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Page 2 of 7 Onzi et al. Hepatoma Res 2019;5:7 I http://dx.doi.org/10.20517/2394-5079.2018.114

diagnosis of NAFLD requires the exclusion of excessive alcohol consumption, defined separately for men
and women, and other secondary causes of liver disease. For definitive diagnosis of NASH, currently, a liver
[4]
biopsy is needed .
A hypercaloric diet with excess saturated fats, refined carbohydrates and high fructose consumption has
[4,5]
been related to weight gain and, more recently, to NAFLD . Thus, NAFLD is associated with metabolic
syndrome and is characterized by adipose tissue dysfunction and insulin resistance. These two factors
generate deregulation in the production of adiponectin, an anti-inflammatory protein, and increase the
release of several proinflammatory cytokines, such as tumor necrosis factor alpha, leptin and interleukin-6.
The effects of this imbalance lead to the deposition of lipids in hepatocytes, causing lipotoxicity and the
production of free radicals by the oxidation of fatty acids. The progression to NASH occurs in 25 percent of
[1]
cases . Also, gut microbiota plays a role in inflammation, through alterations in gut epithelial permeability,
choline metabolism, endogenous alcohol production, release of inflammatory cytokines, regulation of
[6]
hepatic toll-like receptor, and bile acid metabolism .

Estimates of NAFLD prevalence range from 25%-45% in the US, while NASH currently affects 5 percent of
[7]
the population . As diabetes and obesity have become global epidemics, the WHO predicts an exponential
[2]
increase in cases of NAFLD in the coming decades . The objective of this study is to review the literature
on the occurrence of hepatocellular carcinoma (HCC) in the context of NAFL/NASH with or without
associated cirrhosis.

CASE REPORT
A 67-year-old female patient, from Caxias do Sul, sought care due to a complaint of asthenia, inappetence
and a weight loss of 3 kg over the last month. The patient displayed metabolic syndrome, with a previous
diagnosis of grade I hepatic steatosis, diabetes mellitus type 2, mild obesity and arterial hypertension. The
patient was admitted in the hospital for investigation of hepatic nodules identified in an ultrasonography.
Magnetic resonance imaging showed a heterogeneous nodule, in hepatic segment I, measuring 5.7 cm (largest
measurement) and another nodular image in segment II measuring 1.9 cm (largest measurement), with
homogeneous arterial impregnation (suspected for HCC - Figure 1). A biopsy of both nodules and of the
liver was performed, guided by ultrasonography.

The patient remained in good general condition throughout the hospital stay. Hemoglobin 11.3 g/dL,
hematocrit 32.9%, prothrombin time 11.1 s, total bilirubin 0.2 mg/dL, alkaline phosphatase 113 U/L,
aspartate aminotransferase 25 U/L, alanine aminotransferase 28 U/L, gama glutil transferase 73 U/L, albumin
5.01 g/dL and alpha-fetoprotein of 6.7 ng/mL were performed. The biopsy revealed that liver presented:
nodulo I with macrovacuolar steatosis in 10 percent of hepatocytes, portal lymphocytic infiltrate, no fibrosis
and hepatocellular ballooning and nodule II with hepatic lesion with desmoplastic stroma and small cells
with mild nuclear pleomorphism, an image corresponding to HCC.

The patient was diagnosed with NASH associated to HCC. After histological confirmation, she was referred
to the clinical and surgical oncology service for tumor resection.

DISCUSSION
[1,3]
NASH has gained attention in recent years because of its association with HCC . It is known that there is
a risk of progression to advanced fibrosis in up to 20 percent of patients with this pathology, thus increasing
the chance of developing liver cancer [1,8-11] . Studies have found that 11.3% of patients with cirrhosis due to
NASH developed HCC within 5 years, while in patients with cirrhosis due to alcohol, the rate is 12.5% over
[1]
the same time frame . Compared with the benign course of NAFL, NASH patients have an 8-fold increased
chance of progressing to advanced fibrosis, in addition to an increased risk of liver-related death and of