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Patients treated with chemotherapy for haematological disease have a known risk of reactivation of hepatitis B virus (HBV) with an estimated incidence of 14-72%. Conversely, very little data exist on viral B reactivation in patients receiving chemotherapy for a digestive malignancy. In this review, a search of the literature data was carried out in an attempt to evaluate the risk of reactivation of HBV during treatment for a digestive malignancy. Based on these data, a ranking of the risk of HBV reactivation and recommendations for the most commonly used anticancer drugs in solid tumors was performed. The majority of anti-cancer drugs can in patients with HBs-positive antigen induce reactivation of HBV. Screening for HBs antigen should be recommended before chemotherapy. Thus, preventive antiviral therapy can therefore reduce the risk of reactivation of HBV. [ABSTRACT FROM AUTHOR]

Competing Interests: S. Pol déclare des liens ponctuels avec AbbVie, Gilead, MSD, BMS, Roche, BioTest, Shinogi et ViiV

Competing Interests: S. Pol déclare être orateur pour BMS, Boehringer Ingelheim, Janssen, Gilead, MSD, Abbvie ; avoir reçu des bourses de Gilead, Abbvie, MSD et être membre de boards de BMS, Boehringer Ingelheim, Janssen, Gilead, MSD, Abbvie.

Competing Interests: S. Pol déclare être orateur pour BMS, Boehringer Ingelheim, Janssen, Gilead, MSD, Abbvie ; avoir reçu des bourses de Gilead, Abbvie, MSD et être membre de boards de BMS, Boehringer Ingelheim, Janssen, Gilead, MSD, Abbvie.

Hepatitis C facing the challenge of healing. Hepatitis C virus (HCV) infection affects 71 million people worldwide. It is a systemic disease associating hepatic manifestations, extra-hepatic manifestations by cryoglobulinemic vasculitis and general manifestations related to chronic inflammation (diabetes, cardio-, reno- or cerebrovascular manifestations and extrahepatic cancers including non-Hodgkin's lymphoma). The significant morbidity and mortality related to HCV therefore justifies its screening, access to treatments that have significantly increased over the past two decades. Understanding the replicative cycle of HCV allowed indeed the development of HCV-specific direct antivirals targeting viral proteins (NS3/4A protease, NS5B polymerase with nucleos(t)idic inhibitors, NS5A multifunctional replication complex protein). The combination of two to three specific inhibitors, sometimes coformulated in a single tablet regimen, without pegylated interferon and most often without ribavirin, allows a high antiviral efficacy (more than 95% cure) for treatment durations of 8 to 12 weeks with a satisfactory tolerance. HCV infection is the only chronic infection that can be cured and hepatic or extrahepatic manifestations are mostly reversible. It underscores the importance of strengthening screening and access to care policies to hope for the elimination of viral C infection in the short term., Competing Interests: S. Pol déclare être orateur pour BMS, Boehringer Ingelheim, Janssen, Gilead, MSD, Abbvie ; avoir reçu des bourses de Gilead, Abbvie, MSD et être membre de boards de BMS, Boehringer Ingelheim, Janssen, Gilead, MSD, Abbvie.

In twenty years, significant progress was made in the knowledge of viral hepatitis. Alphabet of hepatotropic viruses has extended, and C, D, E and G viruses have been added to hepatitis A and B viruses; their genomes have been characterized, allowing defining various types, subtypes and isolates with different pathological and therapeutic implications. Our knowledge regarding the epidemiology, virology and treatment of viral hepatitis is in constant evolution, allowing a better diagnostic and therapeutic approach of patients with acute and chronic hepatitis. Markers of infection and early viral kinetics provide important prognostic and therapeutic information to determine the best moment for the treatment of acute and chronic B (HB V) or C (HCV) viral hepatitis. Finally, the improved definition of risk factors for fibrosis progression to cirrhosis in chronic hepatitis may lead to preventive therapies (alcohol withdrawal, treatment of immune deficiencies) and early antiviral treatments. Progresses in liver transplantation and in the treatment of viral recurrence post-transplantation, improved prognosis of cirrhosis and small hepatocellular carcinomas. For HBV and HCV around half of french infected patients are aware of their infection (seroprevalence of 0.65 % and 0.84 % of the adult population respectively) ; access to care is easy and completly covered by the social security. Second generation-nucleos(t)idic analogues allow HBV viral suppression in all the adherent patients but have to be maintai- nedfor the whole life, by contrast with interferon which a 48 weeks course achieve sustained viral virosuppression in one third of patients, including 10 % of HBs Ag loss. HCV infection may be cured by the combination of oral direct acting antivirals in more than 95 %: hepatic and extra-hepatic manifestations are mainly reversible when a sustained virologic response corresponding to a viral cure is achieved.

The treatment of hepatitis C virus (HCV) infection has significantly improved these last two decades. For nearly 15 years, the association of pegylated interferon alfa and ribavirin (PR) has allowed a sustained virologic response (SVR), i.e., a viral cure of the infection, in 45% of genotype 1-infected patients, 65% of genotype 4-, 70% in genotype 3- and around 85% of genotype 2-infected patients. A better understanding of the HCV life-cycle has led to the development of direct-acting antiviral drugs (DAAs) targeted against viral proteins (NS3/4A protease, NS5B polymerase with nucleos(t)idic and non nucleos(t)idic inhibitors, NS5A viral replication complex). The combination of first generation protease inhibitors with PR has showed a high antiviral efficiency (75% of SVR in genotypes 1) with substantial side effects for the first generation protease inhibitors, which have obtained approval to market in 2011 (Telaprevir and Boceprevir) and recommandations of use in HCV mono-infected patients in 2012 and in HCV/HIV coinfected in 2013. Then, the combination of second generation protease inhibitors with PR has increased SVR rates from 75 to 90%, while reducing treatment duration, side effects and number of pills. Next step is now interferon and ribavirin free combination of DAAs, about to become the standard of care in 2015. These excellent results in 'easy-to-treat' patients and in small population studies has now been confirmed in phase III studies and in 'difficult-to-treat' patients (treatment - especially protease inhibitors-experienced patients, cirrhotic patients, liver and renal transplant patients, HIV co-infected patients, and subjects with polypharmacy, at increased risk of drug interaction).

Epidemiological, virological and therapeutic knowledge in the field of viral hepatitis is constantly growing, resulting in the improved management of the diagnosis and treatment of patients with acute or chronic hepatitis.

Epidemiological advances, new vaccines, early diagnosis as well as research into the ways the different forms of hepatitis are transmitted, have resulted in better prevention.The treatment of populations is more effective and faster.

The treatment of hepatitis C virus (HCV) infection markedly progressed these two last decades. Since 15 years, the combination of pegylated interferon α and ribavirin led to a sustained virologic response (SVR) which corresponds to a complete recovery in around 45 % of patients with HCV genotype 1, 65 % with HCV genotype 4, 70 % with HCV genotype 3 and around 85 % with HCV genotype 2. A better understanding of the HCV life-cycle recently resulted in the development of several potential direct-acting antiviral drugs (DAA) targeting viral proteins (NS3/4A protease inhibitors, NS5B nucleosidic and non nucleosidic polymerase inhibitors, NS5A replication complex inhibitors). A lot of data has been reported with the combinations of pegylated interferon α/ribavirin and the first generation oral DAA, Telaprevir and Boceprevir. These regimens have demonstrated a high level of antiviral efficacy (75 % of SVR) and an acceptable safety profile. After this first major step, the combination of the second generation DAA with pegylated interferon α/ribavirin will impact antiviral potency (75 to 90 % of SVR) and tolerance and will reduce the duration of therapies and the pill burden. The next step, which is an actual revolution, will be the oral combination of new DAA which is likely to become the standard of care for chronic HCV after 2015. Most studies have been conducted in small numbers of "easy-to-treat" patients with short post-treatment period with outstanding results but we are now waiting for confirming these results in more difficult-to-treat patients (experienced genotype 3-infected or genotype 1-infected patients who failed to first generation protease inhibitors, cirrhotic, HIV co-infected patients, allograft recipients or candidates to transplantation)., (© 2013 médecine/sciences – Inserm.)

The evaluation of liver fibrosis in chronic viral hepatitis is of paramount importance since secondary complications, including hepatocellular carcinoma, occur in patients with extensive fibrosis and cirrhosis. Clinical examination and some simple biological and morphological tests represent the first step to appraise liver fibrosis in viral hepatitis. Biochemical (Fibrotest, Hepascore, Fibrometre) or morphological (Fibroscan) methods have emerged over the past ten years to avoid--in more than half of patients--the systematic use of the liver biopsy to appraise liver fibrosis in chronic hepatitis C virus infection. The liver biopsy remains however essential in many situations--especially for demonstrating regression of cirrhosis after viral inactivation. Regression of cirrhosis is now a recognized concept, thanks to the next generation of antiviral treatments. Today, the inactivation of viral hepatitis is an achievable primary goal and regression of cirrhosis becomes a reasonable secondary goal.

Hepatitis C treatment has made a lot of progress in the last two decades. Treatment with pegylated interferon and ribarin is associated with sustained virological response in more than 50% of patients. This improvement is due in one part to the adaptation of treatment dose and duration according to genotype, liver fibrosis and response-guided therapy, fibrosis in another part to a better pretreatment management of co-morbidities and a better prevention and management of side effects. New direct antiviral agents will become soon available and will lead to an improvement of sustained virological response with maybe more complex therapy leading to a new management of patients.

The case of a human immunodeficiency virus (HIV) and hepatitis C virus (HCV)-coinfected patient with a medical history of deep venous thrombosis is presented. A liver biopsy, performed for unexpected portal hypertension, showed vascular lesions presenting as nodular regenerative hyperplasia. Vascular liver diseases seem to be a new cause of chronic liver disease in HIV-infected patients receiving combined antiretroviral therapy. The syndrome of HIV-associated liver vasculopathy is discussed.

Reciprocal interactions between Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) are characterized by the absence of clear impact of HCV on HIV; by contrast, HIV markedly modified the natural history of HCV (high viral load, more severe liver disease) at least before the introduction of highly active antiretroviral therapies (HAART). HAART has completely modified the pattern of hepatic events in HIV infection and the liver disease is one of the leading causes of morbidity and mortality nowadays, reflecting several non-exclusive pathogenic processes that include drug-related hepatotoxicities, chronic hepatitis C infection, other liver diseases such as steatosis or non-alcoholic steato-hepatitis (NASH) and other liver diseases that are common in the setting of alcohol or drug abuse. The harmful impact of HIV underlines the need for improving:

The transmission of the hepatitis B virus (HBV) is parenteral, sexual and perinatal. If a fulminant hepatitis may occur in 1% of cases of symptomatic acute hepatitis, the main problem of HBV infection is its chronicity, as defined by HBs antigen carriage for more than 6 months. It occurs in only 0.5 to 3% of immunocompetent adults but more frequently in children (up to 90%) or in immunocompromised patients (30 to 100%). Evolution of HBV chronic infection is characterized by variations of viral replication with spontaneous reactivations or discontinuations with potential clinical and biochemical exacerbations. Pathogeny of HBV infection is mainly immune-mediated, resulting from the host-virus interactions but also from the complexity of HBV (integration, mutation, occult replication), explaining the polymorphism of chronic HBV infection; it includes immune tolerance, inactive carriage of HBs antigen but also immune elimination with chronic active hepatitis which may lead to cirrhosis (yearly incidence of 1.3 to 5.9%). Cirrhosis may result in complications of portal hypertension and liver failure or hepatocellular carcinoma which explain 80% of morbidity and mortality of HBV: the 5-year survival of HBV-related cirrhosis ranges from 52 to 82%. Immunosuppression, delta virus superinfection or chronic alcohol consumption are the main factors which modify the natural history of HBV infection. HBV chronic infection is a problem of public health, particularly in developing countries, evidencing the need for universal HBV vaccination.