ICAM-1 triggers liver regeneration through leukocyte recruitment and Kupffer cell-dependent release of TNF-alpha/IL-6 in mice

BACKGROUND & AIMS: Tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mediate hepatocyte proliferation in vivo, suggesting that local and systemic inflammatory reactions may trigger hepatic regeneration after major tissue loss. METHODS: Wild-type, intercellular adhesion molecule (ICAM)-1-/-, and neutropenic-induced mice were subjected to 70% hepatectomy. Three different approaches to block and/or deplete liver macrophages (Kupffer cells) were used. RESULTS: We found that liver from ICAM-1-deficient mice exhibited impaired regeneration after partial hepatectomy. This finding is associated with dramatic decrease in leukocyte recruitment and tissue TNF-alpha and IL-6 levels. All markers of hepatocyte proliferation were restored in ICAM-/- mice by injections of recombinant IL-6. Neutropenic animals and liver macrophage (Kupffer cell) depletion resulted in similar failure of regeneration with low levels of TNF-alpha and IL-6. CONCLUSIONS: The data suggest a novel pathway in which ICAM-1 binds to leukocytes after hepatectomy, triggering hepatocyte proliferation through Kupffer cell-dependent release of TNF-alpha and IL-6.     

One year of hepatitis B immunoglobulin plus tenofovir therapy is safe and effective in preventing recurrent hepatitis B infection post-liver transplantation

BACKGROUND:

Hepatitis B immunoglobulin (HBIG) given in combination with a nucleos(t)ide analogue has reduced the rate of recurrent hepatitis B virus (HBV) infection following liver transplantation (LT); however, the most effective protocol remains unclear.

OBJECTIVE:

To evaluate the use of tenofovir disoproxil fumarate (TDF) in combination with one year of low-dose HBIG.

METHODS:

Twenty-four adults who underwent LT for HBV-related liver disease at the University Health Network (Toronto, Ontario) and received TDF (± lamivudine) and one year of HBIG to prevent recurrent HBV infection from June 2005 to June 2011 were evaluated.

RESULTS:

The median length of follow-up post-LT was 29.1 months. Three patients died during the follow-up period. Patient survival was 100% and 84.1% at one and five years, respectively. None of the patients developed recurrent HBV infection. No significant adverse event was observed due to TDF administration; renal function pre- and post-LT were also acceptably preserved.

CONCLUSION:

The present study demonstrated that a short, finite course of low-dose HBIG combined with maintenance of long-term TDF staring before LT is cost-effective and safe. However, further prospective study involving a larger patient cohort with a longer followup period is required to confirm the results.     

Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: comparable survival and recurrence

Several studies have reported higher rates of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT) versus deceased donor liver transplantation (DDLT). It is unclear whether this difference is due to a specific biological effect unique to the LDLT procedure or to other factors such as patient selection. We compared the overall survival (OS) rates and the rates of HCC recurrence after LDLT and DDLT at our center. Between January 1996 and September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58 (17%) had LDLT. The OS rates were calculated with the Kaplan-Meier method, whereas competing risks methods were used to determine the HCC recurrence rates. The LDLT and DDLT groups were similar with respect to most clinical parameters, but they had different median waiting times (3.1 versus 5.3 months, P = 0.003) and median follow-up times (30 versus 38.1 months, P = 0.02). The type of transplant did not affect any of the measured cancer outcomes. The OS rates at 1, 3, and 5 years were equivalent: 91.3%, 75.2%, and 75.2%, respectively, for the LDLT group and 90.5%, 79.7%, and 74.6%, respectively, for DDLT (P = 0.62). The 1-, 3-, and 5-year HCC recurrence rates were also similar: 8.8%, 10.7%, and 15.4%, respectively, for the LDLT group and 7.5%, 14.8%, and 17.0%, respectively, for the DDLT group (P = 0.54). A regression analysis identified microvascular invasion (but not the graft type) as a predictor of HCC recurrence. In conclusion, in well-matched cohorts of LDLT and DDLT recipients, LDLT and DDLT provide similarly low recurrence rates and high survival rates for the treatment of HCC.     

Preconditioning, postconditioning, and remote conditioning in solid organ transplantation: basic mechanisms and translational applications

Ischemia and reperfusion (I/Rp) injury is inherent to solid organ transplantation and can result in primary nonfunction or delayed function of grafts, which is associated with a significant morbidity and mortality posttransplantation. It is also a major obstacle for the use of marginal grafts to increase the donor pool, as these grafts are prone to a higher degree of I/Rp injury. Pre-, post-, and remote conditioning are protective strategies against I/Rp injury, which can be applied in the transplant setting. These strategies hold the potential to reduce graft injury and to safely expand the donor pool. However, despite convincing experimental data, the protective effects of the "conditioning" protocols remain unclear, and only few have translated to clinical practice. This review summarizes pre-, post-, and remote conditioning strategies in clinical use in solid organ transplantation and discusses an overview of the mechanistic pathways involved in each strategy.     

Angiotensin Blockade Does Not Affect Fibrosis Progression in Recurrent Hepatitis C After Liver Transplantation

Background

Liver transplantation (LT) for hepatitis C virus (HCV)–related end-stage liver disease is impaired by universal disease recurrence and suboptimal response to antiviral therapy. Inhibition of angiotensin-II signalling by angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin-II receptor blockers (ARB) decreases hepatic stellate cell activation in vitro and hepatic fibrogenesis in animal models. A single-center retrospective analysis suggested that angiotensin blockade (AB) inhibits fibrosis progression in recurrent HCV post-LT. This study assessed the effect of AB on fibrosis progression in an independent patient cohort.

Methods

Chart review of all patients who underwent transplantation in our institution for HCV-related ESLD between January 2000 and February 2008 revealed 109 patients with ≥2 protocol liver biopsies and free of antiviral therapy post-LT up to the last biopsy analyzed; 27 of 109 patients were treated with ACE-I/ARB for ≥12 months, 82 were not. Fibrosis was staged using METAVIR.

Results

Live-donor LT was more frequent in controls than in the AB group (25% vs 11%; P < .05). However, parameters known to affect outcome of recurrent HCV, including donor age, prevalence of diabetes, acute cellular rejection, and immunosuppression, were similar in both groups. Time between first and last biopsy (median, 23 months), stage of fibrosis, fibrosis progression rates (median 0.47 vs 0.45 unit/y; P = .46), and time to develop fibrosis stage ≥2 did not differ between groups. Results held true if deceased-donor LT were analyzed separately.

Conclusion

Our study does not support the contention of a previous report that use of AB reduces fibrosis progression in recurrent HCV post-LT.     

Living donor versus deceased donor liver transplantation: a surgeon‐matched comparison of recipient morbidity and outcomes

Informed consent for living donor liver transplantation (LDLT) requires that patients are provided with accurate information on the relative benefits and risks of this procedure compared with deceased donor liver transplantation (DDLT). There is strong evidence to suggest that LDLT facilitates timely transplantation to patients; however, information on the relative morbidity and death risks after LDLT as compared with DDLT is limited. A matched cohort comparison was performed matching recipients for age, MELD, date of transplant, gender, primary diagnosis, and recipient surgeon. A total of 145 LDLT were matched with 145 DDLT. LDLT had a higher overall rate of perioperative surgical complications (P = 0.009). Most of this difference was caused by a higher rate of biliary complications. However, the complications that occurred in the DDLT group tended to be more serious (P = 0.037), and these complications were strongly associated with graft loss in multivariate analysis. The 3‐ and 5‐year graft and patient survivals were similar. In conclusion, DDLT and LDLT have different complication profiles, but comparable hospital stays and survival rates. In areas of deceased donor organ shortages, LDLT offers an excellent alternative to DDLT because it facilitates access to a liver transplant without compromising short‐ or medium‐term recipient outcomes.     

Journey of begomovirus betasatellite molecules: from satellites to indispensable partners

Betasatellites are a group of circular, single-stranded DNA molecules that are frequently found to be associated with monopartite begomoviruses of the family Geminiviridae. Betasatellites require their helper viruses for replication, movement, and encapsidation and they are often essential for induction of typical disease symptoms. The βC1 protein encoded by betasatellites is multifunctional that participates in diverse cellular events. It interferes with several cellular processes like normal development, chloroplasts, and innate immune system of plants. Recent research has indicated βC1 protein interaction with cellular proteins and its involvement in modulation of the host’s cell cycle and symptom determination. This article focuses on the functional mechanisms of βC1 and its interactions with other viral and host proteins.

     

Pleomorphic Adenoma of Hard Palate: An Experience

Introduction

Pleomorphic adenoma of minor salivary glands of hard palate is a rare benign tumour. It usually presents as slow growing submucosal mass on hard palate. The purpose of this study was to collect observational data regarding age, size, symptoms, CT findings and treatment of pleomorphic adenoma of hard palate.

Material and methods

The prospective observational study was done in the Department of ENT, Department of Oral and maxillofacial surgery at SKIMS Medical College and at Peoples Care Polyclinic for a period of 2 years. Twenty cases were enrolled in the study. After clinical suspicion, computed tomography, FNAC and core needle biopsy was done in all twenty cases before any surgical intervention was done.

Results

Most common age group seen to be involved was 16–30 years. Most common symptom was submucosal slow growing mass. Core biopsy was diagnostic with 100 % efficacy. On CT scan twelve patients (60 %) were seen to have intact hard palate even without minor erosions while four patients had full thickness erosion of hard palate. Surgical wide excision was done in all cases and one patient needed total maxillectomy. All treated patients were followed for one year and none showed signs of recurrence

Conclusion

Pleomorphic adenoma of hard palate is usually seen in adults. Definitive diagnosis lies on histopathological examination. CT is necessary for ruling out any bony erosion. Treatment is by wide local excision.     

Pulmonary function in advanced uncomplicated singleton and twin pregnancy

Objective:

Pregnancy brings about significant changes in respiratory function, as evidenced by alterations in lung volumes and capacities, which are attributable to the mechanical impediment caused by the growing foetus. This study was undertaken in order to identify changes in respiratory function during normal pregnancy and to determine whether such changes are more pronounced in twin pregnancy than in singleton pregnancy.

Methods:

Respiratory function was assessed in 50 women with twin pregnancies and in 50 women with singleton pregnancies (during the third trimester in both groups), as well as in 50 non-pregnant women. We measured the following pulmonary function test parameters: FVC; FEV₁; PEF rate; FEV₁/FVC ratio; FEF_25-75%; and maximal voluntary ventilation.

Results:

All respiratory parameters except the FEV₁/FVC ratio were found to be lower in the pregnant women than in the non-pregnant women. We found no significant differences between women with twin pregnancies and those with singleton pregnancies, in terms of respiratory function.

Conclusions:

Despite its higher physiological demands, twin pregnancy does not appear to impair respiratory function to any greater degree than does singleton pregnancy.     

Prevalence of Symptoms of Gastroesopahgeal Reflux in a Cohort of Saudi Arabians: A Study of 1265 Subjects

Background/Aims:

In this study, we aimed to determine the prevalence of gastroesophageal reflux disease (GERD) in the general population of the capital city of Riyadh and to assess its association with other factors including age, smoking, body mass index (BMI), asthma, as well as the presence of other co-morbid diseases.

Materials and Methods:

We used the Gastroesophageal Reflux Disease Questionnaire (GerdQ) for diagnosing GERD, based on a GerdQ score of 8 or more. Riyadh was divided into four quadrants, and from each area, a single shopping mall was chosen randomly to conduct our surveys. Data collected included age, sex, history of smoking, history of asthma or any other medical condition, dietary habits, monthly household income, history and frequency of heartburn, epigastric pain, regurgitation of food, nausea, sleep disturbance from heartburn, the use of common over-the-counter antacids for the control of their symptoms, and their height and weight.

Results:

Over a 4-week period from the 19 December 2012 to 17 January 2013, a total of 1265 individuals were included in the survey. The mean age was 29.97 ± 11.58 years. Females formed 67.81% of the respondents and 62.73% had one or more episodes of heartburn per week. Based on a cutoff GERDQ score of 8, the prevalence of GERD in the surveyed population was 45.4%. GERD was more prevalent in older individuals (mean age 31.9 vs. 30.0 years, P < 0.001) and in those with a higher BMI (27.29 vs. 26.31 kg/m², P = 0.02). There was no difference between males (45.43%) and females (45.13%) (P = 0.92); there was a trend of a higher prevalence in smokers (51.63% vs. 44.41%), but it did not reach statistical significance (P = 0.09).

Conclusion:

Symptoms suggestive of GERD as determined by the translated GerdQ are prevalent among this study population.