Highlights
- •Hepatic steatosis was associated with a 3-fold increase in likelihood of HBsAg seroclearance in quiescent CHB infection.
- •Cumulative probability of HBsAg seroclearance at 3 years was 18.4% in those with steatosis and low serum HBV DNA (<200 IU/ml).
- •Fibrosis progression was still observed in 25.2% patients despite virological quiescence.
- •Persistent severe hepatic steatosis was associated with a 2-fold increased risk of fibrosis progression at 36 months.
- •Routine CAP measurement in patients with apparently low-risk CHB has prognostic value.
Background & Aims
Concomitant non-alcoholic fatty liver disease is common in patients with chronic hepatitis
B (CHB) infection, although its impact on liver-related outcomes remains controversial.
We aimed to study the effect of hepatic steatosis on the risk of fibrosis progression
and the likelihood of HBsAg seroclearance.
Methods
Treatment-naïve patients with CHB, normal alanine aminotransferase and low viraemia
(serum HBV DNA <2,000 IU/ml) were prospectively recruited for baseline and 3-year
transient elastography assessment. Fibrosis staging was defined according to the EASL-ALEH
guidelines, with fibrosis progression defined as ≥1 stage increment of fibrosis. Hepatic
steatosis and severe hepatic steatosis were defined as controlled attenuation parameter
(CAP) ≥248 dB/m and ≥280 dB/m, respectively.
Results
A total of 330 patients (median age 50.5 years, 41.2% male, median HBV DNA 189 IU/ml)
were recruited. Twenty-two patients (6.7%) achieved HBsAg seroclearance during follow-up,
and the presence of hepatic steatosis was associated with a significantly higher chance
of HBsAg seroclearance (hazard ratio 3.246; 95% CI 1.278–8.243; p = 0.013). At baseline, 48.8% and 28.8% of patients had steatosis and severe steatosis,
respectively, while 4.2% had F3/F4 fibrosis at baseline, increasing to 8.7% at 3 years.
The rate of liver fibrosis progression in patients with persistent severe steatosis
was higher than in those without steatosis (41.3% vs. 23%; p = 0.05). Persistent severe hepatic steatosis was independently associated with fibrosis
progression (odds ratio 2.379; 95% CI 1.231–4.597; p = 0.01).
Conclusions
CAP measurements have predictive value in patients with virologically quiescent CHB.
The presence of hepatic steatosis was associated with a higher risk of fibrosis progression
but, paradoxically, a 3-fold increase in HBsAg seroclearance rate.
Lay summary
Co-existing fatty liver disease in patients with chronic viral hepatitis B infection
leads to worsening liver fibrosis, but also increases the chance of cure from hepatitis
B virus. Routine bedside assessment of liver fat content is important for risk assessment
in treatment-naïve patients with chronic hepatitis B.
Graphical abstract
Graphical Abstract
Keywords
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References
- Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes.Hepatology. 2016; 64: 73-84
- Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.Lancet Gastroenterol Hepatol. 2018; 3: 383-403
- Interactions of hepatitis B virus infection with nonalcoholic fatty liver disease: possible mechanisms and clinical impact.Dig Dis Sci. 2015; 60: 3513-3524
- Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States.Gastroenterology. 2015; 148: 547-555
- Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis.Hepatology. 2017; 65: 1557-1565
- Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease.Gastroenterology. 2004; 126: 586-597
- Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients.J Gastroenterol Hepatol. 2011; 26: 1361-1367
- Inverse relationship between hepatic steatosis and hepatitis B viremia: results of a large case-control study.J Viral Hepat. 2018; 25: 97-104
- Inverse association between hepatitis B virus infection and fatty liver disease: a large-scale study in populations seeking for check-up.PLoS One. 2013; 8: e72049
- Relationship between hepatic steatosis and the elevation of aminotransferases in HBV-infected patients with HBe-antigen negativity and a low viral load.Medicine (Baltimore). 2016; 95: e3565
- Does increased body mass index with hepatic steatosis contribute to seroclearance of hepatitis B virus (HBV) surface antigen in chronic HBV infection?.Int J Obes (Lond). 2007; 31: 871-875
- Clinical and virological characteristics post HBsAg seroclearance in hepatitis B virus carriers with hepatic steatosis versus those without.Dig Dis Sci. 2013; 58: 275-281
- Association between hepatic steatosis, measured by controlled attenuation parameter, and fibrosis burden in chronic hepatitis B.Clin Gastroenterol Hepatol. 2018; 16: 575-583.e2
- Fibrosis evolution in chronic hepatitis B e antigen-negative patients across a 10-year interval.J Viral Hepat. 2019; 26: 818-827
- Metabolic syndrome–a new world-wide definition. A consensus statement from the international diabetes federation.Diabet Med. 2006; 23: 469-480
- Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter.J Hepatol. 2017; 67: 577-584
- EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis.J Hepatol. 2015; 63: 237-264
- Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis.J Hepatol. 2017; 66: 1022-1030
- Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis.Hepatology. 2011; 53: 726-736
- Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: a systematic review and meta-analysis.Gastroenterology. 2019; 156: 635-646.e9
- Hepatic steatosis is highly prevalent in hepatitis B patients and negatively associated with virological factors.Dig Dis Sci. 2014; 59: 2571-2579
- The role of steatosis in HBsAg seroclearance for patients with chronic hepatitis B infection: fact or fiction?.Dig Dis Sci. 2013; 58: 20-22
- Hepatitis B and concomitant hepatic steatosis.Ann Transl Med. 2017; 5: 38
- Long-term outcomes and predictive scores for hepatocellular carcinoma and hepatitis B surface antigen seroclearance after hepatitis B e-antigen seroclearance.Hepatology. 2018; 68: 462-472
- Serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.Hepatol Int. 2012; 7: 119-126
- Impact of age and gender on risk of hepatocellular carcinoma after hepatitis B surface antigen seroclearance.J Hepatol. 2017; 67: 902-908
- HBsAg seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma.Gastroenterology. 2008; 135: 1192-1199
- EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis.J Hepatol. 2015; 63: 237-264
- Correlation of serum Mac-2-binding protein glycosylation isomer (M2BPGi) and liver stiffness in chronic hepatitis B infection.Hepatol Int. 2019; 13: 148-156
- American Gastroenterological Association Institute guideline on the role of elastography in the evaluation of liver fibrosis.Gastroenterology. 2017; 152: 1536-1543
- Transient elastography for screening of liver fibrosis: Cost-effectiveness analysis from six prospective cohorts in Europe and Asia.J Hepatol. 2019; 71: 1141-1151
- Insulin resistance: a metabolic pathway to chronic liver disease.Hepatology. 2005; 42: 987-1000
Article Info
Publication History
Published online: June 02, 2020
Accepted:
May 17,
2020
Received in revised form:
April 24,
2020
Received:
March 20,
2020
Identification
Copyright
© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
