MONITORING OF PATIENTS WITH CHRONIC HEPATITIS DURING AND AFTER THERAPY

Unatoč razvoju učinkovitih lijekova koji umanjuju nepovoljni ishod akutnih i kroničnih bolesti izazvanih infekcijom virusima hepatitisa B i C te su bolesti i nadalje globalni zdravstveni i socijalno društveni medicinski problem. Danas su na raspolaganju osjetljivi i specifični testovi za HCV i HBV kojima se ne testira opća populacija nego samo rizične skupine. Kod sumnje na infekciju C hepatitisom određuju se antiHCV antitijela, potom HCV RNK kvantitativno i uvodi terapija prema nalazu genotipa, viremiji i prihvaćenim kriterijima. Težina oštećenja jetre i fibroza određuju se biopsijom jetre ili danas češće sveopće prihvaćenim neinvazivnim metodama: uglavnom elastografijom ili serološkim biljezima za fibrozu. Neliječeni HCV bolesnici također se prate do mogućnosti liječenja. Bolesnici s HCV cirozom jetre prate se u smislu detekcije hepatocelularnog karcinoma (HCC), odnosno najčešća su indikacija za ortotopnu transplantaciju jetre. Sva se novorođenčad cijepi protiv virusa hepatitisa B, a rizične se skupine testiraju na HBsAg, antiHBc i antiHBs protutijela. Bolesnicima s pozitivnim HBsAg, HBeAg ili antiHBe, te HBV DNK kvantitativno se određuje HBAg i HBV DNK, jer su vrijednosti prediktori uspješnog liječenja. Utvrđuje se težina jetrene bolesti i uvodi liječenje interferonom ili analozima nukleoz(t)ida. Terapija peroralnim antivirusnim lijekovima je pretežno doživotna. Bolesnici s HBV cirozom i inaktivni HBsAg nosioci doživotno se prate zbog rane detekcije HCC-a odnosno liječe se prema indikaciji transplantacijom jetre.Different effective treatments, which are today available for chronic virus hepatitis C and B, reduce the rate of adverse outcomes but HCV and HBV infections are still one of the major health and public medical problems. Screening for HCV and HBV is performed only in high-risk groups with diagnostic tests with high sensitivity and specificity. In HCV antibody positive patients, serum HCV RNA has to be determined by quantitative assay and virus genotype identified. Liver fibrosis is determined by liver biopsy or widely accepted elastography and different serum fibrosis markers. In patients with HCV cirrhosis, HCC has to be detected by expert ultrasound performer or MSCT, MR, and liver transplantation performed according to indications. The current hepatitis B vaccination policy is universal neonatal vaccination. The risk population undergo screening for HBsAg, antiHBc and antiHBs antibodies. The HBsAg, HBeAg and antiHBe positive individuals undergo quantitative testing for HBsAg and HBV DNA. According to the stage of their liver disease, patients are treated with interferon or nucleos(t)ide analogues. The optimal treatment with oral antivirals are entecavir and tenofovir, but the duration of treatment with nucleos(t)ide analogues is generally life-long. In HBV cirrhosis and HBsAg inactive carriers, detection of HCC is essential, and liver transplantation is successfully performed in these patients

Wilsonova bolest u trudnoći

Wilson’s disease is a rare autosomal recessive disorder of copper metabolism. It causes cirrhosis of the liver, consequently followed by disorder of the menstrual cycle and infertility. Successful decopperizing may lead to restoration of the ovulatory cycle and enable pregnancy. Increased copper levels may cause preeclampsia, intrauterine growth restriction and neurologic damages in the fetus. Pregnant women with decompensated liver cirrhosis face more complications, including bleeding from esophageal varices, liver failure, encephalopathy, and rupture of the splenic artery. We present a case of Wilson’s disease in a patient who had spontaneously conceived three times. The first pregnancy ended with delivery of a healthy baby at term. In second pregnancy, medically induced abortion was performed in the 12th week because of deterioration of the underlying disease, liver cirrhosis with portal hypertension. In the same year, the patient underwent liver transplantation. Two years after the transplantation, the patient spontaneously conceived and delivered vaginally a healthy child.Wilsonova bolest je rijedak autosomno recesivni poremećaj metabolizma bakra. Uzrokuje cirozu jetre te posljedično poremećaj menstruacijskog ciklusa i infertilitet. Uspješna dekuprinizacija može dovesti do ponovne pojave ovulacijskih ciklusa i omogućiti trudnoću. Povećane vrijednosti bakra mogu uzrokovati preeklampsiju, intrauterini zastoj u rastu te neurološka oštećenja ploda. Trudnoća kod trudnica s dekompenziranom cirozom jetre povećava komplikacije kod majke, uključujući krvarenje iz varikoziteta jednjaka, zatajenje jetre, encefalopatije i rupture lijenalne arterije. Prikazuje se bolesnica s Wilsonovom bolešću koja je tri puta spontano zanijela. Prva trudnoća okončana je porodom zdravog djeteta u terminu. Druga trudnoća prekinuta je u 12. tjednu medicinski induciranim pobačajem zbog pogoršanja osnovne bolesti, ciroze jetre s portalnom hipertenzijom. Iste godine u bolesnice je učinjena transplantacija jetre, a dvije godine nakon transplantacije spontano je zanijela i vaginalno rodila zdravo dijete

LIVER TRANSPLANTATION IN HEPATITIS B VIRAL INFECTION

Infekcija hepatitis B virusom (HBV) izaziva cirozu jetre i hepatocelularni karcinom koji su indikacija za ortotopnu transplantaciju jetre (OTJ). Ishod OTJ ovisi o prevenciji HBV reinfekcije i recidiva bolesti. U KB Merkur od 692 bolesnika s transplantatom u 30 je izvršena OTJ zbog HBV infekcije. Bolesnici su primali post OTJ imunoprofilaksu HBIGom i liječeni su prije i nakon OTJ lamivudinom, entekavirom, adefovirom, tenofovirom. Svi su bolesnici postignuli HBsAg i HBV DNK negativizaciju, a četvero je bolesnika nakon godinu dana dobilo HBsAg recidiv. Bolesnici nakon OTJ žive od 2 mjeseca do 7 godina. Uvođenjem dugotrajne imunoprofilakse hepatitis B imunoglobulinima i liječenjem učinkovitijim novim antivirusnim lijekovima rizik povratka bolesti smanjen je na <10 %, a dugotrajno preživljavanje istovjetno je kao u bolesnika transplantiranih zbog drugih indikacija. Zbog dugotrajnosti liječenja imunoprofilaksom i visokih troškova postavljaju se novi kriteriji za kraće liječenje HBIG-om, uvođenjem potentnih analoga nukleos(t)ida prije i nakon transplantacije jetre a prema nalazu viremije tijekom liječenja prije i nakon ortotopne transplantacije jetre.Hepatitis B infection (HBV) causes liver cirrhosis and hepatocellular carcinoma that are indications for orthotopic liver transplantation (OLT). The outcome of OLT depends on the prevention of HBV reinfection and disease relapses. Out of 692 liver transplantations performed at Merkur University Hospital, 30 were done for HBV infection. These patients were treated with HBIG post OLT and lamivudine, entecavir, adefovir, tenofovir prior and post OLT. All patients became HBsAg and HBV DNA negative but four of them became HbsAg positive one year post OLT. The patients survived for 2 months to 7 years post OLT. With the introduction of HBIG immunoprophylaxis and new efficient antiviral treatment, the risk of relapse is only <10%, and survival is the same as in other indications for OLT. Because of the high cost and long-term treatment, efforts have been made to prevent recurrent HBV disease by using the schedules according to pre- and post-transplant HBV viremia and introducing the new potent antiviral analogue nucleos(t)ides

TREATMENT OF RECURRENT HCV INFECTION AFTER LIVER TRANSPLANTATION

Recidiv HCV infekcije nakon transplantacije jetre univerzalna je pojava povezana s učestalijim morbiditetom i mortalitetom bolesnika te gubicima presatka. Za razliku od imunokompetentnih bolesnika, HCV infekcija u imunosuprimiranih bolesnika s trans-plantiranom jetrom uglavnom ima ubrzani tijek. Akutni hepatitis pojavljuje se u 75 % bolesnika u prvih 6 mjeseci od transplantacije. Do 5. godine nakon transplantacije više od 80 % HCV inficiranih bolesnika razvije znakove kroničnog oštećenja presatka, a 30 % cirozu. Odabir kalcineurinskog inhibitora nije se pokazao ključnim u analizi rizika histoloških znakova recidiva bolesti kao niti učestalosti pojave akutnog odbacivanja. Kumulativna ekspozicija kortikosteroidima povezana je sa značajno većim mortalitetom bolesnika, višom razinom viremije i težim oblicima histoloških promjena presatka. Uspješno liječenje HCV infekcije povezano je s povoljnim učinkom na preživljenje presatka i primatelja. Prema nalazima objavljenih studija kombiniranu terapiju pegiliranim interferonom alfa i ribavirinom preporuča se provesti kod bolesnika s histološki potvrđenim recidivom HCV infekcije. Razlog tome je mnogostruk: 1) recidiv HCV infekcije najčešće se pogoršava nakon prve godine od transplantacije, 2) odnos pogodnosti i rizika za terapiju je optimalan jer je to ujedno i vrijeme manje učestalosti epizoda odbacivanja, funkcija presatka je bolja, a razina primjenjene imunosupresivne terapije niža. Postignuti SVR kombiniranom terapijom u randomiziranim studijama na bolesnicima s histološki dokazanom bolesti iznosi 33 % do 42 %. Potencijalni faktori koji utječu na niži SVR su: 1) genotip 1; 2) visoka razina viremije; 3) nepovoljan pred-transplantacijski odgovor na terapiju i 4) nuspojave antiviralnih lijekova. Otvoreno je pitanje rutinske primjene faktora rasta i učinaka pojedinih imunosupresivnih lijekova. U terapiji se primjenjuje pegilirani interferon alfa u standardnoj dozi i ribavirin. Zbog često prisutne bubrežne insuficijencije terapiju ribavirinom započinje se u reduciranim dozama (prema klirensu kreatinina) uz postupno povišenje doze. Terapija se provodi tokom 48 tjedana neovisno o genotipu virusa i povezana je većim rizikom komplikacija i nuspojava nego kod bolesnika koji nisu dobili transplantat.Recurrent infection with HCV after liver transplantation (LT) is almost universal and is associated with substantial morbidity, mortality and graft loss. In contrast to immunocompetent individuals, HCV infection in immunosuppressed transplant recipients usually has an accelerated course. Acute hepatitis develops in approximately 75% of HCV recipients in the first six months following LT. Within the five years after LT, over 80% of HCV-infected liver transplant recipients develop histologic evidence of chronic allograft injury secondary to HCV, with up to 30% of cirrhosis. While the choice of calcineurin inhibitors has not clearly shown to affect the histologic HCV recurrence or the frequency of rejection in HCV-infected recipients, the cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia, and more severe histologic recurrence. Successful therapy has been shown to have a positive impact on both graft and patient survival. Combination therapy with interferon (pegylated and non-pegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially due to cytopenias, and drug discontinuation in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virologic response rates (SVR). The SVR achieved is between 33% and 42% in randomized studies treating patients with histologic recurrence. The potential factors that influence this low SVR rate are: 1) genotype 1 virus; 2) high viral load; 3) prior nonresponding to therapy; 4) side effects of antiviral treatment; 5) use of growth factors; and 6) effect of immunosuppression. In post-transplant patients with recurrent HCV disease, combination peg alpha-2b or alpha-2a in standard dose and ribavirin (800-1200 mg either ab initio or as an increasing dose) regimen for 48 weeks was significantly better than no therapy but not than any other therapy

Role of Fine Needle Aspiration Cytology in Management of Hepatocellular Carcinoma: A Single Centre Experience

Hepatocellular carcinoma (HCC) mostly occurs in chronic liver disease and cirrhosis. Liver resection and liver transplantation (LT) represent potentially curative treatments of choice and if not feasible, palliative strategies such as percutaneous interventional techniques (PITs) and chemotherapy (ChT) are considered. Elevated alfa-fetoprotein, typical imaging pattern, needle core biopsy (NCB) and fine needle aspiration cytology (FNAC) complement diagnostic assessment of HCC. We have retrospectively analyzed all patients with contraindications for NCB in which HCC was diagnosed by FNAC during consecutive 5 years in our hospital. Ultrasound guided FNAC provided a safe method of approach and, except for mild transitory discomfort at the site of puncture, no complications were documented. The diagnosis was established on May-Grünwald-Giemsa (MGG) stained aspirates and additional immunocytochemistry. Of our 62 patients, HCC developed in 61.3% cirrhotic and 38.7% non-cirrhotic livers. In the setting of cirrhosis 18.4% of patients underwent LT, 15.8% PITs, 26.3% ChT and 39.5% symptomatic therapy. In non-cirrhotic setting 46% of patients underwent liver resection, and PIT, ChT, and symptomatic therapy were applied in 4%, 25%, 25% of cases, respectively. Pathohistology of resected and explanted livers (18 cases) confirmed the initial diagnosis made on FNAC. Since only early stage of HCC has a better prognosis, every effort should be made to establish prompt and accurate diagnosis. Our observations demonstrate that FNAC offers minimally invasive, rapid and uncomplicated diagnostic approach, with sensitivity from 67% to 93% and specificity from 96% to 100%. FNAC, is of utmost importance in the setting of abnormal coagulation tests and ascites commonly seen in advanced liver disease, facilitating diagnostic workup and treatment decisions

Parvovirus B 19 (PVB19) Induced Pure Red Cell Aplasia (PRCA) in Immunocompromised Patient after Liver Transplantation

Presented here is a case of human parvovirus B19 (PVB19) induced pure red-cell aplasia (PRCA) in immunocompromised patient after orthotopic liver transplantation (OLT). PVB19 is a small, single-stranded DNA whose target cell is the erythroid progenitor in bone marrow. Manifestations of PVB19 infection vary with the immunologic status of the patient, ranging from asymptomatic to severe infections and PRCA. Post-transplant PRCA is induced either by immunosuppressive agents or PVB19. In the presented case, bone marrow aspiration characterized by the absence of mature erythroid precursors and detection of PVB19 DNA in blood led to treatment with high-dose intravenous human immunoglobulins (IVIG) and subsequent recovery of erythropoiesis. Due to insufficient antibody response in immunocompromised patients, suppression of the PVB19 infection is delayed and repetitive treatments may be administrated in attempt of reversing PRCA

Parvovirus B 19 (PVB19) induced pure red cell aplasia (PRCA) in immunocompromised patient after liver transplantation [Izolirana aplazija crvene krvne loze uzrokovana infekcijom Parvovirusom B 19 nakon transplantacije jetre]

Presented here is a case of human parvovirus B19 (PVB19) induced pure red-cell aplasia (PRCA) in immunocompromised patient after orthotopic liver transplantation (OLT). PVB19 is a small, single-stranded DNA whose target cell is the erythroid progenitor in bone marrow. Manifestations of PVB19 infection vary with the immunologic status of the patient, ranging from asymptomatic to severe infections and PRCA. Post-transplant PRCA is induced either by immunosuppressive agents or PVB19. In the presented case, bone marrow aspiration characterized by the absence of mature erythroid precursors and detection of PVB19 DNA in blood led to treatment with high-dose intravenous human immunoglobulins (IVIG) and subsequent recovery of erythropoiesis. Due to insufficient antibody response in immunocompromised patients, suppression of the PVB19 infection is delayed and repetitive treatments may be administrated in attempt of reversing PRCA

Epitheloid Hemangioendothelioma in Patient with Liver Transplantation

Malignant hepatic epithelioid hemangioendothelioma (HEH) is a rare malignant tumor of vascular origin with unknown aetiology and a variable natural course. At the time of diagnosis, most patients present with multifocal tumours lesions that involve both liver lobes. From the therapeutic aspect, liver resection (LRx), liver transplantation (LTx), chemotherapy, radiotherapy, and/or immunotherapy have been used in the treatment of patients with HEH. However, because of the rarity of this tumor and its unpredictable natural history, it is impossible to assess the effectiveness of these respective therapies. In this report, our objective was to present clinical aspects, diagnostic options, therapeutic modalities, and the clinical outcome of single patient with LTx because of this rare tumor

VIRAL HEPATITIS - CROATIAN CONSENSUS STATEMENT 2013

Hrvatske konsenzus konferencije o virusnim hepatitisima održane su 2005. i 2009. g. (1). S obzirom na brojne nove spoznaje o epidemiologiji, dijagnostici i liječenju virusnih hepatitisa (poglavito kroničnog hepatitisa C genotipa 1) u protekle četiri godine, 28. veljače 2013. g. održana je nova Hrvatska konsensus konferencija o virusnim hepatitisima u Zagrebu. Sažeti tekst ove Hrvatske konsenzus konferencije o virusnim hepatitisima sadrži prikaz novih spoznaja o epidemiologiji virusnih hepatitisa, serološkoj i mo¬lekularnoj dijagnostici virusnih hepatitisa, određivanju polimorfizma promotora gena za IL-28, procjeni stadija fibroze, algoritmu dijagnostičkog praćenja bolesnika, liječenju kroničnog hepatitisa C (genotipovi 1-6) i hepatitisa B, liječenju specijalnih populacija (djeca, bolesnici na dijalizi, bolesnici liječeni transplantacijom, osobe s HIV/HCV koinfekcijom) i nuspojavama liječenja.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, fi¬brosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treat¬ment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects