Optimizing Survival for Hepatocellular Carcinoma After Liver Transplantation: A Single-Center Report and Current Perspectives.

BACKGROUND: Hepatocellular carcinoma (HCC) is the leading primary liver tumor and a main indication for transplant. Transplant criteria are based on clinicopathologic features, meanwhile adequate downstaging and molecular mechanisms are getting more attention in evolving therapeutic algorithm of HCC. The aim of our study was to overview the results of the Hungarian Liver Transplant Program in the field of HCC and introduce new aspects of personalized treatment options. METHODS: We performed retrospective analysis of survival and tumor recurrence of HCC-associated liver transplant recipients between October 2013 and December 2020. Patients were categorized in Milan criteria (MC), beyond MC but within University of California, San Francisco (UCSF), and beyond UCSF criteria groups after pathologic examination of the explanted liver. Demographic data and preoperative locoregional treatments were assessed. RESULTS: A total of 529 primer liver transplants were performed, 88 because of HCC. A total of 87 patients had underlying cirrhosis because of hepatitis C (54%), alcohol-related liver disease (33.7%), hepatitis B (4.5%), or unknown etiology. A total of 55.6% of the patients had at least one locoregional treatment. A total of 67.4% of the patients were within MC, 5.6% were within UCSF criteria, and 27% were beyond UCSF criteria. The 1-, 3-, and 5-year survival rates were 80%, 79%, and 75%. The outcome was better in early-stage tumors, but the difference was not significant (P = .745) CONCLUSIONS: The favorable survival in our department legitimates the strict transplant criteria of HCC. Adequate locoregional therapy as downstaging can expand recipient pool. Molecular tumor profiling may lead to personalized treatment of HCC.

Evolution of liver transplant waiting list in Hungary between 1995 and 2019. / Májvárólista 1995-2019: a hazai adatok nemzetközi összehasonlítása.

Összefoglaló. Bevezetés: A májtranszplantációs program részeként 1995 óta létezik folyamatosan vezetett várólista Magyarországon. Célkituzés: A legfontosabb várólista-paraméterek megállapítása és nemzetközi összehasonlítása. Módszer: A szerzok az 1995. január 1. és 2019. december 31. között elso májátültetés céljából várólistára helyezett betegek adatait elemezték. Eredmények: Összesen 1722 beteget helyeztek várólistára, 1608 felnottet, 114 gyermeket. A férfiak aránya 51,2%, az átlagéletkor 45,6 év. Az évente regisztrált új jelöltek száma 25 év során közel az ötszörösére emelkedett. A listára helyezés leggyakoribb indikációja a víruseredetu cirrhosis volt (n = 451). Ezt követte a cholestaticus (n = 314) és az alkoholos májbetegség (n = 264). Rosszindulatú daganat, 82%-ban hepatocellularis carcinoma miatt 215 beteget regisztráltak. Krónikus betegségekben az átlagos Model for End-Stage Liver Disease pontszám a regisztráláskor 13,5 volt. A 2018. december 31-ig listára helyezettek (n = 1618) 61%-a részesült májátültetésben, 24%-a várakozás közben meghalt, 7%-a a mutétre alkalmatlanná vált. A mutét elotti medián várakozási ido 248 nap volt a krónikus és 2 nap az akut betegek listáján. A transzplantált tumoros betegek (n = 132) szignifikánsan rövidebb ideig vártak mutétre (medián 115,5 nap), mint a többi krónikus beteg (n = 803, medián 282 nap). Az Eurotransplanthoz való csatlakozás utáni idoszakban (2013. július 1. és 2018. december 31. között) a transzplantációs arány növekedett (67%), a várólista-halálozás (meghaltak + mutétre alkalmatlanná váltak) 24%-ra csökkent. Megbeszélés: A várólista folyamatos bovülése hozzájárult a hazai májátültetési program fejlodéséhez. A hazai várólista diagnózis szerinti összetétele a mások által közöltekkel nagyrészt egyezik. A transzplantáltak aránya a nemzetközi átlagnak megfelelo. A várólista-halálozás és a mutét elotti várakozási ido a magyarországinál alacsonyabb donációs aktivitású vagy jelentosen nagyobb várólistával rendelkezo országokéhoz hasonló. Következtetés: Várólista-paramétereink javításához a transzplantációk számának további növelése szükséges. Orv Hetil. 2022; 163(8): 301-311. INTRODUCTION: The Hungarian liver transplant program including waiting list started in 1995. OBJECTIVE: Evaluation of the wait-list parameters and comparing them with those in the literature. METHOD: Data of patients listed for primary liver transplantation between 1995 and 2019 were analyzed. RESULTS: A total of 1722 recipient candidates were registered on the liver transplant waiting list: 1608 adults (51.2% men) with mean age of 45.6 year and 114 patients aged <18 year. Virus-induced cirrhosis was the leading indication of listing (n = 451) and cholestatic liver diseases (n = 314) and alcoholic cirrhosis (n = 264) thereafter. The mean Model for End-Stage Liver Disease score was 13.5 for those with chronic disease. 61% of 1618 patients listed before December 31, 2018 underwent liver transplantation and 31% were removed from the wait-list for death or clinical deterioration. After joining Eurotransplant (period of 01. 07. 2013-31. 12. 2018), the transplant rate was 67%, the waiting list removal due to death/too sick for operation decreased to 24%. The median waiting time till transplantation was 248 days for those on elective and 2 days on acute list. Patients grafted with malignancy (n = 132) waited significantly shorter time than those with chronic non-malignant liver disease (median 115.5 versus 282 days). DISCUSSION: The composition of our waiting list by primary liver disease was similar to that of countries with large burden of hepatitis C. Transplant rate was average, wait-list mortality and waiting time were in line with those observed in low-donation countries or in the case of large volume waiting list. CONCLUSION: Listing of increasing the number of patients contributed to evolution of our liver transplant program. To improve our parameters, increasing transplant activity is warranted. Orv Hetil. 2022; 163(8): 301-311.

Steroid pretreatment of deceased donors and liver allograft function - Ten years follow-up of a blinded randomized placebo controlled trial.

BACKGROUND: Within the last decade numerous attempts have been reported in order to expand the donor pool and alleviate organ shortage in the setting of liver transplantation. Aim of this blinded randomized controlled trial was to evaluate the effect of donor steroid pretreatment on outcomes after liver transplantation. METHODS: We performed an international, multi-center double-blinded randomized placebo controlled trial. Donors received 1000 mg methylprednisone or placebo before organ procurement. Primary endpoint were patient and graft survival. Secondary end points were rate of BPAR and liver functions trajectories after transplantation. Follow up was 10 years. RESULTS: There was no effect of steroid pretreatment vs. placebo on overall patient survival (50% vs. 46%, p = n.s.) as well as graft survival (47% vs. 51%, p= n.s.). Further donor steroid pretreatment did not alter the rate of biopsy proven acute rejections (34% steroid group vs. 36% placebo, p = n.s.). Evaluating short term and long term graft function, steroid pretreatment had minor effect on immediate liver function trajectories within the first 2 weeks after transplantation. This was not seen in long-term follow up. CONCLUSION: In conclusion we found no evidence that donor steroid pretreatment translates in improved outcomes after liver transplantation.

Guidance on the special care of liver or kidney transplant recipients diagnosed with COVID-19 / Az új koronavírus (SARS-CoV-2) okozta fertozésben szenvedo vese- és májátültetett betegek ellátásának speciális szempontjai. (A COVID-19-pandémia orvosszakmai kérdései)

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.

[Liver transplantation in Wilson's disease patients, 1996-2017]. / Májátültetés Wilson-kóros betegekben, 1996­2017.

Introduction: Wilson's disease is a lethal-without-treatment inherited disorder of copper metabolism. Despite the increased focus on the diagnosis and treatment, liver transplantation is needed in a number of cases even nowadays. Aim: To collect and analyze the data of the Hungarian Wilson's disease patients who underwent liver transplantation. Method: Data of 24 Wilson's disease patients who underwent liver transplantation at the Semmelweis University have been analyzed retrospectively. The diagnosis of Wilson's disease was based on the international score system. The diagnosis of acute liver failure corresponded to the King's College criteria. All liver transplantations had been performed at the Department of Transplantation and Surgery of Semmelweis University, in 1996 for the first time. Results: The mean age was 26 years, F/M = 13/11. Twelve patients needed urgent liver transplantation for acute liver failure, and 12 underwent transplantation for decompensated liver cirrhosis. One patient had been retransplanted because of chronic rejection. Three patients with acute on chronic liver failure were transplanted via the Eurotransplant program. The mean time on the waiting list was 3 vs 320 days in acute liver failure and chronic liver disease groups, respectively. The overall 5-year survival was 66%, but it was 80% after 2002 indicating both the learning curve effect and the improvement of vigilance in Hungary. Despite difficulties of the diagnostic process, Wilson's disease was identified in 21/24 patients prior to the transplantation. Conclusion: Liver transplantation is needed in a number of cases of Wilson's disease. The ideal indication and timing of transplantation may improve the survival of the patients. Orv Hetil. 2019; 160(51): 2021-2025.

Liver Transplant for Metastatic Neuroendocrine Tumors: A Single-Center Experience in Hungary.

Unresectable liver metastases of gastroenteropancreatic neuroendocrine tumors are an accepted indication for liver transplant. Patients undergoing liver transplant because of neuroendocrine tumor liver metastases have similar long-term survival compared with hepatocellular carcinoma; however, recurrence rates are reported to be higher. METHODS: We performed a retrospective analysis of medical records of patients who received transplants for neuroendocrine tumor liver metastases in the Department of Transplantation and Surgery of Semmelweis University between January 1995 and August 2018. The median follow-up period was 33 months. RESULTS: Ten liver transplants have been performed because of neuroendocrine tumor liver metastases during the observed period. Recurrence occurred in 5 cases, and 3 patients died. Estimated 1- and 5-year patient survival rates after transplant were 89% and 71%, respectively. Estimated 1- and 5-year recurrence-free rates were 80% and 43%, respectively. Every patient whose primary tumor was of pancreatic origin or those recipients who had Ki67 index values in the explanted liver higher than 5% had disease recurrence. CONCLUSION: Patient survival and recurrence rates after liver transplant were comparable with the results reported by other centers. In line with previous findings, primary pancreatic neuroendocrine tumors and higher Ki67 index values in the explanted livers were both associated with higher recurrence rates. We believe that an international registry would be helpful to better understand factors leading to tumor recurrence in these cases.

Ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin in HCV genotype 1 infected patients who failed previous protease inhibitor therapy.

AIM OF THE STUDY: Combination of ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3DDA±RBV) therapy is shown to be effective in HCV genotype 1 (GT1) infected patients. However, sparse data exist in patients who failed previous boceprevir or telaprevir based therapies. Real life efficacy and safety of this combination were evaluated in HCV GT1b infected patients (mostly cirrhotics) with compensated liver disease who failed previous boceprevir or telaprevir based therapies more than a year before. MATERIAL AND METHODS: Data of previous protease inhibitor failure patients, treated with 3DAA+RBV for 12 weeks (GT1b and/or non-cirrhotics) or 24 weeks (non-GT1b cirrhotics), were retrospectively collected. RESULTS: Population characteristics: boceprevir/telaprevir-failure: 82/45, GT1b: 117, cirrhotic: 111 (87.4%). SVR12/24 was observed in 103/105 patients (98.1%) of those who reached either time point. Four SAEs reported: one death due to myocardial infarction, another due to recurrent hepatocellular carcinoma after achieving SVR12, two hospitalizations (elevation of transaminases, pneumonia). Grade ≥ 3 AEs or laboratory abnormalities were reported in < 10% of patients; they were transient in all patients. No early discontinuation of drugs due to SAE has been reported. CONCLUSIONS: One year after previous failure of boceprevir or telaprevir based therapy, 12 weeks of 3DAA+RBV combination in HCV GT1b infected patients is similarly effective and safe as in those with no previous HCV therapy, even in the presence of cirrhosis. These findings might be of particular interest in settings where alternative therapies for such patients are not available or not affordable.

[Benign liver tumours - current diagnostics and therapeutic modalities]. / A jóindulatú májdaganatok korszerû diagnosztikája és kezelési elvei.

The most common benign liver tumours are haemangiomas, focal nodular hyperplasia and hepatocellular adenoma. We perform a review of the literature and show the current diagnostic and therapeutic modalities based on the EASL Clinical Practice Guideline. With the widespread use of ultrasound, the detection of liver lesions is increased. They are usually found in women of childbearing age with atypical abdominal pain or incidentally. Contrast-enhanced US, CT or MRI are usually necessary for differential diagnosis. In atypical appearance or in malignancy suspect cases biopsy could be performed. For symptomatic patients conservative therapy can be sufficient. In haemorrhagic cases transarterial embolisation can be useful, also for tumour size decreasing before surgery. In patients with persisting symptoms, with vessel or soft tissue compression effect or in malignancy suspect cases definitive surgical treatment is advised. In men with hepatocellular adenoma primary resection is appropriate because of the higher risk for malignant transformation. As alternative treatment options radiofrequency ablation, irradiation, chemotherapy, monoclonal antibody therapy or liver transplantation are published.

[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 22 September 2017]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-tol.

The treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. The indication of therapy in patients with no contraindication is based on the demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Interferon-based or interferon-free therapies are available for the treatment. Due to their limited success rate as well as to their (sometimes severe) side-effects, the mandatory use of interferon-based therapies as first line treatment can not be accepted from the professional point of view. However, they can be used as optional therapy in treatment-naïve patients with mild disease. As of interferon-free therapies, priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund of Hungary and patients' organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv Hetil. 2018; 159(Suppl 1): 3-23.

[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 22 September 2017]. / A hepatitis B- és D-vírus-fertozés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-tol.

Diagnosis and treatment of hepatitis B virus (HBV) and hepatitis D virus infection mean for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms from 22 September 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0,5-0,7%. The indications of treatment are based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for a cost-effective approach, the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard as well as the relevance of appropriate consistent follow-up schedule for viral response during therapy. The first choice of therapy in chronic HBV infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Lamivudine is no longer the first choice; patients currently taking lamivudine must switch if the response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv Hetil. 2018; 159(Suppl 1): 24-37.

Reduced neural baroreflex sensitivity is related to enhanced endothelial function in patients with end-stage liver disease.

OBJECTIVES: Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS. MATERIALS AND METHODS: We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery. RESULTS: Integrated BRS was reduced in patients [7.00 (5.80-9.25) vs. 11.1 (8.50-14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.54 ± 1.20 vs. 4.48 ± 1.43 ms/10-3). FMD was higher in patients (9.81 ± 3.77 vs. 5.59 ± 1.36%). FMD and neural BRS were directly related in controls (r = 0.62), but inversely related in patients (r = -0.49). CONCLUSIONS: Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation.

Shear-wave elastography for the assessment of liver fibrosis in liver transplant recipients treated for hepatitis C virus recurrence.

OBJECTIVES: Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE. PATIENTS AND METHODS: A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment. RESULTS: All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P<0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline. CONCLUSION: In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.

[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 15 October 2016]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2016. október 15-tol.

Treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. Indication of therapy in patients with no contraindication is based on demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Therefore, expensive novel direct acting antiviral combinations as first line treatment are reimbursed only, if the freely available, but less effective and more toxic pegylated interferon plus ribavirin dual therapy deemed to prone high chance of adverse events and/or low chance of cure. Priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund and patient's organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv. Hetil., 2017, 158(Suppl. 1), 3-22.

[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 15 October 2016]. / A hepatitis B- és D-vírus-fertozés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2016. október 15-tol.

Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2017, 158(Suppl. 1) 23-35.

Hepatic fibrosis and factors associated with liver stiffness in HIV mono-infected individuals.

BACKGROUND: Liver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake. METHODS: We performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness. RESULTS: Liver stiffness ranged from 3.0-34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated. DISCUSSION: Our findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations.

Rapid height growth after liver transplantation in adulthood.

Glycogen storage disease Ib is a rare, inherited metabolic disorder caused by glucose-6-phosphatase translocase deficiency. Its main symptoms are hypoglycemia, hyperlipidemia, neutropenia, hepatomegaly, liver adenomas and short stature. The exact mechanism of short stature in this disease is unclear, the most feasible possibility is that it is caused by impairment of growth-hormone and insulin-like growth factor I axis. Here we report the case of a patient who showed typical symptoms of glycogen storage disease Ib since his infancy, his height being under 1 percentile since then. Later-developed hypothyroidism and hypogonadism have also contributed to his short stature. Hypothyroidism was treated but sexual steroid substitution was not started because of an increased risk of hepatic adenomas. Because he developed hepatic adenoma at the age of 23, he had to undergo orthotopic liver transplantation. At the time of the transplantation his height was 128cm. The transplantation was followed by rapid height growth; our patient's height reached 160.3cm 62months after transplantation. We observed that while his IGF-I level increased, his GH level remained unchanged. During the post-transplantation period we ensured adequate calcium and vitamin D supplementation, leaving hormonal substitution unchanged. According to our knowledge, this is the first report of a rapid height growth as big as 32cm, of an individual over the age of 20, not related to endocrine treatment but liver transplantation.

Quantitative morphometric and immunohistochemical analysis and their correlates in cirrhosis--A study on explant livers.

BACKGROUND: Reproducible structural analysis was made on cirrhotic human liver samples in order to reveal potential connections between morphological and laboratory parameters. MATERIAL AND METHODS: Large histological samples were taken from segment VII of 56 cirrhotic livers removed in connection with liver transplantation. Picro Sirius red and immunohistochemically (smooth muscle actin [SMA], cytokeratin 7 [CK7], Ki-67) stained sections were digitalized and morphometric evaluation was performed. RESULTS: The Picro Sirius-stained fibrotic area correlated with the average thickness of the three broadest septa, extent of SMA positivity, alkaline phosphatase (ALP) values and it was lower in the viral hepatitis related cirrhoses than in samples with non-viral etiology. The extent of SMA staining increased with the CK7-positive ductular reaction. The proliferative activity of the hepatocytes correlated positively with the Ki-67 labeling of the ductular cells and inversely with the septum thickness. These data support the potential functional connection among different structural components, for example, myofibroblasts, ductular reaction and fibrogenesis but challenges the widely proposed role of ductular cells in regeneration. CONCLUSION: Unbiased morphological characterization of cirrhotic livers can provide valuable, clinically relevant information. Similar evaluation of routine core biopsies may increase the significance of this 'Gold Standard' examination.

Predictive value of psychosocial assessment for the mortality of patients waiting for liver transplantation.

Selecting suitable candidates for liver transplantation is the most challenging task of pre-transplant evaluation. In addition to somatic assessment, psychosocial evaluation has been proven important in identifying patients at high risk of potential failure. The Transplant Evaluation Rating Scale (TERS) is a widely used rating instrument for the assessment of psychosocial risk factors before liver transplantation. The aim of this study was to explore the predictive value of TERS for mortality in liver transplant patients before and after transplantation. The medical records of patients referred for psychiatric evaluation before liver transplantation between 2003 -2013 were analysed. Administering TERS was part of the pre-transplant evaluation. The TERS scores of patients who died before and after transplantation were compared with those who survived following transplantation. One hundred and sixteen patients were referred for pre-transplant psychiatric evaluation. Patients with successful liver transplants scored significantly lower on TERS than those who died before transplantation (30.65 ± 6.06 vs. 34.75 ± 8.25, p = .031). Patients who died after transplantation scored significantly better on TERS than those who died before transplantation (28.79 ± 2.81 vs. 34.75 ± 8.25, p = .003). There was no significant difference between the deceased and surviving transplanted patients' TERS scores (28.79 ± 2.81 vs. 31.19 ± 6.66, p = .365). TERS appears to be a suitable rating instrument to help select candidates who have higher chance to survive prior to transplantation but it could not predict post-transplant mortality.

Liver transplantation in Central Europe.

INTRODUCTION: Transplant hepatologists convened in Warsaw on 20-21 November 2015 at a meeting of the Initiative Group for Central European Hepatologic Collaboration to exchange their experience in liver transplantation in their respective countries. MATERIAL AND METHODS: The description is based on narration of individual country representatives, supplemented by data from additional queries, and from publicly accessible sources. RESULTS: Liver transplantation programs were launched, in the Czech Republic in 1983, in Poland in 1990 (paediatric) followed by the adult program 1994; the first liver transplant in Hungary was performed in 1995, with Slovakia launching its liver transplantation program in 2008. Currently, there are 2 centres for liver transplantation in Slovakia, 1 centre in Hungary, 6 centres in Poland, and 2 centres in the Czech Republic. The rates of liver transplantation correspond to the number of cadaveric donations being the highest in the Czech Republic (15.8 per million population) and the lowest in Slovakia (4.2 per million population) (2014 data). Live donation is utilized systematically in Poland. Indications vary from country to country, but the 3 most frequent ones include hepatitis C and B cirrhosis, alcoholic cirrhosis, and cholestatic liver disorders. There is a growing incidence of hepatocellular carcinoma among adult liver transplant recipients. Biliary atresia and hereditary diseases are the most frequent indications among children. Hungary became a member of Eurotransplant, other countries are not a part of any international organization for organ sharing. CONCLUSIONS: Despite some differences, liver transplant programs seem to be compatible honouring the same values and principles universal to liver transplant programs in most parts of the world.

A hepatitis B- és D-vírus-fertozés diagnosztikája, antivirális kezelése. Magyar konszenzusajánlás. Érvényes: 2015. szeptember 12-tol.

Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2016 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous ente- cavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2015, 156(Suppl. 2) 25-36.