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Despite treatment, severe steatosis predicts severe fibrosis in HBV
Severe steatosis correlated with severe fibrosis in patients with chronic hepatitis B, whether patients were on treatment or treatment-naive, according to recently published study results.
“On-treatment population of [chronic HBV] is increasing worldwide, exceeding 40% in endemic regions of Asia,” Wai-Kay Seto, MD, from the University of Hong Kong, and colleagues wrote. “While the effects of diabetes, obesity and metabolic syndrome on [chronic HBV] had been previously described, our study results demonstrated hepatic steatosis to be an additional metabolic risk factor of [chronic HBV]-related fibrosis.”
The researchers enrolled 1,606 patients with chronic HBV from Hong Kong, 708 of whom were treatment-naive. Among those receiving nucleos(t)ide analogue treatment, treatment duration was 3 or more years (75.8%), 5 or more years (61.2%) or 7 or more years (39.9%).
At baseline, 40.8% of patients had steatosis and 22.6% had severe steatosis. Among the severe steatosis cohort, there was a significantly increased proportion of severe fibrosis vs. patients with no, mild or moderate steatosis in the full cohort (21.4% vs. 11.9%; P < .001), treatment-naive patients (11.3% vs. 2.4%; P < .001) and patients on treatment (29.1% vs.19.5%; P = .003).
The researchers observed that increased continued attenuation parameter (CAP) measurements in treatment-naive patients was significantly correlated with severe fibrosis (OR = 1.015; 95% CI, 1.004-1.027). Each increased CAP value by 10 dB/m indicated a 15% increased risk for severe fibrosis. Other significant factors for severe fibrosis included aspartate aminotransferase levels (OR = 0.247; 95% CI, 0.062-0.983), reduced platelet counts (OR = 0.979; 95% CI, 0.968-0.989) and HBeAg-negative status (OR = 1.109; 95% CI, 1.044-1.177).
Increased CAP measurements were also an independent risk factor for severe fibrosis (OR = 1.008, 95% CI, 1.003-1.014) in patients on nucleos(t)ide analogue treatment, among whom each increased CAP value by 10 dB/m indicated an 8% increased risk factor for severe fibrosis. Diabetes (OR = 2.487; 95% CI, 1.344-4.608), decreased serum albumin (OR = 0.842; 95% CI, 0.773-0.916), increased bilirubin (OR = 1.046; 95% CI, 1.015-1.098), increased AST (OR = 1.056; 95% CI, 1.015-1.098) and reduced platelet count (OR = 0.985; 95% CI, 0.985; 0.981-0.99) were also significant independent factors for severe fibrosis among on-treatment patients.
Treatment duration effects
Among patients with 5 years or more (OR = 1.008; 95% CI, 1.002-1.014) and 7 years or more (OR = 1.007; 95% CI, 1-1.015) of nucleos(t)ide analogue therapy, increased CAP measurements remained independently associated with severe fibrosis. Each increased CAP value by 10 dB/m increased the risk for severe fibrosis by 7% to 8%. Severe steatosis was the only metabolic risk factor found to be significantly associated with severe fibrosis.
Compared with patients without severe steatosis, severe fibrosis was more common among patients on treatment for 3 or more years (30.2% vs. 19.0%; OR = 1.85; 95% CI, 1.24-2.77), 5 or more years (31.1% vs. 17.5%; OR = 2.13; 95% CI, 1.36-3.33) and 7 or more years (29.2% vs. 16.7%, OR = 2.05, 95% CI 1.18-3.59).
After replacing CAP measurements with ordinal steatosis assessment, the researchers observed that severe steatosis was consistently correlated with severe fibrosis. These results increased incrementally according to treatment duration of 3 or more years (OR = 1.95; 95% CI, 1.06-3.61), to 5 or more years (OR = 2.28; 95% CI, 1.13-4.61), up to 7 or more years (OR = 2.79; 95% CI, 1.17-6.62).
“The invasive nature of a liver biopsy would limit its widespread usage especially in stable and asymptomatic on-treatment patients. Since the measurement of CAP by transient elastography is fast and easy to perform, it can potentially be implemented with ease as a monitoring strategy for large numbers of on-treatment patients,” the researchers concluded. – by Talitha Bennett
Disclosure: Seto reports he is an advisory board member of Gilead Sciences and Bristol-Myers Squibb and received speaker fees from Gilead Sciences, Bristol-Myers Squibb and Novartis.