Short article: Hepatitis delta in patients with resolved hepatitis B virus infection.

Background: The hepatitis delta virus (HDV) causes the most aggressive form of chronic viral hepatitis. As HDV replication requires hepatitis B virus (HBV), HDV screening is limited to HBsAg+ carriers. To date, individuals with HDV-antibodies and markers of resolved hepatitis B are considered cured.

Treatment of hepatitis C with new fixed dose combinations.

The advent of oral direct-acting antivirals (DAA) has revolutionized the hepatitis C virus (HCV) therapeutic landscape providing cure rates over 90%. However, a subset of patients remains at higher risk for treatment failure, including those infected with: i) genotype 3 and cirrhosis; ii) resistance-associated substitutions (RAS) occurring either as natural polymorphisms or selected after prior DAA failure; and iii) poor drug adherence associated with social disabilities (homeless, psychiatric illnesses, injection drug use, alcoholism, etc.).

New antivirals for the treatment of chronic hepatitis B.

Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers.

Characterization of Free Phenytoin Concentrations in End-Stage Renal Disease Using the Winter-Tozer Equation.

Background: The Winter-Tozer (WT) equation has been shown to reliably predict free phenytoin levels in healthy patients. In patients with end-stage renal disease (ESRD), phenytoin-albumin binding is altered and, thus, affects interpretation of total serum levels. Although an ESRD WT equation was historically proposed for this population, there is a lack of data evaluating its accuracy.

HTLV infection in HCV-antibody positive patients in Spain.

Since hepatitis C virus (HCV) and human T-lymphotropic virus (HTLV) share transmission routes, dual infection could be frequent. In Spain, HTLV underdiagnosis is highlighted by the high proportion of patients presenting either with tropical spastic paraparesis (TSP) or adult T-cell leukemia (ATL) at first diagnosis. We examined whether the renewed efforts for expanding HCV testing may provide a sentinel population that might selectively be targeted to unveil asymptomatic HTLV carriers.

Hepatitis delta and HIV infection.

Viral liver diseases are frequent comorbidities and major contributors to death in HIV-positive individuals on antiretroviral therapy. Although cure of hepatitis C and control of hepatitis B with antivirals avert liver disease progression in most HIV-coinfected patients, the lack of satisfactory treatment for hepatitis delta virus (HDV) infection remains a major threat for developing cirrhosis and liver cancer in this population. In the European Union (EU) and North America, sexual contact has replaced injection drug use that has been the major transmission route for HDV in HIV-positive persons.

The global spread of HIV-1 subtype B epidemic.

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood.

New hepatitis C therapies for special patient populations.

Introduction: Chronic hepatitis C virus (HCV) infection has become a curable disease. More than 90% sustained virologic response rates have been obtained with 8-24 weeks of treatment with distinct combinations of direct-acting antivirals (DAA) in most registration trials. However, outcomes in real-world patients tend to be lower and treatment of special patient populations is often challenging.

IFNL4 rs368234815 polymorphism is associated with innate resistance to HIV-1 infection.

The interferon (IFN)L4 polymorphism rs368234815 is associated with hepatitis C virus (HCV) spontaneous clearance and response to IFN-based treatments. The role of this polymorphism in HIV-1 infection is controversial. We investigated whether genetic variation at IFNL4 is associated to HIV-1 acquisition.

Emerging challenges in managing hepatitis B in HIV patients.

Roughly 10 % of HIV-positive individuals worldwide have concomitant chronic hepatitis B virus (HBV) infection, with large differences between geographical regions and/or risk groups. Hepatitis B is a preventable infection with vaccines. However, it cannot be eradicated once acquired, resembling HIV and in contrast with HCV.

Hepatitis C cure with antiviral therapy--benefits beyond the liver.

Liver disease is the major complication of chronic HCV infection. However, extrahepatic complications are common (50-75%), including mixed cryoglobulinaemia and B-cell lymphomas. Given that chronic hepatitis C has become curable using expensive oral direct-acting antivirals (DAAs), it seems worth revisiting the whole spectrum and burden of disease in HCV carriers.

Hepatic decompensation with sofosbuvir plus simeprevir in a patient with Child-Pugh B compensated cirrhosis.

A 75-year-old male with compensated Child-Pugh B cirrhosis initiated sofosbuvir plus simeprevir, and developed hepatic decompensation and died a few days thereafter. High exposure to simeprevir leading to hepatotoxicity most likely explained this fatal outcome. This observation, along with similar cases recently reported in the literature, should raise awareness of the potential for decompensation in patients with advanced cirrhosis treated with simeprevir.

Hepatitis C seroconversions in HIV infection across Europe: which regions and patient groups are affected?

Background & Aims: In the last decade, several outbreaks of sexually acquired acute hepatitis C (HCV) infection have been described in HIV-positive men who have sex with men (MSM). The aims of this study were to determine whether there has been an increase in the number of acute HCV infections in different parts of Europe.

Methods: HCV seroconversion was defined as an HCV-antibody test change from negative to positive within the observation period in EuroSIDA.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

Background: Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.

Methods And Findings: We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals.

Dolutegravir for the treatment of HIV-2 infection.

Background: Therapeutic options are limited for HIV-2 infected persons, largely in part due to the lack of susceptibility to HIV-1 non-nucleoside reverse transcriptase inhibitors and poor susceptibility to some HIV-1 protease inhibitors. This is particularly worrisome for HIV-2 patients with prior antiretroviral failure.

Objectives: Report the virological response to dolutegravir in HIV-2-infected individuals.

Differential regulation of cytotoxicity pathway discriminating between HIV, HCV mono- and co-infection identified by transcriptome profiling of PBMCs.

Background: Despite the easy accessibility and diagnostic utility of PBMCs and their potential to show distinct expression patterns associated with the accelerated disease progression in HIV/HCV co-infection, there has not been a systematic study focusing on the global dysregulations of the biological pathways in PBMCs from HIV, HCV mono- and co-infected individuals. This study aimed at identifying the transcriptome distinctions of PBMCs between these patient groups.

Methods: Genome-wide transcriptomes of PBMCs from 10 HIV/HCV co-infected patients, 7 HIV+ patients, 5 HCV+ patients, and 5 HIV/HCV sero-negative healthy controls were analyzed using Illumina microarray.

Drug interactions with new hepatitis C oral drugs.

Introduction: Chronic hepatitis C virus (HCV) infection has recently become a curable disease with antiviral therapy. The knowledge of drug interactions using direct-acting antivirals (DAA) may permit maximizing antiviral efficacy and avoiding drug-related toxicities. Ageing in the chronic hepatitis C population, along with added co-morbidities that require other medications, has increased the attention on drug interactions using DAA.

Liver fibrosis progression despite HCV cure with antiviral therapy in HIV-HCV-coinfected patients.

Background: Accelerated liver fibrosis and more frequent hepatic decompensation events and liver-related deaths are characteristically seen in chronic hepatitis C patients coinfected with HIV compared with HCV-monoinfected individuals. Quantitative estimates of long-term clinical benefits derived from curing HCV with antiviral therapy in coinfected patients are scarce, despite being needed for accurate cost-effectiveness decisions using expensive direct-acting antivirals in this population.

Methods: We retrospectively examined all HIV-HCV-coinfected patients followed at one reference clinic in Madrid since 2004.

Efficacy of prolonged tenofovir therapy on hepatitis delta in HIV-infected patients.

Background: Hepatitis delta virus (HDV) produces the most severe form of chronic viral hepatitis. We explored whether prolonged tenofovir exposure might be beneficial on hepatitis delta in HIV-infected patients.

Methods: All HIV-infected patients with hepatitis delta followed at our institution since year 2000 were retrospectively examined.

Long-term survival and liver-related events after pegylated interferon/ribavirin therapy in HIV-infected patients with chronic hepatitis C.

Background: Sustained HCV clearance after hepatitis C therapy is associated with reduced liver-related complications and death. It is unknown if treatment may provide any clinical benefit in patients that fail therapy. This could be particularly relevant in HIV-HCV-coinfected patients, in whom liver disease progresses more rapidly.