Background Of Chronic Liver Disease Research Articles

Nutrition Parameters for Assessing Malnutrition in a Population of US Veterans With Hepatitis C Virus

Chronic liver disease often leads to malnutrition in patients. Patients with hepatitis C virus (HCV) are at greater risk for misclassification due to disease-specific changes in fluid, muscle, and fat status. Tools traditionally used to diagnose malnutrition may not be applicable in the HCV population, and delaying malnutrition diagnosis may contribute to disease progression. The aim of the present study is to determine and compare the incidence of malnutrition in US veterans with HCV by using 3 different malnutrition assessment tools (subjective global assessment [SGA], American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics [ASPEN-AND], and Royal Free Hospital Global Assessment [RFH-GA]). Thirty-three US veterans were evaluated for malnutrition according to SGA, ASPEN-AND, and RFH-GA protocols using a prospective, descriptive study design. Fifteen participants (45.5%) were classified with malnutrition using any criteria (SGA, ASPEN, or RFH-GA). All 3 tools had good agreement, with ASPEN-AND to RFH-GA having the highest specificity and sensitivity. Of those classified with malnutrition using any assessment tool, mean body mass index was 26.6 (P = .014), subjective muscle loss was the most frequently encountered parameter, and 6 (40%) of 15 also had fluid accumulation. The results indicate that malnutrition and particularly muscle wasting is common in US veterans with HCV. All 3 tools had good agreement and the most commonly used nutrition parameter was muscle loss (subjective). In a malnutrition assessment tool for the HCV population, both subjective and objective measures of body composition should be included.

Hemoperitoneum caused by spontaneous rupture of hepatocellular carcinoma in noncirrhotic liver. A case report and systematic review.

IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer. Spontaneous rupture of HCC is an acute complication with a high mortality rate. The HCC principally arises in the background of chronic liver disease and cirrhosis of the liver. In the last few years, the rising incidence of HCC in noncirrhotic liver suggests the presence of other factors that may play a role in liver carcinogenesis.MethodsWe reviewed all cases treated at the University Surgical Department of Ospedali Riuniti of Foggia from 2009 to 2018. Only a single case of hemoperitoneum caused by spontaneous rupture of HCC in noncirrhotic liver was found. An extensive search of the relevant literature was carried out using MEDLINE, and a total of 58 published studies were screened from the sources listed.ConclusionsThe management of this devastating emergency should be carefully analyzed, with stabilization of vital signs as soon as possible. Patient with ruptured HCC and hemoperitoneum without a prior history of cirrhosis and viral infections benefited from the role of transcatheter arterial embolization (TAE) as the preliminary treatment in order to have a more precise diagnosis and an optimal stabilization of the patient. Delayed or staged hepatectomy after TAE represents the definitive treatment.

The Enhanced Liver Fibrosis test is associated with liver-related outcomes in postmenopausal women with risk factors for liver disease

BackgroundChronic liver disease (CLD) is usually asymptomatic but earlier detection is critical to permit life-saving interventions for those at risk due to high alcohol consumption and increased body mass index (BMI). The aim of this study was to estimate the association between the Enhanced Liver Fibrosis (ELF) test and liver-related events (LRE) and its performance in predicting LRE in postmenopausal women with risk factors in a nested case-control study within the United Kingdom Trial of Ovarian Cancer Screening (UKCTOCS).MethodsIn a cohort of 95,126 we performed a case-control study measuring ELF in blinded samples from 173 participants with self-reported high alcohol use and / or BMI ≥25 kg/m2 comprising all 58 cases who developed LRE and 115 controls matched for age, alcohol and BMI who did not develop LRE during median follow-up of 8.5 years.ResultsUsing Cox regression at an ELF threshold of 10.51 hazard ratios (HR) for LRE were 4.88 (95% confidence interval (CI) 2.37–10.03) (unadjusted model) and 4.62 (95% CI 2.12–10.08) (adjusted for deprivation and self-reported hypertension, heart disease, hypercholesterolaemia and diabetes). At a threshold of 9.8 HR for LRE were 2.21 (95% CI 1.22–3.97) (unadjusted model) and 2.18 (95% CI 1.19–4.01) (adjusted). ELF was evaluated as a time dependent variable by generating time-dependent Cox models; HRs at an ELF threshold of 10.51 were 1.94 (95% CI 1.10–3.39) (unadjusted) and 2.05 (95% CI 1.16–3.64) (adjusted) and at a threshold of 9.8 HRs were 1.85 (95% CI 1.09–3.15) (unadjusted) and 1.80 (95% CI 1.04–3.13) (adjusted). Area under the receiver operating characteristic curve for recruitment ELF predicting LRE was 0.58 (95% CI 0.49–0.68), and for second subsequent ELF 0.61 (95% CI 0.52–0.71).ConclusionThis study demonstrates the association between ELF and CLD in postmenopausal women with risk factors for liver disease, creating the opportunity to intervene to reduce liver-related mortality and morbidity. Although larger studies are required, these results demonstrate the potential of ELF as a prognostic tool in health checks in primary care.Trial registrationThis study is nested in UKCTOCS. UKCTOCS is registered as an International Standard Randomised Controlled Trial, number ISRCTN22488978. Registered 06/04/2000.

Laporan Kasus: Transarterial Chemoembolization (Tace) Sebagai Terapi Pilihan Pada Karsinoma Hepatoselular

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and occupies the top 10 most cancers in Indonesia. Men are likely to develop HCC, and 90% cases of HCC develop in the background of chronic liver disease, which associates with hepatitis B and C virus infection. There are numerous treatment options for HCC, however in intermediate-advanced stage, palliative treatment such as transarterial chemoembolization (TACE) and systemic chemotherapy are the management of choice. A 51 years old male with HCC based on history, physical examination, radiology and laboratory result was referred to interventional radiology department for TACE consideration. Barcelona Clinic Liver Cancer (BCLC) B was concluded in this patient after thorough evaluation. There was history of hepatitis B infection, ascites, low albumin level, high AFP, and from Abdominal CT Scan with contrast showed large lobulated mass on the right lobe, without evidence of portal vein thrombosis. TACE was eligible and done using mixed of doxorubicin 50 mg and lipiodol, and embolization using gel foam. After 8 weeks CT evaluation was done and showed increase area of tumor necrosis, while tumor size was stable. Necrosis area expansion is the standard used for evaluating this patient which fell into partial response criteria. TACE is a palliative therapy of choice in accordance with BCLC B recommendation. Evaluation of TACE performance is more optimal by assessing the size of necrosis area compared to mass measurement.

Prospects and challenges of circulating tumor DNA in precision medicine of hepatocellular carcinoma.

The growing role of precision medicine in hepatocellular carcinoma (HCC) is expected to ameliorate the poor prognosis and high mortality of this highly malignant disease; however, it is faced with challenges such as the low frequency of tissue biopsy. Hence, attention is turning to the circulating tumor DNA (ctDNA), an important component of liquid biopsy. Obtaining molecular information about cancer from blood provides a good prospect in precision oncology including molecular diagnosis, molecular classification, targeted therapy, personalized decision making, and detection of drug-resistance mutations. However, inherent constraints of HCC and ctDNA (like background chronic liver diseases (CLD) and low concentration of ctDNA) along with some technical issues should be well handled and solved before the potential of ctDNA in precision medicine of HCC can be truly realized. In this review, we will focus on the prospects and challenges of ctDNA in HCC precision medicine.

Mast Cell Signaling Regulates Biliary Farnesoid X Receptor and Apical Sodium Bile Acid Transporter Expression During Cholestatic Liver Injury

BackgroundChronic liver diseases and cholangiopathies (targets cholangiocytes) are diagnosed at advanced stages leading to poor prognosis. Mast cells (MCs) infiltrate the liver during damage, release histamine (HA) and act via H1‐H4 HA receptors (HRs). Cholangiocytes and MCs express apical sodium bile acid transporter (ASBT); farnesoid X receptor (FXR) and H2HR. Introduction of MCs into C57BL/6 (WT) and MC deficient (KitW‐sh) mice increases liver damage, biliary proliferation/liver fibrosis, and total bile acid (TBA) levels. We aimed to determine if loss of MC FXR signaling alters biliary FXR and ASBT, injury and hepatic fibrosis via HA/H2HR signaling.MethodsWT or KitW‐sh mice were subjected to tail vein injection of cultured MCs (ATCC®) pretreated with PBS (PBS‐MC) to induce liver damage or the FXR inhibitor, Z‐guggulsterone (10μM, FXR‐MC) and sacrificed after 3 days. H&E was used to determine pathological changes. Ductular reaction was determined by CK‐19 staining. Biliary proliferation and hepatic senescence were evaluated by Ki‐67 and SA‐b‐galactosidase staining. Hepatic fibrosis was determined by Sirius Red staining. Hepatic stellate cell (HSC) presence was determined by immunofluorescence (IF). Biliary senescence was determined by IF and qPCR. Cholangiocyte FXR and ASBT expression was determined by staining and qPCR in cholangiocytes. Senescence associated secretory phenotypes (SASPs) and HA secretion were measured by EIA in serum and cholangiocyte supernatants. H2HR expression was evaluated in isolated cholangiocytes. TBAs were measured in serum and liver tissues. In vitro, cultured MCs were treated with PBS or Z‐guggulsterone (10μM, 48 hr). Treated MC supernatants were placed on cholangiocytes prior to evaluating biliary ASBT and H2HR expression and secretion of HA, TGF‐b1 and IL‐1b by qPCR and EIA, respectively. In human tissue from patients with PSC or PBC, biliary ASBT, FXR and MC infiltration (marked by tryptase) was measured by IHC.ResultsHepatic damage, ductular reaction, biliary senescence, ASBT expression and liver fibrosis were induced in WT and KitW‐sh mice injected with PBS‐MC; whereas, these parameters were reversed in mice injected with FXR‐MCs. HA secretion and H2HR expression increased in serum and cholangiocytes, respectively in WT and KitW‐sh mice injected with PBS‐MC, but were reduced in mice injected with FXR‐MC. Hepatic and serum TBA increased in WT and KitW‐sh mice injected with PBS‐MC and were reduced in FXR‐MC groups. In vitro, stimulation with MC supernatant increased biliary ASBT, FXR, H2HR, HA, TGF‐b1 and IL‐1b expression. These parameters decreased in cholangiocytes treated with FXR‐MC supernatant. In human tissues, upregulation of MCs was coupled with increased biliary FXR and ASBT expression.ConclusionsReintroduction of MCs recapitulates cholestatic liver injury in WT and KitW‐sh mice. Inhibition of MC FXR signaling decreases biliary ASBT expression, liver injury and hepatic fibrosis via downregulation of HA/H2HR signaling. Manipulation of BA transporters, receptors and MC mediators may be a therapeutic route for patients with cholestatic liver damage.Support or Funding InformationNIH NIDDK R01s, VA Merit, IUSOM

Accuracy of real-time shear wave elastography in staging hepatic fibrosis: a meta-analysis

BackgroundChronic liver disease (CLD) is an important cause of morbidity and mortality and can lead to hepatic fibrosis. This study was conducted to evaluate the diagnostic value of real-time shear wave elastography (SWE) in the assessment of hepatic fibrosis.MethodsA systematic search of databases was performed for publications on SWE during the period between 2010 and 2017. The identified studies were analyzed using Meta-disc 1.4 software to integrate and analyze the data.ResultsEleven studies comprising 1560 patients were included for analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.85 (95% CI: 0.82–0.87), 0.79 (95% CI: 0.76–0.82) and 30.81 (95% CI: 16.55–57.34), respectively for patients with a Metavir-score of ≥ F2; 0.87 (95% CI: 0.84–0.91), 0.84 (95% CI: 0.82–0.87), 41.45 (95% CI:18.25–94.45), respectively for patients with ≥ F3; 0.88(95% CI: 0.83–0.91), 0.91 (95% CI: 0.89–0.92), 67.18 (95% CI:30.02–150.31), respectively for patients with ≥ F4. The areas under the receiver operating characteristic curve of the three groups were 0.9147, 0.9223 and 0.9520, respectively.ConclusionsOur work demonstrates that SWE is highly accurate for detecting and staging hepatic fibrosis.

Risk analysis for hypervascular transformation of precancerous lesion of hepatocellular carcinoma

Objective: To investigate the risk factors for diagnosis of transformation of high-grade dysplastic nodules (HGDN) to hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease with gadoxetate disodium-enhanced magnetic resonance imaging (MRI). Methods: 2 037 cases that underwent gadoxetate disodium-enhanced magnetic resonance imaging from January 2012 to December 2014 were retrospectively analyzed. 51 cases of HGDN with a background of chronic liver disease were screened and followed-up for at least 2 times with gadoxetate disodium-enhanced MRI scans and contrast enhanced CT scans was performed within 1 month before and after the first MRI. The endpoint of study was transformation of HGDN to hypervascular hepatocellular carcinoma, with a deadline of April 2019. Transformation was divided into transformed (group A) and untransformed (group B) group according to the presence or absence of hypervascularization. Linear regression was used to analyze the possible risk factors for hypervascular transformation. Results: There were 36 nodules in group A and 79 nodules in group B, and hypervascular transformation rate was 31.3% (36/115). On univariate analysis, the length and diameter of nodule was > 10.2 mm (P = 0.034), with annual growth rate > 2% (P < 0.001), and lipid content (P = 0.007) was related to the occurrence of hypervascularity. On multivariate analysis, the annual growth rate of nodules was an independent risk factor for the occurrence of hypervascularity (P < 0.000 1). Conclusion: The annual growth rate of HGDN in patients with chronic liver disease diagnosed with gadoxetate disodium-enhanced MRI imaging can be used as a potential predictor of hypervascularization.

Do all chronic hepatitis C virus bleeders develop iron deficiency?

Objectives To investigate the changes in hepcidin regulation in anemic chronic hepatitis C virus (HCV) patients with and without bleeding and the role of hepcidin in ameliorating the development of iron deficiency in anemic HCV bleeders. Background Chronic liver disease is frequently associated with anemia in about 75% of patients which is usually multifactorial. One of the causes of anemia in chronic liver disease is acute or chronic blood loss into the gastrointestinal tract, resulting in iron deficiency anemia. Hepcidin, the key regulator of iron homeostasis, has a relatively low expression level in the liver in chronic HCV patients; however, the changes in hepcidin regulation have not been examined previously in anemic chronic HCV bleeders compared with nonbleeders. Patients and methods This case–control study was carried out at the Faculty of Medicine and National Liver Institute, Menoufia University, in the duration between February 2016 and February 2017. The study included 70 individuals: 50 treatment-naive compensated chronic hepatitis C patients (25 anemic nonbleeders and 25 anemic bleeders) and 20 age-matched and sex-matched healthy individuals. Complete blood counts, iron profile, prothrombin, and serum hepcidin using enzyme-linked immunosorbent assay were done. Results Serum hepcidin levels were significantly lower in anemic nonbleeder patients (70.08 ± 13.40) and anemic bleeders (68.91 ± 10.66) than in controls (78.52 ± 7.46). P value is 0.017. There was no significant difference between the patient groups compared with each other. No statistically significant differences between the studied groups were found regarding serum iron, total iron binding capacity, transferrin saturation, and serum ferritin. Conclusion Chronic HCV bleeders do not develop iron deficiency.

Tumour evolution in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, typically develops on the background of chronic liver disease and is an aggressive disease with dismal prognosis. Studies using next-generation sequencing of multiple regions of the same tumour nodule suggest different patterns of HCC evolution and confirm the high molecular heterogeneity in a subset of patients. Different hypotheses have been proposed to explain tumour evolution, including clonal selection or neutral and punctuated acquisition of genetic alterations. In parallel, data indicate a fundamental contribution of nonmalignant cells of the tumour microenvironment to cancer clonal evolution. Delineating these dynamics is crucial to improve the treatment of patients with HCC, and particularly to help understand how HCC evolution drives resistance to systemic therapies. A number of new minimally invasive techniques, such as liquid biopsies, could help track cancer evolution in HCC. These tools might improve our understanding of how systemic therapies affect tumour clonal composition and could facilitate implementation of real-time molecular monitoring of patients with HCC.

Thrombophilia in hepatocellular carcinoma

BackgroundChronic liver disease and hepatocellular carcinoma (HCC) can cause a disturbance in the coagulation system. In this study, we aimed to assess the risk factors for venous thromboembolism either acquired or hereditary in patients with HCC.ResultsSerum levels of proteins C and S, AT activity, and lipoprotein (a) were significantly lower in both HCC and cirrhotic patients while homocysteine levels were significantly higher in HCC patients. The prevalence of activated protein C resistance (APCR) and factor V Leiden (FVL) mutation was higher in HCC patients but with no significant differences between the studied groups. With multivariate analysis, prothrombin time, Fbg, protein C and S deficiency, increased lipoprotein (a), hyperhomocysteinemia, APCR, and FVL mutation were independent risk factors for thromboembolic complications in HCC patients.ConclusionsThrombophilic abnormalities are prevalent in HCC patients, and they have a substantial increased risk of venous thromboembolism.

Assessment of Knowledge About the Risk Factors of Chronic Liver Disease in Patients Admitted in Civil Hospital Karachi.

BackgroundChronic liver disease (CLD) encompasses a series of single or multifactorial insults to the liver, most common of which are hepatitis, alcohol abuse, and non-alcoholic liver disease. CLD represents a major public health problem worldwide as well as in Pakistan. Unfortunately, studies evaluating the awareness of its risk factors among people are quite scarce. The purpose of this study was to assess the knowledge about risk factors of CLD in patients admitted to Dr. Ruth K M Pfau, Civil Hospital Karachi (CHK).MethodsThis quantitative cross-sectional study was conducted at CHK, among 368 patients admitted to CHK, during the period from February 2018 to September 2018. Frequencies and percentages were evaluated for categorical variables using Statistical Package for Social Sciences (SPSS), version 22 (IBM Corp., Armonk, NY). Chi-square test was applied to determine if there was any significant association between the variables. A p-value of <0.05 was considered significant.ResultsA scoring scale was developed to assess the level of knowledge. We found that only 32% of our study population had good knowledge about the risk factors of CLD while majority of them (68%) had poor knowledge. Regarding individual risk factors, >60% patients were aware that obesity, high fat intake, prolonged use of drugs, use of alcohol and hepatitis B and C are risk factors of CLD, while most of them did not know diabetes to be a risk factor as well. 51.4% patients thought that hepatitis B and C could not be transmitted via sexual contact and from mother to her baby. There was a positive association between education level and awareness about the risk factors of CLD (p = 0.006).ConclusionFuture interventions to increase public awareness about CLD should promptly be taken. The lack of knowledge about this disease is the main cause of its rapid increment and the reason why it is so prevalent in our part of the world especially Pakistan. More studies and nationwide awareness programs are needed to control its spread.

Short-term clinical outcomes of patients admitted with chronic liver disease to selected teaching hospitals in Ethiopia.

BackgroundChronic liver disease (CLD) is a progressive destruction of liver tissue with subsequent necrosis that persists for at least 6 months. In Ethiopia, despite the high burden report, data on CLD is limited. The objective of this study was to assess short-term clinical outcomes in patients admitted with chronic liver disease to three tertiary teaching hospitals in Ethiopia and to identify predictors of mortality.MethodsA cohort of 109 patients admitted with CLD to three tertiary teaching hospitals in Ethiopia, were prospectively followed from the time of admission to 30-days of hospital discharge. The study was conducted from April 1, 2018, to October 5, 2018. Kaplan-Maier curve was used to estimate survival and cox-regression analysis to identify predictors of mortality.ResultA total of 109 patients (80% male) diagnosed with CLD were included. Median age of the participants was 38(IQR, 30–48). The overall median length of hospital stay was 7(IQR, 4–11) days. Of the total, 39(35.8%) patients were HBsAg positive, and 12(11%) patients were anti-HCV positive. The 30-day mortality was 38(34.9%), and most of the deaths, 31(81.6%) occurred before hospital discharge. Hepatic encephalopathy at admission; being with unidentified risk factor/etiologies of CLD and total bilirubin level were independent predictors of in-hospital mortality. Patients with hepatic encephalopathy at admission had approximately 11 times increased risk of death as compared to patients without hepatic encephalopathy at admission. Similarly, the hazard of mortality was 5.8 times higher in those patients with unidentified risk factor/etiology as compared to others. The risk of dying had also increased with an increase in bilirubin (1.188[95% CI, 1.0719–1.316]) level.ConclusionApproximately one-quarter of patients with CLD died during their hospital stay, and the risk of death continued after hospital discharge. Hepatic encephalopathy at admission, unidentified risk factor/etiology and increased level of total bilirubin are poor prognostic factors. Given that more than one third the patients had HBV-infection, access to antiviral drugs could help improve the prognosis of patients with end-stage liver disease in Ethiopia, as well as prevent the progression of the disease if initiated earlier.

Hepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. The disease usually develops on a background of chronic liver disease. Until recently, the most common etiology was infection with the hepatitis C virus (HCV). The advent of direct-acting antiviral (DAA) therapies has been a major breakthrough in HCV treatment. Sustained virologic response can now be achieved in almost all treated patients, even in patients with a high risk for the development of HCC, such as the elderly or those with significant fibrosis. Early reports raised concerns of a high risk for HCC occurrence after DAA therapy both in patients with previous resection of tumors and those without previous tumors. As the World Health Organization’s goals for eradication of HCV are being endorsed worldwide, the elimination of HCV seems feasible. Simultaneous to the decrease in the burden of cirrhosis from HCV, non-alcoholic fatty liver disease (NAFLD) incidence has been increasing dramatically including significant increased incidence of cirrhosis and HCC in these patients. Surprisingly, a substantial proportion of patients with NAFLD were shown to develop HCC even in the absence of cirrhosis. Furthermore, HCC treatment and potential complications are known to be influenced by liver steatosis. These changes in etiology and epidemiology of HCC suggest the beginning of a new era: The post–HCV era. Changes may eventually undermine current practices of early detection, surveillance and management of HCC. We focused on the risk of HCC occurrence and recurrence in the post–HCV era, the surveillance needed after DAA therapy and current studies in HCC patients with NAFLD.

Abstract 847: Overexpression of long noncoding RNA FAM promotes cancer invasion and drug resistance in human liver cancer

Abstract Hepatocellular carcinoma (HCC) is one of the most common and aggressive human malignancies worldwide. Most patients with HCC have an established background of chronic liver disease and cirrhosis, with major etiological and risk factors including chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). Long non-coding (lnc)RNAs are a class of non-protein coding transcripts longer than 200 nucleotides that regulate complex cellular functions, such as cell growth, differentiation, metabolism and metastasis. Increasing evidence has shown that lncRNAs regulate gene expression by targeting the production, splicing, decay, or translation of target mRNAs. Although deregulation of lncRNAs expression have been detected in HCC or many tumor types, there are still many novel lncRNAs have not been studied and the mechanisms underlying functional impairment and specific involvement of lncRNAs during hepato-carcinogenesis remain to be established. Here, we aimed to investigate the involvement of specific dys-regulated lncRNA-FAM and its molecular mechanism. FAM is overexpressing in HCC and correlates with tumor size, vascular invasion, and pathology stage. Overexpression FAM accelerates cell proliferation, invasion in HCC cells. Further, FAM is induced in the Doxorubicin (DOX) resistance HCC cells show in the Gene Expression Omnibus (GEO) Datasets analysis. Overexpression FAM did increase DOX-resistant in two HCC cell lines. After overexpression FAM, lysosome-associated membrane protein 2 (LAMP2) expression was enhanced which also correlated with DOX-resistant. From the co-immunoprecipitation analysis, FAM directly interacted with LAMP2 to protect its ubiquitination. Thus, FAM may play an oncogenic role during hepato-carcinogenesis. Citation Format: Po-Shuan Huang, Kwang-Huei Lin. Overexpression of long noncoding RNA FAM promotes cancer invasion and drug resistance in human liver cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 847.

Immunotherapy for hepatocellular carcinoma: Current and future.

Hepatocellular carcinoma (HCC) arises on the background of chronic liver disease. Despite the development of effective anti-viral therapeutics HCC is continuing to rise, in part driven by the epidemic of non-alcoholic fatty liver disease. Many patients present with advanced disease out with the criteria for transplant, resection or even locoregional therapy. Currently available therapeutics for HCC are effective in a small minority of individuals. However, there has been a major global interest in immunotherapies for cancer and although HCC has lagged behind other cancers, great opportunities now exist for treating HCC with newer and more sophisticated agents. Whilst checkpoint inhibitors are at the forefront of this revolution, other therapeutics such as inhibitory cytokine blockade, oncolytic viruses, adoptive cellular therapies and vaccines are emerging. Broadly these may be categorized as either boosting existing immune response or stimulating de novo immune response. Although some of these agents have shown promising results as monotherapy in early phase trials it may well be that their future role will be as combination therapy, either in combination with one another or in combination with treatment modalities such as locoregional therapy. Together these agents are likely to generate new and exciting opportunities for treating HCC, which are summarized in this review.

Hepatocellular Carcinoma in Asia: A Challenging Situation.

ABSTRACTAmongst the primary tumors of the liver, hepatocellular carcinoma (HCC) is the most common. It is also one of the most prevalent types of cancers in Asia. Mostly, HCC occurs on a background of chronic liver disease and liver cirrhosis; however, de novo HCCs can also arise in apparently normal looking livers on imaging. There are multiple risk factors for HCC, including hepatitis B and C infections, diabetes mellitus, alcohol, and nonalcoholic steatohepatitis. Other common risk factors which are known to be involved in the pathogenesis of HCC are obesity, food contaminated with aflatoxin and hemochromatosis. Many of these factors are commonly found in this part of the world, hence the high burden of disease. Besides these, smoking and familial predisposition to HCC also seem to have an important role to play in its development. Majority of HCC are missed at an early stage despite the emphasis on adequate screening and surveillance strategies. Therefore, most of the time these tumors are diagnosed at a fairly advanced stage, when palliative treatment is the only therapeutic option left. Hence, prevention of HCC by controlling and minimizing the possible risk factors is the need of the hour.How to cite this article: Jafri W, Kamran M. Hepatocellular Carcinoma in Asia: A Challenging Situation. Euroasian J Hepatogastroenterol 2019; 9(1):27-33.

Pediatric Chronic Liver Diseases: A Clinicopathological Study from a Tertiary Care Center

Background Chronic liver diseases (CLD) in children represent a growing health problem with significant morbidity and mortality. This study aimed to define the clinicopathological pattern of pediatric CLD in Sohag University Hospital, Sohag,Upper Egypt. Materials and Methods A total of 151children with CLD were included in a prospective hospital-based study from June 2014 to May 2018. Cases of acute liver illness or hepatic focal lesions were excluded. All patients were subjected to detailed history and thorough physical examination. Abdominal ultrasonography, CBC, liver function tests, viral serology, evaluation of autoantibodies for autoimmune hepatitis, and liver core biopsies were performed for all children. Results Pediatric CLD comprised 1.6% of total admissions in pediatric department. Neonatal cholestasis disorders (NCD), and metabolic liver disorders (MLD) were the leading causes of CLD (41.05% and 35.1%, respectively). NCD comprised neonatal hepatitis (25.1%), extrahepatic biliary atresia (13.2%), and paucity of interlobular bile ducts (2.7%). MLD included glycogen storage disease (26.5%), undetermined inborn error of metabolism (5.3%), Gaucher's disease (2.0%), and Niemann Pick disease (1.3%). Other causes of CLD comprised autoimmune hepatitis (8.6%), congenital hepatic fibrosis (5.9%), non-alcoholic fatty liver disease (4.0%), chronic hepatitis C infection (2.7%), and Budd Chiari disease (0.6%). On follow-up of 89 cases, stationary clinical course, clinical improvement, and clinical deterioration were seen in 52.8%, 34.8%, and 12.3% of them, respectively. Conclusion The rate of CLD is growing in Upper Egypt and is mainly caused by neonatal cholestasis and metabolic liver disorders. In general, the outcome of children is favorable and comparable to other countries.

Study of Liver Biopsy in Chronic Liver Diseases

Background Chronic liver disease (CLD) represents liver disorders of varying causes and severity in which hepatic inflammation and necrosis continue for at least 6 months. The treatment of cause leads to regression of fibrosis and parenchymal recovery. Liver biopsy is often used to establish the diagnosis, assess the severity of disease in CLD and its role is evolving with advances in medical technology. To study the histopathological pattern of injury in patients with CLD and thereby establish a possible etiologic diagnosis in correlation with clinical, biochemical and serologic findings. Methods Thirty five cases of CLD with histopathological features of necroinflammation/fibrosis were studied for a period of five years. Along with demographics and laboratory parameters, sections were studied for the pattern and degree of injury. Grading and staging were done using standard systems. Results Nonalcoholic fatty liver disease (31.42%) and alcoholic liver disease (25.71%) were the most common causes followed by viral hepatitis (11.42%) and drug induced liver injury (8.58%). One case each of autoimmune hepatitis and primary biliary cirrhosis were seen. A definitive diagnosis was not possible in six patients, and only a probable etiology was considered. Conclusion The natural history of CLD is changing and is important to establish an etiological diagnosis. Despite the advances in diagnostic techniques, liver biopsy remains a valuable tool to establish the etiology and traditional descriptive reports still hold importance for the treatment and prognosis. However, it remains challenging and should be interpreted in the setting of clinical, biochemical, serological and radiological findings.

Clinical Outcomes and Prognosis Markers of Patients With Liver Disease Undergoing Transcatheter Aortic Valve Replacement: A Propensity Score-Matched Analysis.

Chronic liver disease is a known risk factor for perioperative morbidity and mortality in patients undergoing cardiac surgery. Very little data exist about such patients treated with transcatheter aortic valve replacement (TAVR). Our objective was to evaluate early and late clinical outcomes in a large cohort of patients with liver disease undergoing TAVR and to determine predictive factors of mortality among these patients. This multicenter study collected data from 114 patients with chronic liver disease who underwent TAVR in 12 institutions. Perioperative and long-term outcomes were compared with a cohort of 1118 patients without liver disease after a propensity score-matching analysis (114 matched pairs). In-hospital mortality and vascular and bleeding complications were similar between matched groups. Acute kidney injury was more common in liver disease group (30.8% versus 13.5%; P=0.010). Although cardiovascular mortality was similar between groups (9.4% versus 6.5%; P=0.433) at 2-year follow-up, noncardiac mortality was higher in the liver group (26.4% versus 14.8%; P=0.034). Lower glomerular filtration rate (hazard ratio, 1.10, for each decrease of 5 mL/min in estimated glomerular filtration rate; 95% confidence interval, 1.03-1.17; P=0.005) and Child-Pugh class B or C (hazard ratio, 3.11; 95% confidence interval, 1.47-6.56; P=0.003) were the predictors of mortality in patients with chronic liver disease, with a mortality rate of 83.2% at 2-year follow-up in patients with both factors (estimated glomerular filtration rate <60 mL/min and Child-Pugh B or C). These findings suggested that TAVR is a feasible treatment for severe aortic stenosis in patients with early-stage liver disease or as bridge therapy before a curative treatment of the hepatic condition. Patients with Child-Pugh class B-C, especially in combination with renal impairment, had a very low survival rate, and TAVR should be carefully considered to avoid a futile treatment. These results may contribute to improve the clinical decision-making process and management in patients with liver disease.