Approach to the patient with suspected liver disease

Kliničke manifestacije jetrene bolesti širokog su spektra, počevši od asimptomatskog povišenja jetrenih enzima do mogućeg dramatičnog zatajenja jetre. Bolesnici su dugo vremena bez simptoma, a otkrivaju se u kasnijim fazama bolesti. Loša prognoza i visoki troškovi liječenja uznapredovale jetrene bolesti zahti jevaju rano dijagnosti ciranje bolesti i pravovremeno liječenje. U pristupu bolesniku s povišenim jetrenim enzimima nužna je iscrpna anamneza i detaljan fi zikalni pregled. Pravovremena rana dijagnoza jetrene bolesti može spriječiti razvoj ireverzibilnog oštećenja jetre.Clinical manifestati ons of liver disease are of wide spectra, from asymptomatic elevation of liver enzymes to possible dramatic and progressive liver failure. The liver disease develops subclinically for a long time and the disease is being diagnosed in its later stages. Bad prognosis and high costs of treatment demand early diagnosis and adequate treatment. In the approach to the patient with elevated liver enzymes the most important are detailed medical history and physical exam. Early diagnosis of the liver disease can prevent the development of irreversible liver damage

Primary Biliary Cholangitis – Case Report and Review of Literature

Primarna bilijarna ciroza (PBC), odnosno primarni bilijarni kolangitis, autoimuni je poremećaj koji spada u skupinu kolestatskih bolesti jetre. PBC je kronična upalna bolest jetre koja može dovesti do fibroze i ciroze jetre te razvoja hepatocelularnog karcinoma. Razumijevanje biologije PBC-a važno je kako bi se omogućila učinkovita skrb za bolesnike, povećale terapijske mogućnosti i kako bi liječenje bilo ciljano. Liječenje PBC-a je u pravilu doživotno. Cilj doživotne terapije je sprječavanje progresivne bolesti jetre i smanjenje, odnosno uklanjanje simptoma bolesti, koji smanjuju kvalitetu života pacijenata. U svakodnevnoj kliničkoj praksi nužno je kod svih bolesnika s povišenim parametrima kolestaze, osobito ako ona traje duže od 6 mjeseci, razmišljati o PBC-u. U radu je prikazan slučaj bolesnice s PBC-om čija je dijagnoza bila dugotrajna, a terapija zahtjevna.Primary biliary cirrhosis (PBC), also known as primary biliary cholangitis, is an autoimmune disorder that belongs to the group of cholestatic liver diseases. PBC is a chronic inflammatory liver disease that can lead to liver fibrosis and cirrhosis and the development of hepatocellular carcinoma. Understanding the biology of PBC is important to ensure effective patient care, improve therapeutic options and provide targeted treatment. PBC is typically a disease that requires lifelong therapy aimed at preventing the progression of the liver disease and at reducing or eliminating the symptoms that impair patients’ quality of life. In everyday clinical practice, PBC should be considered in all patients with elevated cholestasis parameters, especially if they last longer than 6 months. The paper presents a case of a female patient suffering from PBC with a persistent diagnosis and demanding treatment

HEPATITIS C - CLINICAL MANIFESTATIONS AND COMPLICATIONS

SAŽETAK Infekcija hepatitis C virusom uobičajeno se prikazuje kao akutna infekcija, kronična infekcija, ili se očituje kao bolest izvan jetre. U kliničkoj praksi akutna se infekcija rijetko prepoznaje, budući da su u većine bolesnika simptomi asimptomatski, ili se razvijaju simptomi koji ne pobuđuju kliničku pozornost, poput mučnine, anoreksije, nelagode ili bolnosti u gornjem desnom kvadrantu trbuha, mialgije i atralgije. Stoga se u većine bolesnika kronični hepatitis dijagnosticira nakon više godina, kada se tijekom rutinske laboratorijske obrade ustanove povišene vrijednosti aminotransferaza. To je u skladu s činjenicom da se u 80% bolesnika inficiranih hepatitis C virusom, razvije kronični hepatitis. Niz je bolesti izravno ili neizravno povezano s kroničnim hepatitisom C. Dok se za pojedine pokazatelje bolesti izvan jetre zna da su združeni s kroničnim hepatitisom C, za druge postoji tek sumnja. Kronični hepatitis C podmukla je bolest koja je tijekom dugotrajna razdoblja bez simptoma, ili simptomi nisu karakteristični, stoga često postaje uočljivom tek kada se razviju komplikacije kronične jetrene bolesti. Smatra se da će 20% bolesnika s kroničnim hepatitisom C u razdoblju od 10 do 30 godina razviti cirozu jetre, uz mogući razvoj hepatocelularnoga karcinoma u 1% – 5% slučajeva tijekom godine dana. Dekompenzacija jetre i hepatocelularni karcinom u bolesnika s kroničnim hepatitisom C, danas su vodeći pokazatelji za transplantaciju jetre.SUMMARY HCV infection usually presents as an acute infection, chronic infection or as an extrahepatic manifestation. Acute infection is rarely recognized in clinical practice because the large majority of the patients are asymptomatic or develop symptoms which don’t attract clinical attention such as sickness, anorexy, anxiety and pain in the upper right quadrant of stomach, mialgy and artralgy. Therefore, chronic hepatitis is diagnosed in a large majority of the patients after many years in case of large values of aminotransferasis during a routine laboratory check. A vast number of diseases are directly or indirectly connected with chronic hepatitis C. It is known for some of the extrahepatic manifestations to be firmly connected with hepatitis C while there is a doubt for others. Chronic hepatitis C is disease with no symptoms manifested for a long time or the symptoms are uncharacteristic, so it often becomes visible after development end-stage liver disease. It is considered that around 20% of the patients with the chronic type of the disease will develop cirrhosis within a period of 10 – 30 years with the possibility of developing hepatocellular carcinoma in 1% – 5% of the cases per year. Furthemore, decompensation of liver cirrhosis and hepatocellular carcinoma are the leading indications for liver transplantation in patients with chronic hepatitis C

Uvodnik: Hepatologija danas - odabrane teme

Kronične bolesti jetre, kao i njihove komplikacije, jedne su od najčešćih bolesti u ordinacijama specijalista gastroenterologije i obiteljske medicine. Zbrinjavanje navedenih bolesnika predstavlja svakodnevni izazov za gastroenterologe i liječnike obiteljske medicine. Zahtijeva pravovremeno otkrivanje bolesti te interdisclipinaran pristup sustavnoj i dugotrajnoj skrbi. Neprepoznato i neliječeno akutno zatajenje jetre povezano je s visokim rizikom smrtnog ishoda i jedna je od najčešćih indikacija za hitnu transplantaciju jetre. S druge strane, neprepoznate i neliječene komplikacije kroničnih bolesti jetre dovode do razvoja ciroze jetre i komplikacija portalne hipertenzije. S porastom učestalosti debljine i metaboličkoga sindroma, učestalost nealkoholne masne bolesti jetre (engl. non-alcoholic fatty liver disease, NAFLD) poprimila je epidemijske razmjere te je danas najčešći uzrok promijenjenih jetrenih parametara. NAFLD je danas rastući etiološki čimbenik hepatocelularnoga karcinoma (HCC), sudjeluje u patogenezi niza izvanjetrenih kroničnih bolesti (kronične bubrežne bolesti, šećerne bolesti tipa 2, kardiovaskularne bolesti, kolorektalnoga karcinoma itd.) i trenutno predstavlja drugu najčešću indikaciju za liječenje transplantacijom jetre. Uz nealkoholnu masnu bolest jetre, u općoj populaciji velik izazov predstavlja dijagnoza bolesnika s virusnim hepatitisima B i C. S obzirom na dostupnost direktnih antivirusnih lijekova s kojima postižemo izlječenje u gotovo 99% bolesnika s kroničnim hepatitisom C, danas je jedan od glavnih izazova kako postići mikroeliminaciju kroničnoga hepatitisa C. Danas infekciju s kroničnim hepatitisom B možemo uspješno kontrolirati širokom paletom dostupnih lijekova, ali ne i izliječiti. Nadalje, alkoholna bolest jetre je i dalje vodeći uzrok terminalne bolesti jetre (ciroze jetre i HCC-a), stoga je nužna, kroz interdisciplinaran pristup, pravovremena protekcija ovih bolesnika. I dalje značajna proporcija bolesnika oboljelih od autoimunih i kolestatskih bolesti jetre dugo vremena ostaje neprepoznata, te ih otkrivamo u već uznapredovanim fazama bolesti. S obzirom na javnozdravstveni značaj navedenih kroničnih bolesti jetre, cilj ovoga tematskog broja je kroz interdisciplinaran pristup liječnika obiteljske medicine te gastroenterologa/specijalizanata gastroenterologije i medicinskih sestara iz područja gastroenterologije, prikazati radove s aktualnim smjernicama o dijagnozi, liječenju i praćenju ovih bolesnika

Clinical Utility of Red Cell Distribution Width in Alcoholic and Non-alcoholic Liver Cirrhosis

Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as a part of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We retrospectively analyzed 241 patients (176 men and 65 women) with liver cirrhosis and anemia, defined as a hemoglobin value <130 g/L in men and <120 g/L in women, which were hospitalized in our Division in a period between 2006 and 2008. Patients were divided in two groups; in first were patients with alcoholic liver cirrhosis, and in second with non-alcoholic cirrhosis. Severity of disease was determined according to Child-Pugh score. Red blood cells distribution width Normal reference range is 11–15%. Alcoholic liver cirrhosis had 204 patients (85%) while non-alcoholic cirrhosis had 37 patients (15%). In group of alcoholic cirrhosis the average RDW was 16.8%. In relation to severity of disease the average RDW for Child-Pugh A was 16.80%, for Child-Pugh B was 16.92%, for Child-Pugh C was 17.10%. In the group of non-alcoholic cirrhosis the average RDW was 16.73% and in relation to severity of disease for Child-Pugh A was 16.25%, for Child-Pugh B 17.01% and for Child-Pugh C was 16.87%. We didn’t find statistically significant difference of RDW between alcoholic and non alcoholic cirrhosis (p>0.05) and we didn’t proved any statistically significant increase of RDW in relation to severity of disease in group of alcoholic cirrhosis (p=0.915) nor in group of patients with non-alcoholic cirrhosis (p=0.697). Our study showed that RDW had not any clinical value in differentiation of anemia neither in alcoholic and non-alcoholic liver cirrhosis nor in severity of liver disease

Endoscopic retrograde cholangiopancreatography-induced and non-endoscopic retrograde cholangiopancreatography-induced acute pancreatitis: Two distinct clinical and immunological entities?

Acute pancreatitis (AP) is common gastrointestinal disease of varied aetiology. The most common cause of AP is gallstones, followed by alcohol abuse as an independent risk factor. With the increased need for invasive techniques to treat pancreatic and bile duct pathologies such as endoscopic retrograde cholangiopancreatography (ERCP), AP has emerged as the most frequent complication. While severe AP following ERCP is rare (0.5%), if it does develop it has a greater severity index compared to non-ERCP AP. Development of a mild form of AP after ERCP is not considered a clinically relevant condition. Differences in the clinical presentation and prognosis of the mild and severe forms have been found between non-ERCP AP and post-endoscopic pancreatitis (PEP). It has been proposed that AP and PEP may also have different immunological responses to the initial injury. In this review, we summarise the literature on clinical and inflammatory processes in PEP vs non-ERCP AP

Vitamin D Deficiency: Consequence or Cause of Obesity?

Obesity is defined as an excess amount of body fat and represents a significant health problem worldwide. High prevalence of vitamin D (VD) deficiency in obese subjects is a well-documented finding, most probably due to volumetric dilution into the greater volumes of fat, serum, liver, and muscle, even though other mechanisms could not completely be excluded, as they may contribute concurrently. Low VD could not yet be excluded as a cause of obesity, due to its still incompletely explored effects through VD receptors found in adipose tissue (AT). VD deficiency in obese people does not seem to have consequences for bone tissue, but may affect other organs, even though studies have shown inconsistent results and VD supplementation has not yet been clearly shown to benefit the dysmetabolic state. Hence, more studies are needed to determine the actual role of VD deficiency in development of those disorders. Thus, targeting lifestyle through healthy diet and exercise should be the first treatment option that will affect both obesity-related dysmetabolic state and vitamin D deficiency, killing two birds with one stone. However, VD supplementation remains a treatment option in individuals with residual VD deficiency after weight loss

Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD)

Gubitak tjelesne težine je primarna terapija za većinu bolesnika s NAFLD-om. Započinje intervencijama s ciljem promjene načina života, primarno izmjene režima prehrane i vježbanja. Bolesnicima koji imaju prekomjernu tjelesnu težinu ili pretilost preporučuje se gubitak 5 – 7 %, a bolesnicima s NASH-om 7 – 10 % tjelesne težine brzinom od 0,5 do 1 kg tjedno. U bolesnika koji tijekom šest mjeseci ne ispune ciljeve moguće je razmotriti opciju liječenja barijatrijskom kirurgijom. Terapija lijekovima opcija je liječenja u dijela bolesnika koji ne dostižu ciljeve potrebnoga gubitka tjelesne težine, a koji imaju biopsijom dokazani NASH sa stadijem fibroze ≥ 2 ili rizičnim čimbenicima povezanima s razvojem i/ili progresijom fibroze. Odabir terapije ovisan je o tome ima li bolesnik šećernu bolest. Prema aktualnim smjernicama, bolesnicima bez šećerne bolesti savjetuje se ponuditi liječenje vitaminom E. Iako je u prvoj liniji terapije šećerne bolesti tipa 2 metformin, zbog blagotvornog učinka ostalih ne-beta citotropnih lijekova (pioglitazon, liraglutid) na histološke promjene jetre u bolesnika s NAFLD-om potrebno ih je uzeti u obzir pri odabiru drugoga lijeka za bolesnike s NASH-om (koji ne mogu uzimati metformin ili trebaju dodatnu terapiju za snižavanje glukoze). Zbog mogućih nuspojava sve terapijske opcije potrebno je preispitati pojedinačno za svakog bolesnika imajući u vidu omjer dobrobiti i štetnih posljedica. Bolesnici s NAFLD-om izloženi su povećanom riziku za kardiovaskularne bolesti i često imaju višestruke faktore rizika povezane s komponentama metaboličkoga sindroma. Stoga liječenje bolesnika s NAFLD-om i šećernom bolesti i/ili hipertenzijom uključuje optimizaciju kontrole glukoze u krvi i arterijskoga tlaka. Bolesnici s hiperlipidemijom kandidati su za terapiju hipolipemicima.Weight loss is the primary therapy for most patients with NAFLD. It begins with lifestyle interventions, primarily diet modification and exercise. Overweight or obese patients are advised to lose 5-7% and patients with NASH 7-10% of body weight at a rate of 0.5 to 1.0 kg per week. Bariatric surgery can be considered for patients who do not meet weight loss goals after six months. Drug therapy is also an option in those patients who have biopsy-proven NASH with fibrosis stage ≥2 or risk factors related to the development and/or progression of fibrosis, and who fail to reach their weight loss goals. Choice of therapy also depends on whether the patient has diabetes mellitus. Current guidelines recommend that patients without diabetes mellitus take vitamin E therapy. Although metformin is considered first-line agent for the treatment of type 2 diabetes mellitus, the beneficial impact of other insulin-sensitizing agents (pioglitazone, liraglutide) on liver histology in patients with NAFLD should be taken into consideration when choosing a secondline agent for patients with NASH (who cannot take metformin or need additional glucose-lowering therapy). Given the possible side effects, all treatment options should be considered individually for each patient based on risk-benefit evaluation. Patients with NAFLD are at increased risk of developing cardiovascular diseases and often have multiple risk factors related to components of the metabolic syndrome. Therefore, the management of patients with NAFLD and diabetes and/or hypertension includes optimization of blood glucose and arterial hypertension control. Patients with hyperlipidaemia are candidates for lipid-lowering therapy