Intraductal papillary neoplasm of the bile duct (IPNB) as an uncommon cause of abdominal pain and cholangitis

INTRODUCTION/OBJECTIVES: Intraductal papillary neoplasm of the bile duct (IPNB) is a relatively new entity characterized by dilation of bile ducts filled with papillary neoplasms, which represents premalignant lesion of cholangiocarcinoma, with common malignant transformation

Extrahepatic Manifestations of Hepatitis C Virus Infection

Chronic hepatitis C virus (HCV) infection causes progressive liver fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Additional to liver damage, HCV infection causes a variety of systemic disorders, some of which sometimes bear more severe morbidity than the liver disease itself. These extrahepatic manifestations represent a wide spectrum of disorders, ranging from the presence of a variety of clinically insignificant autoantibodies to diseases affecting a variety of organ systems. Mixed cryoglobulinemia is a common manifestation, and associated vasculitis can affect many organs (kidney, skin, and joints). The skin can also be affected by porphyria cutanea tarda and lichen planus. Other common extrahepatic manifestations include autoimmune disorders, lymphoproliferative disorders, and a number of neurological and neuropsychiatric disorders such as fatigue, depression, or cognitive impairment. Insulin resistance, diabetes mellitus, accelerated atherosclerosis, and increased cardiovascular disease morbidity and mortality have also been associated with chronic HCV infection. The existence and severity of extrahepatic manifestations do not correlate with the severity of liver disease, and the mainstay of treatment is HCV eradication. Patients with systemic manifestations of HCV infection should be prioritized for treatment, especially in the era of new interferon-free therapies with fewer side effects

Hepatitis C Virus (HCV) Treatment in Croatia: Recent Advances and Ongoing Obstacles

The prevalence of hepatitis C virus (HCV) antibodies in Croatia is low in the general population (reported <1%), similar to the prevalence rates of many European countries, but is higher in the populations at risk, especially among intravenous drug users. With the development of new classes of direct-acting antiviral agents and interferon-free regimens, the landscape of HCV treatment has completely changed. Management of HCV infection in Croatia is in accordance with the European Association for the Study of the Liver (EASL) recommendations published in 2015, recently updated Croatian Guidelines (published in April 2016) and the recommendations of Croatian Health Insurance Fund (HZZO) which covers the costs of treatment. HZZO approved simeprevir at the beginning of 2015. By the end of the 2015 sofosbuvir, combination of sofosbuvir + ledipasvir and the combination of ombitasvir, paritaprevir and ritonavir ± dasabuvir became available. Although the drawback of these new highly effective treatments is their price, prioritization of patients on a national level offers equal opportunities to patients in need for treatment. Due to improvements in therapy and prevention, clinical care for patients with HCV in Croatia advanced significantly during the last two years

Interference of M-protein on prothrombin time test – case report.

The aim of this report was to present a case of interference on prothrombin time (PT) test that directed further laboratory diagnostics and resulted with final detection of monoclonal gammopathy in an 88-year old man. Routine coagulation testing during medical examination at Emergency Department revealed unmeasurable PT (< 7% activity) and activated partial thromboplastin time (aPTT) within reference range. After repeated sampling for coagulation testing, PT was unmeasurable again, as well as fibrinogen level (< 0.8 g/L), thrombin time (TT) was significantly prolonged (107 seconds) and aPTT was within reference range. In both plasma samples refrigerated at 4 °C overnight, white gelatinous precipitate was visible between the cell and plasma layers and the presence of monoclonal protein (M-protein) was suggested in our patient. Further laboratory diagnostics revealed total serum proteins at concentration of 123 g/L and the presence of M-protein IgG lambda (?) at concentration of 47.1 g/L. These results suggested monoclonal gammopathy as an underlying pathophysiological condition in our patient. Activities of coagulation factors II, V, VII and X were within reference ranges or increased. These results and correction of unmeasurable PT result to 67% in mixing test with commercial normal plasma suggest in vitro rather than in vivo interference of M-protein on PT result. In contrast, significantly prolonged TT results in all analysed samples suggest impact of M-protein on this global coagulation test due to possible effect on fibrin polymerization

Adjusted Blood Requirement Index as Indicator of Failure to Control Acute Variceal Bleeding

Aim: To estimate the clinical value of adjusted blood requirement index (ABRI) in relation to other criteria for failure of variceal bleeding control proposed at Baveno consensus workshops and to evaluate ABRI as an early predictor of occurrence of other Baveno criteria and identification of possible predictors of unfavorable ABRI. Methods: We retrospectively analyzed the data on 60 patients admitted to the hospital due to acute variceal bleeding. Number of treatment failures according to Baveno II-III and Baveno IV definitions and criteria was compared. We tested the ABRI’s predictability of other Baveno IV and Baveno II-III criteria. Logistic regression analysis was performed to ascertain independent variables that predict ABRI≥0.75. Results: Failure to control variceal bleeding occurred in 40 of 60 patients according to Baveno II-III criteria, and in 35 of 60 patients according to Baveno IV criteria. Excluding the criterion of “transfusion of 2 units of blood or more (over and above the previous transfusions)”and ABRI criterion, failure to control variceal bleeding was observed in 17 and 14 of 60 patients, respectively. Congruence of ABRI with other criteria was present in about two-thirds of the cases. ABRI≥0.75 was associated with increased risk of positive other Baveno criteria,particularly modified Baveno II-III (odds ratio [OR] 4.10; 95% confidence interval [CI], 1.11-15.05) and Baveno IV without ABRI (OR 4.37; 95% CI, 1.04-18.28). Independent predictors of ABRI≥0.75 identified in logistic regression analysis were male sex (P<0.001) and higher hematocrit values (P=0.004). Conclusion: We found low congruence between ABRI and other Baveno criteria. It seems that criteria related to the quantity of blood transfusions are not reliable indicators of treatment failure

Cholestatic Liver Diseases

Kolestatske bolesti jetre predstavljaju rijetke bolesti koje zahvaćaju hepatocite, ekstrahepatalne i/ili intrahepatalne žučne vodove, a dovode do smetnji u stvaranju ili otjecanju žuči. Primarni bilijarni kolangitis (PBC) predstavlja novi naziv za bolest ranije poznatu kao primarna bilijarna ciroza. Imunološki napad dovodi do progresivnog oštećenja malih žučnih vodova unutar jetrenih lobula s razvojem fibroze, a u konačnici može dovesti do ciroze i zatajenja jetrene funkcije. Primarni sklerozirajući kolangitis (PSC) obilježava kronična upala praćena oštećenjem i fibrozom žučnih vodova s posljedičnom segmentalnom obliteracijom lumena, a može zahvatiti intrahepatalne ili ekstrahepatalne žučne vodove, ili oboje. PBC češće zahvaća žene, a PSC mušku populaciju. Umor, svrbež kože i žutica predstavljaju najčešće simptome kolestatskih bolesti jetre. Obje bolesti često se otkrivaju u asimptomatskoj fazi, kolestatskim profilom jetrenih enzima u laboratorijskim nalazima, odnosno dominantno povišenim vrijednostima alkalne fosfataze (ALP) i gama-glutamil transpeptidaze (GGT). Bolesnici često imaju pridružene druge autoimune bolesti. Za PBC karakterističan je nalaz antimitohondrijskih protutijela (AMA), dok se PSC dokazuje kolangiografijom. Komplikacije bolesti mogu biti posljedica kolestaze, upalnog (autoimunog) zbivanja te ciroze jetre ili razvoja tumora. Ursodeoksikolna kiselina predstavlja terapiju izbora u liječenju PBC-a jer usporava tijek bolesti, dok za PSC ne postoji dokazano djelotvorna medikamentozna terapija koja utječe na tijek osnovne bolesti. U obje bolesti primjenjuju se i simptomatske mjere te postupci usmjereni zbrinjavanju komplikacija, kao što su svrbež, malapsorpcija masti i vitamina topivih u mastima, ili striktura žučnih vodova. Povećana učestalost tumora zahtijeva trajni nadzor i pravodobno liječenje koje utječe na preživljenje bolesnika. Transplantacija jetre predstavlja metodu izbora u završnom stadiju obje bolesti.Cholestatic liver diseases are rare diseases that affect hepatocytes and intrahepatic and/or extrahepatic bile ducts, causing interruptions in bile production or flow. Primary biliary cholangitis (PBC) is a new term for primary biliary cirrhosis. Immune-mediated attack leads to progressive destruction of small intralobular bile ducts and may lead to the development of fibrosis, cirrhosis and liver failure. Primary sclerosing cholangitis (PSC) is characterized by chronic inflammation with damage and fibrosis of bile ducts, causing structuring and obliteration of the lumen. It can affect the intrahepatic and/or extrahepatic biliary tree. PBC mostly affects women, while PSC is more common in men. Fatigue, pruritus and jaundice represent the most common complaints of patients with cholestatic liver diseases. Both diseases are often diagnosed in early, asymptomatic phase, as part of the assessment of abnormal liver tests which demonstrate cholestatic pattern, with predominant elevation of the alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). Patients often have other concurrent autoimmune diseases. PBC is characterized by the presence of anti-mitochondrial antibodies (AMA), while cholangiography is the method of choice for the diagnosis of PSC. Complications can result from cholestasis, inflammatory (autoimmune) process, liver cirrhosis or cancer development. Ursodeoxycholic acid is the therapy of choice for PBC as it slows the disease progression. However, there is no proven treatment that significantly impacts the course of PSC. For both diseases management is aimed at treating symptoms and managing complications such as pruritus, malabsorption of fat and fat-soluble vitamins, or bile duct strictures. Increased incidence of malignant tumours requires ongoing monitoring and timely treatment in order to improve patient survival. Liver transplantation represents the treatment of choice in the advanced stage of both diseases

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