Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis

There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 μg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate.

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Liver Histological Improvement After Administration of High-Dose Vitamin C in Guinea Pig with Nonalcoholic Steatohepatitis

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000515 ◽

2018 ◽

Vol 88 (5-6) ◽

pp. 263-269

Author(s):

Seong-Hoon Park ◽

A Lum Han ◽

Na-Hyung Kim ◽

Sae-Ron Shin

Keyword(s):

Liver Biopsy ◽

Vitamin C ◽

Nonalcoholic Steatohepatitis ◽

Guinea Pigs ◽

Normal Diet ◽

High Dose ◽

Biochemical Tests ◽

Deficient Diet ◽

Histological Improvement ◽

Vit C

Abstract. Background: Vitamin C is a strong antioxidant, and the health effects of vitamin C megadoses have not been validated despite the apparent health benefits. Therefore, the present study sought to confirm the effects of vitamin C megadoses. Materials and Methods : Four groups of six guinea pigs were used. Each group was fed one of the following diets for three weeks: normal diet, methionine choline-deficient diet, methionine choline-deficient diet + vitamin C megadose (MCD + vit C 2.5 g/kg/day), and methionine-choline deficient diet + ursodeoxycholic acid (MCD + UDCA 30 mg/kg/day). The MCD diet was given to induce nonalcoholic steatohepatitis, and UDCA was used to treat nonalcoholic steatohepatitis. Three weeks after initial diet administration, the results of biochemical tests and liver biopsy were compared between the groups. Results: The cytoplasm state was similar in the MCD + vit C and MCD + UDCA groups, exhibiting clearing of the cytoplasm and ballooning degeneration. However, macrovesicular steatosis was not observed in the MCD + vit C group. Aspartate transaminase and alanine transaminase were elevated significantly following vitamin C administration. Conclusions: The present study confirmed that alone vitamin C megadoses are potential remedies for nonalcoholic steatohepatitis, based on the liver biopsy results of guinea pigs that were unable to synthesize vitamin C.

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Value of computed tomography in nonalcoholic steatohepatitis (NASH); comparison with liver biopsy

Journal of Hepatology ◽

10.1016/s0168-8278(01)80719-4 ◽

2001 ◽

Vol 34 (0) ◽

pp. 195-196

Author(s):

D Duman

Keyword(s):

Computed Tomography ◽

Liver Biopsy ◽

Nonalcoholic Steatohepatitis

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The role of preoperative liver biopsy in the diagnosis of hepatocellular carcinoma

Journal of Hepatology ◽

10.1016/s0168-8278(01)80380-9 ◽

2001 ◽

Vol 34 (0) ◽

pp. 106

Author(s):

M Sherman

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Biopsy

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Constructing and model-fitting receiver operator characteristics using continuous data.

10.31234/osf.io/qdgjc ◽

2018 ◽

Author(s):

Josephine Ann Urquhart ◽

Akira O'Connor

Keyword(s):

Signal Detection ◽

Least Squares Method ◽

Model Fitting ◽

Simulated Data ◽

Continuous Variable ◽

Continuous Data ◽

Model Parameters ◽

Operating Characteristics ◽

Unequal Variance ◽

Discrete Discrimination

Receiver operating characteristics (ROCs) are plots which provide a visual summary of a classifier’s decision response accuracy at varying discrimination thresholds. Typical practice, particularly within psychological studies, involves plotting an ROC from a limited number of discrete thresholds before fitting signal detection parameters to the plot. We propose that additional insight into decision-making could be gained through increasing ROC resolution, using trial-by-trial measurements derived from a continuous variable, in place of discrete discrimination thresholds. Such continuous ROCs are not yet routinely used in behavioural research, which we attribute to issues of practicality (i.e. the difficulty of applying standard ROC model-fitting methodologies to continuous data). Consequently, the purpose of the current article is to provide a documented method of fitting signal detection parameters to continuous ROCs. This method reliably produces model fits equivalent to the unequal variance least squares method of model-fitting (Yonelinas et al., 1998), irrespective of the number of data points used in ROC construction. We present the suggested method in three main stages: I) building continuous ROCs, II) model-fitting to continuous ROCs and III) extracting model parameters from continuous ROCs. Throughout the article, procedures are demonstrated in Microsoft Excel, using an example continuous variable: reaction time, taken from a single-item recognition memory. Supplementary MATLAB code used for automating our procedures is also presented in Appendix B, with a validation of the procedure using simulated data shown in Appendix C.

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Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13040730 ◽

2021 ◽

Vol 13 (4) ◽

pp. 730

Author(s):

Moritz Peiseler ◽

Frank Tacke

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Disease ◽

Disease Progression ◽

Immune Cells ◽

Nonalcoholic Steatohepatitis ◽

Adaptive Immune System ◽

Nonalcoholic Fatty Liver ◽

Inflammatory Processes ◽

New Treatment ◽

End Stage

Nonalcoholic fatty liver disease (NAFLD) is a rising chronic liver disease and comprises a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH) to end-stage cirrhosis and risk of hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is multifactorial, but inflammation is considered the key element of disease progression. The liver harbors an abundance of resident immune cells, that in concert with recruited immune cells, orchestrate steatohepatitis. While inflammatory processes drive fibrosis and disease progression in NASH, fueling the ground for HCC development, immunity also exerts antitumor activities. Furthermore, immunotherapy is a promising new treatment of HCC, warranting a more detailed understanding of inflammatory mechanisms underlying the progression of NASH and transition to HCC. Novel methodologies such as single-cell sequencing, genetic fate mapping, and intravital microscopy have unraveled complex mechanisms behind immune-mediated liver injury. In this review, we highlight some of the emerging paradigms, including macrophage heterogeneity, contributions of nonclassical immune cells, the role of the adaptive immune system, interorgan crosstalk with adipose tissue and gut microbiota. Furthermore, we summarize recent advances in preclinical and clinical studies aimed at modulating the inflammatory cascade and discuss how these novel therapeutic avenues may help in preventing or combating NAFLD-associated HCC.

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