Üç sene boyunca inaktif hepatit B taşıyıcılığı kriterlerini taşıyan hastalarda, üç senelik takip sonrasında gelişen alt yüksekliği ile ilişkili parametreler
Küçük Resim Yok
Tarih
2021
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Giriş ve Amaç: Hepatit B enfeksiyonu akut ve kronik hepatit, siroz ve hepatoselüler kansere yol açabilen, önemli bir morbidite ve mortalite nedeni olan küresel bir sağlık sorunudur. Kronik hepatit B virüs enfeksiyonu olan hastaların büyük çoğunluğu eskiden inaktif taşıyıcı denilen HBeAg negatif kronik enfeksiyon fazındadır. Bu şartları ne kadar süreyle taşıyanlara inaktif taşıyıcı denileceği tam olarak belirlenmese de genellikle en az 1 sene boyunca serum aminotransferazları normal ve HBV DNA seviyesinin düşük seyretmesi gerektiği kabul edilmektedir. İnaktif taşıyıcılık fazı, immun temizleme sırasında enfekte hepatositlerin temizlenmesi ve hücre içi virüsün baskılanması sonucunda HBeAg serokonversiyonu ile geçilen fazdır. Serum aminotransferaz düzeyleri normaldir ve HBV DNA düzeyi kanda ölçülemez ya da çok düşüktür (<2000 IU/ml) ve karaciğer histolojileri normaldir. Genel anlamla iyi prognoza sahip olan inaktif hepatit B taşıyıcılarında HCC ve siroz gelişme ihtimali düşüktür. Ancak siroz olmadan, az da olsa HCC gelişme riski bilinen bir gerçektir. Ayrıca hastaların bir kısmında transaminaz değerlerinde yükselme ve hepatik alevlenme görülebilir. Bu dönemdeki HBsAg düzeyinin uzun dönem prognozla ilişkisi bilinmekle beraber rutinde kullanılmayan bu ölçüm dışında hangi hastaların alevlenme göstereceğini ön görebilen kriterler henüz oluşturulmamıştır. Hastaların takiplerinde ALT yükselmesi olacağı ön görülebilirse, bu hastaların daha yakın takip edilmesi için tavsiyeler oluşturulabilir. Çalışmamızda, ALT değerleri normal seyreden ve diğer inaktif hepatit B taşıyıcılığı kriterlerini karşılayan hastaların takiplerinde ALT yüksekliği gelişenler incelendi. Bu çalışmayla, ALT yüksekliğiyle ilişkili parametrelerin araştırılması hedeflendi.
Gereç ve Yöntem: 2005 yılından beri Ege Üniversitesi Hastanesi Gastroenteroloji Kliniği hepatoloji birimine başvuran ve takiplerini burada devam ettiren hastalardan Hepatit B taşıyıcılığı kriterlerini karşıyan poliklinik veri tabanına kayıtlı tüm hastaların dosyaları geriye dönük olarak tarandı. En az 4 yıllık takipte olan, takip edildikleri ilk yıllarda en az 3 sene boyunca aralıklı ölçülmüş iki veya daha fazla ölçümde ALT değerleri normal sınırlarda olan, bu üç sene içinde birbirinden en az 1 sene aralıklı yapılan en az 2 HBV DNA düzeyi <2000 IU/ml olan, ileri fibrozisi gösteren hiçbir delili olmayan (Fib-4 skorunun <1.45 olması, trombosit sayısının >200 000/mm3 olması, biyopsisi varsa fibrozisin olmaması veya minimal olması), antiviral tedavi almamış olan hastalar çalışmaya dahil edildi. Başka karaciğer hastalığı olan (delta hepatiti, hepatit C hastalığı, Wilson hastalığı, otoimmün hepatit vs.), erkekler için günde 2, kadınlar için günde 1 birimden fazla alkol kullanan, HCC’si olan, kontrolsüz kalp yetmezliği, diyabet, tiroid bozukluğu ve diğer sistemik hastalığı olanlar çalışma dışı bırakıldı. Bu hastaların ilk üç sene boyunca yapılan takiplerindeki en yüksek ALT, AST, ALP, GGT, üre, kreatinin, trigliserid, total kolesterol, HDL, LDL, total bilirubin, total protein, albumin, protrombin zamanı, kan şekeri, ürik asit, lökosit, AFP, HBV DNA ve en düşük sodyum, trombosit, hemoglobin, lökosit düzeyleri kaydedildi. Üç senelik normal ALT değerlerinden sonra en az 1 sene daha takip edilen hastalarda ALT yüksekliği görülenler ve görülmeyenler karşılaştırıldı. ALT’nin normalin üst sınırını geçmesi ve ALT’nin normalin iki katını geçmesiyle ilişkili parametreler araştırıldı.
Bulgular: Dahil edilme kriterlerini karşılayan ve hariç edilme kriterlerine sahip olmayan toplam 223 hasta analizlere dahil edildi. Hastaların 106’sı erkek (%47.5), 117’si kadın (%52.5) idi. Yaş ortalaması 45.1±11.8 (19-77), median 46 idi. Ortalama takip süreleri 7.98±2.91 yıldır (median: 7.5 yıl) (en az: 4.04 yıl; en çok: 14.02 yıl). Üç yıldan sonraki takipte en yüksek ALT düzeyi: 9-194 U/L aralığındadır. ALT değeri normalin üst sınırını geçen (>35 U/L) hasta sayısı 26 (%11.7), geçmeyen hasta sayısı 197 (% 88.3)’dir. Bu 26 hastanın 6’sına antiviral tedavi başlanmıştır. 1 hastaya ALT yükselmesi olmamasına rağmen immünsupresif kullandığı için lamivudin başlanmıştır. ALT yükselenler ile yükselmeyenler arasında farklılık gösteren parametrelerden AST, ALP, total protein, albumin, üre, kreatinin, protrombin zamanı, kolesterol ve HBV DNA düzeyi anlamlı saptanırken; yaş ve cinsiyet anlamlı saptanmamıştır. Üç yıllık takipten sonra ALT yükselmesi ile ilişki gösteren parametrelerin çok değişkenli analiz sonuçlarına göre ‘ALT>26 U/l ve albümin>4.3 g/dL olması’ ve en yüksek HBV DNA düzeyi anlamlı saptanmıştır. Üç yıllık takipten sonra 6 hastada (% 2.7) ALT normalin iki katından fazla yükselmiştir. ALT iki katını geçenlerde çok değişkenli analize göre ‘ALT>26 U/L ve albümin>4.3 g/dL olması’, albümin düzeyi ve lökosit sayısı anlamlı saptanırken; cinsiyet ve yaş ALT iki katı yükselenlerde de anlamlı saptanmamıştır.
Sonuç: ALT düzeyinin prognoz için önemli parametre olduğu bilinmektedir. Çalışmamızda takipte ALT yükselenler ve yükselmeyenlerin oranları ve aralarındaki farklılık gösteren parametreler araştırıldı. ALT normalin üst sınırını geçen ve ALT iki katından fazla yükselen hastalarda çok değişkenli analize göre prognostik indeksler elde edildi. ALT iki katından fazla yükselenlerde elde edilen prognostik indeks = -40.05 + 2.71 (eğer ALT>26 ve Alb>4.3 ise) + 6.12*Albumin + 0.00111*Lökosit (x/mm3) şeklindedir. Bu indeksin ALT yükselmesini predikte etme değeri ROC analizi ile araştırıldı. AUC=0.93 saptanarak iyi bir ilişki görüldü. >0.13 cut-off değeriyle % 83 sensivite, % 97 spesifite oranı saptandı. Bu indeks, hastaların takiplerinde ALT yükselmesini tahmin etme konusunda yol gösterici olabilir.
Introduction and aim: Hepatitis B infection is a global health problem that can lead to acute and chronic hepatitis, cirrhosis and hepatocellular cancer, and is an important cause of morbidity and mortality. The majority of patients with chronic hepatitis B virus infection are in the HBeAg negative chronic infection phase, formerly called inactive carrier. Although it is not determined exactly how long those who have these conditions will be called inactive carriers, it is generally accepted that serum aminotransferases should be normal and HBV DNA level should remain low for at least 1 year. The inactive carrier phase is the phase in which HBeAg seroconversion occurs as a result of clearance of infected hepatocytes and suppression of intracellular virus during immune cleansing. Serum aminotransferase levels are normal and the HBV DNA level cannot be measured in the blood (<2000 IU / ml) and liver histology is normal. In general, inactive hepatitis B carriers with a good prognosis are unlikely to develop HCC and cirrhosis. However, it is a known fact that there is a small risk of developing HCC without cirrhosis. In addition, an increase in transaminase values and hepatic exacerbation can be seen in some of patients. Criteria that can predict which patients will experience exacerbation have not yet been established. If it can be predicted that patients will have ALT elevations in their follow-up, recommendations can be made to follow these patients more closely. In our study, patients who had normal ALT values and met other inactive hepatitis B carriage criteria were evaluated who developed ALT elevation during their follow-up. The aim of this study was to investigate the parameters associated with ALT elevation. Materials and Methods: The files of all patients who have applied to the hepatology unit of Ege University Hospital Gastroenterology Clinic since 2005 and continued their follow-ups, who met the Hepatitis B carrier criteria, were retrospectively scanned. Patients were included in the study who at least 4 years of follow-up, whose ALT values within normal limits in two or more measurements measured intermittently for at least 3 years in the first years of follow-up, who have at least 2 HBV DNA levels <2000 IU / ml in these three years at least 1 year apart from each other, who have no evidence of advanced fibrosis (Fib-4 score <1.45, platelet count> 200 000 / mm3, no or minimal fibrosis if biopsy is present), who have not received antiviral therapy. Patients with other liver diseases (delta hepatitis, hepatitis C disease, Wilson's disease, autoimmune hepatitis, etc.), using more than 2 units of alcohol per day for men and 1 unit per day for women, those with HCC, uncontrolled heart failure, diabetes, thyroid disorder and other systemic diseases were excluded from the study. The highest levels of ALT, AST, ALP, GGT, urea, creatinine, triglyceride, total cholesterol, HDL, LDL, total bilirubin, total protein, albumin, prothrombin time, blood sugar, uric acid, leukocyte, AFP, HBV DNA and the lowest levels of sodium, thrombocyte, hemoglobin, leukocyte were recorded. Patients who were followed for at least 1 more year after 3 years of normal ALT values were compared whose ALT elevation or not. The parameters associated with ALT exceeding the upper limit of normal and ALT exceeding twice the normal were investigated. Findings: A total of 223 patients who met the inclusion criteria and did not meet the exclusion criteria were included in the analyzes. 106 of the patients were male (47.5%), 117 of them were female (52.5%). The mean age was 45.1 ± 11.8 (19-77), the median was 46. Average follow-up time is 7.98 ± 2.91 years (median: 7.5 years) (minimum: 4.04 years; maximum: 14.02 years). The number of patients whose ALT values exceeded the upper limit of normal (> 35 U / L) was 26 (11.7%), and the number of patients not exceeding 197 (88.3%). 6 of these 26 patients were treated with antivirals. Although there was no ALT elevation in 1 patient, lamivudine was started because used immunosuppressant. While AST, ALP, total protein, albumin, urea, creatinine, prothrombin time, cholesterol and HBV DNA levels were found to be significant; age and gender were not found to be significant. After three years of follow-up, according to the multivariate analysis results of the parameters associated with ALT elevation, "ALT> 26 U / L and albumin> 4.3 g / dL" and the highest HBV DNA level were found to be significant. ALT increased more than twice the normal in 6 patients (2.7 %) after 3 years of follow-up. According to multivariate analysis, "ALT> 26 U / L and albumin> 4.3 g / dL", albumin level and leukocyte count were found to be significant; gender and age were not found to be significant in those whom ALT rises twice as high. Results: It is known that ALT level is an important parameter for prognosis. In our study, the proportions of those who increased ALT and those who did not and the parameters differing between them were investigated. Prognostic indices were obtained according to multivariate analysis in patients whose ALT exceeded the upper limit of normal and ALT increased more than twice. The prognostic index obtained in those who increased ALT more than twice was = -40.05 + 2.71 (if ALT> 26 and Alb> 4.3) + 6.12 * Albumin + 0.00111 * Leukocyte (x / mm3). The predictive value of this index for ALT elevation was investigated by ROC analysis. A good correlation was observed with AUC = 0.93. With a cut-off value of> 0.13, 83% sensitivity and 97% specificity were determined. This index can be a guide for predicting ALT elevation in patients' follow-up.
Introduction and aim: Hepatitis B infection is a global health problem that can lead to acute and chronic hepatitis, cirrhosis and hepatocellular cancer, and is an important cause of morbidity and mortality. The majority of patients with chronic hepatitis B virus infection are in the HBeAg negative chronic infection phase, formerly called inactive carrier. Although it is not determined exactly how long those who have these conditions will be called inactive carriers, it is generally accepted that serum aminotransferases should be normal and HBV DNA level should remain low for at least 1 year. The inactive carrier phase is the phase in which HBeAg seroconversion occurs as a result of clearance of infected hepatocytes and suppression of intracellular virus during immune cleansing. Serum aminotransferase levels are normal and the HBV DNA level cannot be measured in the blood (<2000 IU / ml) and liver histology is normal. In general, inactive hepatitis B carriers with a good prognosis are unlikely to develop HCC and cirrhosis. However, it is a known fact that there is a small risk of developing HCC without cirrhosis. In addition, an increase in transaminase values and hepatic exacerbation can be seen in some of patients. Criteria that can predict which patients will experience exacerbation have not yet been established. If it can be predicted that patients will have ALT elevations in their follow-up, recommendations can be made to follow these patients more closely. In our study, patients who had normal ALT values and met other inactive hepatitis B carriage criteria were evaluated who developed ALT elevation during their follow-up. The aim of this study was to investigate the parameters associated with ALT elevation. Materials and Methods: The files of all patients who have applied to the hepatology unit of Ege University Hospital Gastroenterology Clinic since 2005 and continued their follow-ups, who met the Hepatitis B carrier criteria, were retrospectively scanned. Patients were included in the study who at least 4 years of follow-up, whose ALT values within normal limits in two or more measurements measured intermittently for at least 3 years in the first years of follow-up, who have at least 2 HBV DNA levels <2000 IU / ml in these three years at least 1 year apart from each other, who have no evidence of advanced fibrosis (Fib-4 score <1.45, platelet count> 200 000 / mm3, no or minimal fibrosis if biopsy is present), who have not received antiviral therapy. Patients with other liver diseases (delta hepatitis, hepatitis C disease, Wilson's disease, autoimmune hepatitis, etc.), using more than 2 units of alcohol per day for men and 1 unit per day for women, those with HCC, uncontrolled heart failure, diabetes, thyroid disorder and other systemic diseases were excluded from the study. The highest levels of ALT, AST, ALP, GGT, urea, creatinine, triglyceride, total cholesterol, HDL, LDL, total bilirubin, total protein, albumin, prothrombin time, blood sugar, uric acid, leukocyte, AFP, HBV DNA and the lowest levels of sodium, thrombocyte, hemoglobin, leukocyte were recorded. Patients who were followed for at least 1 more year after 3 years of normal ALT values were compared whose ALT elevation or not. The parameters associated with ALT exceeding the upper limit of normal and ALT exceeding twice the normal were investigated. Findings: A total of 223 patients who met the inclusion criteria and did not meet the exclusion criteria were included in the analyzes. 106 of the patients were male (47.5%), 117 of them were female (52.5%). The mean age was 45.1 ± 11.8 (19-77), the median was 46. Average follow-up time is 7.98 ± 2.91 years (median: 7.5 years) (minimum: 4.04 years; maximum: 14.02 years). The number of patients whose ALT values exceeded the upper limit of normal (> 35 U / L) was 26 (11.7%), and the number of patients not exceeding 197 (88.3%). 6 of these 26 patients were treated with antivirals. Although there was no ALT elevation in 1 patient, lamivudine was started because used immunosuppressant. While AST, ALP, total protein, albumin, urea, creatinine, prothrombin time, cholesterol and HBV DNA levels were found to be significant; age and gender were not found to be significant. After three years of follow-up, according to the multivariate analysis results of the parameters associated with ALT elevation, "ALT> 26 U / L and albumin> 4.3 g / dL" and the highest HBV DNA level were found to be significant. ALT increased more than twice the normal in 6 patients (2.7 %) after 3 years of follow-up. According to multivariate analysis, "ALT> 26 U / L and albumin> 4.3 g / dL", albumin level and leukocyte count were found to be significant; gender and age were not found to be significant in those whom ALT rises twice as high. Results: It is known that ALT level is an important parameter for prognosis. In our study, the proportions of those who increased ALT and those who did not and the parameters differing between them were investigated. Prognostic indices were obtained according to multivariate analysis in patients whose ALT exceeded the upper limit of normal and ALT increased more than twice. The prognostic index obtained in those who increased ALT more than twice was = -40.05 + 2.71 (if ALT> 26 and Alb> 4.3) + 6.12 * Albumin + 0.00111 * Leukocyte (x / mm3). The predictive value of this index for ALT elevation was investigated by ROC analysis. A good correlation was observed with AUC = 0.93. With a cut-off value of> 0.13, 83% sensitivity and 97% specificity were determined. This index can be a guide for predicting ALT elevation in patients' follow-up.
Açıklama
Anahtar Kelimeler
Kronik Hepatit B, İnaktif Hepatit B Taşıyıcısı, ALT Yükselmesi, Reaktivasyon, İzlem, Chronic Hepatitis B, Inactive Hepatitis B Carriers, ALT Elevation, Reactivation, Monitör
