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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 bla OXA-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.

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.

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.

Aims: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, characterized by its accumulation in tissues which results in hepatic, neurological, and/or psychiatric symptoms. The aim of this study was to investigate the genetics of WD in Croatian patients., Methods: Correlation of the clinical presentation subtype and the age at onset of the diagnosis of WD with the ATP7B genotype was investigated in a group of Croatian WD patients. DNA from peripheral blood samples was tested for the p.His1069Gln by direct mutational analysis and other polymorphisms were identified by sequence analysis of coding and flanking intronic regions of ATP7B gene., Results: In the group of 75 WD patients of Croatian origin, 18 different mutations in ATP7B gene were detected, three of which were novel. The p.His1069Gln mutation was most frequent, being detected in 44 Croatian WD patients (58.7%). Most ATP7B mutations (90.4%) were located in exons 5, 8, 13, 14, and 15., Conclusions: Clinical diagnosis of WD was confirmed in 59 patients by detecting mutations on both ATP7B alleles. The age at onset of WD and the type of WD clinical presentation showed no significant correlation with the ATP7B genotype.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.

We report the case of a 45-year old man with non-healing ulcers located on his chest, lumbal, sacral, retroauricular areas and forehead. Both clinical and histopathological examinations suggested pyoderma gangrenosum (PG). For six months the diagnosis of ulcerative colitis was established. PG in our patient was presented as a rapidly enlarging, painful ulcer with purple, undermined edges and a necrotic, haemorrhagic base. Initially, he was treated with a high dosage of peroral glucocorticosteroid, sulfasalazine, and systemic antibiotics, together with daily wound care. Ulceration partially regressed. Total colonoscopy showed pancolitis. When the dose of glucocorticosteroids was tapered down to 35 mg, new ulcerations on his right thigh and abdomen were formed. He also developed E. coli sepsis and flare up of bowel disease. Azathioprine, together with two pulse doses of glucocorticosteroids and antibiotics, were administered. He was scheduled for a total colectomy. The management of PG continues to be a therapeutic challenge.

There has been a dramatic improvement in diagnostic procedures and therapy of viral hepatitis in the last 20 years. Improvements in therapy caused an increase in actual cost, however, with significant long-term savings through a decreased cost of treatment of advanced liver disease including liver transplantation. The Croatian National Board for Viral Hepatitis has decided to initiate the organization of consensus conference on viral hepatitis enabling the leading experts in the country to give the best possible recommendations for the diagnosis, prophylaxis and therapy in our circumstances. The Consensus Conference took place in Zagreb in June 2004, with update in March 2005, organized by the Croatian National Board for Viral Hepatitis, Reference Centers of the Ministry of Health for Chronic Liver Diseases, Infectious Diseases and AIDS, Croatian Society of Gastroenterology--Hepatology Section, Croatian Society for Nephrology, Dialysis and Transplantation, and Croatian Institute for Health Insurance. Invited experts provided written reports on the respective subjects that appear in this issue and their recommendations resulting in this consensus statement.

Viral factors are important in the pathogenesis of liver disease either directly, through cell injury associated with the accumulation of intact virus or viral proteins, or indirectly, through the host immune response. The immune response of the host is more important than viral factors in the pathogenesis of liver injury caused by HBV. There is little genomic variability in HBV, but mutant forms of HBV with mutations in the precore, surface and X genes, as well as the core promoter region have been implicated in a number of clinical syndromes. The mechanisms of viral persistence and hepatocellular injury in patients with hepatitis C infection are poorly understood. Viral infection can produce cellular injury by direct cytotoxicity and by indirect immune-mediated injury. The range of histologic findings in patients with hepatitis B and C is broad, from minimal inflammatory changes to fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma. The goal of histologic analysis is quantitative and qualitative assessment of necroinflammatory lesions and fibrosis, changes of liver structure and follow-up of histologic changes due to the natural course of the disease or antiviral therapy. Subjective impression in the assessment of histologic changes is not satisfactory and numerical indices should be used. Presently, Knodell's index is being replaced by METAVIR system and Ishak system. Clinical assessment of patients with viral hepatitis must include detailed physical examination, description of the clinical course and extrahepatic manifestations, definition of viral factors, histologic assessment of inflammatory activity and degree of fibrosis, and a number of relevant laboratory parameters.

Gauderer and Ponsky first described percutaneous endoscopic gastrostomy (PEG) in 1979. It was introduced as a routine method in the Division of Gastroenterology, University Hospital Rebro, Zagreb, in 1995. Over the years the number of PEG insertions has increased significantly. We reviewed the available literature and compared the results with our experience according to indications, complications and efficacy of the procedure. We inserted PEG in 86 patients from January 1, 1997 until January 31, 2002. There were 40 females and 46 males. The most frequent indication for PEG insertion was a neurological condition (60/86). There were no deaths directly related to the procedure. One patient had a leakage of PEG feeding into the peritoneal cavity that caused severe peritonitis and required urgent laparatomy within 24 hours of the PEG insertion. Two patients had local infection and the tube had to be removed. The antibiotic prophylaxis has been given to 65 patients. Our experience confirms that PEG is a relatively safe and well tolerated procedure.

The primary sclerotic colangitis is the chronic disease of the liver which in its finish very often requires the liver transplantation. The disease gets diagnosed mainly in males of middle age and is often joined with the inflammation disease of the intestines. The course of the disease not rarely is complicated by the stenosis of the liver ducts or by the occurrence of the concrements. In the presented case it is the word about the young patient in which the is the diagnosis made with the atypical way primarily from the reason that the biopsy of the liver is performed too early and the patohystologic changes were non specific. Immediately after the graft is being developed the biliary peritonitis because of the injury of the gallbladder so is done the cholecystectomy. Only in the later course is performed the endoscopic retrograde colangiography, during which are getting the typical changes of the biliary trunk for the primary sclerotic colangitis. The underlying disease in the demonstrated patient is complicated by the recidivens occurrence of the concrements of the choledokus and stenoses of the bladder ducts primarily for the left slice what, up to new, always successfully was treated by the extraction of the concrements and the dilatation of the liver ducts by endoscopic way.

A massive gelatinous ascites occurred in a 60-year-old patient, with no primary tumor found in the clinical work-up. The malignant cells were not found in the cytological examination of ascites. Explorative laparotomy revealed a gelatinous mass of 14 kg, a cystic tumor of the omentum and an identical cystic tumor of the spleen's lower pole. It was a well differentiated mucinous cystadenocarcinoma, most likely originating in the appendix. Most interesting is the involvement of the spleen with mucinous epithelial cysts, described as a rare finding associated with pseudomyxoma.

The relationship between the complexity of the hypervariable region 1 (HVR1) quasispecies of hepatitis C virus (HCV) and responsiveness to interferon-alpha (IFN) therapy was studied in patients with chronic hepatitis C. Twelve HCV-RNA-positive patients were treated daily with high dose IFN and ribavirin for 4 weeks, and then with IFN 3 MIU (Million International Units) TIW (three times per week) and ribavirin for 6 months. The HVR1 quasispecies complexity was analyzed by nested polymerase chain reaction-mediated single-strand conformation polymorphism (SSCP). The baseline HCV-RNA levels in the study group ranged from 10(6) to 10(7) copies/ml. All patients exhibited HCV genotype 1 b. Initial SSCP analysis revealed four (33.3%) patients with a low complexity pattern (SSCP bands < or =4) and eight (66.6%) patients with high complexity pattern (SSCP bands >4). After 4 weeks of IFN therapy, one patient became HCV negative, and among those remaining positive, the HCV-RNA levels decreased by 2 to 3 logs and the number of SSCP decreased by 2 to 3 bands per sample. After 6 months of IFN therapy, five (41.7%) patients became HCV-RNA-negative. Seven (58.3%) patients did not respond to IFN therapy with sustained viral load from 10(3) to 10(5) copies/ml, and high complexity SSCP patterns. Our data support the HVR quasispecies complexity to be an independent predictive factor for IFN responsiveness in patients infected with HCV.