End-stage Chronic Liver Disease Research Articles

Selection for Liver Transplantation: Indications and Evaluation.

Purpose of ReviewLiver transplantation is an important therapeutic option for patients with life-limiting liver disease, which may present in the form of acute liver failure, end-stage chronic liver disease, primary hepatic cancers, or inborn metabolic disorders. While significant strides have been made with respect to liver transplantation outcomes, the practice is constrained by an organ supply/demand mismatch. The purpose of this review, therefore, is to review the general indications and contraindication to liver transplantation, and to provide an overview of the transplant evaluation process. These considerations ultimately shape the specific criteria for patient selection, which will continue to evolve as means are developed to expand the donor pool, improve surgical techniques, broaden indications for safe transplant, and extend the lifetime of a graft.Recent FindingsSelected patients with unresectable hilar cholangiocarcinoma may be candidates for liver transplantation. Patients over 65 years may be transplant candidates if they possess a favorable comorbidity profile. Patients at body mass index extremes (≥ 40 or < 18.5) have increased post-transplant mortality and require nutritional evaluation.SummaryLiver transplantation may be life saving for patients with acute liver failure or end-stage liver disease. It is therefore critical for healthcare providers caring for patients with liver disease to be familiar with the general indications for transplantation and to know when it is appropriate or inappropriate to refer for transplant evaluation.

Gastrointestinal complications of liver cirrhosis

Liver cirrhosis is the end-stage of chronic liver disease and can affect the function of multiple organs. Gastrointestinal tract damage resulting from cirrhosis is more common in clinic, which may cause gastroparesis, affect the digestion and absorption of nutrients, and destroy the intestinal mucosal barrier function. In addition, it may be accompanied by a series of gastrointestinal complications that affect the patient's prognosis. Clinically, more attention should be paid to early monitoring, early diagnosis and early treatment of cirrhosis-related gastrointestinal complications so to control the progression of liver cirrhosis condition, reduce advanced stage complications, and improve patient's quality of life.

In vitro differentiation of rhesus macaque bone marrow- and adipose tissue-derived MSCs into hepatocyte-like cells.

Orthotopic liver or hepatocyte transplantation is effective for the treatment of acute liver injury and end-stage chronic liver disease. However, both of these therapies are hampered by the extreme shortage of organ donors. The clinical application of cell therapy through the substitution of hepatocytes with mesenchymal stem cells (MSCs) that have been differentiated into hepatocyte-like cells (HLCs) for liver disease treatment is expected to overcome this shortage. Bone marrow and adipose tissue are two major sources of MSCs [bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs), respectively]. However, knowledge about the variability in the differentiation potential between BM-MSCs and AT-MSCs is lacking. In the present study, the hepatogenic differentiation potential of rhesus macaque BM-MSCs and AT-MSCs was compared with the evaluation of morphology, immunophenotyping profiles, differentiation potential, glycogen deposition, urea secretion and hepatocyte-specific gene expression. The results indicated that BM-MSCs and AT-MSCs shared similar characteristics in terms of primary morphology, surface markers and trilineage differentiation potential (adipogenesis, osteogenesis and chondrogenesis). Subsequently, the hepatogenic differentiation potential of BM-MSCs and AT-MSCs was evaluated by morphology, glycogen accumulation, urea synthesis and expression of hepatocyte marker genes. The results indicated that rhesus BM-MSCs and AT-MSCs had hepatogenic differentiation ability. To the best of our knowledge, this is the first report to detect the hepatogenic differentiation potential of rhesus macaque BM-MSCs and AT-MSCs. The present study provides the basis for the selection of seed cells that can trans-differentiate into HLCs for cytotherapy of acute or chronic liver injuries in either clinical or veterinary practice.

Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis.

Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.

The role of Caspase‐1 in diet induced chronic liver injury and blood bile barrier regulation

End‐stage chronic liver disease is a major cause of mortality worldwide. Irrespective of the underlying cause, most chronic liver diseases are characterized by fibrosis, hepatocellular necrosis, inflammation, ductular reactions and proliferation of the liver progenitor cells. Vast differences exist between experimental models that mimic these processes, and their identification is fundamental for translational research. However, the underlying differences in the molecular mechanism driving liver injury in different models remains largely unknown due to our inability to visualize the initiation and progression of liver injury in vivo in mice. Recently we have introduced quantitative Liver Intravital Microscopy (qLIM) that enables real‐time assessment of bile transport and blood‐bile barrier (BBlB) integrity in the intact liver of live mice (Pradhan‐Sundd et al., Gastroenterology, 2018) to visualize injury progression in two widely used experimental models of chronic liver injury ‐the choline‐deficient ethionine‐supplemented (CDE) or 3, 5‐diethoxycarbonyl 1, 4‐dihydrocollidine (DDC) diet, respectively. qLIM analysis revealed that chronic liver injury involves physical breach of BBlB, mixing of blood with bile and loss of bile transport across hepatocytes in both CDE and DDC diet fed mice. Mechanistically we showed an association of disruption of the BBlB and loss of various tight junctional proteins with sustained inflammation and apoptotic cell death (Pradhan‐Sundd et al., Gastroenterology, 2018). Thus, we hypothesized that blocking Caspase ‐1 induced inflammatory response can inhibit the loss of BBlB and thus postpone the chronic liver injury initiation in these diet fed mice. Indeed, mice with deletion of caspase‐1 displayed reduced liver injury, ductular reaction, fibrosis, inflammation, and apoptosis after two weeks of CDE and DDC diet. Remarkably, qLIM analysis showed intact blood biliary barrier at day 4 and 6 of CDE and DDC fed mice suggestive of delay in injury initiation. Furthermore, we demonstrate that the recovery from CDE and DDC diet induced liver injury is significantly accelerated in caspase‐1 KO mouse. We also found upregulation several tight junctional claudins in the liver upon caspase ‐1 knockdown. Current investigation is underway to analyse the regulation of tight junctional claudins by Caspase‐1. These findings may lead insight to disease progression and possible treatment of diet induced chronic liver injury.

Diagnostic value of serum leptin as a tumor marker in hepatocellular carcinoma

Abstract Background Leptin is a peptide hormone produced by adipocytes, acts on the energy balance of reproduction and immunomodulation, and this action is linked to the pathogenesis of many diseases. High levels of this hormone increase hepatic response to various stimuli of liver fibrosis. Leptin acts to mediate hepatic stellate cell activation and liver fibrosis throughout indirect effects on Kupffer cells The aim The aim is to evaluate diagnostic value of serum leptin as a tumor marker in hepatocellular carcinoma (HCC). Methods 90 Egyptian subjects were conducted to this study after their written informed consent. They divided into 4 groups (30 patients with untreated HCC, 30 patients with treated HCC, 15 patients with end stage chronic liver disease without HCC and 15 healthy controls). They subjected to full history, examination, laboratory investigation and abdominal ultrasound. Serum leptin assessment is done using ELISA method. Results Leptin level is increased in all patients groups compared to control ((med. 40 IQR 37-50, med. 8 IQR 3-20, med. 2 IQR 1-4 VS med.1 IQR 1-1 ng/ml respectively) also it was higher in untreated HCC and treated HCC patients than patients without HCC. (med. 40 IQR 37-50, med. 8 IQR 3-20 VS med. 2 IQR 1-4) . Furthermore, leptin level is higher in untreated HCC than treated HCC(med. 40 IQR 37-50 VS med. 8 IQR 3-20) Leptin positively correlated with HCC Conclusion Leptin level in HCC either untreated or treated patients and in end stage CLD patients is higher than healthy .Also, it’s higher in HCC patients either untreated or treated than cirrhotic patients without HCC . Furthermore, leptin level is higher in un treated HCC than treated HCC patients.

Role of Serum Leptin in the Diagnosis and Prognosis of Hepatocellular Carcinoma in Egyptian Cirrhotic Patients

Abstract Background: Hepatocellular carcinoma is the most com-mon primary hepatic malignancy with an average survival rate of 6-20 months. The primary etiology of hepatocellular carcinoma in Egyptian patients is liver cirrhosis. Alfa fetopro-tein is the most commonly used biomarker for HCC diagnosis, in spite of its low sensitivity and specificity in HCC screening; it is usually combined with ultrasound for early detection of HCC. Leptin is a multifunctional peptide hormone that is produced by adipocytes with neuroendocrine activity. Leptin is postulated to increase the hepatic response to different stimuli of liver fibrosis. The actions of leptin are mediated via hepatic stellate cell activation, and liver fibrosis occurs through its indirect effect on the Kupffer cells. Moreover, it regulates the phosphoinositide 3-kinase/protein kinase B (PI-3K/Pkt) pathway, which plays an essential step in the cell motility, proliferation, survival, and angiogenesis in tumor cells including Hepatocellular Carcinoma (HCC). Thus, leptin can promote HCC proliferation, migration, and invasion. Aim of Study: The present study aimed to evaluate the diagnostic and prognostic value of serum Leptin as a tumor marker in Hepatocellular Carcinoma (HCC) in comparison to Alpha-Fetoprotein (AFP). Subjects and Methods: This study included 180 Egyptian patients that were divided into 4 groups (Group 1: 60 patients with untreated HCC, Group 2: 60 patients with treated HCC, Group 3: 30 patients with end-stage chronic liver disease without HCC) in addition to Group 4: 30 age-matched healthy subjects serving as a healthy control group. All patients and controls were subjected to full history, clinical examination, laboratory investigation, and abdominal ultrasonography (U/S). Serum leptin and alpha-fetoprotein were assayed by using Enzyme-Linked Immunosorbent Assay (ELISA) tech-nique. Results: The results of the present study revealed that serum leptin levels were significantly increased in all the patients' groups when compared to controls; besides, it was significantly higher in untreated and treated HCC patients groups when compared to patient’s group without HCC.Furthermore, serum leptin levels were significantly higher in the patients group with untreated HCC compared to the treated HCC patients group with positive correlation with AFP. Conclusion: AFP was more sensitive and specific in differentiation between cirrhotic patients with or without HCC than Leptin. However, Leptin has a good sensitivity and specificity in differentiating between untreated and treated HCC patients, and it is superior to AFP in the specificity of the differentiation between these two categories. Therefore, serum leptin can be used as a useful screening marker for the diagnosis and prognosis of HCC patients combined with Alfa fetoprotein.

Long-chain fatty acyl-coenzyme A suppresses hepatitis C virus infection by targeting virion-bound lipoproteins

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis and end-stage liver diseases. Mature HCV virions are bound by host-derived lipoproteins. Lack of an HCV vaccine warrants a major role of antiviral treatment in the global elimination of hepatitis C. Although direct-acting antivirals (DAAs) are replacing the interferon-based treatment and have dramatically improved the cure rate, the presence of viral variants resistant to DAAs, HCV genotype/subtype-specific efficacy, and high cost of DAAs argue novel and affordable regimens. In this study, we identified the antiviral effects of long-chain fatty acyl-coenzyme A (LCFA-CoA) against the infections of HCV genotypes 1–6 through targeting mature HCV-bound lipoproteins, suggesting novel mechanism(s) of antiviral different from those used by host-targeting agents or DAAs. We found that the antiviral activity of LCFA-CoA relied on the long-chain saturated fatty acid and the CoA group, and was enhanced when combined with pegylated-interferon or DAAs. Importantly, we demonstrated that LCFA-CoA efficiently inhibited the infection of HCV variants carrying DAA-resistant mutations. The mechanistic study revealed that LCFA-CoA specifically abolished the attachment and binding steps and also inhibited the cell-to-cell viral transmission. LCFA-CoA targeted mature HCV-bound lipoproteins, but not apolipoproteins B or E. In addition, LCFA-CoA could also inhibit the infection of the dengue virus. Our findings suggest that LCFA-CoA could potentially serve as a supplement HCV therapy, particularly for the DAA-resistant HCV variants. Taken together, LCFA-CoA may be further developed to be a novel class of antivirals with mechanism(s), different from host-targeting agents or DAAs, of targeting the components associated with mature HCV virions.

Endovascular Treatment of Hepatic Venous Outflow Obstruction after Liver Transplant

AbstractLiver transplantation provides definitive treatment to address acute or chronic end-stage liver disease and its complications. Hepatic venous outflow obstruction is an infrequent complication of liver transplantation that affects graft survival by compromising outflow via transplant hepatic veins or inferior vena cava. It can occur in the early postoperative phase or in a delayed manner, resulting in venous congestion, graft dysfunction, graft failure, and death. This article addresses the pathophysiology of venous outflow obstruction as it relates to different surgical techniques and patient populations, the noninvasive tools for diagnosis, and the endovascular options for treatment along with their safety, efficacy, and durability.

The Burden of Liver Cirrhosis and Underlying Etiologies: Results from the Global Burden of Disease Study 2017

Background: Liver cirrhosis is a major health issues throughout the world and is characterized as the end-stage of chronic liver disease. The etiologies of liver cirrhosis including hepatitis, alcohol, NASH and other causes, but rare study explored the prevalence trend of liver cirrhosis caused by specific etiologies. Aiming to study the pattern and prevalence trend of liver cirrhosis, we conducted the study. Methods: Based on the Global Burden of Disease 2017, we collected detailed data of liver cirrhosis during the period from 1990 to 2017. Age standardized prevalence rate (ASR) and estimated annual percentage changes (EAPC) were used to estimate the trend of liver cirrhosis prevalence by population, etiology and region. Findings: Globally, the prevalence cases of liver cirrhosis increased 74.55% from 1990 to 2017. The worldwide ASR of liver cirrhosis increase 0.75 per year during the period. Among the etiologies, NASH caused liver cirrhosis accounted for 59.46% in 2017. The ASR of liver cirrhosis caused by NASH increased 1.74 per year all over the world during the period. Additionally, the ASR of liver cirrhosis caused by NASH increased in 195 countries and territories and in all 5 SDI regions. Besides, the ASR of liver cirrhosis caused by alcohol use also increased. Contrary, the ASR of liver cirrhosis caused by HBV and HCV decreased. The ASR of liver cirrhosis caused by other causes remained stable during the same period. The increasing pattern was heterogeneous across regions and countries. The most pronounced increases were found in middle-high and high SDI regions, especially in Caribbean, Andean Latin America and Southern Latin America. Interpretation: By using vaccine and direct-acting antiviral therapy, the number of people suffered HBV and HCV decreased, but liver cirrhosis still confirmed to be a major threat to human health. Additionally, the number of people with cirrhosis caused by alcohol use and NASH continues to grow. Thus, more target and specific strategies should be established in various countries based on the etiology and prevalence trend of liver cirrhosis. Funding: This study was supported by the Hunan Provincial Natural Science Foundation of China (No. 2018JJ3715 and No. 2017JJ3448). Declaration of Interest: The authors declare no conflicts of interest. Ethical Approval: Not required.

Resting Energy Expenditure of Children With End-stage Chronic Liver Disease Before and After Liver Transplantation.

Our objective was to test the hypothesis that children with end-stage chronic liver disease (ESCLD) are hypermetabolic when compared to healthy children, and that this hypermetabolism persists for at least 6 months after liver transplant. Seventeen patients with end-stage chronic liver disease and 14 healthy controls had their resting energy expenditure measured (mREE) by indirect calorimetry. Weight, height, and body mass index were converted to standard deviation (SD) scores. Children older than 5 years had air displacement plethysmography and patients older than 5 years also had whole body dual-energy X-ray absorptiometry with characterization of fat mass (FM), fat-free mass (FFM), and bone-free fat free (lean) mass. When compared to the prediction equation 44% of the patients and 50% of the healthy controls were hypermetabolic. The younger patients (0-5 years) had a lower mREE than the healthy controls but were significantly lighter and shorter than their healthy counterparts. mREE correlated strongly for all children with age, weight, height, and FFM. There was a strong negative correlation between age and mREE/kg in both patients (rs = -0.94, P < 0.01) and controls (rs = -0.91, P < 0.01). Almost 84% of the variance in mREE was explained by age (P < 0.001). There were no significant differences between resting energy expenditure (REE)/FFM between the 2 groups. mREE/kg before liver transplant correlated with mREE/kg after transplant (Pearson r = 0.83, P < 0.01). REE mostly reflected the size of the child. The patients were not hypermetabolic when compared to the healthy children. The main determinant of REE/kg after transplant was REE/kg before transplant.

Effect of Fufang Biejia Ruangan Tablet on lowering biochemical and virological parameters of hepatic fibrosis in patients with chronic hepatitis B: Protocol for a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Background:Liver cirrhosis is one of the end-stage chronic liver diseases. Individuals with chronic hepatitis B (CHB) are at an increased risk of developing liver cirrhosis. Practice guidelines underline that Nucleos(t)ide analogs (NAs) should be the first-line treatment for hepatitis B virus (HBV)-related cirrhosis. However, prolonged use of NAs may lead to drug resistance and kidney impair and does not reverse the fibrosis of liver. Fufang Biejia Ruangan Tablet (RGT), as a traditional Chinese medicine (TCM), has been proved to be effective in the treatment of liver fibrosis. Hence, we will perform meta-analysis in order to evaluate the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB.Methods:To search for relative literatures up to February 2019 by computer from the following databases: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodicals Database, Chinese BioMedical Database and Wanfang Data. Included criteria are randomized controlled trials and cohort studies of hepatic fibrosis in patients with CHB treated by RGT. The primary outcome measures include biochemical and virological parameters. We will use Stata 13.0 software for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. The reporting bias will be assessed by a funnel plot and the funnel plot symmetries will be evaluated by Begg and Egger tests. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence.Results:This systematic review will provide a synthesis of RGT for hepatic fibrosis in patients with CHB from various evaluation aspects including biochemical and virological parameters, HBV DNA levels HBeAg status and seroconversion, adverse events incidence.Conclusion:The systematic review will provide evidence to assess the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB.PROSPERO registration number:ROSPERO CRD 42018095122.

Short- and Long-Term Outcomes After Live-Donor Transplantation with Hyper-Reduced Liver Grafts in Low-Weight Pediatric Recipients

ObjectiveTo evaluate short- and long-term outcomes after live-donor liver transplantation (LT) with hyper-reduced grafts in low-weight pediatric recipients. Summary Background DataLT is an established curative therapy for children with end-stage chronic liver disease or acute liver failure. A major problem in pediatric LT has been the lack of size-matched donor organs. The disadvantage of the use of large-for-size grafts is the insufficient tissue oxygenation and graft compression, which result in poor outcomes. The shortage of suitable donors is most notable in children under 10 kg. To overcome such obstacle, in situ hyper-reduced live-donor liver grafts have been introduced. Available articles in the literature are based on small samples and are deficient in long-term follow-up. MethodsA single-cohort, retrospective analysis was conducted including 59 pediatric patients under 10 kg who underwent hyper-reduced (in situ “a la carte” left lateral segment reduction) live-donor LT (LDLT) between February 1994 and February 2018. ResultsThe most frequent cause of liver failure was biliary atresia (70%). Median recipient weight was 8 kg. Vascular complications were confirmed in 15% of the sample, while 45% presented biliary complications. Median follow-up time was 40.3 months. Ten-year overall survival rate was 74%. Pediatric end-stage liver disease score > 23 was associated with a higher risk of post-operative complications. ConclusionLDLT can be undertaken in children with body weight < 10 kg achieving good results in high-volume centers by experienced surgeons.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

The ILTS Consensus Conference on NAFLD/NASH and Liver Transplantation: Setting the Stage.

Hepatocyte-specific suppression of microRNA-221-3p mitigates liver fibrosis

Fibrosis, a cardinal feature of a dysfunctional liver, significantly contributes to the ever-increasing mortality due to end-stage chronic liver diseases. The crosstalk between hepatocytes and hepatic stellate cells (HSCs) plays a key role in the progression of fibrosis. Although ample efforts have been devoted to elucidate the functions of HSCs during liver fibrosis, the regulatory functions of hepatocytes remain elusive. Using an unbiased functional microRNA (miRNA) screening, we investigated the ability of hepatocytes to regulate fibrosis by fine-tuning gene expression via miRNA modulation. The in vivo functional analyses were performed by inhibiting miRNA in hepatocytes using adeno-associated virus in carbon-tetrachloride- and 3,5-di-diethoxycarbonyl-1,4-dihydrocollidine-induced liver fibrosis. Blocking miRNA-221-3p function in hepatocytes during chronic liver injury facilitated recovery of the liver and faster resolution of the deposited extracellular matrix. Furthermore, we demonstrate that reduced secretion of C-C motif chemokine ligand 2, as a result of post-transcriptional regulation of GNAI2 (G protein alpha inhibiting activity polypeptide 2) by miRNA-221-3p, mitigates liver fibrosis. Collectively, miRNA modulation in hepatocytes, an easy-to-target cell type in the liver, may serve as a potential therapeutic approach for liver fibrosis. Liver fibrosis majorly contributes to mortality resulting from various liver diseases. We discovered a small RNA known as miRNA-221-3p, whose downregulation in hepatocytes results in reduced liver fibrosis. Thus, inhibition of miRNA-221-3p may serve as one of the therapeutic approaches for treatment of liver fibrosis.

Transplantation for the Very Sick Patient—Donor and Recipient Factors

Patients with end-stage chronic liver disease (CLD) frequently deteriorate with development of a ‘frail’ state and progress to development of extra-hepatic organ failures. Making the clinical judgement when a patient is ‘too sick’ to proceed with liver transplantation is challenging; we summarise recent studies that may inform decision-making. Reports quantify the impact of both recipient and donor factors related to early post-transplant survival, with consistent adverse association of advanced donor and recipient age, under-nutrition, sarcopenia and impaired functional status, and requirement for critical care unit admission and organ support. Survival for ‘very sick’ recipients has shown progressive improvement over time, but evidence is increasing of much greater post-transplant resource use and cost. Factors associated with adverse outcomes in very sick recipients are becoming more clearly delineated. The increasing success of transplantation and exploration of its extended use must be tempered by the recognition of the consequences upon constrained clinical resources.

Role of Duplex Ultrasonography in Correlation With CT Angiography In Assessment Of Vascular Complications In Recipients Post Liver Transplantation

Background: Liver transplantation is currently accepted as a first line treatment for patients with end-stage acute or chronic liver diseases. Graft survival and overall patient survival have steadily improved since the first transplants were performed in the early 1960s, but a significant percentage of transplants develop complications related to vascular and biliary insufficiency. Graft ischemia after liver transplantation is associated with a high incidence of morbidity and mortality. Aim of the Work: to evaluate the sensitivity and specificity of Duplex ultrasound in detection most of vascular complication after liver transplantation in correlation with CTA. Patients and Methods: The study was done from Aug. 2017 until Aug. 2018, where 50-55 cases who underwent living donor liver transplantation with post-operative complications. The cases were done at Ain Shams University Hospital and other private hospitals. All cases where admitted to post-transplanting intensive care unit in the postoperative period where a routine full laboratory and radiological assessment were done. The laboratory assessment included full liver function tests, kidney function tests, complete blood picture, and C-Reactive Protein. Immunosuppressant level and bilirubin level in drains had also done. Results: The patient age ranges from 36 to 53 years with the mean age of 45 years. Most cases have cases had hepatitis C related cirrhosis (90%). One case had veno-occlusive disease related cirrhosis (Budd Chiari syndrome). About 95% of cases were suffering from end stage liver disease. The results we have reached are that Doppler U/S sensitivity in diagnosis of these complications is 83.8% and CTA sensitivity is about 100%. Conclusion: It could be concluded that colour duplex is the investigations of choice in postoperative liver transplantation. They can be used as routine steps in the assessment of liver transplant graft postoperatively in recipient patient as early as possible within the first 3 days after operation and used as a late follow up, as they are noninvasive, safe, cheap, and accurate. Routine use of gray-scale US and color duplex showed to minimize the impact of postoperative complications and maximize both graft and recipient patient survival and if any complications suspected, it can be confirmed by CTA

Role of Duplex Ultrasonography in Correlation With CT Angiography In Assessment Of Vascular Complications In Recipients Post Liver Transplantation

Background: Liver transplantation is currently accepted as a first line treatment for patients with end-stage acute or chronic liver diseases. Graft survival and overall patient survival have steadily improved since the first transplants were performed in the early 1960s, but a significant percentage of transplants develop complications related to vascular and biliary insufficiency. Graft ischemia after liver transplantation is associated with a high incidence of morbidity and mortality. Aim of the Work: to evaluate the sensitivity and specificity of Duplex ultrasound in detection most of vascular complication after liver transplantation in correlation with CTA. Patients and Methods: The study was done from Aug. 2017 until Aug. 2018, where 50-55 cases who underwent living donor liver transplantation with post-operative complications. The cases were done at Ain Shams University Hospital and other private hospitals. All cases where admitted to post-transplanting intensive care unit in the postoperative period where a routine full laboratory and radiological assessment were done. The laboratory assessment included full liver function tests, kidney function tests, complete blood picture, and C-Reactive Protein. Immunosuppressant level and bilirubin level in drains had also done. Results: The patient age ranges from 36 to 53 years with the mean age of 45 years. Most cases have cases had hepatitis C related cirrhosis (90%). One case had veno-occlusive disease related cirrhosis (Budd Chiari syndrome). About 95% of cases were suffering from end stage liver disease. The results we have reached are that Doppler U/S sensitivity in diagnosis of these complications is 83.8% and CTA sensitivity is about 100%. Conclusion: It could be concluded that colour duplex is the investigations of choice in postoperative liver transplantation. They can be used as routine steps in the assessment of liver transplant graft postoperatively in recipient patient as early as possible within the first 3 days after operation and used as a late follow up, as they are noninvasive, safe, cheap, and accurate. Routine use of gray-scale US and color duplex showed to minimize the impact of postoperative complications and maximize both graft and recipient patient survival and if any complications suspected, it can be confirmed by CTA

An Overview of Liver Transplant Pathology: Data from a Tertiary Referral Centre in Western India

Introduction and aim. 1. Study of liver explants - Etiologic types of end-stage chronic liver disease (ESCLD) and acute liver failure (ALF) in adults and children. 2. Assessment of donor steatosis and incidental granulomas. 3. Post-transplant liver biopsies.Material and methods. Specimens of 180 explant hepatectomies, 173 donor wedge and 30 core liver biopsies, and 58 post transplant liver biopsies received in our department from April 2013 to March 2017.Results. 1. Most common causes of ESCLD in adults were: alcohol related (30.32%), hepatitis virus related (18.71%) and non-alcoholic steatohepatitis related (18.06%); and in children < 12 years were: biliary atresia (27.27%), autoimmune disease (18.18%) and Wilson’s disease (18.18%). Most common causes of ALF in adults and children were anti-tubercular therapy induced and idiopathic, respectively. 2. Prevalence rate of moderate steatosis (between 30-60%) was 4.28%. Incidental granulomas were seen in 5 cases. 3. Most common diagnoses of post-transplant biopsies in adults included acute cellular rejection (ACR) (36.17%), recurrence of viral disease (8.51%) and moderate non-specific portal triaditis (8.51%). Among children < 12 years, most common diagnoses included unremarkable liver parenchyma, ACR and ischemia/reper fusion injury.Conclusion. 1. Alcohol- and hepatitis- virus related ESCLD, and biliary atresia are leading indications for liver transplantation in adults and children, respectively. 2. Prevalence of 4.28% of moderate steatosis, is much lower than that documented in western literature. Only 5 cases of incidental granulomas is unexpectedly low in a country endemic for tuberculosis. 3. Most common diagnoses of post-transplant liver biopsies in adults has been acute rejection, which is similar to the findings from much larger published series.

Chapter 6. ESPGHAN's Contributions to Paediatric Hepatology.

Hepatology played an important role in ESPGAN from the beginning. In 1989, the Hepatology Committee was started. In the early 1990s H for hepatology was included in ESPGHAN. Hepatology Summer schools were held from 1995 and later monothematic conferences met the needs of many young ESPGHAN members. The role of ESPGHAN members in the progress of diagnostic and therapeutic measures in hepatitis B and C will be elucidated (Chapter 6.1) as well as the role of other ESPGHAN members in the understanding of immunological hepatic disorders of childhood (Chapter 6.2). During childhood, many metabolic hepatic disorders threaten the life and health of children making orchestrated measures in diagnostic and therapeutic efforts necessary (Chapter 6.3). The pathophysiology of cholestasis was cleared by the detection of bile salt transporters, which were identified by ESPGHAN members in the Netherlands, France, United Kingdom and Germany (Chapter 6.4). Finally liver transplantation for acute fulminant and chronic end stage liver disease was established as a meanwhile standard treatment option (Chapter 6.5). Immunosupression in liver transplantation was improved and standardized through the cooperation of many ESPGHAN member driven studies (Chapter 6.6).