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Hepatocellular carcinoma is the fifth most common cancer in the world and the third leading cause of cancer-related death. It is currently one of the leading indications for liver transplant, with selected 5-year survival rates after liver transplant of about 70%. Despite excellent results of liver transplant for hepatocellular carcinoma, a number of patients develop metastases after transplant, and multifocal metastatic disease is the most frequent cause of death. In a large autopsy series of patients with hepatocellular carcinoma, adrenal glands were the third most common site of extrahepatic metastasis after lungs and bones. However, isolated metastatic disease in the adrenal glands is rare, and isolated metachronous bilateral metastasis is an even rarer occurrence. Only few reports have been published of metachronous bilateral metastasis of hepatocellular carinoma after liver transplant treated with bilateral adrenalectomy. We describe a case of a 56-year-old man who underwent liver transplant for hepatocellular carcinoma in a cirrhotic liver. Two years after liver tranplant, regular follow-up revealed metastatic disease in the left adrenal gland. Preoperative imaging showed no other metastasis, and he underwent an uneventful left adrenalectomy. A year after surgery, he presented with right flank pain and tenderness. Imaging showed hemorrhage and tumor involvement of the right adrenal gland, and he underwent right adrenalectomy. Two years after surgery, he is alive and well with no signs of disease recurrence. Apparently, in the absence of intrahepatic or other metastases, bilateral metachronous recurrence of hepatocellular carcinoma after liver tranplant can be a good surgical indication with acceptable long-term survival.

Zoonoses represent a problem of rising importance in the transplant population. A close relationship and changes between human, animal and environmental health ("One Health" concept) significantly influence the transmission and distribution of zoonotic diseases. The aim of this manuscript is to perform a narrative review of the published literature on emerging and neglected zoonoses in the transplant population. Many reports on donor-derived or naturally acquired (re-)emerging arboviral infections such as dengue, chikungunya, West Nile, tick-borne encephalitis and Zika virus infection have demonstrated atypical or more complicated clinical course in immunocompromised hosts. Hepatitis E virus has emerged as a serious problem after solid organ transplantation (SOT), leading to diverse extrahepatic manifestations and chronic hepatitis with unfavorable outcomes. Some neglected pathogens such as lymphocytic choriomeningitis virus can cause severe infection with multi-organ failure and high mortality. In addition, ehrlichiosis may be more severe with higher case-fatality rates in SOT recipients. Some unusual or severe presentations of borreliosis, anaplasmosis and rickettsioses were also reported among transplant patients. Moreover, toxoplasmosis as infectious complication is a well-recognized zoonosis in this population. Although rabies transmission through SOT transplantation has rarely been reported, it has become a notable problem in some countries. Since the spreading trends of zoonoses are likely to continue, the awareness, recognition and treatment of zoonotic infections among transplant professionals should be imperative., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Although, liver transplantation serves as the only curative treatment for patients with end-stage liver diseases, it is burdened with complications, which affect survival rates. In addition to clinical risk factors, contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes. Determination of single nucleotide polymorphisms (SNPs) is one of the most important tools in development of personalized transplant approach. To provide a better insight in recent developments, we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation: Acute cellular rejection, development of new-onset diabetes mellitus and non-alcoholic fatty liver disease, hepatocellular carcinoma recurrence, and tacrolimus concentration variability. Reviewed studies confirmed previously established SNP prognostic factors, such as PNPLA3 rs738409 for non-alcoholic fatty liver disease development, or the role of CYP3A5 rs776746 in tacrolimus concentration variability. They also identified several novel SNPs, with a reasonably strong association, which have the potential to become useful predictors of post-transplant complications. However, as the studies were typically conducted in one center on relatively low-to-moderate number of patients, verification of the results in other centers is warranted to resolve these limitations. Furthermore, of 29 reviewed studies, 28 used gene candidate approach and only one implemented a genome wide association approach. Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

The consequences of graft failure after liver transplantation (LT) range far beyond the liver. The kidneys are often affected, where persistent and progressive cholestasis can result in acute kidney injury (AKI) leading to the development of bile cast nephropathy (BCN). BCN is an often unrecognized condition that is characterized by proximal tubulopathy and the formation of bile casts in the distal tubules, which is almost diagnosed exclusively on a kidney biopsy or autopsy. This condition is potentially reversible, provided the bilirubin levels can be reduced early. LT may represent a treatment option in the case of irreversible liver (or liver graft) failure, which is beneficial for both the liver and the kidney. This paper reports a case of BCN in a patient with idiopathic graft failure after LT. Despite his chronic kidney disease, liver re-transplantation led to the successful improvement of his AKI.

Purpose: Data on the seroprevalence of hepatitis E virus (HEV) in heamodialysis (HD) patients are conflicting, ranging from 0 to 44%. The aim of this study was to determine the HEV seroprevalence and risk factors among HD patients in Croatia., Methods: A total of 394 HD patients from six medical facilities in five Croatian cities (three sites in the continental and three sites in the coastal region) were tested for HEV IgM/IgG antibodies using an enzyme-linked immunosorbent assay. Additionally, all samples were tested for HEV RNA by RT-PCR. Sociodemographic data and risk factors were collected using a questionnaire., Results: HEV IgG antibodies were detected in 110 (27.9%) patients. The seroprevalence varied significantly between dialysis centres, ranging from 5.2 to 43.4% (p = 0.001). HEV IgM antibodies were found in 0.04% of IgG positive patients. All patients tested negative for HEV RNA. Factors associated with HEV IgG seropositivity were age > 60 years (OR 8.17; 95% CI 1.08-62.14), living in the continental parts of the country (OR 2.58; 95% CI 1.55-4.30), and transfusion of blood products (OR 1.66; 95% CI 1.01-2.73). After adjusting for age and gender, patients from continental regions had higher odds of HEV seropositivity compared to patients from coastal regions (OR 2.88; 95% CI 1.71-4.85) and those who had RBC transfusions (OR 1.70, 95% CI 1.02-2.69) compared to those who did not., Conclusion: The study showed a high HEV seropositivity among HD patients in Croatia, with significant variations between geographical regions. Continental area of residence and RBC transfusion were the most significant risk factors for HEV seropositivity. Due to the high seroprevalence, routine HEV screening among HD patients, especially in transplant candidates should be considered.

The epidemiology of West Nile (WNV) and Usutu virus (USUV) has changed dramatically over the past two decades. Since 1999, there have been regular reports of WNV outbreaks and the virus has expanded its area of circulation in many Southern European countries. After emerging in Italy in 1996, USUV has spread to other countries causing mortality in several bird species. In 2009, USUV seroconversion in horses was reported in Italy. Co-circulation of both viruses was detected in humans, horses and birds. The main vector of WNV and USUV in Europe is Culex pipiens , however, both viruses were found in native Culex mosquito species ( Cx. modestus, Cx. perexiguus ). Experimental competence to transmit the WNV was also proven for native and invasive mosquitoes of Aedes and Culex genera ( Ae. albopictus, Ae. detritus, Cx. torrentium ). Recently, Ae. albopictus and Ae. japonicus naturally-infected with USUV were reported. While neuroinvasive human WNV infections are well-documented, USUV infections are sporadically detected. However, there is increasing evidence of a role of USUV in human disease. Seroepidemiological studies showed that USUV circulation is more common than WNV in some endemic regions. Recent data showed that WNV strains detected in humans, horses, birds, and mosquitoes mainly belong to lineage 2. In addition to European USUV lineages, some reports indicate the presence of African USUV lineages as well. The trends in WNV/USUV range and vector expansion are likely to continue in future years. This mini-review provides an update on the epidemiology of WNV and USUV infections in Southern Europe within a multidisciplinary "One Health" context., (Copyright © 2019 Vilibic-Cavlek, Savic, Petrovic, Toplak, Barbic, Petric, Tabain, Hrnjakovic-Cvjetkovic, Bogdanic, Klobucar, Mrzljak, Stevanovic, Dinjar-Kujundzic, Radmanic, Monaco, Listes and Savini.)

Purpose of Review: In this review, we present the overview of emerging and neglected viruses associated with liver involvement., Recent Findings: Hepatitis E virus (HEV) emerged in the last two decades, causing hepatitis in many parts of the world. Moreover, liver involvement was also described in some emerging arboviral infections. Many reports showed dengue-associated liver injury; however, chikungunya, West Nile, tick-borne encephalitis, and Zika virus are rarely associated with clinically manifest liver disease. In addition, some neglected highly prevalent viruses such as adenoviruses and parvovirus B19 are capable of causing hepatitis in specific population groups. Anelloviruses (torque teno virus/torque teno mini virus/torque teno midi virus, SEN virus), human bocavirus, pegiviruses, and lymphocytic choriomeningitis virus have shown a little potential for causing hepatitis, but their role in the etiology of liver disease remains to be determined. In addition to the well-known hepatotropic viruses, many emerging and neglected viruses have been associated with liver diseases. The number of emerging zoonotic viruses has been increasingly recognized. While zoonotic potential of HEV is well documented, the recent identification of new hepatitis-related animal viruses such as HEV strains from rabbits and camels, non-primate hepaciviruses in domestic dogs and horses, as well as equine and porcine pegivirus highlights the possible zoonotic transmission in the context of "One Health." However, zoonotic potential and hepatotropism of animal hepatitis viruses remain to be determined.

Background: Refractory ascites is a rare complication following orthotopic liver transplantation (OLT). The broad spectrum of differential diagnosis often leads to delay in diagnosis. Therapy depends on recognition and treatment of the underlying cause. Constrictive pericarditis is a condition characterized by clinical signs of right-sided heart failure. In the advanced stages of the disease, hepatic congestion leads to formation of ascites. In patients after OLT, cardiac etiology of ascites is easily overlooked and it requires a high degree of clinical suspicion., Case Summary: We report a case of a 55-year-old man who presented with a refractory ascites three months after liver transplantation for alcoholic cirrhosis. Prior to transplantation the patient had a minimal amount of ascites. The transplant procedure and the early postoperative course were uneventful. Standard post-transplant work up failed to reveal any typical cause of refractory post-transplant ascites. The function of the graft was good. Apart from atrial fibrillation, cardiac status was normal. Eighteen months post transplantation the patient developed dyspnea and severe fatigue with peripheral edema. Ascites was still prominent. The presenting signs of right-sided heart failure were highly suggestive of cardiac etiology. Diagnostic paracentesis was suggestive of cardiac ascites, and further cardiac evaluation showed typical signs of constrictive pericarditis. Pericardiectomy was performed followed by complete resolution of ascites. On the follow-up the patient remained symptom-free with no signs of recurrent ascites and with normal function of the liver graft., Conclusion: Refractory ascites following liver transplantation is a rare complication with many possible causes. Broad differential diagnosis needs to be considered., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Solid-organ transplant recipients are at risk of hepatitis E virus (HEV) infection. We analyzed the seroprevalence/risk factors of HEV in Croatian liver transplant recipients., Methods: Two hundred forty-two serum samples were tested for HEV immunoglobuline IgG/IgM and HEV RNA. Sociodemographic data and risk factors were collected using a questionnaire., Results: HEV IgG seroprevalence rate was 24.4%. Positive/equivocal HEV IgM were found in two patients. HEV RNA was not detected. Logistic regression showed that older age, female gender, rural area/farm, water well, and septic tank were associated with HEV seropositivity., Conclusions: This study revealed a high exposure rate to HEV in Croatian liver recipients.

Background: Donor-origin cancer is a well-recognized but rare complication after liver transplantation (LT). The rise in the use of extended criteria donors due to the current shortage of organs increases the risk. Data on donor-origin neuroendocrine neoplasms (NENs) and the most appropriate treatment are scarce. Here, we report a case of a patient who developed a NEN confined to the liver after LT and was treated with liver re-transplantation (re-LT)., Case Summary: A 49-year-old man with no other medical co-morbidities underwent LT in 2013 for alcoholic liver cirrhosis. The donor was a 73-year-old female with no known malignancies. Early after LT, a hypoechogenic (15 mm) lesion was detected in the left hepatic lobe on abdominal ultrasound. The lesion was stable for next 11 mo, when abdominal magnetic resonance identified two hypovascular lesions (20 and 11 mm) with atypical enhancement pattern. Follow-up abdominal ultrasound revealed no new lesions for the next 2.5 years, when magnetic resonance showed a progression in size and number of lesions, also confirmed by abdominal computed tomography. Liver biopsy proved a well-differentiated NEN. Genetic analysis of the NEN confirmed donor origin of the neoplasm. As NEN was confined to liver graft only, in 2018, the patient underwent his second LT. At 12 mo after re-LT the patient is well with no signs of NEN dissemination., Conclusion: The benefits of graft explantation should be weighed against the risks of re-LT and the likelihood of NEN dissemination beyond the graft., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

The significance of hepatitis E virus (HEV) as an important public health problem is rising. Until a decade ago, cases of HEV infection in Eur-ope were mainly confined to returning travelers, but nowadays, hepatitis E represents an emerging zoonotic infection in many European countries. The aim of this manuscript is to perform a systematic review of the published literature on hepatitis E distribution in humans, animals and environmental samples ("One Health" concept) in the South-Eastern European countries. Comparison of the available data showed that the anti-HEV seroprevalence in the South-Eastern Europe varies greatly, depending on the population studied, geographical area and methods used. The IgG seroprevalence rates in different population groups were found to be 1.1%-24.5% in Croatia, up to 20.9% in Bulgaria, 5.9-%17.1% in Romania, 15% in Serbia, up to 9.7% in Greece and 2%-9.7% in Albania. Among possible risk factors, older age was the most significant predictor for HEV seropositivity in most studies. Higher seroprevalence rates were found in animals. HEV IgG antibodies in domestic pigs were detected in 20%-54.5%, 29.2%-50%, 38.94%-50% and 31.1%-91.7% in Serbia, Bulgaria, Romania and Croatia, respectively. In wild boars seroprevalence rates were up to 10.3%, 30.3% and 31.1% in Romania, Slovenia and Croatia, respectively. A high HEV RNA prevalence in wild boars in some countries (Croatia and Romania) indicated that wild boars may have a key role in the HEV epidemiology. There are very few data on HEV prevalence in environmental samples. HEV RNA was detected in 3.3% and 16.7% surface waters in Slovenia and Serbia, respectively. There is no evidence of HEV RNA in sewage systems in this region. The available data on genetic characterization show that human, animal and environmental HEV strains mainly belong to the genotype 3., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest. No financial support.

Background: Paraduodenal pancreatitis (PP) is a rare form of chronic pancreatitis presenting with symptoms of duodenal obstruction. Conservative treatment is often unsuccessful and pancreaticoduodenectomy is the preferred surgical approach. A mini review of the outcomes of surgical therapy for PP shows that the results of pancreaticoduodenectomy are predominantly favorable., Case Summary: In our case report of PP, we describe an unusual course first presenting with the symptoms of chronic pancreatitis and a pseudocyst of the pancreatic tail. A pseudocystojejunostomy was performed and the late postoperative course was complicated with the symptoms of duodenal obstruction. At laparotomy, PP was found and the patient was treated with a total pancreatectomy. The postoperative course was uneventful and good weight gain with resolution of pain was demonstrated at follow up visits., Conclusion: Surgery is currently the optimal treatment option for PP. It is also the best diagnostic tool in distinguishing between pancreatitis and pancreatic adenocarcinoma., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare.

Background: To retrospectively analyze the outcomes of interventional radiology treatment of patients with hepatic artery stenosis (HAS) after liver transplantation at our Institution., Material/methods: Hepatic artery stenosis was diagnosed and treated by endovascular technique in 8 (2.8%) patients, who underwent liver transplantation between July 2007 and July 2011. Patients entered the follow-up period, during which we analyzed hepatic artery patency with Doppler ultrasound at 1, 3, 6, and 12 months after percutaneous endovascular treatment (PTA), and every six months thereafter., Results: During the 12-month follow-up period, 6 out of 8 patients (75%) were asymptomatic with patent hepatic artery, which was confirmed by multislice computed tomography (MSCT) angiography, or color Doppler (CD) ultrasound. One patient had a fatal outcome of unknown cause, and one patient underwent orthotopic liver retransplantation (re-OLT) procedure due to graft failure., Conclusions: Our results suggest that HAS angioplasty and stenting are minimally invasive and safe endovascular procedures that represent a good alternative to open surgery, with good 12-month follow-up patency results comparable to surgery.

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.

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.

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.

The synchronous or metachronous coexistence of gastrointestinal stromal tumors (GISTs) with solid and hematologic neoplasms has been addressed in a non-transplant population. However, the association with primary hepatic neoplasms and leukemias is uncommon. Scarce data exist considering association of GISTs and other neoplasms in a transplant population where long-term immunosuppression carries the additional burden of de novo malignancy. We present a case of posttransplant metachronous GIST and acute biphenotypic leukemia in a patient transplanted for intrahepatic cholangiocellular carcinoma, emphasizing the possible link between mechanisms of carcinogenesis and influence of other factors upon their development.

Ultrasound guided fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) are effective methods for the diagnosis of focal hepatic lesions. In case of neoplastic lesions, however, this may be followed by the seeding of malignant cells along the needle tract. We report a case of subcutaneous needle tract seeding of hepatocellular carcinoma (HCC) 25 months after liver transplantation. A 57-year-old man with compensated hepatitis-B-related liver cirrhosis was diagnosed with HCC by CNB, and the lesion was resected. Ten months after the procedure, FNAC of a small hepatic lesion confirmed tumor recurrence. The patient was successfully transplanted and 25 months later, a subcutaneous tumor appeared on the abdominal wall over the previous site of puncture without further dissemination of the disease. Total resection of the lesion confirmed HCC. It remains undetermined whether the seeding appeared after FNAC or CNB. After 18-month follow-up the patient was uneventful. The objectives of this report are to present clinical aspects and outcome of HCC needle tract seeding in a transplanted patient, discussing the problems and pitfalls of diagnostic workup and management of HCC.

Post-transplant lymphoproliferative disorder (PTLD) is an increasingly recognized condition as the number of solid organ and bone marrow transplant recipients increases. It can be a life threatening fulminant disorder and affects approximately 8% of solid organ transplant recipients. Epstein-Barr virus (EBV) is closely involved in the pathogenesis of PTLD and the majority of PTLD cases arise in response to primary infection with EBV or to re-activation of previously acquired EBV. The principal risk factors underlying the development of PTLD are the degree of overall immunosuppression and EBV serostatus of the recipient. The most commonly used pathologic classification of PTLD is the World Health Organization classification, which divides PTLD into three categories: early lesions, polymorphic PTLD, and monomorphic PTLD. Early lesions are characterized by reactive plasmacytic hyperplasia. Polymorphic PTLD may be either polyclonal or monoclonal and is characterized by destruction of the underlying lymphoid architecture, necrosis, and nuclear atypia. In monomorphic PTLD, the majority of cases (>80%) arise from B cells, similar to non-Hodgkin's lymphoma in immunocompetent hosts. The most common subtype is diffuse large B-cell lymphoma, but Burkitt's/Burkitt's-like lymphoma and plasma cell myeloma are also seen. Rarely T-cell variants occur, which include peripheral T-cell lymphomas and, rarely, other uncommon types, including gamma/delta T-cell lymphoma and T-natural killer (NK) cell varieties. Hodgkin's disease-like lymphoma is very unusual. An accurate diagnosis of PTLD requires a high index of suspicion, since the disorder may present subtly and/or extranodally. Radiologic evidence of a mass or the presence of elevated serum markers (such as increased LDH levels) are suggestive of PTLD, with positive finding on ultrasonography, computed tomography, magnetic resonance and/or positron emission tomography scanning (possibly indicating metabolically active areas) also favoring the diagnosis. The management of PTLD poses a major therapeutic challenge and although there is reasonable agreement about the overall principles of treatment, there is still considerable controversy about the optimal treatment of individual patients. EBV-related PTLDs are a significant cause of mortality in patients undergoing orthotopic liver transplantation with the observed mortality rate of up to 50%. This paper presents the experience acquired at Merkur University Hospital in the diagnosis and treatment of patients with liver transplantation and PTLD.

Hepatocellular carcinoma mostly develops in patients with liver cirrhosis due to chronic hepatitis C virus (HCV) infection. A case is presented of a patient with hepatorenal syndrome as a sequel of liver cirrhosis due to HCV infection. Primary tumor of the liver was not diagnosed by routine procedures, but by fine needle aspiration cytology of the extensive osteolytic lesion of the pelvic bone, performed as part of the pre-transplantation workup. Transplantation procedure was abandoned because of inappropriate donor liver (hepatic artery thrombosis), and palliative pain-relieving irradiation was recommended. However, hepatic coma developed very rapidly and the patient died within a month of the diagnosis of metastatic hepatocellular carcinoma. Although hepatocellular carcinoma metastases are not rare, massive bone infiltration from a primary tumor undetectable by routine methods is not frequently encountered.

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.

Recurrent infection with HCV after liver transplantation 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 orthotopic liver transplantation (OLT). By the fifth postoperative year, over 80% of HCV-infected liver transplant recipients will develop histologic evidence of chronic allograft injury secondary to hepatitis C, with up to 30% developing cirrhosis. While the choice of calcineurin inhibitor has not been clearly shown to affect histologic recurrence of hepatitis C or the frequency of rejection in HCV-infected recipients, cumulative exposure to corticosteroids is associated with increased mortality, higher levels of HCV viremia and more severe histologic recurrence. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated 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 initiated for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially for cytopenias, and drug discontinuation in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virologic response rates. The achieved SVR is between 33% and 42% in randomized studies treating patients with histologic recurrence and 0% to 33% when used in a preemptive protocol. The potential factors that influence this low SVR rate are: 1) high percentage of patients with genotype 1 virus; 2) high viral load at the start of treatment; 3) high percentage of prior non-responders to therapy; 4) side effects that often make the use of standard doses and duration of treatment difficult; 5) the use or not of growth factors; and 6) the effect of immunosuppression. In post-transplant patients with recurrent HCV disease, combination Peg alfa-2b or alfa-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.

Stevens-Johnson syndrome mostly involves the skin and mucous membranes. The diagnosis is made when the characteristic rash appears 1 to 3 weeks after exposure to a known stimulus and cannot be explained by some other diagnosis. A 62-year-old woman was admitted for evaluation of toxo-allergic dermatitis and collagenosis. Ten days prior to admission she was taking a course of azithromycin for upper respiratory tract infection. After a few days she was feeling better but maculopapular, erythematous rash developed over her palms, accompanied by fever and chills as well as reddish discoloration around her eyes. Within the next few days the rash progressed to the feet. Routine hematologic, biochemical and immunologic studies did not confirm the diagnosis of inflammatory rheumatic disease. Corticosteroid therapy with methylprednisolone (1 mg/kg) for the presumed Stevens-Johnson syndrome was started and her condition improved in several days; she became afebrile and her skin lesions gradually disappeared. There is only one report, in a child, documenting the association of Stevens-Johnson syndrome with azithromycin, as in this patient.