Prophylaxis and treatment of hepatitis B infection in the setting of liver transplantation

Without any treatment, the prognosis of hepatitis B in liver transplant recipients is very poor. So, antiviral prophylaxis is very important in patients with hepatitis B who undergo liver transplantation. Before liver transplantation, a suppression of viral replication has to be achieved by nucleos(t)ide analogs. Drugs used in the prophylaxis of post-transplant hepatitis B include immunoglobulin against HBV and nucleos(t)ide analogs. Prophylaxis against graft infection must be based on the individual risk of recurrence. When prophylactic measures have failed and graft infection has occurred, treatment of recurrent hepatitis B may be based on the resistance profile of the virus and previous antiviral exposure. Finally, lamivudine seems to be very effective in the prevention of de novo hepatitis B in patients transplanted with a graft from an anti-HBc positive donor

Experimental Models of Liquid Biopsy in Hepatocellular Carcinoma Reveal Clone-Dependent Release of Circulating Tumor DNA.

Liquid biopsy, the molecular analysis of tumor components released into the bloodstream, has emerged as a noninvasive and resourceful means to access genomic information from cancers. Most data derived from translational studies showcase its numerous potential clinical applications. However, data from experimental models are scarce, and little is known about the underlying mechanisms and factors controlling the release of circulating tumor DNA (ctDNA) and cells (CTCs). This study aimed to model liquid biopsy in hepatocellular carcinoma xenografts and to study the dynamics of release of ctDNA and CTCs; this included models of intratumoral heterogeneity (ITH) and metastatic disease. We quantified ctDNA by quantitative polymerase chain reaction (PCR) targeting human long interspersed nuclear element group 1; targeted mutation analysis was performed with digital droplet PCR. CTCs were traced by flow cytometry. Results demonstrated the feasibility of detecting ctDNA, including clone-specific mutations, as well as CTCs in blood samples of mice. In addition, the concentration of ctDNA and presence of tumor-specific mutations reflected tumor progression, and detection of CTCs was associated with metastases. Our ITH model suggested differences in the release of DNA fragments impacted by the cell-clone origin and the treatment. Conclusion: These data present new models to study liquid biopsy and its underlying mechanisms and highlighted a clone-dependent release of ctDNA into the bloodstream

Risk factors of lung, head and neck, esophageal, and kidney and urinary tract carcinomas after liver transplantation: the effect of smoking withdrawal

Liver transplant recipients have an increased risk of malignancy. Smoking is related to some of the most frequent causes of posttransplant malignancy. The incidence and risk factors for the development of neoplasia related to smoking (head and neck, lung, esophageal, and kidney and urinary tract carcinomas) were studied in 339 liver transplant recipients. Risk factors for the development of smoking-related neoplasia were also studied in 135 patients who had a history of smoking so that it could be determined whether smoking withdrawal was associated with a lower risk of malignancy. After a mean follow-up of 7.5 years, 26 patients were diagnosed with 29 smoking-related malignancies. The 5- and 10-year actuarial rates were 5% and 13%, respectively. In multivariate analysis, smoking and older age were independently associated with a higher risk of malignancy. In the smoker subgroup, the variables related to a higher risk of malignancy were active smoking and older age. In conclusion, smoking withdrawal after liver transplantation may have a protective effect against the development of neoplasia

High-density single cell mRNA sequencing to characterize circulating tumor cells in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) release tumor cells to the bloodstream, which can be detected using cell surface markers. Despite numerous reports suggest a direct correlation between the number of circulating tumor cells (CTCs) and poor clinical outcomes, few studies have provided a thorough molecular characterization of CTCs. Due to the limited access to tissue samples in patients at advanced stages of HCC, it is crucial to develop new technologies to identify HCC cancer drivers in routine clinical conditions. Here, we describe a method that sequentially combines image flow cytometry and high density single-cell mRNA sequencing to identify CTCs in HCC patients. Genome wide expression profiling of CTCs using this approach demonstrates CTC heterogeneity and helps detect known oncogenic drivers in HCC such as IGF2. This integrated approach provides a novel tool for biomarker development in HCC using liquid biopsy

Aszites, Pfortaderthrombose und hepatische Enzephalopathie bei Leberzirrhose: Aktuelle Therapieempfehlungen

Treatment of Ascites, Portal Vein Thrombosis and Hepatic Encephalopathy in Patients with Cirrhosis of the Liver Background: Ascites, portal vein thrombosis and hepatic encephalopathy are important complications of cirrhosis of the liver. Guidelines for the treatment of ascites have recently been published. Method: This manuscript summarizes up-to-date recommendations on the basis of the DGVS S3 guideline and of other guidelines as well as of the authors' experience. Results and Conclusions: TIPS (transjugular intrahepatic porto-systemic shunt) is the preferred treatment for refractory or recidivant ascites unless there are contraindications. The therapy of hepatorenal syndrome type 1 with albumin and the vasoconstrictor Terlipressin has been proven effective. Treatment of portal vein thrombosis comprises a strategy of anticoagulation, TIPS and liver transplantation. The most important therapeutic strategy for hepatic encephalopathy is the search for as well as the treatment of trigger events. Rifaximin is being increasingly used for the treatment and prophylaxis of hepatic encephalopathy

Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study

Summary: The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. Introduction: The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. Methods: Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0–22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0–100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0–1; OPAQ-SV, score 0–100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. Results: A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1 % of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, −0.43; OPSAT-Q, −5.68; EQ-5D, −0.04 (new users) and −0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, −4.17 (experienced users); emotional status, −4.28 (new users) and −5.68 (experienced users); back pain, −5.82 (new users) and −11.33 (experienced users), all P < 0.01. Conclusions: Patients with GI symptoms have lower treatment adherence and treatment satisfaction and worse HRQoL than patients without GI symptoms

Prophylaxis and treatment of hepatitis B infection in the setting of liver transplantation

Without any treatment, the prognosis of hepatitis B in liver transplant recipients is very poor. So, antiviral prophylaxis is very important in patients with hepatitis B who undergo liver transplantation. Before liver transplantation, a suppression of viral replication has to be achieved by nucleos(t)ide analogs. Drugs used in the prophylaxis of post-transplant hepatitis B include immunoglobulin against HBV and nucleos(t)ide analogs. Prophylaxis against graft infection must be based on the individual risk of recurrence. When prophylactic measures have failed and graft infection has occurred, treatment of recurrent hepatitis B may be based on the resistance profile of the virus and previous antiviral exposure. Finally, lamivudine seems to be very effective in the prevention of de novo hepatitis B in patients transplanted with a graft from an anti-HBc positive donor

The role of ribavirin in the combination therapy of hepatitis C virus infection

Ribavirin is a verb, broad-spectrum anti-viral agent used clinically to treat infections by Lassa fever virus, respirator), syncytial virus (RSV) and, in combination with Interferon-alpha (IFN-alpha), hepatitis C virus (HCV). Although it was originally synthesized over 30 years ago, the precise mechanisms of its therapeutic activities are still not fully understood. Ribavirin was shown to possess both direct and indirect action mechanisms against several DNA and RNA viruses. These include direct inhibition of viral RNA-dependent RNA polymerases, inhibition of the host inosine monophosphate dehydrogenase, modulation of the host immune response and inhibition of viral capping enzymes. More recently, ribavirin was demonstrated to be able to act as an RNA virus mutagen, increasing mutations in the RNA virus genome and reducing their infectivity. Still the real challenge is to identity which of its biological properties is responsible for the observed clinical efficacy on specific infections. Under this aspect, renewed interest results from its synergistic enhancement of interferon-alpha (IFN-alpha) therapy, which could open the way to develop more powerful anti-HCV compounds. This work purpose is to provide a broad overview of all the recognized ribavirin action mechanisms against HCV, which call possibly also explain its synergistic behavior with IFN-alpha. An overview on the corresponding HCV treatment clinical observations is also provided in the second part of this work