Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation

Brunt, Elizabeth M.

doi:10.1002/hep4.1055

Cited by 48 publications

(49 citation statements)

References 63 publications

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“…Evidence suggests that fibrosis can progress but it may also regress during the disease course of NAFLD . Considering the biochemically stable nature of elastin compared with collagen, elastin accumulation in the liver may contribute to the irreversibility of the disease.…”

Section: Discussionsupporting

confidence: 88%

“…(9,43,44) Previous evidence has shown that advanced fibrosis is associated with increased risk of all-cause and liver-related mortality. (10,45) Intriguingly, our quantitative analysis did not show any significant differences in fiber area ratios between stages 2 and 3. A histologic difference between the two stages is the presence or absence of bridging fibrosis.…”

Section: Discussionmentioning

confidence: 52%

“…The extent of liver fibrosis in NASH has been frequently discussed as defining two risk groups: early fibrosis (stages1/2) and advanced fibrosis (stages 3/4) . Previous evidence has shown that advanced fibrosis is associated with increased risk of all‐cause and liver‐related mortality . Intriguingly, our quantitative analysis did not show any significant differences in fiber area ratios between stages 2 and 3.…”

Section: Discussionmentioning

confidence: 99%

“…Although there were wide variations in the severity of bridging within advanced NAFLD, we found relatively limited areas of bridging fibrosis at stage 3, which likely helps to explain the absence of a statistically significant increase in the amount of fiber between stages 2 and 3. Because bridging fibrosis links vascular structures, leads to alteration of the regional blood flow, and may thereby promote liver injury, the detection of the architectural histologic feature of bridging fibrosis by pathologists is noteworthy . Nonetheless, the retrospective study with a large sample size (n = 619) has demonstrated an increased mortality risk for patients with NAFLD with each successive fibrosis stage (ranging from 0 to 4), suggesting that the binary staging system (early versus advanced fibrosis) is likely arbitrary.…”

Section: Discussionmentioning

confidence: 99%

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Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

Masugi

Abe

Tsujikawa

et al. 2017

Hepatology Communications

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Accurate staging of liver fibrosis is crucial to guide therapeutic decisions for patients with nonalcoholic fatty liver disease (NAFLD). Digital image analysis has emerged as a promising tool for quantitative assessment of fibrosis in chronic liver diseases. We sought to determine the relationship of histologic fibrosis stage with fiber amounts quantified in liver biopsy specimens for the better understanding of NAFLD progression. We measured area ratios of collagen and elastin fibers in Elastica van Gieson‐stained biopsy tissues from 289 patients with NAFLD from four hospitals using an automated computational method and examined their correlations with Brunt's fibrosis stage. As a secondary analysis, we performed multivariable logistic regression analysis to assess the associations of the combined area ratios of collagen and elastin with noninvasive fibrosis markers. The combined fiber area ratios correlated strongly with Brunt's stage (Spearman correlation coefficient, 0.78; P < 0.0001), but this relationship was nonlinear (P = 0.007) with striking differences between stage 4 (median area ratios, 12.3%) and stages 0‐3 (2.1%, 2.8%, 4.3%, and 4.8%, respectively). Elastin accumulation was common in areas of thick bridging fibrosis and thickened venous walls but not in areas of perisinusoidal fibrosis. The highest tertile of the combined fiber area ratios was associated with the fibrosis‐4 index and serum type IV collagen 7s domain (7s collagen) levels, whereas the upper two tertiles of the fiber amounts significantly associated with body mass index, aspartate aminotransferase, and 7s collagen in the multivariable analysis. Conclusion: Quantitative fibrosis assessment reveals a nonlinear relationship between fibrosis stage and fiber amount, with a marked difference between stage 4 and stage 3 and much smaller differences among stages 0‐3, suggesting a heterogeneity in disease severity within NAFLD‐related cirrhosis. (Hepatology Communications 2018;2:58–68)

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

Masugi

Abe

Tsujikawa

et al. 2017

Hepatology Communications

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“…Classical pathological staging systems have no stage beyond F4; however, it appears that fibrosis progresses and parenchymal remodeling continues even within the final fibrotic stage F4 . Furthermore, fibrosis not only progresses but may also regress during the disease course . These results indicate that an accurate assessment of fibrosis using quantitative computational fiber measurements combined with the classical pathological grading of structural changes might be able to predict more precisely the outcomes in patients with NAFLD.…”

Section: Assessment Of Liver Fibrosismentioning

confidence: 91%

Precision pathology analysis of the development and progression of hepatocellular carcinoma: Implication for precision diagnosis of hepatocellular carcinoma

Ueno

Masugi

Yamazaki

et al. 2020

Pathology International

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Outcomes for patients with hepatocellular carcinoma (HCC) remain poor because the condition is often unresponsive to the available treatments. Consequently, the early and precise diagnosis of HCC is crucial to achieve improvements in prognosis. For patients with chronic liver disease, the assessment of liver fibrosis is also important to ascertain both the staging of fibrosis and the risk of HCC occurrence. Early HCC was first described in 1991 in Japan and was defined internationally in 2009. As the concept of early HCC spread, the multistage hepatocarcinogenesis process became accepted. Consequently, improvements in imaging technology made the early diagnosis of HCC possible. At present, the most appropriate therapeutic strategy for HCC is determined using an integrated staging system that assesses the tumor burden, the degree of liver dysfunction and the patient performance status; however, pathological and molecular features are not taken into account. The recent introduction of several new therapeutic agents will change the treatment strategy for HCC. Against this background, HCC subclassification based on tumor cellular and microenvironmental characteristics will become increasingly important. In this review, we give an overview of how pathological analysis contributes to understanding the development and progression of HCC and establishing a precision diagnosis of HCC.

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qFIBS: An Automated Technique for Quantitative Evaluation of Fibrosis, Inflammation, Ballooning, and Steatosis in Patients With Nonalcoholic Steatohepatitis

Goh²,

et al. 2020

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Background and Aims Nonalcoholic steatohepatitis (NASH) is a common cause of chronic liver disease. Clinical trials use the NASH Clinical Research Network (CRN) system for semiquantitative histological assessment of disease severity. Interobserver variability may hamper histological assessment, and diagnostic consensus is not always achieved. We evaluate a second harmonic generation/two‐photon excitation fluorescence (SHG/TPEF) imaging‐based tool to provide an automated quantitative assessment of histological features pertinent to NASH. Approach and Results Images were acquired by SHG/TPEF from 219 nonalcoholic fatty liver disease (NAFLD)/NASH liver biopsy samples from seven centers in Asia and Europe. These were used to develop and validate qFIBS, a computational algorithm that quantifies key histological features of NASH. qFIBS was developed based on in silico analysis of selected signature parameters for four cardinal histopathological features, that is, fibrosis (qFibrosis), inflammation (qInflammation), hepatocyte ballooning (qBallooning), and steatosis (qSteatosis), treating each as a continuous rather than categorical variable. Automated qFIBS analysis outputs showed strong correlation with each respective component of the NASH CRN scoring (P < 0.001; qFibrosis [r = 0.776], qInflammation [r = 0.557], qBallooning [r = 0.533], and qSteatosis [r = 0.802]) and high area under the receiver operating characteristic curve values (qFibrosis [0.870‐0.951; 95% confidence interval {CI}, 0.787‐1.000; P < 0.001], qInflammation [0.820‐0.838; 95% CI, 0.726‐0.933; P < 0.001), qBallooning [0.813‐0.844; 95% CI, 0.708‐0.957; P < 0.001], and qSteatosis [0.939‐0.986; 95% CI, 0.867‐1.000; P < 0.001]) and was able to distinguish differing grades/stages of histological disease. Performance of qFIBS was best when assessing degree of steatosis and fibrosis, but performed less well when distinguishing severe inflammation and higher ballooning grades. Conclusions qFIBS is an automated tool that accurately quantifies the critical components of NASH histological assessment. It offers a tool that could potentially aid reproducibility and standardization of liver biopsy assessments required for NASH therapeutic clinical trials.

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Nonalcoholic fatty liver disease and the ongoing role of liver biopsy evaluation

Cited by 48 publications

References 63 publications

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

Quantitative assessment of liver fibrosis reveals a nonlinear association with fibrosis stage in nonalcoholic fatty liver disease

Precision pathology analysis of the development and progression of hepatocellular carcinoma: Implication for precision diagnosis of hepatocellular carcinoma

qFIBS: An Automated Technique for Quantitative Evaluation of Fibrosis, Inflammation, Ballooning, and Steatosis in Patients With Nonalcoholic Steatohepatitis

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