Original article
Progression from isolated steatosis to steatohepatitis and fibrosis in nonalcoholic fatty liver disease

https://doi.org/10.1016/j.gcb.2010.06.004Get rights and content

Summary

In patients with nonalcoholic fatty liver disease (NAFLD) isolated steatosis is considered a benign condition with no or minimal rate of progression, in contrast to nonalcoholic steatohepatitis (NASH) which can progress to cirrhosis. We report on a series of six patients with isolated steatosis on an initial liver biopsy, and NASH on a follow-up biopsy performed five years after. All but one of the initial biopsies were longer than 15 mm. At follow-up, inflammation and ballooning were present in all patients and mild fibrosis in three. All patients had one or more features of metabolic syndrome at baseline. Progression to steatohepatitis occurred independent of aminotransferase changes. Five patients experienced an increase in one or several metabolic risk factors during follow-up: body mass index, triglyceride levels, arterial hypertension and/or the HOMA index. One patient did not exhibit progression but was still exposed to metabolic risks factors at the end of follow-up. This report demonstrates that isolated steatosis is not necessarily a benign, non-progressive condition. Current recommendations for the absence of hepatic monitoring in patients with isolated steatosis are not adequate. If metabolic risk factors persist or deteriorate during follow-up and/or non-invasive markers suggest disease progression, a control liver biopsy should be considered.

Section snippets

Patients and methods

We reviewed the records of six patients (four men) who had been initially diagnosed with bland steatosis related to primary NAFLD seen in a tertiary referral center between 1998 and 2009 and who had undergone a follow-up liver biopsy more than one year after the index biopsy. At the baseline evaluation, other causes of liver disease were ruled out in these patients:

  • daily alcohol consumption greater than 30 g for men and 20 g for women;

  • drug-induced hepatotoxicity;

  • infection with HBV or HCV viruses;

Patient characteristics at baseline and follow-up

The clinical and biological characteristics of the individual patients are presented in Table 1. The median body mass index (BMI) was 27 kg/m2 (range from 22.5 to 31.6) at baseline; only one patient had grade I obesity, four other patients had overweight, and one patient had a normal weight. The median ALT was 61 IU/l (range from 30 to 114 IU/l); the median serum glucose, fasting insulin and HOMA levels were 5.28 mmol/l (range from 5.1 to 5.6 mmol/l), 10.85 μIU/ml (range from 5 to 30 μIU/l) and 2.57

Histological progression

The median interval between the two biopsies was five years (range two to ten years). The median sample size was 18.5 mm (range 13 to 25 mm) and 26 mm (range 10 to 33 mm) for the initial and follow-up biopsies, respectively, with a median number of portal tracts of 12.5 (range 6–16) and 17.5 (range 2–24), respectively. At baseline, all patients had isolated steatosis without associated inflammation or liver cell injury. Four patients had significant steatosis involving more than 66% of the liver

Discussion

This retrospective case series clearly documents that patients with isolated steatosis can progress to NASH. All patients had a second liver biopsy compatible with steatohepatitis, as ballooning was present in all patients and most displayed lobular inflammation in addition to ballooning. Another element indicative of real disease progression in these patients is the occurrence of fibrosis along with steatohepatitis in some of the patients described here. Remarkably, the occurrence of

Conflict of interest

There is no conflict of interest.

References (15)

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