Explore the vast range of titles available.

BACKGROUND/AIMS Most patients infected with hepatitis C virus (HCV) develop chronic infection and persistent viraemia. The immune mechanisms responsible for resolution of viraemia remain poorly understood. HCV specific humoral and cellular immune responses in patients with and without viraemia were investigated. METHODS In vitro T helper (TH) lymphocyte responses to structural and non-structural HCV proteins were determined by means of proliferative response and cytokine production in 35 anti-HCV positive/HCV RNA negative patients and in 31 patients with chronic HCV infection and persistent viraemia. Humoral responses were determined by measuring HCV specific antibody quantity and specificity. RESULTS A TH response to two or more HCV proteins was present in 18 of 35 patients with serological viral clearance compared with just one of 31 viraemic patients (p = 0.00001). HCV specific interferon-γ production was increased only in the former group. In contrast, the antibody levels were significantly lower and directed at fewer HCV antigens in patients with undetectable HCV RNA. CONCLUSIONS Patients without viraemia after HCV infection frequently have strong TH lymphocyte responses of the TH1 type to multiple HCV antigens many years after the onset of infection, whereas antibody responses are less marked. These results suggest that control of HCV replication may depend on effective TH lymphocyte activation.

The effect of HIV-related immunosuppression and antiretroviral therapy on the reactivation of latent hepatitis B virus (HBV) infection is unclear. We report four patients with advanced HIV-related immunosuppression and abnormal liver function tests who had evidence of HBV reactivation. Reclearance of hepatitis B occurred in two cases with HIV treatment regimens not containing lamivudine, suggesting that improved immune function may be responsible. In three cases, HBV reactivation was recognized during investigation for abnormal liver function initially attributed to drug toxicity. The possibility of HBV reactivation must be considered in the differential diagnosis of abnormal liver function in cases with advanced HIV.

IntroductionLiver transplantation (LTx) is the only curative therapeutic modality for patients with end-stage liver disease (ESLD). A detailed evaluation of the liver transplant patient is critical to identify patients most likely to benefit from LTx in an era of organ donor shortage to optimise use of a scarce resource.AimThe aim of this study was to analyse the profile and outcome of LTx referrals in a ‘hub and spoke’ LTx service.MethodA retrospective study of all patients referred to the South West Liver Unit, liver transplant service between April 2007 and April 2011. Patients with acute liver failure were excluded from the analysis. Pre-transplant and post-operative follow-up was performed at the South West Liver Unit. All operations were performed at King's College Hospital, London. Pre-LTx demographic and laboratory data were analysed using descriptive methods. Comparisons (Mann–Whitney) and survival (Kaplan–Meier) were estimated. α level of 0.05 was accepted as significant.Results191 consecutive patients (n=128, 67% males) underwent elective pretransplant assessment and posttransplant management. Mean age was 53 years, SD 10.3 (range 19–70). Currently, 9.4% (18/191) patients are under assessment, 10.5% (20/191) are on the waiting list for LTx, 29.8% (57/191) have been transplanted, 7.9% (15/191) died on the list and 42.4% (81/191) were assessed but not listed (too advanced disease in 12%, not fulfilling minimal listing criteria 14.7% and contraindicated 15.7%). Among patients who met minimal listing indications 21% (n=19) were diagnosed with hepatocellular carcinoma (chronic HCV infection or/and alcohol background), 30% (n=28) had alcoholic liver disease, 9% (n=8)—chronic HCV infection, 11% (n=10) exhibit both alcohol and viral aetiology, 4% (n=4)—autoimmune hepatitis, 11% (n=10) - PBC/PSC, 4% NASH (n=4), 2% (n=2) cryptogenic cirrhosis and in 9% (n=8) rare diseases (vascular, metabolic, congenital or chronic rejection). These proportions did not deviate from the whole assessed cohort. Mean UKELD, MELD and CTP scores of all assessed patients were 52 (SD 5.2), 12 (SD 5.6) and 8 (SD 1.9). UKELD correlated strongly with MELD and CTP (Spearman's ρ 0.68 and 0.72, p<0.01) and was slightly higher in listed for LTx group. CTP score did not differ between transplanted and not transplanted patients. Among the liver recipients 36% were blood group A, 12% B, 10% AB and 42% O, similar to the distribution in the whole group. Mean BMI was 26.2, not different between transplanted and not listed patients. However, a third of all assessed patients had severe protein malnutrition, evaluated with hand dynamometry and estimated energy expenditure/intake ratio. The prevalence of HPS and PPH were 9% (11/122) and 3% (4/135) respectively. Three months-, 1- and 3-year survival of the patients and the grafts were 98%/97%/97% and 98%/95%/90%. Abstract P80 figure 1 illustrates the differences in survival of transplanted and not transplanted patients.Abstract P80 Figure 1Survival of all patients.ConclusionGraft and patient survival in the ‘hub and spoke’ model is good. Alcohol and hepatoma are the commonest reasons for listing. Protein malnutrition is common in this patient cohort suggesting improved patient nutrition and early dietician involvement is needed.

[...]we would contend that genotype and patient age should be incorporated into any algorithm as should factors known to accelerate the natural history of the disease including: co-infection with human immunodeficiency virus (HIV), alcohol excess, obesity, and male gender. 2 Patients with a liver stiffness measurement between 6 and 12 kPa are likely to receive treatment and do not need long-term follow-up should SVR be achieved, so why subject these patients to biopsy?

Background Prisons are a potential setting for hepatitis C screening. This study describes prisoner flows through such screening for all prisoners entering Dartmoor prison between 1 January 1998 and 30 June 2001. Methods We identified numbers at each step of the screening pathway, from screening to result, referral, biopsy and outcome. We describe the proportions of those screened who were seropositive; seropositives who were confirmed virus-positive; virus-positive cases attending for biopsy; and virus-positive cases eligible for treatment. Results Of 3034 entries into Dartmoor, 12 per cent were screened, with 16 per cent of these seropositive. Seventynine per cent of seropositive prisoners with a polymerase chain reaction result were confirmed virus-positive, and 27 per cent of these prisoners had a biopsy. Two prisoners were eligible for treatment. Conclusions Screening uptake is low. Attrition rates are high, especially at the referral interface between the prison and specialist care. Finally, the yield of individuals eligible for treatment is low, at 7/1000 tested.

IntroductionWe have identified a cohort of injection drug users (IDU) who, despite long-term high risk sharing of drug injection equipment, remain seronegative and aviraemic for HCV. These exposed uninfected (EU) IDU appear resistant to HCV infection. This resistance is associated with the same Natural Killer (NK) immunoglobulin-like receptor (KIR)/HLA genotype known to favour spontaneous HCV clearance. Whether there is a functional alteration in NK cell cytotoxicity in these individuals is unknown.AimTo investigate cytotoxic function of NK cells in EU.MethodPeripheral blood mononuclear cells (PBMC) were isolated from 16 EU (HCV-Ab positive and HCV-RNA negative), 10 IDU with untreated chronic HCV (cHCV) and five IDU with spontaneous resolution (SR) of HCV (HCV-Ab positive but HCV RNA negative). NK cytotoxicity was assessed against the NK-sensitive K562 cell line. PBMC incubated for 48 h with or without interleukin-2 (IL-2) were co-cultured with K562 for 4 h at an E:T ratio of 10:1. Flow cytometry was used to assess the frequency of NK cells [CD56(+) CD3(−)] in PBMC and cytotoxicity quantified by CFSE/7-AAD co-staining and expressed as the percentage of cells lysed.ResultsNatural killer cell cytotoxicity, in the absence of IL-2 stimulation, was no different between the groups. With IL-2 stimulation, EU demonstrated significantly higher cytotoxicity compared to cHCV (32.8±4.4% vs 17.6±3.2%, p=0.023), with similar levels to SR (27.7±9.9%, p=0.50). The proportion of NK cells in PBMC was not significantly different between the groups.ConclusionThe current findings point to enhanced NK cytotoxicity in EU cases compared to those with chronic infection and suggests a role for NK cells in early viral clearance and resistance to HCV infection.

Both hepatitis B virus (HBV) and HCV are transmitted parenterally and coinfection is not uncommon, particularly in intravenous drug users and in countries with a high prevalence of HBV infection. 2 Coinfection with evidence of chronic HBV and HCV seems to result in more severe liver disease than either infection alone, 3 with an increased risk of liver cancer 2 and probably an increased risk of fulminant hepatitis when superinfection with HCV occurs on the background of chronic HBV. 4 The presence of hepatitis B surface and/or hepatitis B core antibodies (anti-HBs and anti-HBc) in the absence of hepatitis B surface antigen (HBsAg) is generally taken to indicate resolution of infection and provides evidence of previous HBV infection.

Natural killer (NK) cells provide a central defense against viral infection by using inhibitory and activation receptors for major histocompatibility complex class I molecules as a means of controlling their activity. We show that genes encoding the inhibitory NK cell receptor KIR2DL3 and its human leukocyte antigen C group 1 (HLA-C1) ligand directly influence resolution of hepatitis C virus (HCV) infection. This effect was observed in Caucasians and African Americans with expected low infectious doses of HCV but not in those with high-dose exposure, in whom the innate immune response is likely overwhelmed. The data strongly suggest that inhibitory NK cell interactions are important in determining antiviral immunity and that diminished inhibitory responses confer protection against HCV.

Between 1996 and 2003, 186 cases of hepatitis E were serologically diagnosed. Of these, 17 (9%) were not associated with recent travel abroad. Patients were >55 years old (range, 56–82 years old) and tended to be male (76%). Two patients presented with fulminant hepatitis. A total of 129 (69%) cases were associated with recent travel to countries where hepatitis E virus (HEV) is hyperendemic. Compared with patients with travel-associated disease, patients with non–travel-associated disease were more likely to be older, living in coastal or estuarine areas, not of South Asian ethnicity, and infected by genotype 3 strains of HEV. The genotype 3 subgenomic nucleotide sequences were unique and closely related to those from British pigs. Patients infected by HEV indigenous to England and Wales tended to belong to a distinct demographic group, there were multiple sources of infection, and pigs might have been a viral reservoir