Ueno T, Inuzuka S, Sata M, Koh H, Tamaki S, Kin M, Sugawara H, Sakata R, Torimura T, Tanikawa K
Second Department of Medicine, Kurume University School of Medicine.
Hepatogastroenterology. 1995 Sep-Oct;42(5):522-7.
BACKGROUND/AIMS: The response to interferon therapy for chronic hepatitis is known to decrease with progression of the hepatic fibrosis. On the other hand, serum hyaluronate reflects hepatic sinusoidal capillarization or liver cirrhosis, and also serum type IV collagen, which is one of the main components of the basement membrane, rises with the progression of hepatic fibrosis. In this study, the relationship between the degree of hepatic fibrosis and the response to interferon-alpha was determined retrospectively in patients with chronic hepatitis C. In addition, whether the measurement of serum hyaluronate and type IV collagen before interferon-alpha therapy was useful for predicting the response to interferon-alpha therapy in chronic hepatitis C was determined.
Thirty-seven patients with elevated serum ALT levels for at least 6 months and histologically determined chronic hepatitis were studied. All patients were positive for anti-HCV and negative for hepatitis B surface antigen. Twenty-eight healthy adults with normal blood biochemical data, who were negative for hepatitis B antigen and HCV antibody tests, had limited alcohol intake were used as controls. The test group was given IFN-alpha by intramuscular injection for 14 days, and then were treated 3 times per week for 24 weeks.
The extent of hepatic fibrosis, particularly, perisinusoidal fibrosis (P < 0.01) was significantly greater in nonresponders than in responders. The mean serum hyaluronate and type IV collagen levels were more elevated in nonresponders than in responders, especially, the serum hyaluronate level showed a significant difference (P < 0.01). Most of the patients having a serum hyaluronate level of more than 100 ng/ml were nonresponders who had chronic active hepatitis with bridging necrosis on liver biopsy. Serum hyaluronate and type IV collagen levels showed significant positive correlation with degree of the portal fibrosis (P < 0.01), perisinusoidal fibrosis (P < 0.001) and focal necrosis (P < 0.01) in histological findings of liver biopsy specimens.
These results suggest that serum hyaluronate and type IV collagen levels reflect the extent of the hepatic fibrosis in chronic hepatitis C and also that serum hyaluronate level predicts the response to interferon-alpha therapy in patients with chronic hepatitis C.
背景/目的:已知慢性肝炎患者对干扰素治疗的反应会随着肝纤维化的进展而降低。另一方面,血清透明质酸反映肝窦毛细血管化或肝硬化,并且作为基底膜主要成分之一的血清IV型胶原也会随着肝纤维化的进展而升高。在本研究中,对丙型肝炎慢性患者肝纤维化程度与对α干扰素反应之间的关系进行了回顾性研究。此外,还确定了在α干扰素治疗前检测血清透明质酸和IV型胶原是否有助于预测丙型肝炎慢性患者对α干扰素治疗的反应。
研究了37例血清ALT水平至少升高6个月且经组织学确诊为慢性肝炎的患者。所有患者抗-HCV均为阳性,乙肝表面抗原均为阴性。28例血液生化数据正常、乙肝抗原和HCV抗体检测均为阴性、酒精摄入量有限的健康成年人作为对照。试验组肌肉注射α干扰素14天,然后每周治疗3次,共24周。
无反应者的肝纤维化程度,尤其是窦周纤维化程度(P<0.01)明显高于有反应者。无反应者的血清透明质酸和IV型胶原平均水平高于有反应者,尤其是血清透明质酸水平有显著差异(P<0.01)。大多数血清透明质酸水平超过100 ng/ml的患者是无反应者,这些患者在肝活检中表现为慢性活动性肝炎伴桥接坏死。在肝活检标本的组织学检查结果中,血清透明质酸和IV型胶原水平与门脉纤维化程度(P<0.01)、窦周纤维化程度(P<0.001)和局灶性坏死程度(P<0.01)呈显著正相关。
这些结果表明,血清透明质酸和IV型胶原水平反映了丙型肝炎慢性患者的肝纤维化程度,并且血清透明质酸水平可预测丙型肝炎慢性患者对α干扰素治疗的反应。