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Concept: Cirrhosis

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In northeastern Thailand, prevalent risks for cholangiocarcinoma (CC) include infestation with liver fluke O. viverrini (OV), infection with HBV and HCV, and consumption of nitrosamine-rich foods. The ASR for intrahepatic cholangiocarcinoma (ICC) is the highest in the world (44 and 16 per 100,000 males and females). ICC accounts for 58% of cases, exceeding that of hepatoma (42%). As per the AJCC-2009, the spectrum of CC among the 221 patients operated at Khon Kaen University Hospital included: perihilar CC (52.9%); ICC (37.1%); distal extrahepatic CC (4.1%) and combined ICC and extrahepatic CC (5.8%). Peak age incidence was in the sixth decade, about 5-10 years younger than sporadic CC. Chronic inflammation associated with OV infestation may be a contributing factor for the spectrum of CC vs HBV or HVC, since ICC with cirrhosis is rare and the phenotypes related to chronic hepatitis (CC and cholangio-hepatoma) account for <3%. Studies comparing OV-associated CC and sporadic CC shared similar pathological features, precursor lesions, growth factors and molecular alterations (like pancreatic ductal carcinoma).

Concepts: Inflammation, Cancer, Cirrhosis, Hepatology, Hepatitis C, Hepatitis B, Cholangiocarcinoma, Khon Kaen

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Staging for liver fibrosis is recommended in the management of hepatitis C as an argument for treatment priority. Our aim was to construct a noninvasive algorithm to predict the significant liver fibrosis (SLF) using common biochemical markers and compare it with some existing models.

Concepts: Cirrhosis, Hepatitis, Liver, Hepatocellular carcinoma, Bilirubin, Hepatitis C, Hepatitis B, Hepatitis A

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Compare surgical outcomes for hepatitis B virus (HBV)-hepatocellular carcinoma (HCC) versus hepatitis C virus (HCV)-hepatocellular carcinoma (HCC).

Concepts: Cirrhosis, Hepatitis, Hepatocellular carcinoma, Interferon, Hepatitis C, Hepatitis B, Hepatitis A, North America

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Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disorders in industrialized countries. NAFLD develops in the absence of alcohol abuse and encompasses a wide spectrum of disorders ranging from benign fatty liver to non-alcoholic steatohepatitis (NASH). NASH often leads to fibrosis, cirrhosis and, finally, hepatocellular carcinoma (HCC). Therefore the earlier NAFLD is diagnosed, the better the patient’s outlook. A tightly connected basic and applied research is essential to find the molecular mechanisms that accompany illness and to translate them into the clinic. From the simple starting point for triacylglycerol (TG) accumulation in the liver to the more complex implications of phospholipids in membrane biophysics, the influence of lipids may be the clue to understand NAFLD pathophysiology. Nowadays, it is achievable to diagnose non-invasively the initial symptoms to stop, revert or even prevent disease development. In this context, merging metabolomics with other techniques and the interpretation of the huge information obtained resembles the ‘Rosetta stone’ to decipher the pathological metabolic fluxes that must be targeted to find a cure. In the present review, we have tackled the application of metabolomics to find out the metabolic fluxes that underlie membrane integrity in NAFLD.

Concepts: Cirrhosis, Hepatitis, Non-alcoholic fatty liver disease, Fatty liver, Steatosis, Steatohepatitis

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In Ohio, the obesity rate has increased from 21.5% in 2000 to 30.1% in 2012. Nonalcoholic steatohepatitis is believed to be increasing as an indication for orthotopic liver transplantation.

Concepts: Cirrhosis

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Hospital-based, cross-sectional study to determine whether exposure to hepatitis B virus (HBV) has an independent effect on the risk of developing chronic kidney disease (CKD).

Concepts: Chronic kidney disease, Cross-sectional study, Cirrhosis, Hepatitis, Hepatitis B, Viruses, Hepatitis B virus, Hepadnaviridae

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Chronic viral hepatitis B and C infections are highly prevalent and create a substantial burden to healthcare systems globally. These two chronic infections are the cause of significant global morbidity and mortality with approximately 1 million annual deaths attributable to them and their sequelae. Children are vulnerable to both infections. The availability of new drugs and new therapeutic strategies are increasing the complexity and individualizing the management of children with viral hepatitis. Therefore, it is extremely important to educate and advise pediatricians concerning the new lines of treatment. More than 350million persons worldwide are infected with HBV. Although its incidence has dramatically declined since the implementation of universal immunization programs in many countries, scores of children are still being infected each year. Despite its benign course, chronic hepatitis B (CHB) during childhood and adolescence, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma (HCC), respectively, before adulthood. Treatment of CHB in childhood has been hampered by the long delay in licensing new drugs for pediatric use. Safe and effective antiviral therapies are available in adults, but few are labeled for use in children, and an accurate selection of whom to treat and the identification of the right timing for treatment are needed to optimize response and reduce the risk of antiviral resistance. Although several guidelines on the management of adult patients with CHB have been published by major international societies, the clinical approach to infected children is still evolving, and is mostly based on the expert opinions. Standard interferon (IFN)-α is still the treatment of choice for most children with HBV infection. Licensing of highly-effective nucleoside/nucleotide analogues (NA) for older children and adolescents has opened new possibilities of treatment. However, the risk of emergence of drug resistant strains is a public health problem and a major long-term issue for young patients. Before starting a child on NAs, the risks of treatment should be carefully weighed against the possible benefits. As the management of special patient populations is problematic and not evidence-based, their referral to highly specialized centers is strongly recommended. The World Health Organization estimates that over 250 million people worldwide are chronically infected with HCV. In countries where adults have a high prevalence of HCV infection, an increased prevalence in children can also be expected. In Egypt, for example, approximately 1-2% of children are infected. The child infected with HCV must be over 2 years old in order to be treated by a licensed drug. The standard of care therapy is pegylated IFN-α plus ribavirin with success rates as similar in adults. The first-wave, first-generation oral direct acting anti-virals (DAAs) telaprevir and boceprevir were licensed by the FDA for use in HCV genotype 1 infection in adults in 2011. Telaprevir and boceprevir must be coadministered with pegylated IFN-α and ribavirin. Sofosbuvir, the second-wave DAA has been approved in adults in January 2014 and other DAAs are on the way of approval soon in adults. Some DAAs are being tested for children and the results are eagerly awaited.

Concepts: Cirrhosis, Hepatitis, Hepatocellular carcinoma, Interferon, Hepatitis C, Hepatitis B, Hepatitis A, Viral hepatitis

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Chemoprevention of hepatocellular carcinoma (HCC) is listed as a yet highly debated long-term benefit of a successful treatment of patients with chronic viral hepatitis. In the hepatitis B virus (HBV) arena, the retrospective scrutiny of both interferon and nucleos(t)ide analogues (NUC) studies failed to provide robust evidence for HCC chemoprevention, due to a number of confoundings in the studies that were originally designed to assess the antiviral activity of interferon therapy. However, the reanalysis of outcomes following patients stratification for risk factors of HCC, provided a clue to find an association between NUC therapy and a reduced risk of liver cancer in non cirrhotic patients, only. In the hepatitis C scenario, a meta analysis of 30 observational studies of patients treated with interferon demonstrated a more than 70% reduction of HCC risk occurring independently of severity of underlying liver fibrosis which was less pronounced in aged patients and those with more advanced liver fibrosis. While the reasons for the residual risk of HCC in virological responders remain largely unexplained, international societies recommend surveillance for HCC of both HBV and HCV responders to antiviral therapy.

Concepts: Cancer, Cirrhosis, Hepatitis, Hepatocellular carcinoma, Interferon, Hepatitis C, Hepatitis B, Hepatitis A

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When hepatocellular carcinoma presents with symptoms cure is seldom possible and death usually follows within months. However, it is possible to detect HCC early, at which stage it is curable. This requires a surveillance program. The components of such a program include: identification of the at risk population, provision of appropriate surveillance tests, and an appropriate method of determining whether the abnormalities found on screening are cancer or not. Surveillance for liver cancer meets all these criteria. Unfortunately high quality evidence showing benefit of liver cancer surveillance is lacking, but lesser quality evidence is plentiful, including several cost efficacy analyses that all show that surveillance does decrease mortality. Therefore all the continental liver disease societies and all national liver disease societies have recommended that surveillance should be undertaken.

Concepts: Epidemiology, Cancer, Disease, Death, Demography, Cirrhosis, Hepatocellular carcinoma, Hepatitis C

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Liver transplantation (LT) is the best option of cure for hepatocellular carcinoma (HCC). Notwithstanding several alternatives, Milan Criteria remain the cornerstone for patient selection. Currently, expanded criteria patients are unsuitable for LT without taking downstaging approaches and response to therapies into consideration. Relative weight of HCC as indication to LT is increasing and that generates competition with MELD-described non-cancer indications. Allocation policies should be adjusted accordingly, considering principles of urgency and utility in the management of the waiting list and including transplant benefit to craft equitable criteria to deal with the limited resource of donated grafts. Maximization of cost-effectiveness of LT in HCC can be also pursued through changes in immunosuppression policies and multimodal management of post-transplant recurrences. This review is focused on those constantly mutating challenges that have to be faced by anyone dealing with the management of HCC in the context of liver transplantation.

Concepts: Cancer, Cirrhosis, Hepatocellular carcinoma, Hepatology, Organ transplant, Transplantation medicine, Liver transplantation, Milan criteria