Hepatocellular Adenoma Cases Research Articles

Hepatocellular adenoma, approximately half and predominantly inflammatory subtype, in 38 Japanese patients with several differences in age, gender, and clinical background factors from Western populations.

Hepatocellular adenoma (HCA) has a lower prevalence in Japan than in Western countries and HCA subtypes have been reported for only a few Japanese patients. We analyzed HCA subtype data 38 patients from 23 hospitals in Japan in order to examine character and difference between Western countries. To confirm HCA and to analyze subtypes, we performed immunohistochemical examinations. Thirty-eight cases were found to have HCA without cirrhosis. The male/female ratio was 18/20. Ages ranged from 15 to 79 (average, 43.2) years. Male and elder patients are not rare, furthermore, most of elder patients are male. Glycogen storage disease, past history of medicament use, hepatitis B virus surface antigen-positivity, antihepatitis C virus -positivity, diabetes mellitus, obesity, lipid metabolism disorder and alcoholism were present in of 6, 8, 1, 1, 6, 6, 4, and 6 cases, respectively. As to HCA subtypes, HNF1alpha-inactivated HCA, beta-catenin activated HCA (b-HCA), inflammatory HCA (IHCA) and unclassified HCA (U-HCA) accounted for nine (23.7%), four (10.5%), 17 (44.7%) and eight (21.1%) cases, respectively. Two cases showed coexistence of HCA and hepatocellular carcinoma (HCC) at surgery, and another had HCC which had been detected 23years after HCA diagnosis. The HCA subtype of one of the former cases was U-HCA, while the remaining two had b-HCA and U-HCA. In Japanese HCA cases, the proportions of U-HCA, male and elder cases were slightly higher than in Western countries, and most of elder patients were male. IHCA was however common regardless of race, and was assumed to be the predominant subtype of HCA.

Hepatic CYP1A2 activity in liver tumors and the implications for preoperative volume-function analysis.

Dynamic liver function assessment by the [13C]methacetin maximal liver function capacity (LiMAx) test reflects the overall hepatic cytochrome P-450 (CYP) 1A2 activity. One proven strategy for preoperative risk assessment in liver surgery includes the combined assessment of the dynamic liver function by the LiMAx test, the volumetric analysis of the liver, and calculation of future liver remnant function. This so-called volume-function analysis assumes that the remaining CYP1A2 activity in any tumor lesion is zero. The here presented study aims to assess the remaining CYP1A2 activities in different hepatic tumor lesions and its consequences for the preoperative volume-function analysis in patients undergoing liver surgery. The CYP1A2 activity analysis of neoplastic lesions and adjacent nontumor liver tissue from resected tumor specimens revealed a significantly higher CYP1A2 activity (median, interquartile range) in nontumor tissues (35.5, 15.9-54.4 µU/mg) compared with hepatocellular adenomas (7.35, 1.2-32.5 µU/mg), hepatocellular carcinomas (0.18, 0.0-2.0 µU/mg), or colorectal liver metastasis (0.17, 0.0-2.1 µU/mg). In nontumor liver tissue, a gradual decline in CYP1A2 activity with exacerbating fibrosis was observed. The CYP1A2 activity differences were also reflected in CYP1A2 protein signals in the assessed hepatic tissues. Volume-function analysis showed a minimal deviation compared with the current standard calculation for hepatocellular carcinomas or colorectal liver metastasis (<1% difference), whereas a difference of 11.9% was observed for hepatocellular adenomas. These findings are important for a refined preoperative volume-function analysis and improved surgical risk assessment in hepatocellular adenoma cases with low LiMAx values. NEW & NOTEWORTHY The cytochrome P-450 (CYP) 1A2-dependent maximal liver function capacity test reflects the overall functional capacity of the liver. To which extent hepatocellular tumors harbor CYP1A2 activity and thus contribute to the maximal liver function capacity test outcome is unknown. We here show that hepatocellular adenomas but not hepatocellular carcinomas or colorectal liver metastasis contain significant residual CYP1A2 activity. These findings are important for an improved preoperative volume-function analysis and an accurate surgical risk assessment in hepatocellular adenoma cases.

Diagnostic Value of Gd-EOB-DTPA-MRI for Hepatocellular Adenoma: A Meta-Analysis.

Objective: This study aimed to systematically review the gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) findings of hepatocellular adenoma (HCA), especially focusing on the diagnostic value of low signal intensity (SI) in the hepatocyte-phase (HBP) for differentiating HCA from focal nodular hyperplasia (FNH).Methods: A thorough literature search was conducted in PubMed, Excerpta Medica Database (EMBASE) and China National Knowledge Infrastructure databases (CNKI) to identify studies evaluating Gd-EOB-DTPA-MRI presentations of HCA. Published studies using pathological examinations as the gold standard were included. The pooled proportions of low SI in the HBP, arterial-phase, portal venous-phase (PVP) in HCA were calculated, as well as pooled proportions of bleeding, fatty degeneration, and central scar. Meta-analysis was used to evaluate the diagnostic value of low SI in the HBP for HCA.Results: The search yielded 90 studies, with 8 assessing a total of 256 HCA cases included in this study, total of 229 lesions showed low signal in the HBP. Pooled proportions of low SI in the arterial-phase, PVP, and HBP were 2% (95% CI: 0.01-0.05), 39% (95% CI: 0.25-0.55), and 89% (95% CI: 0.80-0.94), respectively. Pooled proportions of bleeding, fatty degeneration, and central scar in HCA were 11% (95% CI: 0.03-0.19), 37% (95% CI: 0.27-0.49), and 10% (95% CI: 0.03-0.27), respectively. The meta-analysis revealed the following characteristics of low SI in the HBP for HCA diagnosis: 1) pooled sensitivity, 0.917 (95% CI: 0.86-0.96); 2) pooled specificity, 0.952 (95% CI: 0.91-0.98); 3) pooled positive likelihood ratio, 15.028 (95% CI: 7.10-31.82); 4) pooled negative likelihood ratio, 0.105 (95% CI: 0.07-0.17); 5) area under the ROC, 0.9802 (Q value of 0.9375), The sensitivity analysis showed that no single study was found to influence the overall pooled estimates significantly, which indicated the stability of the meta-analysis results were good.Conclusions: Low SI on the HBP of Gd-EOB-DTPA-MRI was helpful for the diagnosis of HCA and differentiating from FNH, but it was overvalued, especially for some HCA pathological subtypes. Combining low SI in the HBP with routine MRI presentations and the risk factors of liver diseases could substantially improve its diagnosis value for HCA as well as differential diagnosis.

Hepatocellular adenomas in a large community population, 2000 to 2010: reclassification per current World Health Organization classification and results of long-term follow-up.

The data used for the World Health Organization classification of hepatocellular adenoma (HCA) is largely based on cases from tertiary level centers in Europe. This study examines the distribution of HCA subtypes in a large community population and determines the impact of immunohistochemistry (IHC) on reclassification, diagnosis, and management. All cases diagnosed as HCA in a large community hospital network from 2000 to 2010 were reviewed. The following immunohistochemical stains were evaluated in cases where paraffin-embedded tissue was available (n = 35): β-catenin, glutamine synthetase, serum amyloid A, C-reactive protein, liver fatty acid binding protein. Twenty-eight of 35 cases were confirmed to be HCA, 5 cases were reclassified as well-differentiated hepatocellular carcinoma, and 2 cases were reclassified as focal nodular hyperplasia. The HCA cases were further subclassified into hepatocyte nuclear factor 1α inactivated (29%), inflammatory (32%), inflammatory with β-catenin activation (3%), noninflammatory β-catenin activated (0%), and unclassified (36%). Long-term follow-up was available on 33 of 35 cases, and there were no cases of recurrence or distant metastasis. IHC can provide a definite HCA subtype in two-thirds of cases. HCA subtypes in this large community-based population differed from the prior large French studies, in that there were a greater proportion of unclassified adenomas and a virtual absence of β-catenin-activated adenomas. It is likely that most β-catenin-activated hepatocellular tumors show morphologic and reticulin staining abnormalities indicative of well-differentiated hepatocellular carcinoma. IHC for glutamine synthetase and serum amyloid A can identify cases with β-catenin activation and aid in the distinction of inflammatory adenoma and focal nodular hyperplasia.

Characterization of hepatocellular adenoma based on the phenotypic classification: The Kanazawa experience

Hepatocellular adenoma (HCA) represents a heterogeneous entity, and recently four major subgroups were identified based on genotype and phenotype classification from Europe. HCA is rare in Asian countries including Japan and there has been no study regarding the subgroups of HCA in Japan. We took advantage of the reported genotype/phenotype classification to analyze 14 HCA (seven women) in Japan. We identified one hepatocyte nuclear factor (HNF)1α-inactivated HCA (one woman), two β-catenin-activated HCA (one woman), seven inflammatory HCA (IHCA, two women); four additional cases (three women) had no known phenotypic marker (unclassified HCA). The use of oral contraceptives was found only in two unclassified HCA (29%) cases. Fatty change of the background liver was seen in one β-catenin-activated HCA cases, four IHCA (57%) and two unclassified HCA (50%). Hepatic fibrosis was seen in five IHCA (71%) and two unclassified HCA (50%) cases. Four IHCA patients (one woman) were alcohol drinkers and one had alcoholic steatofibrosis and three had alcoholic cirrhosis. Eight HCA (57%) were multiple; one HNF1α-inactivated HCA (100%), four IHCA (57%) and three unclassified HCA (75%). The tumor was significantly larger in β-catenin-activated HCA than in other subgroups. The association of hepatocellular carcinoma was seen only in one case of unclassified HCA. This study suggests that IHCA arising in men with alcoholic liver disease may be a major subtype of HCA in Japan.

Chromosomal and genetic alterations in human hepatocellular adenomas associated with type Ia glycogen storage disease

Hepatocellular adenoma (HCA) is a frequent long-term complication of glycogen storage disease type I (GSD I) and malignant transformation to hepatocellular carcinoma (HCC) is known to occur in some cases. However, the molecular pathogenesis of tumor development in GSD I is unclear. This study was conducted to systematically investigate chromosomal and genetic alterations in HCA associated with GSD I. Genome-wide SNP analysis and mutation detection of target genes was performed in ten GSD Ia-associated HCA and seven general population HCA cases for comparison. Chromosomal aberrations were detected in 60% of the GSD Ia HCA and 57% of general population HCA. Intriguingly, simultaneous gain of chromosome 6p and loss of 6q were only seen in GSD Ia HCA (three cases) with one additional GSD I patient showing submicroscopic 6q14.1 deletion. The sizes of GSD Ia adenomas with chromosome 6 aberrations were larger than the sizes of adenomas without the changes (P = 0.012). Expression of IGF2R and LATS1 candidate tumor suppressor genes at 6q was reduced in more than 50% of GSD Ia HCA that were examined (n = 7). None of the GSD Ia HCA had biallelic mutations in the HNF1A gene. These findings give the first insight into the distinct genomic and genetic characteristics of HCA associated with GSD Ia. These results strongly suggest that chromosome 6 alterations could be an early event in the liver tumorigenesis in GSD I, and may be in general population. These results also suggest an interesting relationship between GSD Ia HCA and steps to HCC transformation.

Hepatocellular adenoma: what is new in 2008

Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1α (HNF1α) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1α-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1α germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating β-catenin mutation was found in 10% of HCA. These β-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress β-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express β-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1α-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of surveillance and treatment.