoracic and abdominal imaging by radiography, ultrasound or computed tomography. RESULTS: Fifty dogs were included. Thoracic imaging revealed abnormalities in 10 dogs (20%) of which lymphadenopathy and cardiomegaly were documented in four dogs (8%) each, and pleural effusion and pleural thickening in one dog (2%) each. Abdominal imaging revealed abnormalities in 43 dogs (86%), in which hepatomegaly and peritoneal effusion were documented in 20 (40%) and 19 dogs (38%), gallbladder wall thickening and sludge in 16 (32%) and 14 dogs (28%) and splenic nodules and splenomegaly in 13 (26%) and seven dogs (14%), respectively. Hepatic and splenic abnormalities were further investigated via fine needle aspirates in 18 dogs and revealed extramedullary haematopoiesis in 12 hepatic (66.7%) and 14 splenic (77.8%) fine needle aspirate samples. Cholecystocentesis was performed in nine dogs with gallbladder abnormalities and revealed bactibilia in three samples (33.3%). CLINICAL SIGNIFICANCE: In this population of dogs with immune-mediated haemolytic anaemia, thoracic imaging abnormalities were uncommon. Hepatomegaly, peritoneal effusion and gallbladder wall thickening were the most common abdominal imaging findings with bactibilia confirmed in one third of collected bile samples. Hepatosplenomegaly and abdominal lymphadenopathy were not associated with neoplasia in any of the dogs included in this study.

Abdominal wall hernia is a frequent complication of polycystic liver disease and associated with hepatomegaly.

BACKGROUND AND AIM: Polycystic liver disease (PLD) is related to hepatomegaly which causes an increased mechanical pressure on the abdominal wall. This may lead to abdominal wall herniation (AWH). We set out to establish the prevalence of AWH in PLD and explore risk factors. METHODS: In this cross-sectional cohort study, we assessed the presence of AWHs from PLD patients with at least 1 abdominal computed tomography or magnetic resonance imaging scan. AWH presence on imaging was independently evaluated by two researchers. Data on potential risk factors were extracted from clinical files. RESULTS: We included 484 patients of which 40.1% (n = 194) had an AWH. We found a clear predominance of umbilical hernias (25.8%, n = 125) while multiple hernias were present in 6.2% (n = 30). Using multivariate analysis, male sex (odds ratio [OR] 2.727 p < .001), abdominal surgery (OR 2.575, p < .001) and disease severity according to the Gigot classification (Type 3 OR 2.853, p < .001) were identified as risk factors. Height-adjusted total liver volume was an independent PLD-specific risk factor in the subgroup of patients with known total liver volume (OR 1.363, p = .001). Patients with multiple hernias were older (62.1 vs. 55.1, p = .001) and more frequently male (22.0% vs. 50.0%, p = .001). CONCLUSION: AWHs occur frequently in PLD with a predominance of umbilical hernias. Hepatomegaly is a clear disease-specific risk factor.

Self-limiting COVID-19-associated Kikuchi-Fujimoto disease with heart involvement: case-based review.

BACKGROUND: The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin. OBJECTIVE: Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case. METHODS: We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar. RESULTS: Only two cases of KFD after COVID infection have been described so far. CONCLUSION: SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.

Relation of Liver Volume to Adverse Cardiovascular Events in Adolescents and Adults With Fontan Circulation.

Elevated central venous pressure in those with Fontan circulation causes liver congestion and hepatomegaly. We assessed if liver volume by magnetic resonance imaging (MRI) is associated with adverse cardiovascular outcomes. Retrospective study of 122 patients with Fontan circulation who were >10 years old and had a liver MRI with magnetic resonance elastography. Liver volume (ml) was measured by manual segmentation from axial T2-weighted images and was indexed to body surface area. The composite outcome included death, heart transplant, ventricular assist device placement, or nonelective cardiovascular hospitalization. The median age at the time of MRI was 18.9 (interquartile range 15.8 to 25.9) years, and 47% of the patients were women. The mean indexed liver volume was 1,133 ± 180 ml/m2. Indexed liver volume was not significantly associated with age, years since Fontan, or with liver stiffness (r = 0.15, p = 0.10), but was positively correlated with Fontan pressure (r = 0.32, p = 0.002). Over a median follow-up of 2.1 (0.8 to 4.2) years, 32 patients (26%) experienced the composite outcome. Higher indexed liver volume was associated with a greater hazard for the composite outcome (hazard ratio per 1 SD increase = 1.74, 95% confidence interval 1.27 to 2.35, p = 0.0004) but increased liver stiffness was not significantly associated with the composite outcome (hazard ratio per 1 SD increase 1.44, 95% confidence interval 0.90 to 2.21, p = 0.11). In conclusion, greater liver volume indexed to body surface area is associated with unfavorable hemodynamics and adverse outcomes in patients with Fontan circulation. Liver volume may be a useful, simple imaging biomarker in adolescents and adults with Fontan circulation.

Deep Learning CT-based Quantitative Visualization Tool for Liver Volume Estimation: Defining Normal and Hepatomegaly.

Background Imaging assessment for hepatomegaly is not well defined and currently uses suboptimal, unidimensional measures. Liver volume provides a more direct measure for organ enlargement. Purpose To determine organ volume and to establish thresholds for hepatomegaly with use of a validated deep learning artificial intelligence tool that automatically segments the liver. Materials and Methods In this retrospective study, liver volumes were successfully derived with use of a deep learning tool for asymptomatic outpatient adults who underwent multidetector CT for colorectal cancer screening (unenhanced) or renal donor evaluation (contrast-enhanced) at a single medical center between April 2004 and December 2016. The performance of the craniocaudal and maximal three-dimensional (3D) linear measures was assessed. The manual liver volume results were compared with the automated results in a subset of renal donors in which the entire liver was included at both precontrast and postcontrast CT. Unenhanced liver volumes were standardized to a postcontrast equivalent, reflecting a correction of 3.6%. Linear regression analysis was performed to assess the major patient-specific determinant or determinants of liver volume among age, sex, height, weight, and body surface area. Results A total of 3065 patients (mean age ± standard deviation, 54 years ± 12; 1639 women) underwent multidetector CT for colorectal screening (n = 1960) or renal donor evaluation (n = 1105). The mean standardized automated liver volume ± standard deviation was 1533 mL ± 375 and demonstrated a normal distribution. Patient weight was the major determinant of liver volume and demonstrated a linear relationship. From this result, a linear weight-based upper limit of normal hepatomegaly threshold volume was derived: hepatomegaly (mL) = 14.0 × (weight [kg]) + 979. A craniocaudal threshold of 19 cm was 71% sensitive (49 of 69 patients) and 86% specific (887 of 1030 patients) for hepatomegaly, and a maximal 3D linear threshold of 24 cm was 78% sensitive (54 of 69) and 66% specific (678 of 1030). In the subset of 189 patients, the median difference in hepatic volume between the deep learning tool and the semiautomated or manual method was 2.3% (38 mL). Conclusion A simple weight-based threshold for hepatomegaly derived by using a fully automated CT-based liver volume segmentation based on deep learning provided an objective and more accurate assessment of liver size than linear measures. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sosna in this issue.

Sarcoidosis with marked necrosis in enlarged lymph nodes mimics mycobacterial infection: a case report.

BACKGROUND: Sarcoidosis is pathologically characterized by the formation of non-necrotizing epithelioid cell granulomas. However, pathological findings of patients with sarcoidosis have rarely revealed necrosis. We report here on a patient with sarcoidosis which needed to be distinguished from infectious disease because of marked necrosis in the lymph nodes. CASE PRESENTATION: A 46-year-old Japanese woman was referred to our hospital due to a dry cough and appetite loss. A chest X-ray and computed tomography revealed markedly enlarged mediastinal and hilar lymph nodes and hepatosplenomegaly. Surgical biopsy of these lymph nodes was performed in order to make a diagnosis. Pathological findings revealed epithelioid cell granuloma with marked necrosis that suggested infectious etiology such as mycobacterial and fungal infections. In addition to the pathological findings, immunoglobulin A (IgA) antibody for Mycobacterium avium complex (MAC), enlargement of lymph nodes and hepatosplenomegaly indicated disseminated MAC, while sarcoidosis was considered as another important differential diagnosis according to elevated angiotensin-converting enzyme, soluble interleukin-2 receptor and uveitis. While waiting for the results of the cultures of acid-fast bacilli, the symptoms of cough and consumption had worsened, and initiation of therapy was required before the confirmed diagnosis. The therapy for MAC was initiated because it was feared that immunosuppressive therapy containing corticosteroid for sarcoidosis could worsen the patient's condition if MAC infection was the main etiology. However, the treatment for MAC was not effective, and it was clarified that no acid-fast bacilli were cultured in the liquid culture medium, so the diagnosis was corrected to sarcoidosis after reconsideration of clinical and pathological findings. Prednisolone (30 mg/day) was administered orally, and the patient's symptoms and radiological findings improved. CONCLUSION: Sarcoidosis must be considered even if pathological findings reveal marked necrosis, because rare cases of sarcoidosis exhibit extensive necrosis in lymph nodes. It is extremely important to carefully examine the clinical and pathological findings through discussion with the examining pathologist to reach the correct diagnosis.