Endothelial Dysfunction and Systemic Inflammation in the Pathogenesis and Progression of Portal Hypertension

Hepatic and extrahepatic factors contribute to mortality related to liver cirrhosis and therefore much research is still to be done in order to understand the condition thoroughly and to possibly intervene in the process. It is considered that the currently applied prognostic scores are not ideal mortality predictors. On the other hand, recent scientific concepts have revealed the significant contributing role of endothelial dysfunction and of systemic inflammation in the pathogenesis of portal hypertension. Consequently, these concepts are inevitably leading towards proposing and validating new prognostic indicators in cirrhotic patients. Von-Willebrand factor as an indicator of endothelial dysfunction and C-reactive protein as a surrogate marker of systemic inflammation and several other parameters and biological markers have been emerging as a relevant and potentially useful prognostic indicators. Also, the coagulopathy associated to liver disease is in close relation with these entities and still an important research topic. Despite the promising data regarding their prognostic potential, additional research is needed in order to define and validate their value more precisely in clinical and prognostic settings

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

Patient with Antineutrophil Cytoplasmic Antibody Associated Small Vessel Vasculitis, Acute Renal Failure, and Coronavirus Disease-19 Pneumonia: A Diagnostic and Therapeutic Challenge

BACKGROUND: Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) has a predilection for the kidney and more than three quarters of patients have renal involvement with rapidly progressive glomerulonephritis. Small-vessel systemic vasculitis may present as pulmonary-renal syndrome and is characterized by necrotizing glomerulonephritis and pulmonary hemorrhage. Diagnosis and therapy for AAV in coronavirus disease (COVID) COVID-19 pandemic require multi-disciplinary collaboration due to the affection of multiple systems and risks associated with immunosuppressive medications. CASE REPORT: A 69-year-old non-smoker, non-diabetic female presented in the outpatient unit at the department of pulmonology with dry cough, malaise, and sub-febrile temperature, lasting for 1 month. The patient had a high suspicion of severe pulmonary-renal syndrome, ANCA-AAV, and acute renal failure requiring hemodialysis. She was treated with corticosteroids, cyclophosphamide, and plasma exchange. The treatment led to temporary improvement. Infections with COVID-19, Enterococcus in the urine, and Acinetobacter in the tracheal aspirate further complicated the clinical picture and despite antibiotic treatment, use of tocilizumab and convalescent plasma, the outcome was lethal. CONCLUSION: It is important to establish the diagnosis and distinguish accurately between vasculitis and infection to provide adequate and timely therapy

Проценка на остеопорозата и појава на вертебрални фрактури кај постменопаузни пациентки со ревматоиден артритис третирани со мали дози на гликокортикоиди

Osteoporosis (OP) is a serious extracorporeal manifestation that occurs in patients with rheumatoid arthritis (RA). One of the risk factors is long-term use of glucocorticoids (GC). Osteoporosis together with the increased risk of vertebral (VF) and non-vertebral fractures (non-VF) in particular has a negative impact on quality of life in patients with rheumatoid arthritis. The aim of the study was to detect the occurrence of OP and VF in postmenopausal patients with RA and their association with long-term use of small doses of glucocorticoids. Material and methods: A total of 46 patients were analyzed. All respondents underwent imaging for osteoporosis evaluation with a DXA scanner (Lunar iDXA, GE) and VF&nbsp; with incorporated Vertebral Fracture Assessment (VFA). Results: The values of bone mineral densities (BMD) were significantly smaller in the group that received glucocorticoids. According to VFA, 37,0% of patients were registered to have a fracture of middle degree, a mild fracture was registered in 19.6% of patients, and severe fractures were registered in 3 patients (6.5%). Conclusion: In postmenopausal patients with RA receiving GC therapy, a more common occurrence of osteoporosis and vertebral fractures was reported compared with the remaining group of RA patients. All patients with RA in menopause need to be screened for timely detection and treatment of osteoporosis and prevention of its complications.Остеопорозата (OP) е сериозна вонзглобна манифестација која се јавува кај пацинетки со ревматоиден артритис (RA). Еден од ризик-факторите претставува долготрајната примена на гликокортикоиди (GC). Остеопорозата заедно со зголемениот ризик од вертебрални (VF) и невертебрални фрактури (non-VF) има негативно влијание врз квалитетот на живот кај пациентките со ревматоиден артритис. &nbsp;Целта на трудот беше да се детектира&nbsp; појавата на&nbsp; OP и VF&nbsp; кај постменопаузни пациентки со RА и нивната поврзаност со долготрајната примена на мали дози гликокортикоиди. Материјал и методи: Беа анализирани 46 пациентки. Кај сите беше направенo снимање за евалуација на остеопороза со апарат за двојно-енергетска x-зрачна aпсорпциометрија - DXA скен, “Lunar iDXA”, производство на GE, со вграден софтвер за проценка на VF, VFA (Vertebral Fracture Assessment). Резултати: Вредностите на коскениот минерален дензитет (BMD) беа сигнификантно помали во групата која примала гликокортикоиди. Според VFA, кај 37,0% од пациентките беше регистрирана фрактурa од среден степен, кај 19,6% леснa фрактурa, a&nbsp; тешка фрактура беше регистрирана кај три пациентки (6,5%). Заклучок: Кај постменопаузните пациентки со RA кои примаа терапија со GC беше регистрирана&nbsp; почеста појава на OP како и VF споредено со останатата група пациентки со ревматоиден артритис. Кај сите пациенки со RA во менопауза,&nbsp; потребно е навремено детектирање и третман на остеопорозата и превенирање на нејзините компликации

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