Triglyceride-Glucose Index and Hepatic Steatosis Index for the assessment of liver steatosis in HCV patients.

BACKGROUND: Liver steatosis in patients with chronic infection of hepatitis C virus (HCV) is important from multiple standpoints: faster disease progression, more frequent hepatocellular carcinoma and cirrhosis development or worse therapy response. Liver biopsy as diagnostic method, is in recent years more and more challenged due to its well-known flaws. Hepatic steatosis index (HSI) and triglyceride-glucose (TyG) Index, are surrogate scores developed in the first place for noninvasive assessment of steatosis in patients with nonalcoholic fatty liver disease (NAFLD). However, their use in the context of chronic hepatitis C (CHC) virus infection is still unclear. Aim of our study was to assess the accuracy of both HSI and TyG index in patients with CHC. METHODS: The cohort included 814 patients with CHC infection in whom liver biopsy was performed. After implementing strict criteria for sample adequacy and necessary data, 424 patients were finally enrolled in our study. Histological findings were used as a reference point, and surrogate scores HSI and TyG index were expressed through receiver operating characteristic (ROC) curves in order to assess their ability in determining patients without (<5%) or with steatosis (>5%), but also to address their ability in assessing between different degrees of steatosis. RESULTS: The average age of study population was 37.09 years and the majority of patients were men (67%). Liver steatosis was detected in approximately half of the liver biopsy samples (50.4%). About 5% of them had severe steatosis. The area under the ROC curve values for HSI and TyG index when detecting liver steatosis were 0.76 and 0.629, respectively. Similar values were obtained comparing between absence of steatosis and mild steatosis (5-30%). CONCLUSIONS: Non-invasive surrogate scores HSI and TyG index in CHC patients, have good performance to detect the presence of steatosis. In this context, these tools are cheap, widely available and could be valuable asset in liver steatosis assessment outside liver biopsy.

Implementation of Microelimination Strategy in Eradication of Chronic Hepatitis C Infection in Patients with Hemophilia in the Northern region of Serbia: Is Eradication Possible?

BACKGROUND: Treating HCV in people with hemophilia prevents the development of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) and greatly increases the quality of life for people living with hemophilia. There are many obstacles in reaching the WHO goal of globally eradicating HCV by 2030, mainly its scale, complexity, and implementation. That is why many countries have implemented a micro-elimination strategy: a pragmatic elimination approach in populations with the most efficacy. The aim of this publication is to present the morbidity and mortality rates, the clinical course and treatment outcomes of chronic HCV infection in people with hemophilia (PwH), as well as to show an example of a successfully conducted HCV micro-elimination strategy among people with hemophilia in the Province of Vojvodina. METHODS: A retrospective, single-center study, performed using medical documentation of all registered PwH in the Clinical Center of Vojvodina from 1994. until 2020. It included 74 hemophilia patients, out of which 32 were patients with hemophilia and chronic HCV infection. RESULTS: The mean age of HCV-positive positive people with hemophilia (PwH) was 42.3 years, with the duration of infection of 30-35 years. Co-infection with HIV was observed in 6.25% of cases. Furthermore, 18.75% of patients had spontaneous HCV elimination, and 75% were treated with antiviral protocols. Cirrhosis developed in 21.87% with an incidence rate of 0.6 per 100 patient-years. After treatment with Pegylated IFN and ribavirin (RBV), 58.3% achieved SVR. Side effects of IFN-based therapy regimens were recorded in 20.8% of treated (PwH). In 37.5% PWH, DAA protocols were administered, and these patients achieved SVR. HCV- PwH have a statistically higher mortality rate than non-infected people with hemophilia. Among the HCV-positive PwH, hemophilia-related deaths were 6.25%, and HCV-related deaths were 9.37%. Currently, in the Registry of PwH in Vojvodina, there are no patients with active HCV infection. CONCLUSION: The micro-elimination strategy in the subpopulation of PwH was successfully implemented in Vojvodina by hematologists and infectious diseases specialists in close collaboration.

Noninvasive assessment of liver fibrosis in chronic hepatitis C virus patients compared to liver biopsy: the experience of tertiary level hospital in Serbia.

BACKGROUND: Chronic hepatitis C virus (HCV) infection, that is defined by active carriage of HCV RNA in the blood, is represents one of the major public health problems worldwide. In Serbia, the prevalence of anti-HCV positive persons in the general population, is estimated on average 1.13%. METHODS: The aim of our study was to evaluate the ability of noninvasive scores in order to define the degree of liver fibrosis, and to assess the effect of host and viral factors on fibrosis in chronic HCV patients. In a retrospective analysis a total of 814 patients with chronic HCV infection were included. Liver fibrosis scores were calculated, and in particular AST/ALT Score APRI, Forns Index, and FIB-4 score, and all of them compared with histological classification. RESULTS: We found that noninvasive biochemical scores of fibrosis, have a good performance especially to distinguish mild and moderate fibrosis to advanced fibrosis. In particular, we found that FIB-4 score is a useful screening tool to accurately exclude patients with advanced disease. CONCLUSIONS: Noninvasive liver fibrosis scores are efficient tools in the management and follow-up of HCV patients in clinical practice.

Gut microbiota changes and chronic hepatitis C virus infection.

INTRODUCTION: Hepatitis C virus (HCV) infection is a global health problem with 150 million infected people worldwide. Liver can be greatly affected by changes in gut microbiota due to increased intestinal permeability with passage of microbial antigens into the liver through the portal circulation. The concept of 'gut-liver' axis is important to understand the pathophysiology of several liver diseases. Several recent studies also revealed that an altered gut microbiota can be implicated in the pathogenesis of HCV-induced chronic liver disease (CHC). Areas covered: An overview of intestinal microflora composition, host reaction during CHC, and a description of relevant clinical trials on the use of probiotics in this field. Expert commentary: HCV patients gut microbiota composition is stable over liver disease stages. This is a unique example of gut disbiosis stability vs. NAFLD, HBV, HIV, and HCV co-infected patients. The impact of HCV infection on intestinal permeability allows gut disbiosis starting, maintenance and its proinflammatory effect until liver cirrhosis and HCC development. HCV eradication has unraveled the strong impact of gut microbiota unbalance on liver disease development with possible future implications for probiotics use to change the natural history of cirrhosis progression.

Metabolic aspects of adult patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD.

Chronic Hepatitis C and Alcohol Abuse: The Single Center Experience of Novi Sad - Serbia.

BACKGROUND: Chronic ethyl alcohol consuming is well known independent negative predictor of unfavorable natural course and therapy outcome of Chronic Hepatitis C (CHC) infection. OBJECTIVE: The aim of the present study was to clarify the impact of alcohol consumption on fibrosis rate progression in patients with CHC and Sustained Virologic Response (SVR) rates in patients undergoing treatment with pegylated interferon and ribavirin. METHOD: This cross sectional retrospective study included 807 CHC patients underwent liver biopsy and hospitalized at Clinical center of Vojvodina, Novi Sad, Serbia. According to the alcohol consumption equal or greater than 50 g/day prior to liver biopsy, patients were divided into two groups. We compared demographic, clinical, virologic and histopathological markers of CHC, as well as response to antiviral therapy. RESULTS: We find statistically significant difference (p=0.001) in gender, but not in age (p=0.081), estimated duration of the CHC (p=0.470) and hepatitis C genotype (p=0.545) between two groups. Among patients with CHC who consume alcohol ≥50 g/day there were significantly higher incidence of intravenous drug users (p=0.000). Binary logistic regression showed that the only independent predictors of moderate to severe fibrosis (fibrosis ≥2) were age (p=0.000) and alcohol use (p=0.027). There was not statistically significant difference in SVR rate between two groups (p=0.810). CONCLUSION: We believe that this good result in treatment outcome was the consequence of proper selection of patients based primarily on regulations of Republic of Serbia on the necessity of abstinence from the use of alcohol and psychoactive substances at least one year before starting antiviral therapy.

BACTERIAL INFECTIONS IN PATIENTS WITH LIVER CIRRHOSIS.

INTRODUCTION: Liver cirrhosis is characterized by a reduced defensive reaction to bacterial infections and patients with cirrhosis are at increased risk of developing infections, sepsis and death. The most common bacterial infections in these patients are spontaneous bacterial peritonitis, urinary tract infection, pneumonia, skin and soft tissue infection and bacteremia. The most common causes are Gram negative bacteria. The aim of this study was to determine the prevalence, localization and etiology of bacterial infections in hospitalized patients with liver cirrhosis. MATERIAL AND METHODS: This retrospective study included 401 patients with liver cirrhosis hospitalized at the Department of Infectious Diseases, Clinical Center of Vojvodina Novi Sad in the period from 2006 to 2010. Bacterial infection was diagnosed according to clinical examination, laboratory findings, radiological examination and bacterial positive culture. RESULTS: The prevalence of bacterial infection was 38.15% (153/401). The most common infections were pneumonia (21.56%), urinary tract infection (20.91%), and spontaneous bacterial peritonitis (18.95%). Localization of infection remained undetermined in as many as 37 patients (24.18%). Bacterial cultures were positive in 32 patients (20.91%), Gram negative bacteria were commonly isolated, mostly Escherichia coli (71.87%). The mortality rate among patients with bacterial infections was 31.37% (48/153). CONCLUSION: Bacterial infections are often found in patients with liver cirrhosis, the most frequent being pneumonia, urinary tract infection and spontaneous bacterial peritonitis. Gram negative bacteria, especially Escherichia coli were predominant in the etiology. The extent to which bacterial infections are taken into consideration in cases with liver cirrhosis is rather high; however, they are not proved etiologically to the satisfactory level.

The success of treatment of chronic hepatitis C in opiate addicts in Clinical Center of Vojvodina.

INTRODUCTION: Chronic hepatitis C is a disease with a high prevalence in the population of intravenous drug users. Serious clinical course of the disease, which can lead to cirrhosis of the liver with all its complications, has a large epidemiological and clinical significance. This study was aimed at assessing the success of antiviral treatment of chronic hepatitis C in intravenous drug users and defining indicators of successful treatment in this population. MATERIALS AND METHODS: This retrospective study included 316 patients treated with standard therapy for chronic hepatitis C, pegylated interferon and ribavirin, at the Department of Infectious Diseases, Clinical Center of Vojvodina in Novi Sad in the period from January 2007 to December 2012. The patients were divided into a group of intravenous drug users (n = 163) and a group of other modes of transmission of hepatitis C virus (n = 153). The indicators of successful treatment were measured in both groups. RESULTS: A total 51.57% of the subjects belonged to the group of intravenous drug users. The therapy was successful in 87.15% of cases, while the success was achieved in only 53.47% of cases in the group of patients infected otherwise. The positive effect of therapy was associated with younger age, shorter duration of infection, low levels of fibrosis and a higher percentage of infected with hepatitis C virus genotypes 2 and 3. CONCLUSION: The population of intravenous drug users can be effectively treated with the standard therapy for chronic hepatitis C, even more successfully than the population infected in some other way.

Treatment of chronic hepatitis C in injecting drug users--a 5-year follow-up.

BACKGROUND/AIM: Hepatitic C infection (HCV) is a systemic, generalised disease with the prevalence of inflammation in the liver. The aim of this study was to determine the success of treatment for chronic hepatitis C with pegilated interferon alfa 2a and ribavirin in injecting drug users. METHODS: This a 5-year follow-up study included 30 patients [63.3% men and 36.7% women, average age 30.2 years (SD 7.1 years)] injecting drug users in one-year abstinence, with chronic hepatitis C, treated with the pegilated interferon alpha 2a and ribavirin. Complete history with possible route of infection, the standard biochemical tests, liver biopsy, quantification of the viral genome in sera and HCV genotyping and subtyping were done prior to the therapy initiation. Depending on the HCV genotype, the therapy was conducted over a period of 48 weeks for genotype 1 and 24 weeks for genotype non 1. Five years later all 30 patients were invited on control examination; 22 of them appeared at the check-up and quantification of the viral genome in their sera were analized. RESULTS: The established degree of liver fibrosis was: F0 in 40%, F1 in 23.33%, F2 in 26.67%, F3 in 3.33% and F4 in 6.67% of the patients. Genotype 3a was dominant (50.0%), 1b was registered in 40.0%, 1a in 6.66% and 2b in 3.33% of the patients. Sustained virologic response (SVR) was achieved in 86.7% of the patients, 10.0% of the patients were non-responders, while 3.33% of them revealed recurrence of HCV. Opiate abuse recurrence during antiviral therapy happened in 6.7% of the patients. Five years after the antiviral therapy 73.3% of the patients appeared at the check-up and all of them were in stable abstinence from opiate abuse. All of those, with a sustained viral response of five-year duration, had the negative PCR HCV RNA test (< 50 IU ml(-1)). In the patients showing unsatisfactory therapy response 5 years before, antiviral therapy was repeated by the same therapeutic regimen, but without adequate therapeutic response. A total of 26.7% of the patients were lost from the records. CONCLUSION: In a 5-year follow-up period 73.3% of the patients used to come regularly to check-ups and among them neither the opiate abuse recurrence nor HCV infection recurrence were registered.

[Extrahepatic manifestations of chronic hepatitis C and their influence on response to treatment with pegylated interferon alfa-2a and ribavirin].

INTRODUCTION: Thirty to 50% of patients with chronic hepatitis C (CHC) have one or more extrahepatic manifestations (EHMs) of hepatitis C virus (HCV) infection. OBJECTIVE: The aim of this study was to evaluate the frequency of EHMs and to investigate the efficacy of pegylated interferon (Peg-IFN)-alpha-2a plus ribavirin therapy in patients with HCV-related EHMs. METHODS: The study included 280 patients suffering from CHC and treated with Peg-IFN-alpha-2a and ribavirin.The patients were divided in two groups according to presence or absence of EHMs. We evaluated virological response to antiviral therapy. RESULTS: One or more EHMs were found among 27.9% of patients. Most frequently they had rheumatoid factor in serum (12.5%), organ-nonspecific antibodies ANA and AGMA (12.4%), thyroid hormone disorders (9.3%), vasculitis (5.7%), diabetes mellitus (4.65%), glomerulonephritis (0.71%), and porphyria cutanea tarda (0.36%). Among the patients with EHMs there was 52.6% of females vs. 30.2% of females in the group of patients without EHMs (p=0.001). HCV genotypes 1 and 4 had 85.9% patients with EHMs vs. 58.4% of patients without EHMs (p=0.000). Progressive fibrosis and cirrhosis were more frequently recorded in the EHM group of patients (32% vs. 23.2%), but without statistically significant difference (p=0.532). Serious adverse events of Peg-IFN-alpha-2a and ribavirin were statistically significantly recorded among the patients with EHMs (46.1% vs. 12.9%; p=0.000). Sustained virological response among the patients with and without EHMs rated 56.9% and 70.8% respectively (p=0.125). CONCLUSION: Patients with CHC and EHMs treated with combined Peg-IFN-alpha-2a and ribavirin experience handling difficulties, more often have serious adverse events, while successful outcome is achieved in about 50% of patients.

[On the development of the infectology service in Novi Sad].

INTRODUCTION: Infectious diseases are a part of the history of this region. Devastating epidemics of plague, smallpox, and cholera were frequent during the 18th and the 19th centuries. Other infectious diseases were a serious problem as well: alimentary tract infections, scarlet fever, diphtheria, whooping cough. Geographic position, climate, migrations, as well as the tradition and lack of medical staff and medications, affected the frequency and outcome of infections. THE HISTORY OF THE TREATMENT OF INFECTIOUS DISEASES: Patients with infectious diseases were first treated at home. Later, a hospital in Visarion street was opened as an isolation facility and a hospital for homeless patients. The development of science and the education of medical personnel exerted the greatest influence on the control and later treatment of infectious diseases. These measures resulted in the establishment of the first specialized medical institutions in Novi Sad during the cholera outbreak in 1884. After that, temporary pediatric units were organized for the treatment of scarlet fever, diphtheria and smallpox. A ward for infectious diseases was founded in the The Great City Hospital in the second half of the 19th century (1892). The 20th century was a period of control and eradication of infectious diseases in Vojvodina (smallpox, malaria, diphtheria, polio). MODERN INFECTIOUS DISEASES: Nowdays, major infectious deseases include respiratory, alimentary and parasitic infections. However, new diseases are being registered as well - hemorrhagic fevers, Lyme disease, HIV infection. The Infectologic Service in Novi Sad was developed from an Infectology Departement as part of the Departement of Internal Diseases in the new Provincial Hospital (1909) to the independent Departement for Infectious Diseases (1945). Today, Clinic of lnfectious Diseases is an integral part of the Clinical Center of Vojvodina. DEPARTMENT OF INFECTIOUS DISEASES: The Department of Infectious Diseases of the Faculty of Medicine in Novi Sad was founded in 1960. Undergraduate studies started in 1963/64 for students of medicine and in 1978/79 jor dentistry students. Today. the faculty of the Department takes part in undergraduate studies of medicine, dentistry, health care, as well as in graduate programs. The faculty members are also taking part in specialization programs at the Faculty of Medicine. Infectious disease physicians are involved in the activities of the Infectology Section (founded in 1979) of the Society of Physicians of Vojvodine of the Medical Society of Serbia. The first president of the Infectology Section was Dr. Vera Mudric, professor, infectologists, whereas Dr. Grozdana Canak, professor, was the vice-president from 2000-2004. The Infectology Section collaborates with various national and international societies for infectious diseases.

[Clinical characteristics of coinfection with hepatitis C virus in HIV-positive patients].

INTRODUCTION: Patients with HIV are commonly coinfected with hepatitis C virus (HCV) mostly due to similar routes of transmission, especially in areas with high prevalence of intravenous drug use. In the era of highly active antiretroviral therapy (HAART), life expectancy of these patients has increased and end-stage liver disease is a common cause of death. MATERIAL AND METHODS: This study included 387 HIV-positive patients treated at the Institute of Infectious and Tropical Diseases "Dr. Kosta Todorovic" in Belgrade. We investigated epidemiological and clinical features of patients who underwent biochemical liver tests, ultrasonography and some of them blind liver biopsies. RESULTS: The prevalence of HCV infection among these patients was 58.13% with 225/387 ELISA anti-HCV-antibody positive patients. HCV coinfection was statistically more significant among male patients aged between 30 and 34, and among intravenous drug users. None of the biochemical parameters were statistically significant among coinfected patients, except aminotraspherase levels which were significantly higher among patients with chronic hepatitis C and HIV. 44 patients underwent biopsy and pathohistological findings showed that every 4th patient (25%) had chronic hepatitis C infection. The average survival rate in coinfected patients in the pre HAART era was the same as in AIDS patients. CONCLUSIONS: Liver biopsy, elevated aminotraspherase and positive serology can help in making the diagnosis of chronic hepatitis C, and possible future treatment options.

[Chronic infectious mononucleosis]. / Hronicna infektivna mononukleoza.

INTRODUCTION: Chronic infectious mononucleosis is a clinical entity recognized 15 years ago with clearly defined serological criteria: high titres of IgG Epstein-Barr virus (EBV) virus capsid antigen (VCA), IgG EBV early antigen without IgG Epstein-Barr nuclear antigen (EBNA) antibodies. MATERIAL AND METHODS: This follow-up study lasted for 2 years and included 100 acute infectious mononucleosis patients who were investigated every 6 months. Apart from physical examination we evaluated history, complete blood count and liver function together with 5 commercial ELISA tests: IgM EBV VCA, IgG EBV VCA, IgG EB NA, IgG EBV EA and IgA EBV EA. RESULTS: Although malaise and fatigue with cervical lymphoadenopathy were the most frequent symptoms, their statistical significance was most established. All laboratory analyses were completely normal during the follow-up period, but there were four patients with acute hepatitis due to hepatitis A virus and adenoviruses. After 6 months of acute illness, two patients without IgG EB NA antibodies who were candidates for chronic disease, presented no other serological findings for chronic disease. It was confirmed that they had delayed serological response due to EBV infection, because one year later they had a completely normal immune status on EBV infection. CONCLUSION: Chronic infectious mononucleosis seems to be an extraordinary event after acute disease. This conclusion corresponds with literature reports of sporadic cases of this disease.

Serologic profile of Epstein-Barr virus infection in acute infectious mononucleosis.

The aim of our study was to determine classes of antibodies in different clinical forms of Epstein-Barr Virus (EBV) primary infections. The investigation included 100 patients with acute mononucleosis who were hospitalized at the Clinic for Infectious Diseases in Novi Sad during 1995-1997. Apart from clinical and laboratory parameters, 5 different ELISA assays were performed: IgM EBVVCA, IgG EBVVCA, IgG EBNA, IgA EBVEA and IgG EBVEA. All patients were IgM EBVVCA positive, only 42% IgG EBVVCA positive and 6% IgG EBNA positive. Antibodies due to EBVEA IgA were established in 58% of patients and IgG class in 41%. Serologic profile of early EBV primary infection was established in 25%, acute EBV primary infection in 69% and late EBV primary infection in 6%. A statistically significant difference regarding absolute lymphocyte count and serologic response to early antigens of EBV infection was established in patients with positive findings. Clinical findings in the throat correlated with serologic response to early EBV proteins. We didn't find any correlation due to duration of illness, fever, clinical forms of EBV primary infection and liver damage. Paul Bunnell test was positive only in 42% of our patients, with significantly higher number of negative results in groups of early and late EBV primary infections.

[Clinical importance of adenoviral infections]. / Klinicki znacaj adenovirusnih infekcija.

INTRODUCTION: The aim of this article was to point to ubiquitous adenoviral infections and to give a literature overview. Adenoviral infections present with a variety of clinical manifestations, causing many differential diagnosis problems. DIAGNOSIS AND EPIDEMIOLOGY: In our country diagnosis is made using the complement fixation test (CFT), which detects antibodies due to soluble group specific antigen. In acute infections, we need two sera samples given in 2 weeks period with 4-fold rise or fall in titers. Due to many asymptomatic infections which can given increased titer by CFT, many physicians think that patients have a persistent infection. Persistent adenoviral infections need not be accompanied by any special clinical symptomatology. However, adenoviral infections still play an important role in acute respiratory infections. The most severe respiratory infection is pneumonia which can be associated with acute respiratory distress syndrome and death. Disseminated adenoviral diseases appear in 2.5% of all adenoviral infections with the same percentage between immunocompetent and immunocompromised persons. In immunocompromised persons adenoviral infections manifest as haemorrhagic cystitis, fulminant or acute hepatitis or meningoencephalitis. THERAPY AND CONCLUSION: We still don't have a special treatment for these kinds of infections. Variety of antiviral drugs with controversial effects have been reported in management of adenoviral infections in immunocompromised persons. In USA adenoviral vaccine has been excluded from vaccine schedules among military personnel, but morbidity and the first two deaths due to these infections in the last 30 years reported by MMWR in 2000, may change this policy.