Nonalkolik yağlı karaciğer hastalığında histolojik progresyon ile klinik ve laboratuvar parametrelerin ilişkisi

Öz

Giriş ve Amaç: Nonalkolik steatohepatit nonalkolik yağlı karaciğer hastalığının ilerleyici bir formudur. Nonalkolik steatohepatit, zamanla siroz ve hepatosellüler karsinomaya sebep olabilir. Bu çalışmada nonalkolik yağlı karaciğer hastalığı tanılı olgularda zamanla karaciğer histolojisindeki değişikliklerin araştırılması ve histolojik progresyonla ilişkli klinik ve laboratuvar değişkenlerin saptanması amaçlanmıştır. Gereç ve Yöntem: Bu çalışmada 1994-2009 yılları arasında hepatoloji veri tabanına kayıtlı toplam 783 nonalkolik yağlı karaciğer hastalıklı olgu retrospektif olarak tarandı. En az 2 yıl arayla yapılan 2 karaciğer biyopsisi olan 29 hasta çalışmaya alındı. Vücut kitle indeksi, glukoz intoleransı veya diyabetes mellitus varlığı, karaciğer fonksiyon testi dahil biyokimyasal parametreler kaydedildi. Nonalkolik yağlı karaciğer hastalığı aktivite skoru steatoz, lobüler inflamasyon ve hepatosellüler balonlaşma skorlarının toplamı ile hesaplandı. Fibroz skorları ayrı rapor edildi. Bulgular: Ortalama yaş 45.2±11 yıl, olguların 17’si (%58.6) erkekti. Başvuruda ortalama vücut kitle indeksi 29.5±4 kg/m2, 15'i (%51.7) fazla kilolu, 12'si (%41.4) obezdi. Toplam 11’inde (%37.9) diyabetes mellitus, 6’sında (%20.7) glukoz intoleransı vardı. Aspartat aminotransferaz düzeyi ortalama 51±36 IU/ml, alanin aminotransferaz düzeyi ortalama 79±50 IU/ml, albümin ortalama 4.5±0.4 gr/dL, trigliserit ortalama 197±106 mg/dL saptandı. Hastaların 14'ünde (%48.3) “nonalkolik steatohepatit” ve 6’sında (%20.6) basit steatoz vardı. Egzersiz ve diyet önerisiyle kontrol biyopsi için medyan takip aralığı 4.8 yıl (2-9 yıl) saptandı. Kontrol biyopsi anında vücut kitle indeksi ortalama 29.6±4 kg/m2, aspartat aminotransferaz ortalama 38.8±14 IU/ml, alanin aminotransferaz ortalama 59.2±32 IU/ml, 13’ünde (%44.8) diyabetes mellitus ve 7’sinde (%24.1) glukoz intoleransı saptandı. İkinci karaciğer biyopsilerinde nonalkolik yağlı karaciğer hastalığı aktivite skoru; 9 (%31) hastada ilerlemiş, 17’sinde (%58.6) gerilemiş, 3’ünde (%10.3) aynı bulundu. Fibrozis skorunda ise 6 (%20.1) hastada ilerleme, 3 (%10.3) hastada ise iyileşme görüldü. Nonalkolik yağlı karaciğer hastalığı aktivite skoru ilerlemesiyle başlangıç yaşı arasında negatif, başlangıç vücut kitle indeksi ile pozitif korelasyon saptandı, sırasıyla (r=-0.370, p=0.047 ve r=0.485, p=0.007). Fibrozis skoru ilerlemesiyle, başlangıç yaşı arasında negatif, başlangıç vücut kitle indeksi ile pozitif ve kontrol biyopsileri anındaki aspartat aminotransferaz düzeyiyle pozitif korelasyon saptandı, sırasıyla (r=-0.503 p=0.005; r=0.382 p=0.04 ve r=0.546 p=0.007). Sonuç: Basit yağlanma yaşla ve yüksek vücut kitle indeksi ile ilişkili olarak nonalkolik steatohepatite progrese olabilir. Genç yaştakiler, yüksek vücut kitle indeksi ve aspartat aminotransferaz düzeyinde yükseklik olanlar fibrozis progresyonu açısından daha riskli bulunmuştur.

Anahtar Kelimeler

• Nonalkolik karaciğer yağlanması
• nonalkolik steatohepatit
• karaciğer histolojisi
• nonalkolik karaciğer yağlanma aktivite skoru
• fibrosiz

The relationship between clinical and laboratory parameters and histological progression in nonalcoholic fatty liver disease

Öz

Background and Aims: Nonalcoholic steatohepatitis is the progressive form of nonalcoholic fatty liver disease and can cause cirrhosis and hepatocellular carcinoma. We aimed to investigate the changes in liver histology and determined the relationship between histologic progression and clinical and laboratory parameters in patients with nonalcoholic fatty liver disease. Materials and Methods: We retrospectively screened 783 patients with nonalcoholic fatty liver disease who had enrolled in the hepatology database between 1994 and 2009. Among the 783, there were 29 patients with two liver biopsies performed at least two years apart. Body mass index, presence of glucose intolerance or diabetes, and biochemical parameters including liver function test were noted. Nonalcoholic fatty liver disease activity score was the sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. The fibrosis scores were reported separately. Results: Mean patient age was 45.2±11years, and 17 (58.6%) patients were men. Mean body mass index was 29±4 kg/m2, and 15 (51.7%) patients were overweight and 12 (41.4%) were obese. Twelve (41.4%) patients had diabetes mellitus and five (17.2%) patients had glucose intolerance. Mean aspartate aminotransferase level was 51±36 IU/ml, mean alanine aminotransferase level was 79±50 IU/ml, mean albumin level was 4.5±0.4 g/dL, and mean triglyceride level was 197±106 mg/dL at baseline. Fourteen (48.3%) patients had nonalcoholic steatohepatitis and six (20.6%) patients had simple steatosis. The patients followed the recommended exercises and diet for therapy, and control liver biopsies were performed. The median follow-up duration was 4.8 years (2–9). Mean body mass index was 29.6±4 kg/m2, mean aspartate aminotransferase level was 38.8±14 IU/ml, and mean alanine aminotransferase was 59.2±32 IU/ml. Thirteen (44.8%) patients had diabetes mellitus and seven (24.1%) had glucose intolerance at the time when their control biopsies were collected. According to nonalcoholic fatty liver disease activity score, nonalcoholic steatohepatitis progression was detected in 9 (31%) patients, while improvement was detected in 17 (58.6%) patients. In control liver biopsies, nonalcoholic fatty liver disease activity score remained the same in three (10.3%) patients. Six (20.1%) patients experienced progression and three (10.3%) patients showed improvement in fibrosis scores in the control biopsies. Regarding the basal parameters, age was negatively correlated and body mass index was positively correlated with the nonalcoholic steatohepatitis progression (r=−0.370, p=0.047 and r=0.485, p=0.007, respectively). The progression of fibrosis scores was negatively correlated with baseline age and positively correlated with baseline body mass index and aspartate aminotransferase levels when control biopsies were taken (r=−0.503, p=0.005; r=0.382, p=0.04; and r=0.546, p=0.007, respectively). Conclusion: Simple steatosis may progress to nonalcoholic steatohepatitis in patients with younger age and high body mass index. Patients with younger age and higher body mass index at baseline and higher aspartate aminotransferase at the time of collecting the control biopsies were more likely to experience progression of liver fibrosis.

Anahtar Kelimeler

• Nonalcoholic fatty liver disease
• nonalcoholic steatohepatitis
• liver histology
• nonalcoholic fatty liver disease activity score
• fibrosis

Kaynakça

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