In the Journals

Fibrosis, not NASH, Predicts Death, Disease in Fatty Liver

Nonalcoholic steatohepatitis did not increase the risk for liver-related morbidity, overall mortality or the time to development of severe liver disease in patients with nonalcoholic fatty liver disease, according to recently published data. However, fibrosis stage can be used as a significant marker.

“Although patients with NASH seemed to have a small increase in risk for overall mortality and liver-specific morbidity in univariate analyses compared to a reference population, this was generally not significant when adjusting for confounders including fibrosis stage, and no added risk was seen for presence of NASH after adjusting for confounders,” the researchers wrote.

The researchers analyzed 646 patients with biopsy-proven NAFLD and 6,345 controls for a mean period of 19.9 years. Data confirmed the presence of NASH in 577 cases. During follow-up, 214 patients and 1,903 controls died (7.9% vs. 1.4%; P < .001) and 76 patients and 139 controls developed severe liver disease.

Patients with fibrosis stage 2 (HR = 1.36; 95% CI, 1.02-1.8), stage 3 (HR = 2.54; 95% CI, 1.79-3.6) and stage 4 (HR = 5.19; 95% CI, 3.06-8.79) had significantly higher rates of mortality than those with stage 0 or 1. The presence of NASH showed a slight increase in overall mortality (HR = 1.22; 95% CI, 1.02-1.46).

Fibrosis stage

After adjusting for age, sex and type 2 diabetes and using fibrosis stage 0 as control, fibrosis stage 3 (HR = 1.76; 95% CI, 1.02-3.06) and stage 4 (HR = 3.75; 95% CI, 1.81-7.73) remained significant predictors for mortality. Using the same adjustment, stage 3 (HR = 4.31; 95% CI, 1.63-11.36) and stage 4 (HR = 42.41; 95% CI, 15.6-115.34) were also significant predictors for severe liver disease.

Patients with NAFLD were significantly more likely to develop severe liver disease (HR = 4.25; 95% CI, 3.09-5.84) compared with controls, especially among those with fibrosis stage 2 (HR = 5.48; 95% CI, 3.1-9.7), stage 3 (HR = 14.28; 95% CI, 7.9-25.8) and stage 4 (HR = 104.52; 95% CI, 57.2-191.1).

NASH did not add to predictive capacity for mortality with stage of fibrosis as an independent variable, whereas information on fibrosis stage significantly improved the model for mortality with NASH as an independent variable (likelihood ratio test, P < .001). NASH did not affect estimates for severe liver disease risk significantly.

There was no significant difference in the number of severe liver disease cases in patients with or without NASH; however, patients with NASH did develop severe liver disease slightly earlier than patients without (17.7 vs. 19.4 years; P = .02).

The presence of NASH slightly increased the risk for severe liver disease in univariate analysis (HR = 2.04; 95% CI, 1.01-4.11), but not after adjusting for age, sex, type 2 diabetes and fibrosis stage. Similarly, patients with fibrosis stage 0 to 2 and NASH did not have increased risk for severe liver disease compared with those without NASH.

In conclusion, the researchers wrote that patients with fibrosis stage 3 and 4 should be closely monitored to assess liver-related complications. Those with stage 2 should have examination within a period of 10 years to assess progression and while stage 0 and 1 do not develop severe liver disease within 20 years, follow-up is important to identify progression in select patients. – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.

Nonalcoholic steatohepatitis did not increase the risk for liver-related morbidity, overall mortality or the time to development of severe liver disease in patients with nonalcoholic fatty liver disease, according to recently published data. However, fibrosis stage can be used as a significant marker.

“Although patients with NASH seemed to have a small increase in risk for overall mortality and liver-specific morbidity in univariate analyses compared to a reference population, this was generally not significant when adjusting for confounders including fibrosis stage, and no added risk was seen for presence of NASH after adjusting for confounders,” the researchers wrote.

The researchers analyzed 646 patients with biopsy-proven NAFLD and 6,345 controls for a mean period of 19.9 years. Data confirmed the presence of NASH in 577 cases. During follow-up, 214 patients and 1,903 controls died (7.9% vs. 1.4%; P < .001) and 76 patients and 139 controls developed severe liver disease.

Patients with fibrosis stage 2 (HR = 1.36; 95% CI, 1.02-1.8), stage 3 (HR = 2.54; 95% CI, 1.79-3.6) and stage 4 (HR = 5.19; 95% CI, 3.06-8.79) had significantly higher rates of mortality than those with stage 0 or 1. The presence of NASH showed a slight increase in overall mortality (HR = 1.22; 95% CI, 1.02-1.46).

Fibrosis stage

After adjusting for age, sex and type 2 diabetes and using fibrosis stage 0 as control, fibrosis stage 3 (HR = 1.76; 95% CI, 1.02-3.06) and stage 4 (HR = 3.75; 95% CI, 1.81-7.73) remained significant predictors for mortality. Using the same adjustment, stage 3 (HR = 4.31; 95% CI, 1.63-11.36) and stage 4 (HR = 42.41; 95% CI, 15.6-115.34) were also significant predictors for severe liver disease.

Patients with NAFLD were significantly more likely to develop severe liver disease (HR = 4.25; 95% CI, 3.09-5.84) compared with controls, especially among those with fibrosis stage 2 (HR = 5.48; 95% CI, 3.1-9.7), stage 3 (HR = 14.28; 95% CI, 7.9-25.8) and stage 4 (HR = 104.52; 95% CI, 57.2-191.1).

NASH did not add to predictive capacity for mortality with stage of fibrosis as an independent variable, whereas information on fibrosis stage significantly improved the model for mortality with NASH as an independent variable (likelihood ratio test, P < .001). NASH did not affect estimates for severe liver disease risk significantly.

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There was no significant difference in the number of severe liver disease cases in patients with or without NASH; however, patients with NASH did develop severe liver disease slightly earlier than patients without (17.7 vs. 19.4 years; P = .02).

The presence of NASH slightly increased the risk for severe liver disease in univariate analysis (HR = 2.04; 95% CI, 1.01-4.11), but not after adjusting for age, sex, type 2 diabetes and fibrosis stage. Similarly, patients with fibrosis stage 0 to 2 and NASH did not have increased risk for severe liver disease compared with those without NASH.

In conclusion, the researchers wrote that patients with fibrosis stage 3 and 4 should be closely monitored to assess liver-related complications. Those with stage 2 should have examination within a period of 10 years to assess progression and while stage 0 and 1 do not develop severe liver disease within 20 years, follow-up is important to identify progression in select patients. – by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.