Croatian genetic heritage: an updated Y-chromosome story.

AIM: To analyze an additional set of ˝Y-chromosome genetic markers to acquire a more detailed insight into the diversity of the Croatian population. METHODS: A total of 518 Yfiler Plus profiles were genotyped. Allele frequencies, haplotype frequencies, and haplotype diversity were calculated by using the STRAF software v. 2.0.4. Genetic distances were quantified by Rst with AMOVA online tool from the YHRD. The evolutionary history was inferred with the neighbor-joining method of phylogenetic tree construction in the MEGAX software. Whit Athey's Haplogroup Predictor v. 5 was used for additional comparison with regional and other European populations. RESULTS: A total of 507 haplotypes were used for genetic STR analysis. An interpopulation study on 17 Y-STR markers showed the lowest genetic diversity between the Croatian and Bosnian-Herzegovinian populations and the highest between the Croatian and Irish populations. Additional interpopulation comparison with the original 27 Y-STR markers (for the population with available data) was also performed. A total of 518 haplotypes were used in the determination of haplogroup diversity. Haplogroup I with its sublineage I2a expressed the highest prevalence. The second most prevalent haplogroup was R, with its major sublineage R1a, except for the subpopulation of Hvar, where E1b1b was the second most prevalent haplogroup. Rare haplogroups also confirmed in this study were L, T, and Q. G1 was detected for the first time in the Croatian population. CONCLUSION: We obtained a new insight into the differences between examined subpopulations of Croatia and their possible (dis)similarities with neighboring and distant populations.

CROATIAN GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF NONALCOHOLIC FATTY LIVER DISEASE.

Nonalcoholic fatty liver disease (NAFLD) is a term describing excessive accumulation of fat in hepatocytes, and is associated with metabolic syndrome and insulin resistance. NAFLD prevalence is on increase and goes in parallel with the increasing prevalence of metabolic syndrome and its components. That is why Croatian guidelines have been developed, which cover the screening protocol for patients with NAFLD risk factors, and the recommended diagnostic work-up and treatment of NAFLD patients. NAFLD screening should be done in patients with type 2 diabetes mellitus, or persons with two or more risk factors as part of metabolic screening, and is carried out by noninvasive laboratory and imaging methods used to detect fibrosis. Patient work-up should exclude the existence of other causes of liver injury and determine the stage of fibrosis as the most important factor in disease prognosis. Patients with initial stages of fibrosis continue to be monitored at the primary healthcare level with the management of metabolic risk factors, dietary measures, and increased physical activity. Patients with advanced fibrosis should be referred to a gastroenterologist/hepatologist for further treatment, monitoring, and detection and management of complications.

Liver Disease During Pregnancy: A Challenging Clinical Issue.

One of the least studied topics in the field of obstetrics is liver disease during pregnancy, which creates a challenge for both gynecologists and hepatologists. Approximately 3% of pregnant women are affected by some form of liver disease during pregnancy. Some of these conditions can be fatal for both the mother and child. In addition, 3 types of liver disease need to be differentiated during pregnancy. One type is liver disease directly related to pregnancy, which can occur at a specific time during pregnancy. Another type is liver disease not related to pregnancy, which can occur at any time, such as viral- or drug-induced hepatitis. Furthermore, pregnancy can occur in women with pre-existing liver disease. It is essential that the clinicians are familiar with this disorder so they can respond promptly and appropriately in all of these situations, especially when emergency delivery is needed and must not be postponed.

Metabolic syndrome and non-alcoholic fatty liver disease after liver or kidney transplantation.

Transplantation is a definitive treatment option for patients with end-stage liver disease, and for some patients with acute liver failure, hepatocellular carcinoma or end-stage renal disease. Long-term post-transplantation complications have become an important medical issue, and cardiovascular diseases (CVD) are now the leading cause of mortality in liver or kidney transplant recipients. The increased prevalence of metabolic syndrome (MS) likely plays a role in the high incidence of post-transplantation CVD. MS and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), are prevalent among the general population and in pre- and post-transplantation settings. MS components are associated with recurrent or de novo NAFLD in transplant recipients, potentially influencing post-transplantation survival. Moreover, recent data reveal an important association between NAFLD and risk of incident of chronic kidney disease (CKD). Therefore, NAFLD identification could represent an additional clinical feature for improving the stratification of liver and kidney transplant recipients with regards to risks of CVD, CKD and renal allograft dysfunction. All MS components are potentially modifiable; therefore, it is crucial that hepatologists, nephrologists and primary care physicians become more engaged in managing post-transplantation metabolic complications. The present review discusses the recent clinical evidence regarding the importance of MS and its components after liver and kidney transplantation, as well as the link between MS and NAFLD after liver and kidney transplantation.

Liver steatosis replaced with non-invasive viral and host parametars can serve as negative predictive model in patients with chronic hepatitis-C.

Almost 70% of chronic hepatitis C (CHC) patients will have concomitant hepatic steatosis (HS) usually determined with invasive method. HS serve as negative predictive factor for lower sustained viral response (SVR) in CHC patients treated with standard of care (SOC) (PEG-IFN and Rib). Retrospective analysis of biochemical, virological and histological data in CHC patients treated with PEG-IFN and Ribavarin. Statistical analysis was carried out by Biometriha Healthcare Research. Level of significance was set to 95% (p < 0.05). 72 patients (43 M; 29 F; median age 41 y) with CHC (60 G1; 12 G3) with no concomitant metabolic syndrome were analyzed. HS ranged from 5 to 30% (median 15%). Overall accuracy of prediction of SVR based on the levels of HS was AUC=0.71 (95% CI=0.58-0.84; p=0.005). When HS was split regarding cut-off value of 5% significant difference was found between responders and non-responders to treatment (chi2 = 10.025; df = 1; p = 0.002). Overall sensitivity was 48% and specificity 91%. Conventional predictive variables (gender, age, fibrosis and genotype) where combined with HS (>5%) and all together achieved Nagelherke R squared of 34.0% in prediction of SVR, with accuracy rate of 75.0%. Further, invasive variables (fibrosis and HS) where replaced with vire mia and body mass index (BMI). All noninvasive variables together achieved Nagelkerke R squared of 26.5% in prediction of SVR with 74% accuracy rate of the logistic regression model. Very low HS (<5%) is negative predictor of SVR and can be replaced with noninvasive variables (gender, age, viremia and BMI) with same accuracy rate of the logistic regres- sion model.

[Chronic hepatitis B treatment]. / Lijecenje kronicnog hepatitisa B.

Clinical practice guidelines for the management of chronic hepatitis B infection continue to evolve from year to year but the goal remains the same, i.e. long-term continued suppression of viral replication to prevent disease progression and development of cirrhosis and hepatocellular carcinoma. Out of seven drugs approved for the treatment of chronic hepatitis B, current guidelines recommend entecavir and tenofovir from the nucleos(t)ide analogues and pegylated interferon alfa-2a for the selected group of patients as first-line monotherapies. Both groups showed good results in a number of clinical trials and are used according to the consensus criteria. The treatment of special populations with chronic HBV infection, i.e. those with HCV/HDV/HIV co-infections, immunocompromised patients, patients who have undergone transplantation, patients with solid tumor and cirrhosis, patients with chronic renal failure on dialysis, pregnant women and children, is more often required and more demanding than for usual chronic hepatitis B.

[Treatment of non-1 genotype chronic hepatitis C patients]. / Lijecenje bolesnika s kronicnim hepatitisom C genotipa 2, 3, 4, 5 i 6.

Infection with non-1 genotype in Croatia is detected in 41.2% of patients with chronic hepatitis C. Since the last treatment guidelines for hepatitis C patients, little has been changed. With today's standard of care, sustained viral response can be achieved in 43% to 85% of non-1 CHC patients, which is not satisfactory at all. The lowest cure rate is usually found among patients with genotype 3 and 4 infection. The grouping of genotype 2 and genotype 3 patients to "easy to treat" genotypes was an unfortunate consequence of their underrepresentation in previous large registration clinical trials. Careful re-examination of the data obtained shows clearly enough that patients with genotype 3 infection respond less to treatment than genotype 2 patients. They sometimes behave more like patients with genotype 1 infection. Small progress is found in treatment approach and viral kinetics might be a useful tool for tailoring therapy to improve efficacy. Rapid virologic response is the best parameter to predict success of therapy. For patients who achieve a rapid viral response, consideration of shortened therapy (< 24 weeks) may be reasonable although sustained viral response is still slightly higher with 24 weeks of therapy. Nevertheless, the presence of poor prognostic factors (high viral load, advanced fibrosis, obesity, increased age, insulin resistance and liver non-viral steatosis) may discourage a shortened course of therapy. Extending therapy (> 24 weeks) in patients who do not achieve a rapid viral response would be beneficial, particularly in patients with genotype 3 infection and poor prognostic factors, but formal recommendation should be confirmed in prospective trails. New data suggest a prognostic role for IL28B polymorphisms mostly in genotype 3 patients not achieving a rapid viral response and these could also be considered for improved tailoring of therapy. In conclusion, new treatments are urgently needed for non-1 genotype chronic hepatitis C patients. So far, telaprevir and boceprevir have failed to show a satisfactory activity in these genotypes. Evaluation of many promising molecules such as second generation of protease inhibitors or NS5B nucleos(t)ide inhibitors, NS5A inhibitors, cyclophilin inhibitors or their combinations with or without pegylated interferon or ribavirin is still in progress.

[Assessment of liver disease severity in patients with chronic viral hepatitis]. / Procjena tezine ostecenja jetre u bolesnika s kronicnim virusnim hepatitisom.

The best indicator of the severity of liver damage and prognosis in chronic viral hepatitis is extension of liver fibrosis. Extension of liver fibrosis can be assessed by liver biopsy and non-invasive physical or biological methods. Biopsy is used to define ethiology, severity (stage of fibrosis) and prognosis of liver disease. These informations are also usefull when estimating the risk-benefit and deciding on the modalities of antiviral therapy. Serological tests and elastography may distinguish significant fibrosis (F > or = 2) from baseline fibrosis (AUROC 0.77-0.83 for serology and 0.84 for elastography) and cirrhosis from noncirrhotic stages (AUROC 0.77-0.86 for serology and 0.9-0.94 for elastography). Individual method of choice with best performance to distinguish cirrhosis from noncirrhotic stages of liver is elastography. Combination of serological tests and transient elastography has 93-95% accuracy to predict liver cirrhosis, and in case of concordant values of both tests biopsy could be avoided in 77-80% of patients. In case of discordant values or those in favour of intermediate stages of fibrosis liver biopsy should be performed because in these situations non-invasive tests are less reliable. According to several studies liver stiffness as assessed by transient elastography has high predictive value for the development of decompensated cirrhosis and portal hypertensive complications and may also discriminate the patients with respect to the predicted 5-year survival.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

Dissemination of Clinical Acinetobacter baumannii Isolate to Hospital Environment during the COVID-19 Pandemic.

The aim of this study was to find the source of Acinetobacter baumannii in the intensive care unit (ICU) after an outbreak during the coronavirus disease 2019 (COVID-19) pandemic, as there was no A. baumannii detected on usually screened susceptible surfaces. The screening of the ICU environment was done in April 2021 when eleven different samples were taken. One A. baumannii isolate was recovered from the air conditioner and was compared with four clinical A. baumannii isolates obtained from patients hospitalized in January 2021. Isolates were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), minimum inhibitory concentrations (MICs) were determined, and the multilocus sequence typing (MLST) was performed. The molecular identification of A. baumannii isolates as ST208, the presence of the same blaOXA-23 carbapenemase gene, and the same antibiotic susceptibility profile suggest that the isolate recovered from the air conditioner is the same as the isolates recovered from hospitalized patients. The environmental isolate was recovered three months later than the clinical isolates, emphasizing the ability of A. baumannii to survive on dry abiotic surfaces. The air conditioner in the clinical environment is an important but undoubtedly neglected source of A. baumannii outbreaks, hence, frequent disinfection of hospital air conditioners with appropriate disinfectants is mandatory to mitigate the circulation of A. baumannii between patients and the hospital environment.

Pegylated interferon for treatment of chronic hepatitis C in hemodialysis patients in Croatia.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is a frequent complication among long-term dialysis patients. The aim of the present study was to evaluate the efficacy and side effects of pegylated interferon-α(2a) (PEG-IFN-α(2a)) treatment in hemodialysis patients. METHODS: We retrospectively reviewed charts of 16 HCV-RNA-positive hemodialysis patients. RESULTS: There were 11 male and 5 female patients treated with dialysis for 6-28 years. Twelve patients had HCV genotype 1b, 2 patients had 3a, and 1 patient had genotype 2a. Although only 10 out of 16 patients completed 48 weeks of treatment, early virological response and end-of-treatment virological response were achieved in 9 and 13 patients, respectively. Sustained virological response was recorded in 9 patients. The most common side effect was anemia. A flu-like syndrome was documented in 6, myalgia in 4, and arthralgia in 5 patients. Rectorrhagia, endocarditis and severe cough were recorded in 1 patient each. Nine patients received a renal transplant, and all 6 responders remained HCV-RNA-negative. CONCLUSIONS: PEG-IFN-α(2a) has limited efficacy in dialysis patients. A significant proportion of patients discontinued treatment because of side effects. Additional studies with long-term follow-up are needed to determine the optimal treatment of HCV infection in the dialysis population.

[Chronic liver diseases in patients with chronic kidney disease]. / Kronicne bolesti jetre u bolesnika s kronicnom bolesti bubrega.

The morphological and functional integrity of the liver is vital to human health in general as well as to patients with renal disease. Any chronic liver disease will eventually lead to liver insufficiency. Liver enzymes are routinely measured to assess liver function in patients with or without renal failure. The use of standard reference values of aminotransferases to help detect liver disease is less useful in patients on chronic dialysis therapy. Some investigators have suggested that, to increase the sensitivity of liver function tests among dialysis patients, lower "normal" values of aminotransferases should be adopted. Liver biopsy may be helpful for assessing the activity and severity of liver disease, especially in chronic viral liver diseases. The most widely used scores are Ishak (6-point scale) and METAVIR (4-point scale). The most important chronic liver diseases associated with chronic renal disease are hepatitis B and C. Several types of renal disease have been recognized: mixed cryoglobulinemia, membranoproliferative glomerulonephritis, membranous nephropathy and polyarteritis nodosa. In any patient first ever diagnosed with any of the mentioned features, serologic and molecular tests for hepatitis B and/or C should be done. There is limited information on the treatment of HBV-associated renal diseases. Nonrandomized studies suggest that antiviral therapy may be beneficial in patients with glomerular disease or vasculitis due to HBV. According to Croatian National Guidelines for Hepatitis B and C, treatment with antiviral drug is recommended for patients with chronic renal disease, especially those on the waiting list for kidney transplantation. Decision on the type and duration of treatment is based on the level of viremia and biochemical and histological activity of liver disease. Several antiviral drugs are currently used for hepatitis B: pegylated interferon alpha-2a and nucleot(z)id analogues. The choice of analogues is based on their genetic barrier and resistance. The probability to develop resistance is much higher in prolonged treatment, more than 1 year. To avoid it, regular check-ups are mandatory. First check-up is recommended after 12 weeks of treatment to detect the possible primary resistance to treatment. Similar approach is used in patients with hepatitis C. Today's standard of care is treatment with a combination of pegylated interferon alpha and ribavirin. Serum concentration of both drugs rises in patients with impaired renal function. The dosage should be corrected according to the glomerular filtration rate. Treatment with pegylated interferon alpha is not recommended in patients with glomerular filtration rate less than 15 mL/min and ribavirin less than 50 mL/min. Recent evidence suggest that nonalcoholic fatty liver disease is associated with an increased prevalence and incidence of chronic renal disease. Current treatment recommendations for nonalcoholic fatty liver disease are limited to weight reduction and treatment of any component of the metabolic syndrome. Liver cirrhosis is the terminal stage of any chronic liver disease. Mortality differs according to the stage of cirrhosis evaluated with Child-Turcotte-Pugh score. The worst prognosis have patients with grade C cirrhosis, which should be borne in mind when evaluating patients with terminal renal disease for treatment with kidney transplantation.

[Consensus guidelines for diagnosis, treatment and follow-up of patients with gastrointestinal stromal tumors]. / Prijedlog postupnika za dijagnostiku, lijecenje i pracénje oboljelih od gastrointestinalnih stromalnih tumora.

Gastrointestinal stromal tumors are the most common mesenchymal tumors in gastrointestinal tract. They are often asymptomatic and discovered incidentally during endoscopic or barium studies. About 80% GISTs have a KIT (CD 117 antigen) gene mutation. Most affect exon 11, less commonly exon 9,13 or 17, that results in uncontrolled KIT signaling. This led to effective systemic therapies in the form of small molecule inhibitors of the receptor tyrosine kinase such as imatinib mesylat. With the purpose of providing standardized approach to rational and effective diagnostic and treatment algorithm in Croatia, a multidisciplinary session was organized. Results of the session are given in the form of Consensus guidelines.

Seroepidemiology of hepatitis E in patients on haemodialysis in Croatia.

PURPOSE: Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to determine the HEV seroprevalence and risk factors among HD patients in Croatia. METHODS: A total of 394 HD patients from six medical facilities in five Croatian cities (three sites in the continental and three sites in the coastal region) were tested for HEV IgM/IgG antibodies using an enzyme-linked immunosorbent assay. Additionally, all samples were tested for HEV RNA by RT-PCR. Sociodemographic data and risk factors were collected using a questionnaire. RESULTS: HEV IgG antibodies were detected in 110 (27.9%) patients. The seroprevalence varied significantly between dialysis centres, ranging from 5.2 to 43.4% (p = 0.001). HEV IgM antibodies were found in 0.04% of IgG positive patients. All patients tested negative for HEV RNA. Factors associated with HEV IgG seropositivity were age > 60 years (OR 8.17; 95% CI 1.08-62.14), living in the continental parts of the country (OR 2.58; 95% CI 1.55-4.30), and transfusion of blood products (OR 1.66; 95% CI 1.01-2.73). After adjusting for age and gender, patients from continental regions had higher odds of HEV seropositivity compared to patients from coastal regions (OR 2.88; 95% CI 1.71-4.85) and those who had RBC transfusions (OR 1.70, 95% CI 1.02-2.69) compared to those who did not. CONCLUSION: The study showed a high HEV seropositivity among HD patients in Croatia, with significant variations between geographical regions. Continental area of residence and RBC transfusion were the most significant risk factors for HEV seropositivity. Due to the high seroprevalence, routine HEV screening among HD patients, especially in transplant candidates should be considered.

Comparative analysis of hepatocellular carcinoma in men and dogs.

Concerning the important differences in the ethiopathology of hepatocelular carcinomas (HCC) in humans and dogs, our work describes the expression of epidermal growth factor receptor (EGFr), cytokeratine 19 (CK19), vascular endothelial growth factor (VEGF) and transforming growth factor beta receptor (TGFbeta-r) in tumors arising in both species. Investigation included 25 cases of human and 8 cases of dog tumors. All human cases were noted in cirrhotic livers, while in dogs the tissue adjacent to tumor was not changed. In humans in two cases hepatitis B virus (HBV) and in one case hepatitis C virus (HCV) were determined. Investigation showed lack of TGFbeta-r reaction in six cases of canine HCC, while in humans only one case was negative. In most tumors specific hepatocyte antigen Hepatocyte Paraffin 1 marker (Hep Par 1) was mainly positive with markedly decreased reaction compared to the normal hepatocytes, while cytokeratine 19 for billiary epithelium was negative. The result of our investigation rise the question about the possible role of tumor suppressor gene TGFbeta-r in the development of HCC in dogs and in the same time emphasizes its importance in human diseases.

[Assessment of hepatic injury in patients with chronic viral hepatitis]. / Procjena ostecenja jetrenog parenhima u bolesnika s kronicnim virusnim hepatitisom.

The management and prognosis of chronic viral hepatitis greatly depend on the extent and progression of liver fibrosis. Although liver biopsy is still considered as the gold standard to evaluate hepatic fibrosis, it is an invasive procedure with rare but potentially severe complications. It is also prone to sampling errors. These limitations have stimulated the search for new noninvasive approaches. A number of noninvasive techniques such as indirect or direct markers and measurement of liver stiffness using transient elastography have been proposed for the assessment of hepatic fibrosis. The performance of simple tests derived from routine laboratory parameters appears to be similar to that of more complex and expensive fibrosis panels. Transient elastography seems to be more accurate than blood tests for diagnosing cirrhosis. The goal of disease specific, accurate and sensitive markers of fibrosis is worth the effort. The true success in such an attempt can be characterized as hopeful; however, these noninvasive methods can be anticipated to become an important tool in clinical practice.

[Retreatment options for patients with chronic hepatitis C]. / Mogucnosti reterapije bolesnika s kronicnim hepatitisom C.

Despite impressive therapy improvements, there still are a huge proportion of patients that will fail to achieve undetectable HCV. On the other hand, not all patients that demonstrate some response to treatment attain a sustained viral response. Patients with HCV non-response can be classified into several groups: 1) non-response (where the patient does not achieve undetectable HCV RNA at any time); 2) partial response (when the patient experiences some drop in HCV viremia but never below the detectable limit); 3) viral breakthrough (those associated with an initial virologic response, which is subsequently lost during treatment); and 4) relapse (those with an initial virologic response, which is lost upon treatment discontinuation). Most studies suggest that the major reason for breakthrough is missing the peginterferon alfa and/or ribavirin doses for various causes (significant adverse events, poor compliance, etc.). The main reasons for relapse include treatment initiation with insufficient ribavirin dosage or failure to continue treatment long enough, especially in patients with a slow virologic response. Patients with a well-defined non-response are poor candidates for retreatment. Such patients have no significant decline in HCV RNA during treatment and are essentially refractory to the effects of interferon. Patients with partial virologic response are excellent candidates for retreatment and can achieve undetectable HCV RNA if switched to a more intensive interferon regimen. Many other patients can be retreated successfully. The likelihood of achieving SVR (Sustained Virologic Response) with peginterferon alfa plus ribavirin retreatment depends on several factors, e.g., the agents used in previous treatment courses, total dose and duration of treatment, HCV genotype, level of viremia and previous drop in viremia. Patients previously treated with standard interferon alpha monotherapy are good candidates for retreatment, regardless of baseline liver histology. In this group, those that were previous responder-relapsers are most likely to respond to a course of peginterferon/ribavirin combination therapy, whereas previous non-responders can also achieve significant rates of SVR, particularly those infected with genotype 2 or 3 HCV There are several options for peginterferon alpha/ribavirin non-responders: 1) retreatment with the same protocol if adherence was a major problem; 2) administration of a longer treatment course (72 weeks) in slow responders; 3) retreatment with another interferon-based product (different peginterferon alpha, consensus interferon); 4) maintenance therapy; 5) clinical trials; and 6) wait and watch approach (respectable in many non-responders, particularly if fibrosis is not advanced and/or the patient experienced difficulties in tolerating therapy). Ongoing retreatment trials using specific antiviral drugs (valopicitabine, boceprevir, telaprevir) are of great interest, particularly in triple combination regimens.

[Chronic hepatitis B therapy]. / Terapija kronicnog hepatitisa B.

Chronic hepatitis B is associated with the development of cirrhosis in more than one third of patients and in a large proportion of patients with hepatocellular carcinoma. Current standard treatment includes pegylated interferon alfa-2a and five oral nucleoside/nucleotide analogues: entecavir, tenofovir, adefovir, telbivudine and lamivudine (listed according to antiviral efficacy). The advantage of interferon treatment is the possibility of long-term remission in one third of carefully selected HbeAg+ patients without development of resistance. However, interferon treatment is not efficient in the majority of patients. The advantage of treatment with nucleoside and nucleotide analogues is the possibility to suppress HBV DNA to undetectable levels in 70%-90% of patients. However, analogue treatment is a long-term treatment (possibly life-long) and is associated with the development of resistance.

[Viral hepatitis. Croatian consensus conference--2009]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2009.

Summarized text of Croatian Consensus Conference on Viral Hepatitis of 2009 comprises the following chapters: 1) Epidemiology, 2) Clinical Picture, 3) Diagnostic Procedure, 4) Aims of Treatment of Viral Hepatitis, 5) Terminology, 6) Medicaments (6.1. Interferon, 6.2. Analogues of Nucleozides and Nucleotides), 7) Hepatitis B (7.1. Serologic and Molecular HBV Diagnostics, 7.2. Terminology, 7.3.Whom to Treat? 7.4. Therapy), 8) Hepatitis C (8.1. Serologic and Molecular HCV Diagnostics, 8.2. Terminology, 8.3. Whom to Treat? 8.4. Therapy). Clinical, laboratory and histologic assessment of patients with chronic viral hepatitis (algorythm of pretherapeutic treatment; histologic evaluation) and notions related to therapy of viral hepatitis (category of the patient and category of the response to treatment) are presented in related tables.

Colonic duplication in an adult who presented with chronic constipation attributed to hypothyroidism.

Gastrointestinal duplications are an uncommon congenital abnormality that manifest before the age of two in 80% of cases. Ileal duplication is the most common while colonic duplication, either cystic or tubular, occurs in 10%-15% of cases and remains asymptomatic and undiagnosed in most cases. Mostly occurring in pediatric patients, colonic duplication is encountered in adults in only a few cases. The most common clinical manifestations are abdominal pain and intestinal obstruction. Rarely, duplications present with signs of acute abdomen or acute bleeding. This study reports a case of colonic duplication in an adult who presented with chronic constipation. Complete diagnostic workup was made on several occasions during the previous eight year period, but no pathology was found and chronic constipation was attributed to hypothyroidism caused by long standing Hashimoto thyroiditis. Multislice CT, performed because of abdominal distension, defined colonic pathology but the definite diagnosis of duplication of the transversal colon was made at operation. The cystic duplication and the adjacent part of the ascending and transversal colon were excised en-block. This study implies that colonic duplication, though uncommon, should be included in the differential diagnosis of chronic constipation even when precipitating factors for constipation, such as hypothyroidism are present.