Hepatocellular Adenoma Research Articles

Multidisciplinary Simulation Improves Resident Confidence for Pregnant Patients Requiring Surgical Intervention.

Introduction: Hepatocellular adenomas are a rare but serious cause of bleeding, which is further complicated by pregnancy. Interprofessional cooperation is a key component of residency education, thus simulations designed to integrate multiple programs are mutually beneficial. This simulation details surgical and obstetric management of a pregnant patient in hemorrhagic shock from a bleeding hepatocellular adenoma. Objectives for the study were to evaluate learners’ confidence to 1) prioritize the care of a pregnant patient with hemoperitoneum and hemorrhagic shock, 2) demonstrate interdisciplinary collaboration with other specialties, 3) apply massive transfusion protocol (MTP) in the appropriate clinical setting, and 4) analyze critical decisions for evaluating pregnant females with severe abdominal pain.Methods: Obstetric, general surgery, and anesthesia residents, along with labor and delivery nurses participated in a simulated clinical scenario that focused on the management of a pregnant patient in hemorrhagic shock. The learners evaluated the educational session using a standard Return on Investment in Learning survey immediately following the session.Results: A total of 23 residents and medical students gave feedback on the experience. The main learning objectives were met with increased confidence in the four learning objectives by 77.3-95.4% of responders. Overall, greater than 90% of participants felt the simulation was relevant to their training and realistic, with 100% responding that the course provided new, or clarified existing information for them.Conclusion: A multidisciplinary simulation-based educational intervention was successful in improving learner confidence in managing a complicated surgical emergency in a pregnant patient with inter-residency cooperation.

Large Hepatic Adenomas and Hepatic Adenomatosis: A Multicenter Study of Risk Factors, Interventions, and Complications.

Beyond oral contraceptives (OCs), metabolic factors have been suggested to increase the risk of hepatocellular adenoma (HCA). The impact of risks remains poorly defined, particularly among men and those with adenomatosis. Thus, we aimed to examine HCA clinical and outcome characteristics through a large multicenter cohort. HCA diagnosis was made based on a combination of clinical, radiologic, and histologic criteria. Patient and clinical data including follow-up imaging, complications, and interventions were collected between 2004 and 2018 from 3 large academic centers. Among 187 patients (163 female and 24 male) with HCA, 75 had solitary HCA, 58 had multiple HCAs, and 54 had adenomatosis. Over a median follow-up of 3.3 years (quartile 1: 1.2, quartile 3: 8.8), 34 patients (18%) had radiologic interventions, 41 (21%) had surgical resections, 10 (5%) developed tumoral hemorrhage, and 1 had malignant transformation. OC and corticosteroid use were present in 70% and 16%, respectively. Obesity (51%), type 2 diabetes (24%), hypertension (42%), and hypertriglyceridemia (21%) were also common. Metabolic comorbidities were more common in patients with large HCAs and adenomatosis. Compared with women, men had less hepatic steatosis (4% vs 27%), smaller HCAs (2.3 cm vs 4.4 cm), and more corticosteroid use (38% vs 11%) ( P < 0.05 for all). With OC cessation, 69% had a decrease in size of HCA, but 25% eventually required advanced interventions. In this large HCA cohort, obesity and metabolic comorbidities were important risk factors associated with large HCAs and adenomatosis. Long-term adverse outcomes were infrequent, 5% had tumor hemorrhage, and 1 patient exhibited malignant transformation.

Hepatic Adenomas and Hormone Use in Adolescents and Young Adults: a Case Control Study

Background: Hepatic adenomas (HA) are benign liver masses commonly found incidentally in reproductive aged women and are classically associated with exogenous estrogen use and obesity. Most data on this association is based on 50mcg ethinyl-estradiol doses, though one case control study with modern hormone doses suggests no increased risk of HA formation with estrogen use. This study aims to describe risk of HA development with hormone use in an adolescent and young adult population.

Hepatocellular adenoma: what we know, what we do not know, and why it matters.

In the last two decades there has been significant progress in research on and diagnosis of hepatocellular adenoma (HCA), resulting in the establishment of a molecular and immunohistological HCA classification. This review aims to fine-tune the current expertise in order to enhance the histopathological diagnostic possibilities, by refining issues that are already known, addressing diagnostic difficulties, and identifying still unknown aspects of HCA. We discuss novel methods to identify HCA subtypes, in particular the sonic hedgehog HCAs and the interpretation of glutamine synthetase patterns for the recognition of β-catenin-mutated HCAs. The major complications of HCAs, i.e. bleeding and malignant transformation, are considered, including the dilemmas of atypical and borderline lesions. HCAs in different clinical and geographical settings, e.g. pregnancy, cirrhosis and non-western countries, are also discussed. The natural history of the different HCA subtypes in relation to age, sex and risk factors is a feature that is still insufficiently investigated. This is also true for the risks of clinical bleeding and malignant transformation in association with HCA subtypes. As HCA is a relatively rare tumour, a multicentre and multidisciplinary approach across geographical boundaries will be the appropriate method to establish prospective programmes with which to identify, classify and manage HCAs, focusing on several aspects, e.g. aetiology, underlying liver disease, complications, regression, and growth. Updating what we know and identifying and addressing what we do not know matters for optimal patient management.

Hepatocellular adenoma in a goat: An incidental abattoir finding in Oman

In the present study, a hepatic mass measured 9×11×5 cm in the right hepatic lobe was detected incidentally in a less than two years old male Somali goat during routine meat inspection at the Central Muscat Municipality Slaughterhouse, Oman. Gross and microscopic examination revealed a hepatocellular adenoma, a rare finding in goats.

Deep Learning-Based Classification of Hepatocellular Nodular Lesions on Whole-Slide Histopathologic Images

Hepatocellular nodular lesions (HNLs) constitute a heterogeneous group of disorders. Differential diagnosis among these lesions, especially high-grade dysplastic nodules (HGDNs) and well-differentiated hepatocellular carcinoma (WD-HCC), can be challenging, letalone biopsy specimens. We aimed to develop a deep learning system to solve these puzzles, improving the histopathologic diagnosis of HNLs (WD-HCC, HGDN, low-grade DN, focal nodular hyperplasia, hepatocellular adenoma), and background tissues (nodular cirrhosis, normal liver tissue). The samples consisting of surgical and biopsy specimens were collected from 6 hospitals. Each specimen was reviewed by 2 to 3 subspecialists. Four deep neural networks (ResNet50, InceptionV3, Xception, and the Ensemble) were used. Their performances were evaluated by confusion matrix, receiver operating characteristic curve, classification map, and heat map. The predictive efficiency of the optimal model was further verified by comparing with that of 9 pathologists. We obtained 213,280 patches from 1115 whole-slide images of 738 patients. An optimal model was finally chosen based on F1 score and area under the curve value, named hepatocellular-nodular artificial intelligence model (HnAIM), with the overall 7-category area under the curve of 0.935 in the independent external validation cohort. For biopsy specimens, the agreement rate with subspecialists' majority opinion was higher for HnAIM than 9 pathologists on both patch level and whole-slide images level. We first developed a deep learning diagnostic model for HNLs, which performed well and contributed to enhancing the diagnosis rate of early HCC and risk stratification of patients with HNLs. Furthermore, HnAIM had significant advantages in patch-level recognition, with important diagnostic implications for fragmentary or scarce biopsy specimens.

An Extreme Case of Liver Adenomatosis: Are They All the Same?

Hepatocellular adenoma (HCA) is a rare and benign liver tumor that affects predominantly young and middle-aged women, especially between 30–40 years old. Liver adenomatosis (LA) is defined as the presence of 10 or more HCA. There are authors that report eight different subtypes of HCA, that correlates with clinical and histopathological features, being the inflammatory subtype the most common. We present a case of a 32-year-old Caucasian woman with a history of self-limited episodes of right abdominal pain and an abdominal ultrasound with multiple hypoechogenic liver nodules, suspected of metastasis. She was taking combined oral contraceptive for 6 years. Magnetic Resonance Imaging (MRI) disclosed around 40 nodules, suggestive of HCA. Liver biopsy confirmed HCA, inflammatory subtype. Oral contraceptive was stopped and control MRI 6 months later disclosed reduction of nodules’ dimensions. Management of patients with LA should be based on the size of the largest tumor, as clinical presentation and risk of bleeding or malignancy do not differ between patients with single or multiple HCAs. However, even with biopsy, there is a risk of missampling, raising concern about the real risk of bleeding and malignant potential in patients with different subtypes coexisting in the same liver.

KETOgenic diet therapy in patients with HEPatocellular adenoma: study protocol of a matched interventional cohort study

IntroductionHepatocellular adenoma (HCA) is an uncommon, solid and benign liver lesion, mainly occurring in women using oral contraceptives. Patients are advised to stop using oral contraceptives (OC) and, as overweight...

Role of perfusion features in contrast-enhanced ultrasound differential diagnosis of hepatocellular adenoma and carcinoma: Far beyond the gray-scale ultrasound.

Role of perfusion features in contrast-enhanced ultrasound differential diagnosis of hepatocellular adenoma and carcinoma: Far beyond the gray-scale ultrasound.

Hepatocellular neoplasms with loss of liver fatty acid binding protein: Clinicopathologic features and molecular profiling

HNF1A-inactivated hepatocellular adenomas (H-HCA) show steatosis, no atypia and loss of liver fatty acid binding protein (LFABP). LFABP loss also occurs in hepatocellular carcinoma (HCC). This study examines 68 LFABP-negative tumors: 33 typical H-HCA, 10 atypical hepatocellular neoplasms (AHN), 7 well-differentiated (WD) HCC, 18 moderately or poorly differentiated (MD/PD) HCC. Capture based sequencing was performed in 13 cases (8 AHN, 5 WD-HCC). Patients with HCA, AHN and WD-HCC were nearly all women. AHN and WD-HCC resembled H-HCA but had higher degree of atypia and/or reticulin loss. Variant features like inconspicuous fat (59% vs. 12%, p=0.03), predominance of eosinophilic cells (59% vs. 21%, p=0.01) and pseudoacini were more common in AHN and WD-HCC. Myxoid change and prominent lipofuscin were more common in WD-HCC (29% each) than H-HCA and AHN combined (2% and 7% respectively). Compared to WD-HCC, LFABP-negative MD/PD HCC were more commonly associated with male gender, viral hepatitis and cirrhosis. Biallelic HNF1A alterations were seen in all 13 (100%) sequenced cases. Additional mutations and/or copy number alterations were observed in 38% of AHN and 100% of WD-HCC. Diffuse glutamine synthetase (GS) staining was seen in 13% of cases, with no nuclear β-catenin or Wnt signaling alterations. In conclusion, variant features such as lack of fat, peliosis, myxoid change, pseudoacini and abundant lipofuscin are more common in AHN and/or WD-HCC. LFABP-negative MD/PD HCC have different clinicopathologic features compared to WD-HCC. The significance of diffuse GS in a subset of these cases is unclear.

Diagnostic value of color parametric imaging and contrast-enhanced ultrasound in the differentiation of hepatocellular adenoma and well-differentiated hepatocellular carcinoma.

To investigate the differential diagnostic value of computer-aided color parametric imaging (CPI) and contrast-enhanced ultrasound (CEUS) in hepatocellular adenoma (HCA) and well-differentiated hepatocellular carcinoma (wHCC). A total of 38 patients who underwent CEUS and were pathologically diagnosed with HCA (10 cases) and wHCC (28 cases) were reviewed retrospectively. The differences between the radiological features of HCA and wHCC were compared by two readers, blinded to the final diagnosis. (a) Sonographic features: on gray-scale ultrasound, halo sign was more common in wHCC than in HCA (60.7% vs. 10.0%, p=0.009). On CEUS, hyper- or isoenhancement was more common in HCA in the portal phase (90.0% vs. 50.0%; p=0.022). On CPI mode, HCA was inclined toward centripetal enhancement (60.0% vs. 14.3% p=0.010). HCA was characterized by the presence of pseudocapsule enhancement (50.0% vs. 14.3%; p=0.036). Quantitative analysis showed that the arrival time of HCA was earlier than that of wHCC (12.4 ± 3.7s vs. 15.9 ± 3.2s; p=0.006). (b) Interobserver agreement was improved by using CPI compared with CEUS. The diagnostic sensitivity, specificity, and accuracy of the combination were 80.0%, 85.7%, and 84.2%, respectively. CEUS combined with CPI can provide effective information for the differential diagnosis of HCA and wHCC, especially for the non-experienced radiologists.

Preneoplastic lesions in the liver: Molecular insights and relevance for clinical practice.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are the most frequent primary liver cancers, accounting for approximately 80% and 15%, respectively. HCC carcinogenesis occurs mostly in cirrhosis and is a complex multi-step process, from precancerous lesions (low-grade and high-grade dysplastic nodules) to progressed HCC. During the different stages of liver carcinogenesis, there is an accumulation of pathological, genetic and epigenetic changes leading to initiation, malignant transformation and finally tumour progression. In contrast, a small subset of HCC occurs in normal liver from the transformation of hepatocellular adenoma (HCA), a benign hepatocellular tumour. The recent molecular classification enables to stratify HCAs according to their risk of complication, in particular malignant transformation, associated with mutations in exon 3 of the catenin beta 1 (CTNNB1) gene. Cholangiocarcinoma (CCA) derives from the multistep malignant transformation of preneoplastic lesions, like biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB), for which a pre-operative diagnosis remains difficult. Different genetic alterations are involved in BilIN and IPNB progression, leading to the development of tubular or intestinal adenocarcinoma. The aims of this review are to describe the main clinical and molecular features of preneoplastic lesions leading to the development of HCC and CCA, their implications in clinical practice and the perspectives for future research.

Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature.

Liver transplantation (LT) has been employed for hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. All patients listed or transplanted for HA in the United States were identified in the United Network for Organ Sharing (UNOS) database (1987-2020). A systematic literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. A total of 199 HA patients were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 HA patients underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 mo, death was reported in 18.3%. The 1-, 3-, and 5-y patient survival rates were 94.2%, 89.7%, and 86.3% in the UNOS cohort. The systematic review yielded 61 articles reporting on 99 nonoverlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), whereas 53.1% had glycogen storage disease. Over a median follow-up of 36.5 mo, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-y patient survival rates were all 95.0% in the systematic review. LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.

Diagnosis and Follow-up of Incidental Liver Lesions in Children.

Incidental liver lesions are identified in children without underlying liver disease or increased risk of hepatic malignancy in childhood. Clinical and imaging evaluation of incidental liver lesions can be complex and may require a multidisciplinary approach. This review aims to summarize the diagnostic process and follow-up of incidental liver lesions based on review of the literature, use of state-of-the-art imaging, and our institutional experience. Age at presentation, gender, alpha fetoprotein levels, tumor size, and imaging characteristics should all be taken into consideration to optimize diagnosis process. Some lesions, such as simple liver cyst, infantile hemangioma, focal nodular hyperplasia (FNH), and focal fatty lesions, have specific imaging characteristics. Recently, contrast-enhanced ultrasound (CEUS) was Food and Drug Administration (FDA)-approved for the evaluation of pediatric liver lesions. CEUS is most specific in lesions smaller than 3 cm and is most useful in the diagnosis of infantile hemangioma, FNH, and focal fatty lesions. The use of hepatobiliary contrast in MRI increases specificity in the diagnosis of FNH. Recently, lesion characteristics in MRI were found to correlate with subtypes of hepatocellular adenomas and associated risk for hemorrhage and malignant transformation. Biopsy should be considered when there are no specific imaging characteristics of a benign lesion. Surveillance with imaging and alpha fetoprotein (AFP) should be performed to confirm the stability of lesions when the diagnosis cannot be determined, and whenever biopsy is not feasible.

Liver Transplantation for Hepatic Adenoma: A UNOS Database Analysis and Systematic Review of the Literature

Introduction: Liver transplantation (LT) has been employed for the management of hepatic adenoma (HA) on a case-oriented basis. We aimed to describe the characteristics, waitlist, and post-LT outcomes of patients requiring LT for HA. Methods: All patients listed and/or transplanted for HA in the USA were identified in the United Network for Organ Sharing (UNOS) database (1987-2020). A systematic literature review was performed according to the PRISMA statement. Results: A total of 199 patients with HA were listed for LT in UNOS and the crude waitlist mortality was 9.0%. A total of 142 patients with HA underwent LT; 118 of these were among those listed with an indication of HA who underwent LT, and 24 were diagnosed incidentally. Most did not experience hepatocellular carcinoma transformation (89.4%). Over a median follow-up of 62.9 months, death was reported in 18.3%. The 1-, 3-, and 5-year patient survival rates were 94.2%, 89.7%, and 86.3% (Figure). The systematic review yielded 61 articles reporting on 99 non-overlapping patients undergoing LT for HA and 2 articles reporting on multicenter studies. The most common LT indications were suspected malignancy (39.7%), unresectable HA (31.7%), and increasing size (27.0%), while 53.1% had glycogen storage disease. Over a median follow-up of 36.5 months, death was reported in 6.0% (n=5/84). The 1-, 3-, and 5-year patient survival rates were all 95.0%. Conclusion: LT for HA can lead to excellent long-term outcomes in well-selected patients. Prospective granular data are needed to develop more optimal selection criteria and further improve outcomes.

Study Protocol for a Multicenter Nationwide Prospective Cohort Study to Investigate the Natural Course and Clinical Outcome in Benign Liver Tumors and Cysts in The Netherlands: The BELIVER Study

Introduction: Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic hemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or hemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient reported outcomes (PROs) of patients with BLTCs, with special regard to the influence of invasive treatment as compared to the natural course of the disease. Methods and analysis: A nationwide observational cohort study of BLTC patients will be performed between August 2021 and August 2026. Inclusion will be open from August 2021 until August 2025. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on patient reported outcomes (PROs) considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerized adaptive testing through the Patient-Reported Outcomes Measurement Information System (PROMIS). Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course.

Focal Nodular Hyperplasia-Like Lesion in a Girl with Obesity and Fatty Liver.

Focal Nodular Hyperplasia-Like Lesion in a Girl with Obesity and Fatty Liver.

Relief of Symptoms and Quality of Life after Conservative versus Surgical Treatment of Benign Liver Tumors (CONSULT): A Retrospective Propensity Score Matched Study

Introduction: Surgery can be considered for patients with benign liver tumours (BLTs) with risk of malignancy, complications, or severe symptoms. The effect of surgery on symptoms and quality of life (QoL) remains debatable. The aim of this study was to compare symptoms and QoL after surgical or conservative management of BLTs. Methods: In this dual-site retrospective study, adult patients with hepatocellular adenoma, focal nodular hyperplasia, or haemangioma diagnosed between 2000 and 2019 were included. SumScores and general QoL scores at follow-up were compared between propensity-score matched, surgically and conservatively managed patients. Higher scores indicate more symptoms and a higher QoL, respectively. Results: Among 221 included patients, 50 (22.6%) were treated surgically and 171 (78.4%) conservatively. Surgical patients were younger, with lower baseline QoL, and more often had left-sided and larger tumours. At follow-up, median 91-100 months after diagnosis, surgical patients had higher SumScores (mean difference 9.2, 95%CI 1.0-17.4, p=0.028) but not higher general QoL scores (p=0.331) than their propensity-score matched, conservatively treated counterparts. Surgical patients also had higher emotional (p=0.010) and cognitive (p=0.009) functioning scores, less insomnia (p=0.026), less appetite loss (p=0.012), less bloating (p=0.006), less weight gain (p=0.035) and less pain (p=0.027). Most reported stable, improved or disappearance of symptoms (41/47 patients) and would undergo surgery again (44/47 patients). Conclusion: More than seven years after diagnosis, surgical patients had less symptoms than conservatively managed patients, although QoL was not significantly different. These results may support currently available recommendations and further guide treatment selection.

GLUCOGENOSIS AS A CAUSE OF INTRAHEPATIC CHOLESTASIS

Hepatic glycogen storage pathologies are very rare diseases among inborn errors of metabolism caused by the alteration of the enzymes involved in the metabolism of glycogen. GSDs are classified according to enzyme deficiency and affected tissue, including types 0, Ia, Ib, III, IV, VI, and XI. The clinical presentation can be very varied, including intolerance to fasting, growth retardation and hepatomegaly. It can present with hypoglycemia, hyperlactatemia, increased liver enzymes, and hyperlipidemia. The most common type of glycogen storage disease is GDS IX, its incidence is 1: 100,000 births and it is responsible for 25% of all cases. The most common GSD IX subtype is subtype IX a caused by mutations in PHKA2, which accounts for 75% of cases. Long-term complications include liver adenomas, kidney disease, cardiomyopathy, and muscle symptoms. 27-year-old male patient. Important history, positive smoking with IT 1, positive alcoholism with consumption of 8 grams of alcohol per day for 10 years. During childhood, he presented hepatomegaly and an isolated event of jaundice. He began his condition one month before with asthenia, adynamia and weight loss (9 kg / 30 days), accompanied by generalized jaundice, later he presented abdominal pain in the right upper quadrant, with early satiety, acholia and choluria. On physical examination: hepatosplenomegaly, jaundice of the skin and integuments. Paraclinical: BT: 5.3 mg / dl, BD: 1.2 mg / dl 8, DHL: 444IU / L, TGP: 89 U / L, TGO: 168 U / L FA: 1050 U / L. HIV: non-reactive, HBV HCV non-reactive. Ultrasound with multiple nodular echogenic lesions without bile duct dilation, a 1.8 mm common bile duct, a 7 mm portal vein, and an enlarged spleen. Endoscopy: portal hypertensive gastropathy, extrinsic compression of the body and gastric fundus without evidence of varicose veins. Cholangioresonance without intra- and extra-hepatic bile duct dilation. Normal alpha 1 antitrypsin (2.08 g / dl). Given the evidence of intrahepatic cholestasis, it was decided to perform an ultrasound-guided liver biopsy where it was observed positive for intracytoplasmic glycogen in the hepatocytes, thus establishing a definitive diagnosis of Glycogenosis. Due to its low incidence, the diagnostic approach of Glycogenosis presents a challenge. The diagnosis is made at an early age; the clinical data will depend on the affected tissue and type of Glycogenosis. The histopathological report is the mainstay of diagnosis in this type of case and making a differential diagnosis with other entities and a genetic study. Glycogen storage disorders are part of a group of rare and few suspected pathologies. It is not frequent to find them in adult patients due to their complications. The prognosis must be individualized based on the affected tissue and the subtype presented. The authors declare that there is no conflict of interest.

Hepatocellular Carcinoma Recurrence with Metachronous Peritoneal Metastasis - A Controversial Surgical Indication

We present the case of a female patient who underwent surgery for a big hepatic adenoma that suffered malignant transformation. Fifteen months later, she had HCC liver recurrence with peritoneal metastases, being submitted to a new surgery with complete resection of the hepatic mass and peritoneal implants.