Genetics and hepatitis C treatment: towards a personalized treatment?

Chronic HCV (hepatitis C virus) infection is an important cause of liver cirrhosis and hepatocellular carcinoma worldwide. HCV-related cirrhosis is the main indication for liver transplantation in our geographical area. Thus, treatment of this disease represents an important economical burden for the Health Care System. Current treatment of hepatitis C consists of pegylated interferon and ribavirin: only half of the patients achieve a sustained virological response after treatment. Factors related to the virus and the host influence response to treatment. Polymorphisms near the gene IL28B (encoding interferon-λ-3) have been recently identified as strong predictors of spontaneous HCV clearance in acute infection and of response to antiviral treatment in chronic hepatitis C. The aim of this article is to review the genetic studies that have emerged during the last months and its clinical implications, as well as to emphasize how Genetics is gaining importance in the management of liver diseases.     

Syphilis and HIV co-infection: when is lumbar puncture indicated?

The rate of syphilis/HIV co-infection amongst men who have sex with men (MSM) in large urban regions ranges from 20 to 70%. Concurrent HIV infection can alter the clinical presentation of syphilis, the response to treatment, and complicate the diagnosis and clinical course of neurosyphilis. Therefore whether to perform a lumbar puncture (LP) on every co-infected patient in order to diagnose neurosyphilis is controversial. Current clinical guidelines specify the indications for LP, but fall short of recommending LP in certain clinical situations such as early syphilis without neurological involvement. This article reviews the current literature on the relative utility and indications for LP in syphilis/HIV co-infected patients and new research in this area.     

HCV/HIV co-infection, HCV viral load and mode of delivery: risk factors for mother-to-child transmission of hepatitis C virus?

BACKGROUND: Hepatitis C virus (HCV) infection in children is mainly acquired via maternal transmission. Our aim was to identify mother-to-child-transmission (MTC) risk factors, namely those associated with maternal virological characteristics and mode of delivery. METHODS: Women were included between October 1998 and September 2002 in six hospitals in Southern France on the basis of positive HCV serological status. Recorded data included maternal characteristics, circumstances of delivery and laboratory data concerning mother and child. Paediatric follow-up lasted 1 year, and 2 years for children with circulating HCV RNA. RESULTS: A total of 214 mother-and-child pairs were analysed; 55 (26%) were HCV/HIV co-infected. The probability of HCV transmission was three-fold higher for HCV/HIV-co-infected women (P = 0.05). Twelve children were HCV RNA positive at 1 year of age (MTC = 5.6%); three became HCV RNA negative between 12 (M12) and 18 months of age (M18) and recovered normal alanine aminotransferase levels.Circulating HCV RNA was found in 137 (69%) mothers. Mothers of infected children all displayed HCV viraemia (MTC = 8.8%): six children were born of HCV/HIV-co-infected HCV RNA positive women (MTC = 13.6%) and six from HCV monoinfected women with positive HCV RNA (MTC = 6.5%).When maternal HCV RNA levels were below 6 log-IU/ml, the rate of transmission was significantly higher in the case of HCV/HIV co-infection (odds ratio = 8.3, 95% confidence interval, 1.4-47.5) P = 0.01. This association did not, however, exist for HCV RNA-positive mothers with levels of at least 6 log-IU/ml. Rate of transmission did not differ significantly between children born by vaginal delivery or caesarean section after membrane rupture and those born by elective caesarean section independently of HIV status.     

Self-testing for HIV: a new option for HIV prevention?

Self-testing has the potential to be an innovative component to community-wide HIV-prevention strategies. This testing method could serve populations who do not have access to standard voluntary counselling and testing services or because of privacy concerns, stigma, transport costs, or other barriers do not use facility-based, standard HIV testing. This paper reviews recent research on the acceptability, feasibility, and cost of rapid testing and home-specimen collection for HIV, and suggests that self-testing may be another important strategy for diagnosing HIV infection. Several research questions are posed that should be answered before self-testing is realised.     

Fear appeals and treatment side-effects: an effective combination for HIV prevention?

Recent rises in the incidence of HIV infections among gay men in Australia have produced widespread discussion about appropriate health promotion responses. This has sometimes included calls for a return to fear-based campaigns, exemplified by the Grim Reaper advertisements in HIV. This paper discusses results from four focus groups that tested mock campaign material based on an appeal to fear. Five different poster images were tested among groups distinguished by age and HIV serostatus. Three posters used side-effects from treatments as the fear trigger and two used death from AIDS. A number of themes arose in response to the material including 'othering', shame and scepticism about HIV treatments. The meanings of these themes are explored in the light of current health-promotion theory. This data demonstrates that fear is an ineffective tool for HIV health promotion. It further demonstrates that feelings of shame and stigma are likely to be exacerbated in gay men, leading to poorer health outcomes in various ways.     

DGAT and triglyceride synthesis: a new target for obesity treatment?

Because triglycerides are considered essential for survival and their synthesis has been thought to occur through a single mechanism, inhibiting triglyceride synthesis has been largely unexplored as a possible target for obesity treatment. However, recent studies indicate that mice lacking acyl CoA:diacylglycerol acyltransferase (DGAT), a key enzyme in triglyceride synthesis, are viable and resistant to diet-induced obesity. Unexpectedly, this resistance is caused by a mechanism involving increased energy expenditure. These findings suggest that inhibiting specific components of triglyceride synthesis, such as DGAT, is feasible and may represent a novel approach to treating obesity.     

Current treatment for chronic hepatitis?B in Japan

To standardize diagnosis, treatment, and management of chronic hepatitis B, updated treatment guidelines in Japan have been formulated by a research team of the Japanese Ministry of Health, Labor and Welfare (MHLW)’s study project “Research on standardization of treatment for viral liver diseases including liver cirrhosis.” The guidelines recommend first that chronic hepatitis B patients characterized by ALT levels of at least 31 IU/l, with HBe antigen (HBeAg)-positive patients having HBV DNA levels of at least 5 log copies/ml and HBeAg-negative patients with HBV DNA levels of at least 4 log copies/ml, be targeted for treatment. Patients indicated for treatment intervention, for whom are suggested such basic treatments as entecavir therapy, long-term interferon (IFN) therapy, and sequential therapy, are divided into age groups comprising young patients (less than 35 years of age) and middle-aged/elderly patients (35 years and older), HBeAg-positive and HBe-negative patients, and patients with HBV DNA levels of at least 7 log copies/ml and those of less than 7 log copies/ml. As for switching to entecavir for chronic hepatitis B patients currently undergoing lamivudine therapy, the guidelines suggest specific therapies for different groups, dividing patients into those undergoing lamivudine therapy for less than 3 years and those treated for 3 years or longer, as well as those having HBV DNA levels of less than 1.8 log copies/ml and those of 1.8 log copies/ml or more. Formulated on the basis of consideration of chronic hepatitis B patient age, ALT level, HBeAg status, HBV DNA level, and liver disease severity, these guidelines are considered useful for the understanding and implementation of chronic hepatitis B infection diagnosis and treatment, which in recent years have advanced markedly and grown ever more diverse.