Hepatocellular Carcinoma in Nonalcoholic Steatohepatitis

2017 ◽  
Vol 01 (02) ◽  
pp. 066-073
Author(s):  
Sean Koppe ◽  
Hafiz Arshad
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
The United States ◽  
Nuclear Factor ◽  
Obese Patients ◽  
Nonalcoholic Fatty Liver ◽  
Potential Risk Factors ◽  
Factor Α ◽  
Necrosis Factor

AbstractNonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in the United States. Approximately 10 to 20% of patients with NAFLD progress to nonalcoholic steatohepatitis (NASH). NASH can progress to cirrhosis, which, in turn, can lead to hepatocellular carcinoma (HCC). However, evidence also supports that HCC can develop in patients with NASH who do not have cirrhosis or advanced fibrosis. Obesity, diabetes mellitus, hepatic iron deposition, and insulin resistance are potential risk factors for HCC in NASH. Mechanisms proposed include a role for tumor necrosis factor-α, interleukin-6, insulinlike growth factor, and nuclear factor κβ activation in progression of NASH to HCC. Polymorphisms in patatin-like phospholipase domain-containing 3 also support a genetic influence in NASH-related HCC. Surgical resection, liver directed therapy, and liver transplant remain the mainstay of therapy. Ultrasound has reduced sensitivity for surveillance of HCC in obese patients and alpha fetoprotein may have more value for HCC surveillance in the NASH patient as compared with the HCV patient. Although HCC can develop in noncirrhotic NASH, currently there are no guidelines to recommend surveillance in noncirrhotic NASH patients.

scholarly journals Inflammatory Mechanisms Underlying Nonalcoholic Steatohepatitis and the Transition to Hepatocellular Carcinoma

Cancers ◽  
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.

scholarly journals Emerging Roles of T Cells in the Pathogenesis of Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Petra Hirsova ◽  
Adebowale O. Bamidele ◽  
Haiguang Wang ◽  
Davide Povero ◽  
Xavier S. Revelo
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Liver Disease ◽  
T Cell ◽  
Nonalcoholic Steatohepatitis ◽  
Immune Cell ◽  
Current Knowledge ◽  
Significant Proportion ◽  
Nonalcoholic Fatty Liver ◽  
Integral Role

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. A significant proportion of patients with NAFLD develop a progressive inflammatory condition termed nonalcoholic steatohepatitis (NASH), which may eventually advance to cirrhosis and hepatocellular carcinoma (HCC). NASH is characterized by steatosis, hepatocyte ballooning, and lobular inflammation. Heightened immune cell infiltration is a hallmark of NASH, yet the mechanisms whereby hepatic inflammation occurs in NASH and how it contributes to disease initiation and progression remain incompletely understood. Emerging evidence indicates that intrahepatic T cell immune mechanisms play an integral role in the pathogenesis of NASH and its transition to HCC. In this review, we summarize the current knowledge regarding the T cell-mediated mechanisms of inflammation in NASH. We highlight recent preclinical and human studies implicating various subsets of conventional and innate-like T cells in the onset and progression of NASH and HCC. Finally, we discuss the potential therapeutic strategies targeting T cell-mediated responses for the treatment of NASH.

scholarly journals Sex Hormone Relations to Histologic Severity of Pediatric Nonalcoholic Fatty Liver Disease

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Noel T Mueller ◽  
Tiange Liu ◽  
Elana B Mitchel ◽  
Katherine P Yates ◽  
Ayako Suzuki ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Children And Adolescents ◽  
Nonalcoholic Fatty Liver Disease ◽  
Sex Hormones ◽  
Nonalcoholic Steatohepatitis ◽  
Fatty Liver Disease ◽  
The United States ◽  
Research Network ◽  
Nonalcoholic Fatty Liver

Abstract Context Sex hormones have been linked with presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults, but it is unknown if they affect severity of pediatric NAFLD. Objective To examine associations of circulating SHBG, estrogens, and androgens with key histologic features of pediatric, biopsy-confirmed NAFLD. Design Baseline assessment of longitudinal cohorts and randomized clinical trials. Setting Nonalcoholic Steatohepatitis Clinical Research Network. Patients Children and adolescents ≤18 years with liver biopsy-confirmed NAFLD in the United States. Main Outcome Measures We assayed SHBG, estrone, estradiol, dehydroepiandrosterone (DHEAS), androstenedione, and testosterone in relation to grade/stage of steatosis, portal inflammation, hepatic ballooning, fibrosis, and nonalcoholic steatohepatitis (NASH) severity using linear regression. Results Mean age of 573 children at the time of biopsy was 13.1 years (SD 2.8). Lower SHBG was inversely associated with steatosis severity in boys and girls (P = 0.001), and with portal inflammation in girls only (P for sex interaction <0.001). Higher testosterone was related to improved features of steatosis and fibrosis (P for sex interaction = 0.003 and 0.01, respectively) in boys, but detrimental in girls. In boys and girls, higher estrone, estradiol, and testosterone were associated with lower portal inflammation grade; higher estradiol was positively associated with hepatic ballooning severity; DHEAS was inversely associated with hepatic ballooning and NASH severity (all P < 0.05). Androstenedione was not associated with NAFLD features. Conclusions Largely consistent with findings in adults, sex hormones are associated with distinct histologic features of NAFLD in children and adolescents. These hormone levels relate to differences with gender and pubertal change.

Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009

Hepatology ◽  
2015 ◽  
Vol 62 (6) ◽  
pp. 1723-1730 ◽  
Author(s):  
Zobair M. Younossi ◽  
Munkhzul Otgonsuren ◽  
Linda Henry ◽  
Chapy Venkatesan ◽  
Alita Mishra ◽  
...  
Keyword(s):  
United States ◽  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
The United States ◽  
Nonalcoholic Fatty Liver
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