Establishment of standards for the referral of large nonpedunculated colorectal polyps: an international expert consensus using a modified Delphi process.

BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large nonpedunculated colorectal polyps are often referred to expert centers for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of this study was to establish minimum expected standards for the referral of large non-pedunculated colonic polyps for potential endoscopic resection. METHODS: A Delphi method was used to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and 3 rounds of surveys were conducted to achieve consensus. Quantitative and qualitative data were analyzed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographic characteristics, relevant medications, lesion factors, photodocumentation, and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements, which were scored on a scale of 1 to 10, ranged from 7.04 to 9.29, with high percentages of experts considering most statements as a very high priority. Subgroup analysis according to continent revealed some variations in consensus rates among experts from different regions. CONCLUSIONS: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

Gut peptide changes in patients with obstructive jaundice undergoing biliary drainage: A prospective case control study.

BACKGROUND: Biliary obstruction is a relatively common condition that affects approximately 5 in 1000 people annually. Malnutrition is very common in patients with biliary obstruction and since it is associated with significant morbidity and mortality, it is important to identify factors and mechanisms involved in its development. AIM: To determine the influence of obstructive jaundice on the hormones controlling appetite and nutritive status. METHODS: This was a prospective case control study performed in a tertiary center in Zagreb, Croatia. Patients with biliary obstruction undergoing internal biliary drainage from September 2012 until August 2013 were enrolled. After excluding patients who developed procedure related complications or were lost in the follow-up, out of initial 73 patients, 55 patients were included in the analysis, including 34 with benign and 21 with malignant disease. Meanwhile, 40 non-jaundiced controls were also included. Appetite, nutritional status, and serum ghrelin, cholecystokinin (CCK), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) were determined at admission, 48 h and 28 d after internal biliary drainage. Chi square test was used for categorical variables. Continuous variables were analysed for normality by Kolmogorov-Smirnov test and relevant non-parametric (Mann-Whitney, Kruskal-Wallis, and Friedman) or parametric (t-test and analysis of variance) tests were used. RESULTS: Patients with obstructive jaundice were significantly malnourished compared to controls, regardless of disease etiology. Plasma ghrelin and CCK levels were significantly higher in patients with obstructive jaundice. Serum bilirubin concentrations were negatively correlated with ghrelin levels and positively correlated with TNF-α, but had no correlation with CCK concentrations. After internal biliary drainage, a significant improvement of nutritional status was observed although serum concentrations of ghrelin, IL-6, and TNF-α remained significantly elevated even 28 d after the procedure. CCK levels in patients without malnutrition remained elevated 28 d after the procedure, but in patients with malnutrition, CCK levels decreased to levels comparable with those in the control group. We have not established any correlation between appetite and serum levels of ghrelin, CCK, IL-6, and TNF-α before and after biliary drainage. CONCLUSION: Possible abnormalities in ghrelin and CCK regulation may be associated with the development of malnutrition during the inflammatory response in patients with biliary obstruction.

Role of Endoscopic Ultrasound in Liver Disease: Where Do We Stand?

As the burden of liver disease in the general populace steadily increases, so does the need for both advanced diagnostic and treatment options. Endoscopic ultrasound is a reliable diagnostic and therapeutic method that has an established role, foremost in pancreatobiliary pathology. This paper aims to summarize the growing role of endoscopic ultrasound in hepatology based on the search of the current literature. A number of applications of endoscopic ultrasound are reviewed, including both noninvasive methods and tissue acquisition in focal and diffuse liver disease, portal hypertension measurement, detection and management of gastric and esophageal varices, treatment of focal liver lesions and staging of pancreatobiliary malignancies, treatment of cystic and solid liver lesions, as well as liver abscess drainage. Both hepatologists and endoscopists should be aware of the evolving role of endoscopic ultrasound in liver disease. The inherent invasive nature of endoscopic examination limits its use to a targeted population identified using noninvasive methods. Endoscopic ultrasound is one the most versatile methods in gastroenterology, allowing immediate access with detection, sampling, and treatment of digestive tract pathology. Further expansion of its use in hepatology is immanent.

Liver disease in the era of COVID-19: Is the worst yet to come?

The global social, economic and political crises related to coronavirus disease 2019 (COVID-19) presumably had more indirect than direct negative impacts on health systems. Drastic lifestyle changes, social isolation and distancing, and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages, drugs and unhealthy diets. The inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease, viral hepatitis, acute alcoholic hepatitis, liver cirrhosis decompensation and ultimately liver-related mortality. The inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease (CLD) and has prevented prompt hepatocellular carcinoma detection and treatment. A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver transplantation. The indirect, unavoidable effects of the COVID-19 pandemic in the following years have yet to be determined. Substantial efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be initiated. Several questions regarding the impact of the COVID-19 pandemic on liver disease remain. The most important question for general CLD patients is: How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients? This article reviews the influence of COVID-19 on patients with liver disease during the pandemic, with particular emphasis on the disease course associated with pandemic resolution.

Expression of NEDD9 and connexin-43 in neoplastic and stromal cells of gastric adenocarcinoma.

Gastric cancer is related to high mortality rates and advanced disease stage at the time of diagnosis. Its carcinogenesis is extensively studied and is associated with genetic and epigenetic changes, changed the interaction between tumor and adjacent stromal cells, and changes in the microenvironment molecule status. Neural precursor cell-expressed developmentally down-regulated 9 (NEDD9) affects different signaling proteins and pathways, apoptosis, adhesion, cell migration, and invasiveness. Connexin-43 (Cx43) also assists in intercellular communications and has several channel-independent functions. Aberrant expression of those two gap junction proteins plays an essential role in metastatic processes. Our scope was to detect the expression of Cx43 and NEDD9 in epithelial and stromal gastric cancer compartments and its relation to tumor progression and lymph node metastases. Cancer tissue from 53 cases of node-negative and 55 cases of node-positive primary gastric carcinoma patients was analyzed for Cx43 and NEDD9 expression by immunohistochemical assay, and the results were correlated with the remaining clinical and pathological findings and survival. In our cohort of patients with lymph node metastases, we detected higher expression of epithelial Cx43 in the primary tumor and stromal Cx43 expression correlated with both epithelial NEDD9 (rho = 0.453) and stromal NEDD9 (rho = 0.484). Higher epithelial Cx43 and NEDD9 expression were associated with higher mortality (HR 1.54, 95% CI 1.01-2.37, p = 0.048). Epithelial Cx43 expression, both epithelial and stromal NEDD9 expression, T and N status were all independently associated with shorter survival. In summary, our findings suggest that increased expression of both epithelial and stromal NEDD9 and epithelial Cx43 could potentially be used as prognostic gastric cancer biomarkers.

The Role of the Acute Octreotide Suppression Test in Detecting Patients with Neuroendocrine Neoplasms.

BACKGROUND: Serum chromogranin A (CgA) is routinely used as a biomarker in patients with neuroendocrine neoplasms (NENs). Several conditions and comorbidities may be associated with falsely elevated CgA, often leading to extensive diagnostic evaluation, which may be costly and harmful. The aim of this study was to analyze the effectiveness of the acute octreotide suppression test (AOST) in differentiating falsely elevated serum CgA. METHODS: Our prospective study enrolled 45 patients from two different patient cohorts: (1) 29 patients with suspicion or presence of NENs (extensive workup and subsequent biopsy confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency Department without NENs (non-NENs). AOST was performed after an overnight fast. Baseline CgA was measured, after which 0.25 mg of octreotide was administered subcutaneously. CgA was measured 3 and 6 h after administration. RESULTS: Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST, CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6) in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting patients with NENs. The diagnostic accuracy of the AOST in the entire study population was 86.7%. CONCLUSIONS: AOST is a promising tool to increase the diagnostic accuracy of serum CgA.

Scoring systems for peptic ulcer bleeding: Which one to use?

AIM: To compare the Glasgow-Blatchford score (GBS), Rockall score (RS) and Baylor bleeding score (BBS) in predicting clinical outcomes and need for interventions in patients with bleeding peptic ulcers. METHODS: Between January 2008 and December 2013, 1012 consecutive patients admitted with peptic ulcer bleeding (PUB) were prospectively followed. The pre-endoscopic RS, BBS and GBS, as well as the post-endoscopic diagnostic scores (RS and BBS) were calculated for all patients according to their urgent upper endoscopy findings. Area under the receiver-operating characteristics (AUROC) curves were calculated for the prediction of lethal outcome, rebleeding, needs for blood transfusion and/or surgical intervention, and the optimal cutoff values were evaluated. RESULTS: PUB accounted for 41.9% of all upper gastrointestinal tract bleeding, 5.2% patients died and 5.4% patients underwent surgery. By comparing the AUROC curves of the aforementioned pre-endoscopic scores, the RS best predicted lethal outcome (AUROC 0.82 vs 0.67 vs 0.63, respectively), but the GBS best predicted need for hospital-based intervention or 30-d mortality (AUROC 0.84 vs 0.57 vs 0.64), rebleeding (AUROC 0.75 vs 0.61 vs 0.53), need for blood transfusion (AUROC 0.83 vs 0.63 vs 0.58) and surgical intervention (0.82 vs 0.63 vs 0.52) The post-endoscopic RS was also better than the post-endoscopic BBS in predicting lethal outcome (AUROC 0.82 vs 0.69, respectively). CONCLUSION: The RS is the best predictor of mortality and the GBS is the best predictor of rebleeding, need for blood transfusion and/or surgical intervention in patients with PUB. There is no one 'perfect score' and we suggest that these two tests be used concomitantly.

Biliary leakage after urgent cholecystectomy: Optimization of endoscopic treatment.

AIM: To investigate the results of endoscopic treatment of postoperative biliary leakage occurring after urgent cholecystectomy with a long-term follow-up. METHODS: This is an observational database study conducted in a tertiary care center. All consecutive patients who underwent endoscopic retrograde cholangiography (ERC) for presumed postoperative biliary leakage after urgent cholecystectomy in the period between April 2008 and April 2013 were considered for this study. Patients with bile duct transection and biliary strictures were excluded. Biliary leakage was suspected in the case of bile appearance from either percutaneous drainage of abdominal collection or abdominal drain placed at the time of cholecystectomy. Procedural and main clinical characteristics of all consecutive patients with postoperative biliary leakage after urgent cholecystectomy, such as indication for cholecystectomy, etiology and type of leakage, ERC findings and post-ERC complications, were collected from our electronic database. All patients in whom the leakage was successfully treated endoscopically were followed-up after they were discharged from the hospital and the main clinical characteristics, laboratory data and common bile duct diameter were electronically recorded. RESULTS: During a five-year period, biliary leakage was recognized in 2.2% of patients who underwent urgent cholecystectomy. The median time from cholecystectomy to ERC was 6 d (interquartile range, 4-11 d). Endoscopic interventions to manage biliary leakage included biliary stent insertion with or without biliary sphincterotomy. In 23 (77%) patients after first endoscopic treatment bile flow through existing surgical drain ceased within 11 d following biliary therapeutic endoscopy (median, 4 d; interquartile range, 2-8 d). In those patients repeat ERC was not performed and the biliary stent was removed on gastroscopy. In seven (23%) patients repeat ERC was done within one to fourth week after their first ERC, depending on the extent of the biliary leakage. In two of those patients common bile duct stone was recognized and removed. Three of those seven patients had more complicated clinical course and they were referred to surgery and were excluded from long-term follow-up. The median interval from endoscopic placement of biliary stent to demonstration of resolution of bile leakage for ERC treated patients was 32 d (interquartile range, 28-43 d). Among the patients included in the follow-up (median 30.5 mo, range 7-59 mo), four patients (14.8%) died of severe underlying comorbid illnesses. CONCLUSION: Our results demonstrate the great efficiency of the endoscopic therapy in the treatment of the patients with biliary leakage after urgent cholecystectomy.

Mortality in high-risk patients with bleeding Mallory-Weiss syndrome is similar to that of peptic ulcer bleeding. Results of a prospective database study.

OBJECTIVE: The aim of this study was to identify the predictive factors influencing mortality in patients with bleeding Mallory-Weiss syndrome in comparison with peptic ulcer bleeding. MATERIAL AND METHODS: Between January 2005 and December 2009, 281 patients with endoscopically confirmed Mallory-Weiss syndrome and 1530 patients with peptic ulcer bleeding were consecutively evaluated. The 30-day mortality and clinical outcome were related to the patients' demographic data, endoscopic, and clinical characteristics. RESULTS: The one-year cumulative incidence for bleeding Mallory-Weiss syndrome was 7.3 cases/100,000 people and for peptic ulcer bleeding 40.4 cases/100,000 people. The age-standardized incidence for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding remained unchanged during the observational five-year period. The majority of patients with bleeding Mallory-Weiss syndrome were male patients with significant overall comorbidities (ASA class 3-4). Overall 30-day mortality rate was 5.3% for patients with bleeding Mallory-Weiss syndrome and 4.6% for patients with peptic ulcer bleeding (p = 0.578). In both patients with bleeding Mallory-Weiss syndrome and peptic ulcer bleeding, mortality was significantly higher in patients over 65 years of age and those with significant overall comorbidities (ASA class 3-4). CONCLUSION: The incidence of bleeding Mallory-Weiss syndrome and peptic ulcer bleeding has not changed over a five-year observational period. The overall 30-day mortality was almost equal for both bleeding Mallory-Weiss syndrome and peptic ulcer bleeding and was positively correlated to older age and underlying comorbid illnesses.

Endoscopic balloon dilatation of postsurgical intestinal strictures in Crohn's disease: case report and review of the literature.

Strictures are one of the most common complications of Crohn's disease. If symptomatic and resistant to medical anti-inflammatory therapy, and especially in cases of acute obstruction, surgical correction may be unavoidable. Although surgical treatment is dramatically effective in curing Crohn's disease strictures, a high rate of postsurgical restenosis has been recognized, ultimately requiring additional surgery. To avoid the risks and costs entailed by repeated surgical resection, endoscopic balloon dilatation (EBD) has been proposed as a conservative treatment option for intestinal strictures in Crohn's disease, in which the stricture is pneumatically dilated with through-the-scope balloons of different diameters. The main clinical indication for EBD is the appearance of obstructive symptoms associated with the stricture, especially if they are postoperative and shorter than 4 centimeters. Usually more than one dilatation session is required for every stricture. EBD is applied infrequently, possibly due to the perceived risk of perforation and early stricture recurrence, but studies have demonstrated that EBD has a high success rate, a low chance of complications, excellent symptomatic response, as well as good short-term and long-term outcomes, proving that it is a relatively simple and successful technique that provides long-term effective palliation of the symptoms with minimal risk in patients with simple strictures, and offers a reasonable alternative to surgery.

Nutritional screening model in tertiary medical unit in Croatia.

BACKGROUND/AIMS: Malnutrition of hospitalized patients is often undetected and untreated due to poor awareness and insufficient knowledge of the attending hospital staff. Nutritional screening has not been part of the daily routine in Croatian hospitals. Our aim was to implement nutritional screening as part of the routine medical examination and to assess the nutritional risk at admission for all hospitalized patients. METHODS: All patients hospitalized in departments of internal medicine in tertiary hospitals in Croatia were screened at entry using the Nutrition Risk Screening 2002 (NRS 2002). RESULTS: Between October and December 2010, 1,696 patients were screened and analyzed (948 males and 748 females). 329 (19.4%) had an NRS 2002 score ≥3 and were considered to be at nutritional risk. An NRS 2002 score ≥3 was identified as a significant predictor of the length of hospital stay (beta coefficient = 0.06, p = 0.027) and fatal outcome (OR = 6.18, p < 0.001). Only 32.8% of malnourished patients received some nutritional support. CONCLUSIONS: Every fifth patient hospitalized in a general medical department in Croatia is at nutritional risk and the majority of them does not receive nutritional support. More effort is needed to implement nutritional standards in daily clinical practice.

The influence of etiologic factors on clinical outcome in patients with peptic ulcer bleeding.

BACKGROUND: Peptic ulcer bleeding remains an important cause of morbidity and mortality. AIM: The aim of this study was to evaluate the prevalence of non-steroidal anti-inflammatory drugs (NSAID) use, Helicobacter pylori infection and non-H. pylori-non-NSAIDs causes of peptic ulcer bleeding and to identify the predictive factors influencing the rebleeding rate and in-hospital mortality in patients with bleeding peptic ulcer. METHODS: A total of 1,530 patients with endoscopically confirmed peptic ulcer bleeding were evaluated consecutively between January 2005 and December 2009. The 30-day mortality and clinical outcome were related to patient's demographic data, endoscopic and clinical characteristics. RESULTS: The age-standardized 1-year cumulative incidence for peptic ulcer bleeding was 40.4 cases/100,000 people. The proportion of patients over 65 years increased from 45.7 % in 2005 to 61.4 % in 2009 (p = 0.007). Overall 30-day mortality rate was 4.6 %, not significantly different for conservatively and surgically treated patients (4.9 vs. 4.1 %, p = 0.87). Mortality was significantly higher in patients over 65 years of age and those with in-hospital bleeding recurrence. Patients with non-H. pylori-non-NSAID idiopathic ulcers had significantly higher 30-day mortality rate than those with H. pylori ulcers and NSAID-H. pylori ulcers (7.1 vs. 0 vs. 0.8 %, p = 0.001 and p = 0.007, respectively). There was no statistically significant difference between patients with NSAID ulcers and non-H. pylori-non-NSAID idiopathic ulcers in terms of 30-day mortality rate (5.3 vs. 7.1 %, p = 0.445). CONCLUSION: The incidence of peptic ulcer bleeding has not changed over a 5-year observational period. The overall 30-day mortality was positively correlated to older age, underlying comorbid illnesses, in-hospital bleeding recurrence and the absence of H. pylori infection.

Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent bleeding.

AIM: To compare the recurrent bleeding after endoscopic injection of different epinephrine volumes with hemoclips in patients with bleeding peptic ulcer. METHODS: Between January 2005 and December 2009, 150 patients with gastric or duodenal bleeding ulcer with major stigmata of hemorrhage and nonbleeding visible vessel in an ulcer bed (Forrest IIa) were included in the study. Patients were randomized to receive a small-volume epinephrine group (15 to 25 mL injection group; Group 1, n = 50), a large-volume epinephrine group (30 to 40 mL injection group; Group 2, n = 50) and a hemoclip group (Group 3, n = 50). The rate of recurrent bleeding, as the primary outcome, was compared between the groups of patients included in the study. Secondary outcomes compared between the groups were primary hemostasis rate, permanent hemostasis, need for emergency surgery, 30 d mortality, bleeding-related deaths, length of hospital stay and transfusion requirements. RESULTS: Initial hemostasis was obtained in all patients. The rate of early recurrent bleeding was 30% (15/50) in the small-volume epinephrine group (Group 1) and 16% (8/50) in the large-volume epinephrine group (Group 2) (P = 0.09). The rate of recurrent bleeding was 4% (2/50) in the hemoclip group (Group 3); the difference was statistically significant with regard to patients treated with either small-volume or large-volume epinephrine solution (P = 0.0005 and P = 0.045, respectively). Duration of hospital stay was significantly shorter among patients treated with hemoclips than among patients treated with epinephrine whereas there were no differences in transfusion requirement or even 30 d mortality between the groups. CONCLUSION: Endoclip is superior to both small and large volume injection of epinephrine in the prevention of recurrent bleeding in patients with peptic ulcer.

The role of endoscopic ultrasound in evaluation of gastric subepithelial lesions.

A subepithelial mass is a common finding during endoscopic procedures. Endoscopic ultrasound (EUS) is an important diagnostic modality in the evaluation of subepithelial lesions of the gastrointestinal tract. EUS is the diagnostic test of choice to assess the size, margins, the layer of origin, echotexture, and to differentiate between an intramural and extramural lesion. However, the EUS imaging lacks the specificity. EUS-guided fine needle aspiration (EUS-FNA) or core biopsy can help establish a tissue diagnosis and potentially characterize malignant risk. The aim of this article is to review the diagnosis and management of the most common subepithelial gastric lesions with an emphasis on the role of endoscopic ultrasound.

[Evaluation of upper gastrointestinal submucosal lesions by endoscopic ultrasonography]. / Karakterizacija subepitelnih lezija gornjeg dijela gastrointestinalnog sustava endoskopskim ultrazvukom.

Endoscopy is an established method for diagnosing gastrointestinal tract diseases, however, suspected subepithelial lesions usually cannot be appropriately evaluated by this technique alone. The prevalence of suspected submucosal gastric lesions at routine endoscopy has been estimated to 0.5%-1%. In this review, we evaluated the role of endoscopic ultrasonography (EUS) in the diagnosis of and management strategy for submucosal lesions. EUS has emerged as the most reliable investigative procedure of choice for evaluating submucosal tumors. EUS is the method of choice to differentiate between true intramural tumors and lesions caused by extraluminal compressions due to normal or pathologic structures. It can determine the originating layer(s) of intramural lesions; can differentiate echogenicity (anechoic, hypoechoic, hyperechoic, isoechoic), vascularity, size, shape, and border characteristics. Some endoscopic findings (color, consistency, mobility, 'pillow sign') can be helpful in narrowing the differential diagnosis. On the other hand, determination of the histologic layer and the internal echo patterns of some submucosal tumors are also predictive of benign or malignant tumors. EUS can provide an accurate diagnosis in 80% of patients with benign lesions and 64% of those with malignant lesions. Hypoechoic lesions in the 3rd and 4th layer are most prone to misclassification. If these cannot be differentiated exactly, EUS can serve as a guide on fine needle aspiration (FNA) biopsy or histologic core biopsies, providing samples for cytologic or histologic analysis. After that, the endoscopist can decide whether the lesion should be periodically followed up, or removed by endoscopy, endoscopic submucosal resection (EMR) or surgery.

[The role of endoscopic ultrasonography in the evaluation of pancreatic cancer]. / Uloga endoskopskog ultrazvuka u evaluaciji karcinoma gusterace.

Pancreatic cancer has a dismal prognosis and complete surgical removal remains the only potential curative treatment. The principle goal of preoperative evaluation is to identify patients with potentially resectable disease while avoiding surgical exploration in those with unresectable disease. There is no evidence-based consensus on the optimal preoperative imaging assessment of patients with suspected pancreatic cancer. Because of its widespread availability, computed tomography (CT) is usually the initial study for this indication, although endoscopic ultrasonography (EUS) is the most sensitive imaging modality for the detection of pancreatic masses. Due to anatomical limitations, CT and magnetic resonance (MR) are superior to EUS for detection of metastatic disease. EUS is superior to CT and angiography for detection of tumor invasion of the portal vein or confluence. Most studies found no significant differences between EUS, CT and MRI in determination of pancreatic cancer resectability. The optimal place of EUS within the diagnostic algorithm remains dependent on local referral modalities and availability.

[Hepatitis C--treatment of untreated (naive) patients]. / Hepatitis C--terapijski pristup nelijecenim (naivnim) bolesnicima.

The most important therapeutic advance in recent years considering chronic HCV infection has occurred with the introduction of pegylated interferon (PEG IFN) in the combination therapy with ribavirin, which results in better sustained virologic response (SVR). Although an SVR is difficult to correlate with improved survival because of the necessity for long-term follow up, the absence of detectable serum HCV RNA has been associated with resolution of liver injury, reduction in hepatic fibrosis, and a low likelihood of a relapse of the HCV infection. Two large pivotal trials examined the efficacy of PEG IFN plus ribavirin in the treatment of chronic HCV infection. Overall, PEG IFN plus ribavirin was more effective than the standard interferon-ribavirin combination. SVR rates were similar with both forms of PEG IFN (PEG IFN alfa-2a and PEG IFN alfa-2b) when used in combination with ribavirin. SVR rates of 42% and 46% were achieved in patients with genotype 1 compared to rates of 76% and 82% in patients with genotypes 2 and 3. Factors associated with successful therapy included genotypes other than 1, lower baseline viral levels, less fibrosis or inflammation on liver biopsy, and lower body weight or body surface area. Twenty four weeks of treatment with a combination of PEG IFN and ribavirin appears to be sufficient for patients infected with genotypes 2 and 3, while patients with genotype 1 need 48 weeks of treatment. Early virologic response (EVR), defined as undetectable HCV RNA or a minimum 2 log decrease in viral load (relative to baseline) after the first 12 weeks of treatment, is predictive of SVR and should be a routine part of monitoring patients with genotype 1. Patients who fail to achieve an EVR have only a small chance of achieving an SVR, therefore treatment should be discontinued after 12 weeks. It is also recommended to treat patients with acute hepatitis C to reduce the risk of developing chronic infection. Treatment should start 12 weeks after the onset of symptoms and includes 24 weeks of monotherapy with PEG IFN.