Diverse effects of hepatic steatosis on fibrosis progression and functional cure in virologically quiescent chronic hepatitis B
Both chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) are common conditions, affecting 3.9% and 24% of the global population, respectively, with each condition potentially leading to significant liver-related complications. The prevalence of concomitant CHB and NAFLD is not low, with the reported rate of NAFLD in CHB ranging from 13.6% to 59.3%, highlighting the importance of understanding the interplay between both diseases. Although hepatic steatosis per se is linked with an increased risk of advanced liver disease in terms of cirrhosis, liver cancer and mortality, the effect of hepatic steatosis on the natural history of CHB is not entirely clear. Unlike chronic HCV infection, which is associated with insulin resistance and metabolic syndrome, there is lack of good evidence to demonstrate that HBV exerts a direct causal effect on liver fat accumulation. A meta-analysis has shown that the prevalence of hepatic steatosis in CHB is similar to the general population (29.6%) and lower than in HCV-infected patients. An inverse relationship between serum HBV DNA and hepatic steatosis was observed. Moreover, for unknown reasons, moderate to severe hepatic steatosis on ultrasound was associated with a higher likelihood of HBsAg seroclearance in a cross-sectional study. Patients with concomitant CHB and NAFLD were also younger when HBsAg seroclearance occurred compared with patients with CHB alone (48.7 vs. 53.4 years old, p = 0.001). However, severe hepatic steatosis has been linked with severe liver fibrosis in patients with virologically quiescent CHB in a cross-sectional study. Indeed, any degree of hepatic steatosis was associated with a >7-fold increased risk of fibrosis progression in patients with CHB across 10 years of follow-up, even when serum HBV DNA was at low or undetectable levels. The relationship between hepatic steatosis and CHB is therefore complex and unclear.
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.作者: StephenW 时间: 2021-2-21 10:58
病毒性靜止的慢性乙型肝炎對肝脂肪變性的纖維化進程和功能治癒的影響
慢性乙型肝炎（CHB）和非酒精性脂肪肝疾病（NAFLD）都是常見病，分別影響全球3.9％和24％的人群，每種病均可能導致重大的肝相關並發症。並發CHB和NAFLD的患病率並不低，據報導CHB中NAFLD的發生率在13.6％至59.3％之間，突出了了解兩種疾病之間相互作用的重要性。儘管就肝硬化，肝癌和死亡率而言，肝脂肪變性本身與晚期肝病風險增加有關，但肝脂肪變性對CHB天然病史的影響尚不完全清楚。與與胰島素抵抗和代謝綜合徵相關的慢性HCV感染不同，缺乏充分的證據證明HBV對肝脂肪蓄積起直接因果作用。薈萃分析顯示，CHB的肝脂肪變性患病率與普通人群相似（29.6％），低於HCV感染患者。觀察到血清HBV DNA與肝脂肪變性呈負相關。此外，由於一項未知原因，在一項橫斷面研究中，超聲檢查中至重度肝脂肪變性與HBsAg血清清除的可能性更高。與單獨使用CHB的患者相比，發生HBsAg血清清除的同時發生CHB和NAFLD的患者也更年輕（48.7歲對53.4歲，p = 0.001）。然而，在一項橫斷面研究中，患有病毒性靜止CHB的患者中，嚴重的肝脂肪變性與嚴重的肝纖維化有關。確實，即使在血清HBV DNA處於低水平或無法檢測到的情況下，CHB患者在整個10年的隨訪中，任何程度的肝脂肪變性都與纖維化進展風險增加> 7倍有關。因此，肝脂肪變性與CHB之間的關係複雜且不清楚。
背景與目的：慢性乙型肝炎（CHB）感染患者常伴有非酒精性脂肪肝疾病，儘管其對肝臟相關結局的影響尚存爭議。我們旨在研究肝脂肪變性對纖維化進展風險和HBsAg血清清除的可能性的影響。方法：前瞻性招募初治CHB，丙氨酸轉氨酶正常和低病毒血症（血清HBV DNA <2,000 IU / ml）的患者進行基線和3年瞬時彈性成像評估。纖維化分期是根據EASL-ALEH指南定義的，纖維化進展定義為≥1級的纖維化增量。肝脂肪變性和嚴重肝脂肪變性分別定義為受控衰減參數（CAP）≥248dB / m和≥280dB / m。結果：總共招募了330名患者（中位年齡50.5歲，男性41.2％，中位HBV DNA 189 IU / ml）。隨訪期間有22例患者（6.7％）達到了HBsAg血清清除，並且存在肝脂肪變性與HBsAg血清清除的機會明顯更高（危險比3.246； 95％CI 1.278-8.243； p = 0.013）。在基線時，分別有48.8％和28.8％的患者患有脂肪變性和嚴重脂肪變性，而在基線時有4.2％的患者患有F3 / F4纖維化，在3年時增加到8.7％。持續性嚴重脂肪變性患者的肝纖維化進展速度高於無脂肪變性患者（41.3％vs. 23％； p = 0.05）。持續性嚴重肝脂肪變性與纖維化進展獨立相關（優勢比2.379； 95％CI 1.231–4.597； p = 0.01）。結論：CAP測定對病毒學上靜止的CHB患者俱有預測價值。肝脂肪變性的存在與纖維化進展的較高風險相關，但矛盾的是，HBsAg血清清除率增加了3倍。總結：慢性乙型肝炎病毒感染患者並存的脂肪肝會導致肝纖維化惡化，但也會增加乙型肝炎病毒治癒的機會。在未接受過治療的慢性乙型肝炎患者中，常規的床旁肝脂肪含量評估對風險評估很重要。