The implications of hepatitis B virus (HBV) reinfection after liver transplantation were studied in 29 patients followed for 1.7-15 years. Of 20 patients with HBV infection alone, nine were HBeAg and ...HBV DNA seronegative and 11 had evidence of HBV replication as measured by HBeAg or HBV DNA seropositivity. Nine patients had co-existing HBV and delta virus (HDV) infection. Five patients became HBsAg seronegative after transplantation (four immediately and one after an hepatitic episode). Of the 20 patients with HBV infection alone, 17 had evidence of viral replication after transplantation with markedly increased HBV DNA levels. Five patients with HDV infection had HBV DNA in serum, but in significantly lower amounts than in those with HBV infection alone. Twenty-five episodes of graft dysfunction attributed to recurrent HBV infection occurred in 19 patients (65.5%). Thirteen episodes (in 12 patients) were self-resolving acute hepatitic illnesses. Six patients had a rapidly progressive illness leading to graft loss within 6 weeks, with the distinctive histological features termed fibrosing cholestatic hepatitis (FCH). Liver function tests in these patients showed markedly abnormal serum bilirubin and prothrombin times, but only modest increases in serum transaminase levels. An additional six patients lost their graft as a consequence of HBV recurrence through various pathogenetic mechanisms including possible (but unproven) FCH, chronic active hepatitis or late-onset hepatic failure. Co-existing HDV infection appeared to confer some medium-term protection from graft loss.
Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic ...sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle) daily for 10 days. On day 9, mice were inoculated with human-rhinovirus-1B (or UV-inactivated human-rhinovirus-1B). Forty-eight hours after inoculation, we assessed bronchoalveolar cellular inflammation, levels of relevant cytokines/serum antibodies, lung function and responsiveness/sensitivity to methacholine. House-dust-mite exposure did not result in a classical TH2-driven response, but was more representative of noneosinophilic asthma. However, there were significant effects of house-dust-mite exposure on most of the parameters measured including increased cellular inflammation (primarily macrophages and neutrophils), increased total IgE and house-dust-mite-specific IgG1 and increased responsiveness/sensitivity to methacholine. There were limited effects of human-rhinovirus-1B infection alone, and the combination of the two insults resulted in additive increases in neutrophil levels and lung parenchymal responses to methacholine (tissue elastance). We conclude that acute rhinovirus infection exacerbates house-dust-mite-induced lung disease in adult mice. The similarity of our results using the naturally occurring allergen house-dust-mite, to previous studies using ovalbumin, suggests that the exacerbation of allergic airways disease by rhinovirus infection could act via multiple or conserved mechanisms.
The aim of this study was to describe the natural history of HCV after 16 years of infection, in a cohort of individuals who acquired their infections on a known date in the United Kingdom. A total ...of 924 HCV-infected transfusion recipients (cases) and 475 anti-HCV negative transfusion recipients (controls) were eligible for inclusion in the study. Survival was compared between cases and controls to see if there was any excess mortality attributable to HCV. The results show that all-cause mortality was not significantly different between cases and controls (hazard ratio 1·17, 95% CI 0·92–1·49, P=0·21). However, the risk of death directly from liver disease was higher in cases than controls (hazard ratio 2·71, 95% CI 1·09–6·75, P=0·03). Nearly 30% of those HCV-infected cases who died directly from liver disease were known to have consumed excess alcohol.
Thirty-six of 68 consecutive patients with fulminant hepatic failure (FHF) progressing to grade 4 encephalopathy who had extradural ICP monitors inserted were reviewed to determine the safety and the ...value of ICP monitoring. Only minor complications were encountered. These included local wound bleeding at the burrhole site in four patients and a small cerebral hemorrhage in relation to the monitor in one other patient. No significant long-term sequelae were related to the operative procedure. ICP monitoring identified rises in ICP unaccompanied by clinical signs and as a consequence treatment was given to the monitored patients more often than the non-monitored group (median 6 vs. 2 treatments, P < 0.01). The duration of survival from the onset of grade 4 encephalopathy was significantly greater in the ICP monitored group (median 60 vs. 10 h, P < 0.01) although overall survival was unchanged. Monitoring also provided important prognostic information since the peak ICP was higher in non-survivors than in survivors (median 45 vs. 35 mmHg, P = 0.051). The pattern of clinical signs accompanying episodes of intracranial hypertension differed between survivors and non-survivors. Pupillary abnormalities were detected more often in non-survivors while systolic hypertension occurred more frequently amongst survivors with the peak systolic blood pressure being significantly higher. ICP monitoring proved safe and effective, provided valuable information regarding subclinical intracranial hypertension and prognosis and should be regarded as part of the routine management of intracranial hypertension complicating FHF.
The development of genetically modified pigs has renewed interest in the use of porcine liver perfusion in the treatment of acute liver failure.
A previously developed model of extracorporeal ...perfusion has been used to test the function of porcine livers transgenic for human decay accelerating factor when perfused with fresh, whole, human blood. Three experimental groups were studied: alloperfusions (normal pig livers perfused with pig blood) and xenoperfusions of both unmodified and transgenic pig livers with human blood. All livers were perfused for up to 72 hr.
Alloperfusion resulted in the maintenance of good function and histological structure. Stable hemodynamic, synthetic, and metabolic parameters were demonstrated in both unmodified and transgenic liver xenoperfusions; hyperacute rejection was not seen. In both groups, however, the measured parameters of liver function deteriorated toward the end of the 72 hr perfusion period; deterioration was more marked in the nontransgenic group. Xenoperfusions were characterized by a progressive and marked decrease in hematocrit of the circulating blood. Histologically, patchy necrosis was noted in both groups and more retained erythrocytes were seen in the sinusoids of nontransgenic livers, but no other consistent differences were apparent.
These studies have demonstrated that porcine liver xenoperfusions can be performed for prolonged periods while maintaining good liver function. The use of organs from animals transgenic for a human complement regulator protein confers improvement in some measures of liver function. This preclinical model provides evidence that extracorporeal liver xenoperfusion may be effective in temporary liver support for patients in acute liver failure.
Protoporphyria Cox, T M; Alexander, G J; Sarkany, R P
Seminars in liver disease,
1998, Letnik:
18, Številka:
1
Journal Article
Recenzirano
Human protoporphyria results from mutations in the ferrochelatase gene. Heritable deficiency of ferrochelatase causes overproduction of protoporphyrin IX, principally in the erythron. ...Photosensitivity is a universal feature of protoporphyria but hepatic clearance of the hydrophobic protoporphyrin molecule with excretion in bile may lead to precipitation within biliary pathways. Thus cholestatic injury and protoporphyrin gallstones occur. Minor hepatic abnormalities are frequent, but at least 30 patients have been reported with a progressive liver disease that requires transplantation. Fulminant hepatic disease appears to be recessively inherited in some pedigrees. Hazards of liver transplantation include tissue photolysis, hemolysis, and an unexplained neurological syndrome, but most of the 15 patients reported after transplantation have survived for several months to > 6 years. Aspects of protoporphyria, its pathogenesis and contemporary therapeutic strategies are considered, with emphasis on hepatic sequelae.
The majority of complement protein C3 is synthesized by the liver, but many other cell types produce small amounts of functionally active C3. The overall contribution of such extrahepatic C3 ...production to the total circulating C3 level is unknown. Bone marrow and extrahepatic C3 productions were quantified in bone marrow transplant (BMT) and liver transplant (LT) recipients, respectively, where a mismatch for the C3 allotypes distinguished by the mAb HAV 4-1 had occurred. In the BMT group, donor-derived C3 was detected by ELISA and immunoblotting techniques. It contributed to 0.1 to 2.6% of the total circulating C3 during the immediate post-BMT period in response to inflammatory stimuli. Cell culture and immunostaining techniques demonstrated that monocytes were the source of the C3. By 6 wk following BMT, donor-derived C3 levels had decreased to below the detection limit of the assays. By contrast in the LT group, total extrahepatic C3 levels were higher (3.1-5.7% of the total circulating C3) and remained stable for up to 1 yr post-LT. This study demonstrates that extrahepatic derived C3 forms a larger proportion of the circulating C3 levels than was considered previously and that in the resting state, most of this extrahepatically derived C3 comes from nonmyeloid sources. In addition, monocytes, which in the resting state contribute negligible amounts of C3, have the potential when stimulated to contribute significantly to the total systemic C3 pool. These findings highlight the importance of locally secreted complement proteins.
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