CLINICAL RELEVANCE OF PRECORE MUTATIONS OF HEPATITIS B VIRUS IN CHRONIC LIVER DISEASE

Introduction: Hepatitis B is one of the most frequent etiological factors for chronic liver diseases worldwide. Recent studies have suggested the important role of the genetic diversity of the virus on natural course of hepatitis B. Hepatitis B e-antigen negative type of chronic hepatitis is associated with mutations in the precore region and basic core promoter of hepatitis B viral genome. Aim of study was to identify precore mutations in viral genome of patients with chronic hepatitis B and to evaluate clinical patterns of liver disease related to this type of hepatitis B. Methods: Sixty seven patients with hepatitis B were included in the study. In order to evaluate the clinical patterns of chronic liver disease related to hepatitis B viral infection, biochemical and virological investigations were done, as well as a quantification of serum viral load. All patients under went liver biopsy and semiquantification of necroinflammation and/or fibrosis according to Knodell scoring was done. In the group of e anti en-negative patients, molecular analysis was performed in order to identify presence of mutations in precore region of the virus. Results: Study group was divided in 25 HBe Ag-positive and 42 HBe Ag-negative subjects. Alanin-aminotransferase activity and level of viral load were higher in HBe Ag-positive (p < 0.05), but average age and histology activity index were significantly higher in the HBeAg-negative patients (p < 0.01). Precore mutants were found in 38 of 42 patients with HBe Ag-negative hepatitis (90%). Fibrosis was found in 30/38 cases with mutations. Discussion: Mutations in precore region of HBV in HBe Ag-negative patients were more prevalent in older age and were associated with higher rate of fibrosis in liver tissue, meaning more advanced stage of the disease. This could be a consequence of longer duration of HBV infection or more severe clinical course of the disease. Conclusion: Our results suggest that precore mutations are highly responsible for the development of hepatitis B e antigen-negative chronic liver disease in our patients. These mutations are associated with more progressive liver disease and with older age of the patients

Предиктивен потенцијал на MELD и Child-Turcotte-Pugh II скорот за СБП кај пациенти со црнодробна цироза и асцит

It is very important for patients with spontaneous bacterial peritonitis (SBP) to assess the length of survival and the risk of death, primarily because of the wide range of potential complications that can lead to multisystem organ failure and fatal outcome. The aim of this study was to determine the predictive potential of MELD and Child-Turcotte-Pugh II score for SBP in patients with cirrhosis and ascites. Material and methods: The study was designed as a prospective-analytical-observational and was conducted at the University Clinic for Gastroenterohepatology in Skopje for a period of one year. The study population included 70 hospitalized patients with established liver cirrhosis, regardless of etiology, divided into two groups, 35 patients with SBP and 35 non-SBP. Prognostic scores in patients with liver cirrhosis and ascites: MELD score, according to the formula: MELD = [(0.957 x Ln Creatinin) + (0.378 x Ln Bilirubin) + (1.12 x Ln INR) + (0.643) x 10]. The Child-Turcotte-Pugh II score includes 6 parameters: serum albumin and bilirubin, amount of ascites, degree of encephalopathy ( HE), prothrombin time (PT) and serum creatinine, and assessment of the degree of hepatic encephalopathy according to the West Haven criteria. Results: The average value of the MELD score in patients with SBP was 22.6 ± 8.27 and in non-SBP the average value was lower - 17.83±5.87. According to the Mann-Whitney U test, the difference between the mean values ​​was statistically significant for p &lt;0.05 (z = 2.41; p = 0.015). A score of 30 to 39 was registered in 25.7% of patients with SBP, and only in 2.9% in non-SBP; the percentage difference was statistically significant for p &lt;0.05 (Difference test, p = 0.0064 ). Patients with SBP had an average Child-Pugh score of 13.09 ± 2.48 or 100.0% C-class points. In patients with non-SBP, an average child-Pugh score of 9.63 ± 1.62 was recorded, or class B in 65.7% and class C in 34.3%. The percentage difference was statistically significant for p &lt;0.05 (Difference test, p = 0.000000). According to the Mann-Whitney U test, the difference between the mean values ​​was statistically significant for p &lt;0.05 (z = -5.44; p = 0.00001). ROC analysis indicated that the Child-Turcotte-Pugh II score contributed to the diagnosis of SBP - 90.7% (p = 0.000) (excellent predictor), closer to the ideal value of 1.0 and above the worst value of 0.5. ROC analysis indicated that the MELD score did not contribute to the diagnosis of SBP - 66.7% (p = 0.017) (weak predictor), closer to the worst value of 0.5. Conclusion:Our research confirmed that SBP occurs in patients with severe hepatic dysfunction calculated according to the CTP II score and MELD score. Mean value of the MELD score in patients with SBP was higher then in patients with non-SBP. On the other hand all patients with SBP had an average CTP II score, C-class points,&nbsp; while the largest percentage of patients with non-SBP were class B-class points. MELD score is a weak predictor of SBP.&nbsp; The best predictor for predicting SBP is the CTP II score (rank C).Поради широкиот спектар на потенцијални компликации кои може да доведат до&nbsp; мултисистемско органско попуштање и смрт,&nbsp; многу е важно кај пациентите со спонтан бактериски перитонитис (СБП) да се направи проценка на должината на преживување и ризикот од смртен исход. Целта на трудот беше да се одреди предиктивниот потенцијал на MELD и Child-Turcotte-Pugh II скорот (CTP II) за&nbsp; СБП кај пациентите со црнодробна цироза и асцит. Материјал и методи: Студијата беше дизајнирана како проспективно-аналитичко-опсервациска и се спроведе на Универзитетската&nbsp; клиника за гастроентерохепатологија во Скопје во период од една година. Студиска популација беа хоспитализирани пациенти со етаблирана црнодробна цироза, без оглед на етиологијата, вкупно 70 пациенти, поделени во две групи, 35 пациенти со СБП и 35 без СБП.&nbsp; Прогностички скорови кај пациенти со црнодробна цироза и асцит:&nbsp;&nbsp; MELD скор, според формулата: MELD = [(0,957 х Ln Creatinin) + (0,378 х Ln Bilirubin) + (1,12 х Ln INR) + (0,643) х 10]. СТП II скор вклучува 6 параметри: албумин и билирубин во серум, количина на асцит, степен на енцефалопатија, протромбинско време (ПВ) и креатинин во серум, а проценка на степенот на хепатална енцефалопатија(HE) со West-Haven-овите критериуми. Резултати: Просечната вредност на MELD скорот кај пациентите со СБП изнесуваше 22,6±8,27 а кај&nbsp; оние без СБП просечната вредност беше пониска и изнесуваше 17,83±5,87. Според Mann-Whitney U тестот, разликата помеѓу просечните вредности беше статистички сигнификантна за p&lt;0,05 (z =2,41; p=0,015). Вредност на скорот од 30 до 39 беше регистрирана кај&nbsp; 25,7% од пациентите со СБП, а само кај 2,9% од оние без СБП; процентуалната разлика беше статистички сигнификантна за p&lt;0,05 (Difference тест, p=0,0064).Кај пациентите со СБП беше регистрирана просечна вредност на CTP II скорот од 13,09±2,48 или во поени 100,0%, класа C. Кај пациентите без СБП беше регистрирана просечна вредност на&nbsp; CTP II скорот од 9,63±1,62 или класа B&nbsp; кај 65,7%&nbsp; и&nbsp; класа C кај 34,3%. Процентуалната разлика беше статистички сигнификантна за p&lt;0,05 (Difference тест, p=0,000000). Според Mann-Whitney U тестот, разликата помеѓу просечните вредности беше статистички сигнификантна за p&lt;0,05 (z =-5,44; p=0,00001).ROC-анализата покажа дека CTP II скорот придонесува за дијагностицирање на СБП - 90,7% (p = 0,000) (одличен предиктор), поблизу до идеалната вредност од 1,0 и над најлошата вредност од 0,5.ROC-анализата покажа дека MELD скорот не придонесува за дијагностицирање на СБП&nbsp; со 66,7% (p = 0,017) (слаб предиктор), поблизу e до најлошата вредност од 0,5. Заклучок:Нашето истражување потврди дека СБП се јавува кај пациенти со тешка хепатална дисфункција пресметана според CTP II и MELD скорот. Средната вредност на MELD скорот кај пациенти со СБП беше поголема отколку кај пациенти со не-СБП. Од друга страна, сите пациенти со СБП имаа просечна вредност на CTP II, C-класа, додека најголем процент од пациентите со не-СБП беа B-класа. MELD скорот е слаб предиктор за СБП. Најдобар предиктор за предвидување на СБП е CTP II (ранг C) скор

Atorvastatin in Combination with Pegylated Interferon and Ribavirin Provided High Rate of Sustained Virological Response in Patients with Genotype 3 Hepatitis C Virus

BACKGROUND: Chronic hepatitis C virus infection represents a more frequent cause of liver cirrhosis and hepatocellular carcinoma. Statins, inhibit HCV replication in vitro, enhance the antiviral effect of the already known antiviral drugs and reduce their resistance. AIM: To determine the impact of additional therapy (treatment with Atorvastatin 20 mg) to the standard antiviral therapy (pegylated interferon alpha-peg-IFN α and ribavirin) on achieving sustained virological response (SVR). MATERIAL AND METHODS: In the study which is comparative, open-label, prospective-retrospective, 70 patients diagnosed with chronic hepatitis C virus infection who met criteria for treatment with standard antiviral therapy combined with anti-lipemic therapy (Atorvastatin 20 mg) were included. Patients in the study were divided into two groups: one group of 35 patients receiving combination therapy (Atorvastatin + peg-IFN α + Ribavirin) and another group of 35 patients received only standard antiviral therapy. Those parameters were followed in all patients: genotyping, quantification of the virus, histological assessment of liver inflammation and fibrosis degree (before starting treatment), the presence of steatosis, laboratory analysis: hematology, liver, lipid and carbohydrate status, insulin blood level (the calculation of HOMA-IR) and body mass index (BMI) calculation. The overall treatment of the patients depends from the virus genotype, thus, patients with genotype 1 and 4 received 48 weeks standard antiviral therapy, but patients with genotypes 2 and 3 received 24 weeks of antiviral therapy. SVR was considered an undetectable level of HCV RNA levels 24 weeks after completion of antiviral therapy. The results were statistically analysed, and all results for p &lt; 0.05 were considered statistically significant. RESULTS: Combination therapy leads to a slightly higher percentage of SVR (85.71%) in patients with chronic hepatitis C versus standard therapy (74.29%), but in a group of patients with genotype 3 this rate of SVR amounting to 95.83%. Combination therapy leads to significant improvement of lipid and glucose status after treatment, and in terms of side effects, there was no appearance of serious adverse events that would be a reason for discontinuation of the therapy. CONCLUSION: Combination therapy Atorvastatin + pegylated interferon alpha + Ribavirin leads to high rate of SVR of 95.83% in patients with chronic hepatitis C, genotype 3. Statins can be used safely in patients with chronic hepatitis C