Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B

Aim: The factors associated with hepatitis recurrence after discontinuation of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. Methods: A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. Results: Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core‐related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis. Conclusions: It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core‐related antigens are also significant factors independently associated with relapse of hepatitis.     

Virological response for recurrent hepatitis C improves long‐term survival in liver transplant recipients

Recurrent hepatitis C virus (HCV) infection occurs universally and is regarded as a major cause of mortality after liver transplantation (LT) for HCV‐related end‐stage liver disease. We conducted this large, single‐center, retrospective study to ascertain the long‐term impact of virological response to treatment of recurrent hepatitis C on survival of LT recipients. From August 1987 to October 2011, 285 patients have received interferon‐based antiviral therapy for recurrent hepatitis C. Of these 285, 245 patients were enrolled in this study. One hundred and twenty‐six patients (51.4%) achieved sustained virological response (SVR). Relapsers (undetectable HCV‐RNA at end of treatment, becoming positive afterward) comprised 9.0% (22/245), and nonresponse (NR; never achieving undetectable HCV‐RNA) 39.6% (97/245). The median follow‐up after completion of antiviral treatment was 2081 days. Using Kaplan–Meier method, patients who achieved SVR were shown to have significantly better 5‐year patient survival (95.2%) than the NR group (49.9%) (P < 0.001), and a trend toward better 5‐year survival than relapsers (87.5%) (P = 0.14); relapsers had a significantly longer survival than NR group (P = 0.005). When compared with NR, SVR and relapse appeared to be significant predictors of better survival, independent of underlying characteristics. In conclusion, virological response, especially SVR, translates into markedly improved long‐term patient outcomes in patients transplanted for hepatitis C.     

The role of medial prefrontal cortex in extinction and reinstatement of alcohol‐seeking in rats

The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug‐seeking behaviour. Specifically, the PL promotes drug‐seeking whereas the IL is necessary for the inhibition of drug‐seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context‐induced reinstatement, reacquisition and extinction of alcoholic beer‐seeking. In context‐induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer‐seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug‐seeking. Rather, they support the view that PL is important for retrieval of drug‐seeking contingency information and that the use of contextual information is enhanced with IL manipulation.     

Antagonism of the dopamine D1‐like receptor in mesocorticolimbic nuclei attenuates acute food deprivation‐induced reinstatement of heroin seeking in rats

The neurotransmitter dopamine (DA) plays a critical role in both priming‐and cue‐induced reinstatement of extinguished drug‐seeking behavior, but its role in stress‐induced reinstatement is less clear. Our laboratory has recently demonstrated that systemic administration of the DA D1‐like receptor antagonist, SCH 23390, attenuates acute food deprivation (FD) stress‐induced reinstatement. The current study was designed to elucidate the brain regions critical to the effect of SCH 23390 on FD stress‐induced reinstatement. Rats were trained to press a lever to self‐administer heroin (0.1 mg/kg/inf) over a period of 10 days. Following training, heroin was removed leading to an extinction of lever pressing. Next, rats were tested for reinstatement twice, under extinction conditions: once following 21–48 h FD; and once under sated conditions. Prior to testing, SCH 23390 was administered into the nucleus accumbens (NAc) shell (0.0, 0.3, 0.6 μg/side), NAc core (0.0, 0.3, 0.6 μg/side), dorsomedial prefrontal cortex (dmPFC; 0.0, 0.2, 2.0 μg/side), ventromedial prefrontal cortex (vmPFC; 0.0, 2.0 μg/side) or basolateral amygdala (BLA; 0.0, 1.0, 2.0 μg/side). An attenuation of FD‐induced reinstatement of heroin seeking was seen in rats injected with SCH 23390 into the NAc shell, dmPFC or BLA, but not into the NAc core or the vmPFC. These findings support the hypothesis that DA transmission through the DA D1‐like receptors plays a critical role in stress‐induced reinstatement of heroin seeking.     

Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post‐transplant CDT monitoring for alcohol relapse assessment – a retrospective study

Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT). The utility of fixed intervals of abstinence prior to listing is still a matter of discussion. Furthermore, post‐LT long‐term observation is challenging, and biomarkers as carbohydrate‐deficient transferrin (CDT) may help to identify alcohol relapse. We retrospectively analyzed data from patients receiving LT for ALD from 1996 to 2012. A defined period of alcohol abstinence prior to listing was not a precondition, and abstinence was evaluated using structured psychological interviews. A total of 382 patients received LT for ALD as main (n = 290) or secondary (n = 92) indication; median follow‐up was 73 months (0–213). One‐ and five‐year patient survival and graft survival rates were 82% and 69%, and 80% and 67%, respectively. A total of 62 patients (16%) experienced alcohol relapse. Alcohol relapse did not have a statistically significant effect on patient survival (P = 0.10). Post‐transplant CDT measurements showed a sensitivity and specificity of 84% and 85%, respectively. In conclusion, this large single‐center analysis showed good post‐transplant long‐term results in patients with ALD when applying structured psychological interviews before listing. Relapse rates were lower than those reported in the literature despite using a strict definition of alcohol relapse. Furthermore, post‐LT CDT measurement proved to be a useful supplementary tool for detecting alcohol relapse.     

Relapses from acute malnutrition and related factors in a community‐based management programme in Burkina Faso

Community‐based management of acute malnutrition (CMAM) is effective in treating acute malnutrition. However, post‐discharge follow‐up often lacks. We aimed at assessing the relapse rate and the associated factors in a CMAM programme in Burkina Faso. Discharged children from the community nutrition centre were requested to return at least every 3 months for follow‐up. The data of recovered children (weight‐for‐height z‐score ≥−2) who were discharged between July 2010 and June 2011 were collected in 45 villages, randomly selected out of 210 in January 2012. Sociodemographic data, economic variables, information on household food availability and the child's food consumption in the last 24 h were collected from the parents. A multivariate Cox proportional hazards regression was used to identify the factors associated to relapse. Of the 637 children, 14 (2.2%) died and 218 (34.2%) were lost to follow‐up. The relapse rate [95% confidence interval] among the children who returned for follow‐up was 15.4 [11.8–19.0] per 100 children‐years. The associated factors to relapses in multivariate Cox regression model were mid‐upper arm circumference (MUAC) at discharge below 125 mm, no oil/fat consumption during the last 24 h and incomplete vaccination. To limit relapses, CMAM programmes should avoid premature discharge before a MUAC of at least 125 mm. Nutrition education should emphasize fat/oil as inexpensive energy source for children. Promoting immunization is essential to promote child growth. Periodic monitoring of discharged children should be organized to detect earlier those who are at risk of relapse. The relapse rate should be a CMAM effectiveness indicator.