Soon, Gwyneth Shook Ting

Background and aims To validate the applicability of the new histological criteria for autoimmune hepatitis (AIH) proposed by the International AIH Pathology Group (IAIH‐PG) among Chinese patients with AIH and drug‐induced liver injury (DILI). Methods The gold standard for diagnosis relied on clinical response: discontinuing treatment without relapse supported DILI, while relapse or ongoing immunosuppressive treatment confirmed AIH. This two‐centre retrospective cohort study included inpatients with DILI or AIH from January 2002 to March 2023. Cases that underwent liver biopsy were selected according to inclusion and exclusion criteria. The diagnostic performance of the criteria was assessed by an area under the receiver operating characteristic curve (AUROC). Results Out of 69 patients: AIH (41, 59%) and DILI (28, 41%). The accuracy, sensitivity and specificity of the new histological criteria for likely and possible AIH were 70%, 98% and 29%, respectively, with an AUROC of 0.8236 [95% confidence interval (CI): 0.7533–0.8938]. For likely AIH, the accuracy, sensitivity and specificity were 73%, 61% and 89%, respectively, with an AUROC of 0.9177 [95% CI: 0.8757–0.9596]. Moreover, for possible AIH, significant differences were found in serum alanine aminotransferase levels [178.4 (87.0, 435.0) versus 536.5 (206.9, 930.4) U/L] and antinuclear antibody (ANA) ≥1:160 [10 (67%) versus 1 (6%)], as well as in lobular lymphoplasmacytic infiltrate [15 (100%) versus 12 (71%)] and more than mild inflammation [13 (87%)versus 6 (35%)] between AIH and DILI (all P values were <0.05). Conclusion The new histological criteria exhibit good diagnostic efficacy in distinguishing AIH from DILI in China, with high AUROC. Key discriminators include low aminotransferase, ANA ≥1:160, lobular lymphoplasmacytic infiltrate and more than mild inflammation, which may further improve diagnostic accuracy for AIH.

Subtyping hepatic adenomas is important for patient management due to differing complication risks. Immunohistochemical staining with C-reactive protein (CRP) and serum amyloid-A (SAA) is widely accepted as a surrogate for molecular classification to identify inflammatory hepatocellular adenomas. Limited data, however, has been published on how these 2 stains compare for sensitivity. We conducted a large, multicenter, retrospective study to examine the sensitivity and staining characteristics of CRP and SAA in inflammatory hepatic adenomas, with focal nodular hyperplasia (FNHs) as a control group. Inflammatory adenomas were identified in 133 patients (average age 37 years, 109 were female). In all, 69.9% of cases were resection specimens and 90.2% of all cases showed positive staining for both CRP and SAA; 10 (7.5%) were positive for CRP only and 3 (2.3%) were positive for SAA only. CRP was more sensitive than SAA (97.74% vs. 92.48%, P-value = 0.0961) and showed more extensive and intense staining, with a significantly higher modified H-score (P<0.001). Focal nodular hyperplasia can also show positive CRP and SAA staining but with a lower modified H-score (P<0.0001). Based on beta-catenin and glutamine synthetase staining, 26 of inflammatory adenomas also had beta-catenin activation (19.5%). All 3 cases with positive SAA and negative CRP staining were beta-catenin activated. In contrast, the proportion of cases that were CRP positive and SAA negative was similar regardless of beta-catenin activation. The data affirms the strategy of using both CRP and SAA immunostains for hepatic adenoma subtyping and raises the awareness of the highly variable nature of SAA staining characteristics.

Hepatic angiosarcomas are aggressive malignant tumors of the liver with variable morphology. One of the rare morphologies is that of the sinusoidal growth pattern, which is challenging to diagnose because of its subtle imaging and morphologic findings. This retrospective study characterizes the clinical, histologic, and immunohistochemical features of sinusoidal hepatic angiosarcomas. Thirteen cases were included in the study, comprising 12 (92.3%) needle core biopsies and 1 wedge biopsy; one of the needle biopsies also had a subsequent resection specimen available for review. Multiple biopsies were needed to make the diagnosis in 4 cases. At least moderate sinusoidal dilatation was seen in 53.8% of cases. Increased cellularity within the sinusoids was seen at both low-power and high-power magnification (69.2% and 84.6%, respectively). Cytologic atypia ranged from mild to marked. Multinucleated tumor cells were present in most cases (10/13 cases) but were often sparse. Mitotic activity was identified in 5/13 cases. ERG immunostains were more reliable than CD31 and CD34 in identifying the tumor cells. Ki-67 proliferative index ranged from 5% to 30%. p53 immunostains were available in 9 cases and c-MYC in 7 cases; they were positive in 62.5% and 33.3% of cases, respectively and had a mutually exclusive staining pattern. In summary, this rare pattern of hepatic angiosarcoma is challenging to diagnose but has distinctive morphologic findings that can be supplemented with immunostains to establish the diagnosis.

Newer radiotherapy techniques, such as stereotactic body radiation, have been increasingly used as part of the treatment of cholangiocarcinomas, particularly as a bridge to liver transplantation. Although conformal, these high-dose therapies result in tissue injury in the peritumoral liver tissue. This retrospective study characterized the morphologic changes in the liver after stereotactic body radiation in a series of liver explant specimens with perihilar cholangiocarcinoma. The morphologic changes in the irradiated zone were compared against the nonirradiated background liver parenchyma to control for chemotherapy-related changes. Of the 21 cases studied, 16 patients (76.2%) had underlying primary sclerosing cholangitis, and 13 patients (61.9%) had advanced liver fibrosis. The average duration between completion of radiotherapy and liver transplantation was 33.4 weeks (range: 6.29 to 67.7). Twelve patients (57.1%) had no residual tumor in the liver. The most frequent histologic changes in the peritumoral irradiated liver tissue were sinusoidal congestion (100%), sinusoidal edematous stroma (100%), and hepatocellular atrophy (100%), followed by partial/complete occlusion of central veins (76.2%), sinusoidal cellular infiltrates (76.2%), and hepatocyte dropout (66.7%). The findings in the radiated areas were more extensive than in the background liver (P<0.01). Sinusoidal edematous stroma was striking and dominated the histologic findings in some cases. Over time, there was less sinusoidal congestion but more hepatocyte dropout (rs=−0.54, P=0.012 and rs=0.64, P=0.002, respectively). Uncommon findings, such as foam cell arteriopathy in the liver hilum, were also observed. In summary, postradiation liver specimens have distinctive morphologic findings.

The liver is a major store of glycogen and is essential in maintaining systemic glucose homeostasis. In healthy individuals, glycogen synthesis and breakdown in the liver are tightly regulated. Abnormal glycogen metabolism results in prominent pathological changes in the liver, often manifesting as hepatic glycogenosis or glycogen inclusions. This can occur in genetic glycogen storage disease or acquired conditions with insulin dysregulation such as diabetes mellitus and non-alcoholic fatty liver disease or medication effects. Some primary hepatic tumors such as clear cell hepatocellular carcinoma also demonstrate excessive glycogen accumulation. This review provides an overview of the pathological manifestations and molecular mechanisms of liver diseases associated with abnormal glycogen accumulation.