Validation of the New Diagnostic Criteria for Clinically Significant Portal Hypertension by Platelets and Elastography.

BACKGROUND AND AIMS: We aimed to validate newly proposed noninvasive criteria for diagnosing clinically significant portal hypertension (CSPH) using liver stiffness measurements (LSM) by transient elastography (TE) and platelet count. METHODS: Diagnostic performance of these new criteria for CSPH (LSM ≥ 25 kPa to rule in and Plt ≥ 150 × 109/L + LSM ≤ 15 kPa to rule out CSPH) were retrospectively tested in an independent cohort of consecutive patients who underwent hepatic venous pressure gradient (HVPG) measurements and liver biopsy due to suspicion of compensated advanced chronic liver disease. Suspicion of cACLD was based on LSM ≥ 10 kPa by TE or results of liver imaging, without overt signs of CSPH. Patients with conditions known to affect results of LSM (ALT > 5 × ULN, liver congestion, extrahepatic biliary obstruction, infiltrative liver neoplasms) were excluded. RESULTS: Seventy six (76) patients were included: 78.9% males, mean age 62 years, 36.8% suffered from alcoholic, 30.3% nonalcoholic fatty liver disease, 14.5% chronic viral hepatitis, 30.3% were obese, 52.6% had HVPG ≥ 10 mmHg, 56.6% had platelet count ≥ 150 × 109/L. LSM ≥ 25 kPa had 88.9% specificity (95% CI 73.9-96.9) to rule in, whereas Plt ≥ 150 + LSM ≤ 15 kPa had 100% sensitivity (95% CI 91.1-100) to rule out CSPH. CONCLUSION: By using these simple noninvasive criteria 49/76 (64.5%) patients could be classified correctly for the presence/absence of CSPH, thus obviating the need for HVPG measurements.

External Validation of UDCA Response Score in Slovak and Croatian Patients with Primary Biliary Cholangitis.

Background: Ursodeoxycholic acid response score (URS) is a prognostic model that estimates the baseline probability of treatment response after 12 months of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cholangitis (PBC). Aim: To independently evaluate the predictive performance of the URS model. Methods: We used a cohort of Slovak and Croatian treatment-naïve PBC patients to quantify the discrimination ability using the area under receiver operating characteristic curve (AUROC) and its 95% confidence interval (CI). Furthermore, we evaluated the calibration using calibration belts. The primary outcome was treatment response after 12 months of UDCA therapy defined as values of alkaline phosphatase ≤1.67 × upper limit of normal. Results: One hundred and ninety-four patients were included. Median pretreatment age was 56 years (interquartile range 49-62). Treatment response was achieved in 79.38% of patients. AUROC of the URS was 0.81 (95% CI 0.73-0.88) and the calibration belt revealed that response rates were correctly estimated by predicted probabilities. Conclusion: Our results confirm that the URS can be used in treatment-naïve PBC patients for estimating the treatment response probability after 12 months of UDCA therapy.

Cardiovascular mortality in liver and kidney transplant recipients: A retrospective analysis from a single institution.

ABSTRACT: Previous studies have demonstrated cardiovascular causes to be among the leading causes of death after liver (LT) and kidney transplantation (KT). Although both recipient populations have unique pre-transplant cardiovascular burdens, they share similarities in post-transplant exposure to cardiovascular risk factors. The aim of this study was to compare cardiovascular mortality after LT and KT.We analyzed causes of death in 370 consecutive LT and 207 KT recipients from in-hospital records at a single tertiary transplant center. Cardiovascular causes of death were defined as cardiac arrest, heart failure, pulmonary embolism, or myocardial infarction.After a median follow-up of 36.5 months, infection was the most common cause of death in both cohorts, followed by cardiovascular causes in KT recipients and graft-related causes in LT recipients in whom cardiovascular causes were the third most common. Cumulative incidence curves for cardiovascular mortality computed with death from other causes as the competing risk were not significantly different (P = .36). While 1-year cumulative cardiovascular mortality was similar (1.6% after LT and 1.5% after KT), the estimated 4-year probability was higher post-KT (3.8% vs. 1.6%). Significant pre-transplant risk factors for overall mortality after KT in multivariable analysis were age at transplantation, left ventricular ejection fraction <50%, and diastolic dysfunction grade 2 or greater, while significant risk factors for cardiovascular mortality were peripheral artery disease and left ventricular ejection fraction <50%. In the LT group no variables remained significant in a multivariable model for either overall or cardiovascular mortality.The present study found no significant overall difference in cardiovascular mortality after LT and KT. While LT and KT recipients may have similar early cardiovascular mortality, long-term risk is potentially lower after LT. Differing characteristics of cardiovascular death between these two patient populations should be further investigated.

Nonalcoholic Fatty Liver Disease and Sarcopenia: Where Do We Stand?

The link between metabolic syndrome (MetS) and sarcopenia has not been extensively studied, but it is evident that they share several common features. Crucial mechanisms involved in sarcopenia-nonalcoholic fatty liver disease (NAFLD) interplay are based on effects of insulin resistance, chronic inflammation, oxidative stress, and crosstalk between organs by secretion of cytokines (hepatokines, adipokines, and myokines). Currently, published studies confirm the association of sarcopenia with the degree of NAFLD defined by liver histology. However, prospective studies that will give us information regarding the causal effect of NAFLD and sarcopenia are still needed. Furthermore, there is a need for a patient-friendly, noninvasive, low-cost method for detection of loss of skeletal muscle mass, strength, and physical performance in the context of NAFLD. Moreover, potential treatment strategies such as physical exercise and nutritional supplementation, that are usually a part of management of sarcopenia, should also be investigated in NAFLD patients, especially given the fact that for now, we do not have a good treatment option for NAFLD. Therefore, future investigations should combine studies on NAFLD and sarcopenia in terms of physical activity and nutritional interventions such as vitamin D supplementation. This review aims to report recent evidence concerning the links between sarcopenia and NAFLD and methods to assess sarcopenia.

Constrictive pericarditis as a cause of refractory ascites after liver transplantation: A case report.

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.

Role of total pancreatectomy in the treatment of paraduodenal pancreatitis: A case report.

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.

[Croatian guidelines for diagnostics and treatments of Helicobacter pylori infection]. / Hrvatski postupnik za dijagnostiku i terapiju infekcije Helicobacterom pylori.

In the past 30-year period of investigations, the crucial role of Helicobacter pylori in chronic gastritis, gastric and duodenal ulcer development, and subsequently in gastric cancer and MALT lymphoma pathogenesis, has been recognized. During the first meeting of European Helicobacter Study Group in 1996 in Maastricht, the first recommendations for diagnostics and treatments of Helicobacter pylori infection were published, later reviewed in 2000, 2007 and 2010. The first meeting of Croatian doctors focusing on the same topics, but suitable to specific national circumstances, was held as early as 1998. The need for updating the old guidelines has emerged during the last years. The working expert group of gastroenterologists was formed and gathered on Consesus Conference in December 2012 in Zagreb, to arrive to current guidelines for the clinical management of Helicobacter pylori infection in Croatia. The following topics relating to Helicobacter pylori infection were examined: 1. indications and contraindications for diagnostics and treatments; 2. diagnostic methods and 3. treatments applicable in our country.

Helicobacter pylori: future perspectives in therapy reflecting three decades of experience.

The rising prevalence of antibiotic resistance has created a need to reassess the established Helicobacter pylori (H. pylori) eradication protocols, and to develop new ones. Various bacterial and host factors are evaluated, and their contribution to eradication failure is estimated. For a long time being considered the cornerstone eradication scheme, the standard triple therapy has been replaced with novel, more efficient regimens, namely sequential and concomitant, along with the emergence of a new design of bismuth quadruple therapy. A rescue levofloxacin based regimen has overcome the fear of therapy failure due to higher prevalence of dual resistant (clarithromycin and metronidazole) H. pylori. Culture-free and efficient susceptibility test are reestablishing the concept of tailored therapy, making eradication success close to originally desirable rates. Alleviating therapy side effects and improving patient compliance are as important as choosing appropriate eradication schemes, so various probiotic compound supplements are taken into consideration. Finally, we summarize the emerging efforts and obstacles in creating efficient H. pylori vaccine.

Drug-Induced Liver Injury Associated with Noni (Morinda citrifolia) Juice and Phenobarbital.

Noni (Morinda citrifolia) juice is a popular herbal dietary supplement globally used for preventive or therapeutic purposes in a variety of ailments, claiming to exhibit hepatoprotective properties as well. Herein we present the case of a 38-year-old woman who developed acute liver injury associated with noni juice consumption on a long-term (9 months) anticonvulsant therapy. Clinical presentation and liver biopsy were consistent with severe, predominantly hepatocellular type of injury. Both agents were stopped and corticosteroids were initiated. Five months later the patient had fully recovered. Although in the literature the hepatotoxicity of noni juice remains speculative, sporadic but emerging cases of noni juice-associated liver injury address the need to clarify and investigate potential harmful effects associated with this supplement.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

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.

[Liver transplantation in hepatitis B viral infection]. / Terapija hepatitisa B nakon 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]. / Terapija HCV infekcije nakon transplantacije jetre.

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.

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.

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.