Cytomegalovirus infection after orthotopic liver transplantation is restricted by a pre-existing antiviral immune response of the recipient

Infection of the liver by the human cytomegalovirus (HCMV) frequently occurs after orthotopic liver transplantation (OLT). However, the role of viral replication and the inflammatory reaction in the development of HCMV-associated liver dysfunction is unclear. To address this question in vivo, 84 liver biopsy specimens from 74 patients who received an orthotopic liver transplant were investigated by immunohistochemical detection of viral antigens and cell type specific marker proteins. The extent of viral replication was correlated with the HCMV antibody status of donor and recipient. HCMV immediate early antigens were found in 25 of 84 liver tissue sections investigated, hepatocytes being the predominant target cells. Bile duct epithelial cells, endothelial cells, mesenchymal cells and sinusoidal lining cells were also found susceptible to HCMV infection. The detection of viral capsid antigens, nuclear inclusions in infected cells and foci of infected cells were suggestive of permissive infection in these cells. In 25 HCMV-positive liver biopsy specimens, the median extent of HCMV infection was 0.33 (0.02-5.67) infected cells/mm(2) liver tissue. Primary infection of liver transplant recipients (D+/R-) was associated with a significantly higher extent of organ involvement as compared to reinfection or reactivation (D+/R+). In contrast, the extent of inflammatory infiltrates in areas of infected liver cells was higher in tissues of patients with pre-existing immunoreactivity (R+) compared to patients without pre-existing immunoreactivity (R-). In conclusion, these results favour the assumption that the immune response to HCMV is effective in restricting viral spread in the liver.     

The association between hepatitis C infection and survival after orthotopic liver transplantation

BACKGROUND & AIMS: The effect of hepatitis C viral (HCV) infection on patient and allograft survival after orthotopic liver transplantation is controversial. Hepatitis C recurrence after transplant is inevitable, but studies to date have not found a survival difference between recipients with and without HCV. METHODS: Using data from the United Network for Organ Sharing, we performed a retrospective cohort study of 11,036 patients who underwent 11,791 liver transplants between 1992 and 1998. The hazard rates of patient and allograft survival for patients who were HCV-positive as compared with patients who were HCV-negative were assessed by proportional-hazards analysis, with adjustment for potential confounding variables, including donor, recipient, and transplant center characteristics. RESULTS: Liver transplantation in HCV-positive recipients was associated with an increased rate of death (hazard ratio, 1.23; 95% confidence interval [CI], 1.12-1.35) and allograft failure (hazard ratio, 1.30; 95% CI, 1.21-1.39), as compared with transplantation in HCV-negative recipients. This reduction in survival persisted after adjusting for potential confounders. There was an interaction between HCV and sex (P < 0.001) with the effect of HCV on survival being most pronounced in female recipients (patient survival hazard ratio, 1.56; 95% CI, 1.35-1.81; allograft survival hazard ratio, 1.51; 95% CI, 1.34-1.70). CONCLUSIONS: HCV infection significantly impairs patient and allograft survival after liver transplantation.     

The association of lipopolysaccharide and inflammatory factors with hepatopulmonary syndrome and their changes after orthotopic liver transplantation

Background

The level of lipopolysaccharides (LPS) and inflammatory factors were higher in end stage liver disease patient than in normal person for the damage of intestinal mucosal barrier function. Hepatopulmonary syndrome (HPS) was a common pulmonary complication in end stage liver disease. But the association of LPS and inflammatory factors such as toll like receptor 2 (TLR2), TNF-α and ET-1 with the development of HPS was undefined.

Methods

Thirty-one HPS patients were researched (26 patients were performed liver transplantation, five were not). Ten healthy volunteers were recruited as negative control. Blood was collected from the 26 HPS patients before and 3, 7, 14, 21 and 28 days after orthotopic liver transplantation (OLT), and from five HPS patients without OLT and ten healthy volunteers once to detect TLR2 mRNA and iNOS mRNA in peripheral blood monocytes and plasma LPS, TNF-α and ET-1 level. Their levels before and after OLT were compared.

Results

TLR2 mRNA, iNOS mRNA, LPS, TNF-α and ET-1 before OLT in HPS patients were 336,594.1±366,901.1, 63,982.2±74,127.5 copies/ugRNA, 4.3±3.3, 90.1±76.0 and 319.9±124.4 ng/L, respectively. They were 10,338.3±3,814.6, 19,168.5±2,417.4 copies/ugRNA, 0.94±0.69, 2.7±0.1 and 84.2±10.6 ng/L in normal control group. They were significantly higher in HPS patients than those in control group (P<0.05). After OLT, liver function improved to normal. Also TLR2 mRNA, TNF-α and ET-1 decreased in HPS patients after OLT compared with those before OLT. And PaO₂ and PaO₂/FiO₂ improved greatly with intrapulmonary shunt decreased to normal after OLT.

Conclusions

Lipopolysaccharides at the end stage of liver disease with the release of series of inflammatory factors may be associated with the development of HPS.     

Locoregional Therapy of Hepatocellular-Cholangiocarcinoma versus Hepatocellular Carcinoma: A Propensity Score–Matched Study

PurposeTo compare outcomes of unresectable hepatocellular-cholangiocarcinoma (HCC-CC) with hepatocellular carcinoma (HCC) after locoregional therapy (LRT).Materials and MethodsConsecutive patients with histologically confirmed HCC-CC or HCC treated with LRT between 2007 and 2017 were retrospectively reviewed. Ten patients (8 men; median age, 60 y) with 12 HCC-CCs (mean diameter, 4.2 cm ± 1.9; mean number, 3.7 ± 3.3) treated with chemoembolization (n = 6), yttrium-90 radioembolization (n = 2), RF ablation (n = 1), or chemoembolization/RF ablation (n = 1) were compared with 124 patients (92 men; median age, 59 y) with 134 HCCs (mean diameter, 4.8 cm ± 4.0; mean number, 2.6 ± 2.2) treated with chemoembolization (n = 51), yttrium-90 radioembolization (n = 17), RF ablation (n = 41), or chemoembolization/RF ablation (n = 15). Propensity score–matched analysis with conditional logistic regression adjusted for age, sex, LRT modality, tumor-specific features, and Child-Pugh class. Tumor-volume doubling time (TVDT) before LRT and objective response rates were compared by Kruskal-Wallis and Fisher exact test; progression-free survival (PFS) and transplant-free survival (TFS) were compared by Cox proportional hazards model.ResultsOn univariate analysis, HCC-CC was associated with lower median TVDT (2.4 months vs 5.2 months, P = .03), objective response (30% vs 71%, P = .01), and median PFS (2.4 months vs 7.4 months, HR 4.3, 95% CI 2.2–8.4, P < .0001). Propensity score–matched analysis demonstrated greater distant progression (60% vs 30%, P = .003) and significantly shorter median PFS (2.4 months vs 6.0 months, HR 3.3, 95% CI 1.3–8.9, P = .017) for HCC-CC. No significant difference was observed in TFS (7.5 months vs 13.8 months, HR 1.5, 95% CI 0.4–6.1).ConclusionsHCC-CC was associated with reduced PFS and greater distant progression after LRT compared with HCC, indicating a need for adjunctive treatment strategies to improve outcomes.     

Detection of autoimmune regulator gene mutations in children with type 2 autoimmune hepatitis and extrahepatic immune-mediated diseases

Autoimmune regulator gene mutations were identified in 3 children with type 2 autoimmune hepatitis and extrahepatic immune diseases, including 1 child with immune hepatitis recurrence after liver transplantation. These findings suggest that autoimmune regulator gene variants might predispose children to systemic autoimmune disease, a recurrence of immune disease, or both.     

Recurrent Primary Biliary Cirrhosis After Liver Transplantation

Recurrent primary biliary cirrhosis (PBC) is an important clinical outcome after liver transplantation (LT) in selected patients. Prevalence rates for recurrent PBC (rPBC) reported by individual LT programs range between 9% and 35%. The diagnostic hallmark of rPBC is histologic identification of granulomatous changes. Clinical and biochemical features are frequently absent with rPBC and cannot be used alone for diagnostic purposes. Some of the risk factors of rPBC may include recipient factors such as age, gender, HLA status and immunosuppression, as well as donor factors such as age, gender and ischemic time, although controversy exists. Most patients have early stage disease at the time of diagnosis, and there may be a role for therapy with ursodeoxycholic acid. While short‐ and medium‐term outcomes remain favorable, especially if compared to patients transplanted for other indications, continued follow‐up may identify reduced long‐term graft and patient survival.     

猪原位肝移植的麻醉及管理

目的：采用杂种猪模拟原位肝移植的麻醉及管理。方法：对实验猪行经口气管内插管静吸复合全身麻醉。结果：猪的气管插管术与人体相比有其自身特点。实验猪对氯胺酮基础麻醉有较大的耐受量。转流开始时和新肝期开始时血流动力学有较大的改变。结论：对实验猪进行肌松或非肌松气管内插管是可行的。对血流动力学改变的处理应以预防为主。精确计算失血量并及时进行输血输液和维持适当的麻醉深度，对预防和纠正失血性休克有根重要作用。若麻醉处理得当，术中严重的心律失常是完全可能避免的。