Treatment For End-stage Liver Disease Research Articles

Imaging complications of liver transplantation: a multimodality pictorial review.

Liver transplantation is one of the most commonly performed surgical procedures for the treatment of end-stage liver disease and hepatocellular carcinoma. Post-transplantation complications include vascular, nonvascular, and biliary. Common imaging techniques used to evaluate the hepatic graft are ultrasonography (US), CT, MR imaging, cholangiography, angiography, and scintigraphy. The purposes of this pictorial review are to review imaging findings of complications of liver transplantation and provide a framework for early detection of post-surgical complications.

Updates on extended criteria donor for liver transplantation

Though achieved great success as the only curative treatment for end-stage liver diseases, liver transplantation has been severely restricted by the shortage of donors. The adoption of extended criteria donor (ECD) tackles the donor shortage problem to some extent, thus became an issue we must face in China at present stage. As the transplantation effect and recipient safety is largely decided by the quality of liver graft, ECD graft should be cautiously selected and adopted because of its inherent defects. This relies on individualized decisions made for recipients by transplant surgeons who have a good understanding of the risk factors and evaluation criteria of ECD. In this article, we investigate the risk factors, evaluation criteriaand allocation of ECD liver grafts as well as the application of mechanic perfusion, and we discuss the fundamental issues and prospects of ECD study. Key words: Liver transplantation; Risk factor; Extended criteria donor; Mechanic perfusion

Introducing Palliative Care within the Treatment of End-Stage Liver Disease: The Study Protocol of a Cluster Randomized Controlled Trial.

Introduction: Patients with end-stage liver disease (ESLD) suffer from myriad symptoms due to the systemic effects of the disease and unpredictable acute episodes, which contribute to progressive deterioration in quality of life (QOL). Despite clear evidence that palliative care (PC) improves QOL in other serious illnesses, PC is underutilized and delayed for ESLD patients. Through a comparative effectiveness trial of specialist led consultative PC (Model 1) versus trained hepatologist led PC (Model 2), we aim to build evidence on introducing PC into the routine outpatient care of ESLD patients. Objective: We hypothesize that trained hepatologist led PC model will have a better improvement in QOL compared to consultative PC model. Methods: This two-arm, multicenter cluster-randomized trial assesses the effectiveness of two PC models for patients with ESLD. Fourteen clinical centers will recruit 1260 patient-caregiver dyads. Each center is the unit of randomization. Hepatologists at sites randomized to the Model 2 have undergone web-based training in the principles of PC as pertained to ESLD. PC intervention is delivered over four visits (initial, one, two, and three months). Follow-up assessments occur at 6, 9, and 12 months. Eligible patients are those with new onset or ongoing complications of ESLD with a caregiver willing to participate. Outcomes: The primary outcome is change in patients' QOL from baseline to three months. Secondary outcomes include symptom burden, depression, distress, satisfaction with care, caregiver burden and QOL, goal concordant care, and health care utilization. Challenges and Contributions Engagement: A research advisory board has been developed with representatives from the participating centers, who have provided active feedback on the protocol, outcomes, study methods, and training program. Intervention Fidelity: Intervention fidelity will be maintained by adherence to a visit agenda and providers in both models completing a PC checklist after each study visit.

Alloresponses of Mixed Lymphocyte Hepatocyte Culture to Immunosuppressive Drugs as an In-Vitro Model of Hepatocyte Transplantation.

BackgroundHepatocyte transplantation (HCTx) has the potential for the treatment of end-stage liver disease. However, failure of engraftment and the long-term acceptance of cellular allografts remain significant challenges for its clinical application. The aim of this study was to investigate the efficacy of the immunosuppressive agents, Cyclosporine, Everolimus, and Belatacept to suppress the alloresponse of primary human hepatocytes in a mixed lymphocyte-hepatocyte culture (MLHC) and their potential hepatotoxicity in vitro.Material/MethodsPrimary human hepatocytes were co-cultured with allogeneic peripheral blood mononuclear cells (PBMCs) in an MLHC. Proliferative alloresponses were determined by flow cytometry, and cytokine secretion was measured using Luminex-based multiplex technology. Using an MLHC, the alloresponses of primary human hepatocytes were compared in the presence and absence of Cyclosporine, Everolimus, and Belatacept. Cultured primary human hepatocytes were assessed for the production of albumin, urea, aspartate transaminase (AST) and DNA content. Metabolic activity was determined with the MTT assay.ResultsImmune responses induced by primary human hepatocytes were effectively suppressed by Cyclosporine, Everolimus, and Belatacept. Everolimus significantly reduced the metabolic activity of primary human hepatocytes in vitro, suggesting impairment of cell viability. However, further functional analysis showed no significant differences between treated and untreated controls.ConclusionsCyclosporine, Everolimus, and Belatacept suppressed the alloresponse of primary human hepatocytes in an MLHC without significant cytotoxicity or functional cell impairment.

The role of stem cells in liver injury and repair

ABSTRACTIntroduction: Liver disease is an increasing cause of worldwide mortality, and currently the only curative treatment for end-stage liver disease is whole organ allograft transplantation. Whilst this is an effective treatment, there is a shortage of suitable grafts and consequently some patients die whilst on the waiting list. Cell therapy provides an alternative treatment to increase liver function and potentially ameliorate fibrosis.Areas covered: In this review, we discuss the different cellular sources for therapy investigated to date in humans including mature hepatocytes, hematopoietic stem cells, mesenchymal stromal cells and hepatic progenitor cells. Cells investigated in animals include embryonic stem cells, induced pluripotent stem cells and directly reprogrammed cells. We then appraise the experience and evidence base underlying each cell type.Expert opinion: We discuss how this field may evolve in the years to come focusing on opportunities to enhance the intrinsic regenerative response with therapeutic targets and cell therapies. Growing expertise in tissue engineering will likely lead to increasingly complex bio-reactors and bio-artificial livers, which open a further avenue to restore liver function and delay or prevent the need for transplantation.

The Impact of Steatosis on the Outcome of Liver Transplantation: A Meta-Analysis

Background and Aims Liver transplantation is one of the most effective treatments for end-stage liver disease as well as for cases of acute liver failure. Facing organ donor shortage, liver transplant teams had to use marginal organs. Thus, increasing availability is a key concern of donor liver grafts including steatotic livers. However, the use of steatotic liver is still controversial. The aim of this systematic review and meta-analysis was to analyze the impact of steatosis on the outcome of liver transplantation. Methods We searched PubMed, Cochrane Library, Embase, Web of knowledge, and so on for studies published through May 31, 2018, in which patients experienced liver transplantation using fatty liver. All studies extracted outcome indicators, and we draw conclusions by contrasting outcome indicators in different groups of steatosis. Odds ratios and 95% confidence intervals were calculated. P<0.05 was considered as statistically significant difference. Results 19 publications were included. There was no significant difference between the group of no steatosis and mild group in primary nonfunction rate (P=0.605) or early graft dysfunction rate (P=0.44). The PNF rate was significantly higher in moderate group (P=0.003) and severe group (P <0.001) compared with that in no steatosis group. The same results were seen in early graft dysfunction rate. However, graft survival rate and patient survival rate did not differ between groups. Conclusions Livers with mild steatosis, even with moderate or severe steatosis, could be suitable donor under strict control of transplant conditions.

Bone Marrow Mesenchymal Stem Cells Encapsulated in a Hydrogel System via Bioorthogonal Chemistry for Liver Regeneration.

Liver tissue engineering is going to be an effective treatment for end-stage liver disease. In this work, we distributed bone marrow mesenchymal stem cells (BMSCs) into a fast-forming hydrogel system to develop a liver-mimicking construct for liver regeneration. The advantage of this hydrogel system was that this BMSC-encapsulating hydrogel could be formed via a bioorthogonal reaction between 2-cyanobenzothiazole and cysteine within several seconds. Thereafter, we explored the morphology, biocompatibility, and expressions of hepatic differentiation markers of this hydrogel system. These results illustrated that this system could provide a suitable niche for BMSC proliferation and differentiation, which could aid in future biomedical research of liver regeneration.

Cognitive impairment after liver transplantation: residual hepatic encephalopathy or posttransplant encephalopathy?

Liver transplantation (LT) represents the definitive treatment for end-stage liver disease. Cognitive impairment following LT is frequent, referred to as postliver transplant encephalopathy (PLTE). LT removes the underlying chronic liver disease, and until recently hepatic encephalopathy (HE) was assumed to be fully reversible after LT. However, increasing evidence indicates that some degree of cognitive impairment may be present after LT. To which extent PLTE reflects cognitive impairment caused by residual HE (RHE) or the combined effect of other factors affecting brain function before, during, and after LT is not clarified. None of the available psychometric and neurophysiological tests used for detecting HE is shown to be able to distinguish between etiologies. The available, mostly retrospective, clinical studies indicate a high prevalence of abnormal psychometric tests after LT, and not all seem to recover completely. The patients with earlier HE show the most marked improvements, suggesting that the clinical picture of the early PLTE, in fact, represents RHE. Other early post-LT etiologies for PLTE comprise cerebral ischemia, critical illness encephalopathy, and immunosuppressive therapy. Late-onset etiologies comprise diabetes and hypertension, among others. PLTE regardless of etiology is a worrying issue and needs more attention in the form of mechanistic research, development of diagnostic/discriminative tools, and standardized prospective clinical studies.

Adult-to-adult living-donor liver transplantation: The experience of the Université catholique de Louvain

BackgroundLiver transplantation is the treatment for end-stage liver diseases and well-selected malignancies. The allograft shortage may be alleviated with living donation. The initial UCLouvain experience of adult living-donor liver transplantation (LDLT) is presented. MethodsA retrospective analysis of 64 adult-to-adult LDLTs performed at our institution between 1998 and 2016 was conducted. The median age of 29 (45.3%) females and 35 (54.7%) males was 50.2 years (interquartile range, IQR 32.9–57.5). Twenty-two (34.4%) recipients had no portal hypertension. Three (4.7%) patients had a benign and 33 (51.6%) a malignant tumor [19 (29.7%) hepatocellular cancer, 11 (17.2%) secondary cancer and one (1.6%) each hemangioendothelioma, hepatoblastoma and embryonal liver sarcoma]. Median donor and recipient follow-ups were 93 months (IQR 41–159) and 39 months (22–91), respectively. ResultsRight and left hemi-livers were implanted in 39 (60.9%) and 25 (39.1%) cases, respectively. Median weights of right- and left-liver were 810 g (IQR 730–940) and 454 g (IQR 394–534), respectively. Graft-to-recipient weight ratios (GRWRs) were 1.17% (right, IQR 0.98%-1.4%) and 0.77% (left, 0.59%-0.95%). One- and five-year patient survivals were 85% and 71% (right) vs. 84% and 58% (left), respectively. One- and five-year graft survivals were 74% and 61% (right) vs. 76% and 53% (left), respectively. The patient and graft survival of right and left grafts and of very small (<0.6%), small (0.6%–0.79%) and large (≥0.8%) GRWR were similar. Survival of very small grafts was 86% and 86% at 3- and 12-month. No donor died while five (7.8%) developed a Clavien–Dindo complication IIIa, IIIb or IV. Recipient morbidity consisted mainly of biliary and vascular complications; three (4.7%) recipients developed a small-for-size syndrome according to the Kyushu criteria. ConclusionsAdult-to-adult LDLT is a demanding procedure that widens therapeutic possibilities of many hepatobiliary diseases. The donor procedure can be done safely with low morbidity. The recipient operation carries a major morbidity indicating an important learning curve. Shifting the risk from the donor to the recipient, by moving from the larger right-liver to the smaller left-liver grafts, should be further explored as this policy makes donor hepatectomy safer and may stimulate the development of transplant oncology.

Endoscopic management of anastomotic stricture after living-donor liver transplantation.

The most effective and fundamental treatment for end-stage liver disease is liver transplantation. Deceased-donor liver transplantation has been performed for many of these cases. However, living-donor liver transplantation (LDLT) has emerged as an alternative because it enables timely procurement of the donor organ. The success rate of LDLT has been improved by development of the surgical technique, use of immunosuppressant drugs, and accumulation of post-transplantation care experience. However, the occurrence of biliary stricture after LDLT remains a problem. This article reviews the pathogenesis, diagnosis, endoscopic management, and long-term outcomes of post-liver transplantation biliary stricture, with a focus on anastomotic stricture.

Changing Trends in Etiology-Based and Ethnicity-Based Annual Mortality Rates of Cirrhosis and Hepatocellular Carcinoma in the United States.

With recent improvements in the treatment of end-stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States. A population-based study using the US Census and national mortality database was performed. We identified the age-standardized etiology-specific mortality rates for cirrhosis and HCC among US adults ages 20 years or older from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age-standardized cirrhosis-related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% confidence interval [CI] 2.0-2.7). The APC in mortality rates for hepatitis C virus (HCV)-cirrhosis shifted from a 2.9% increase per year during 2007 to 2014 to a 6.5% decline per year during 2014 to 2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and NAFLD (APC 15.4%) increased over the same period, whereas mortality for hepatitis B virus (HBV)-cirrhosis decreased with an average APC of -1.1%. HCC-related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3-2.6). Etiology-specific mortality rates of HCC were largely consistent with cirrhosis-related mortality. Minority populations had a higher burden of HCC-related mortality. Conclusion: Cirrhosis-related and HCC-related mortality rates increased between 2007 and 2016 in the United States. However, mortality rates in HCV-cirrhosis demonstrated a significant decline from 2014 to 2016, during the direct-acting antiviral era. Mortality rates for ALD/NAFLD-cirrhosis and HCC have continued to increase, whereas HBV-cirrhosis-related mortality declined during the 10-year period. Importantly, minorities had a disproportionately higher burden of ESLD-related mortality.

Hydrogen-rich solution attenuates cold ischemia-reperfusion injury in rat liver transplantation

BackgroundLiver transplantation (LT) is considered the standard treatment for end-stage liver disease, but ideal donors remain in limited supply, resulting in an unavoidable increase in the need to use grafts from marginal donors. The attenuation of ischemia-reperfusion injury (IRI) in such marginal donors is therefore crucial for reducing the possibility of the primary non-function of grafts and graft loss. Some reports have found that molecular-hydrogen showed antioxidant and anti-inflammatory effects in preventing IRI in some non-hepatic transplant models. Therefore, we investigated whether or not molecular-hydrogen could attenuate IRI in LT model rats.MethodsWe used a hydrogen-rich water bath to dissolve hydrogen into solution and graft tissues and performed isogenic and orthotopic LT in Lewis rats with University of Wisconsin (UW) solution. Blood and tissue samples were collected 6 h after the reperfusion. Hepatic enzymes in serum were measured. Pathological findings including the expressions of cytokines and heme oxygenase (HO)-1 in liver tissues were evaluated.ResultsThe concentration of hydrogen inside the graft tissues increased depending on the storage time, plateauing after 1 h. Serum liver enzyme levels were significantly lower and the histology score of liver damage markedly attenuated in the group given grafts preserved in hydrogen-rich UW solution than in the control group. The hydrogen-rich UW solution group also showed less oxidative damage and hepatocyte apoptosis than the control group, and the expression of proinflammatory cytokines tended to be lower while the protein levels of HO-1 were significantly increased (n = 3–12 per group, P < 0.05).ConclusionsStorage of liver grafts in hydrogen-rich UW solution resulted in superior functional and morphologic protection against IRI via the up-regulation of HO-1 expression.

A Review on the Management of Biliary Complications after Orthotopic Liver Transplantation.

Orthotopic liver transplantation is the definitive treatment for end-stage liver disease and hepatocellular carcinomas. Biliary complications are the most common complications seen after transplantation, with an incidence of 10–25%. These complications are seen both in deceased donor liver transplant and living donor liver transplant. Endoscopic treatment of biliary complications with endoscopic retrograde cholangiopancreatography (commonly known as ERCP) has become a mainstay in the management post-transplantation. The success rate has reached 80% in an experienced endoscopist’s hands. If unsuccessful with ERCP, percutaneous transhepatic cholangiography can be an alternative therapy. Early recognition and treatment has been shown to improve morbidity and mortality in post-liver transplant patients. The focus of this review will be a learned discussion on the types, diagnosis, and treatment of biliary complications post-orthotopic liver transplantation.

Comparison of effects of melatonin, pentoxifylline and dimethyl sulfoxide in experimental liver ischemia-reperfusion injury by three different methods

Objectives: Liver transplantation is increasingly being used in the treatment of end-stage liver disease. Ischemia-reperfusion injury is one of the major problems encountered in transplantation. In this study, we aimed to compare the effects of melatonin, pentoxifylline, and dimethyl sulfoxide (DMSO), in hepatic ischemia-reperfusion injury with different methods such as biochemical/ultrastructural changes and hepatobiliary scintigraphy. Methods: Thirty rabbits were used in the Laboratory of Experimental Animals of Trakya University under appropriate conditions. Sham laparotomy and only ischemia reperfusion group were planned. They were used melatonin, pentoxifylline, and DMSO after ischemia-reperfusion in the other three groups. 6 rabbits were randomly selected for each group. Rabbits in all groups were subjected to liver scintigraphy. Following scintigraphy, 2 cm2 of liver tissue was removed to examining for liver antioxidant enzyme levels (superoxide dismutase [SOD] and glutathione peroxidase [GPx]) and for liver electron microscopy. Results: Pentoxifylline and melatonin protected significantly uptake and excretion functions in liver scintigraphy. When the effects of all three substances were examined by electron microscopy, it was found that the three substances protected the liver from the effects of ischemia-reperfusion damage at varying rates. All three agents were found to protect SOD and GPx from falling in various amounts. Conclusions: Studies to prevent ischemia-reperfusion injury, which may develop as a result of the Pringle maneuver applied to liver transplantations as well as to liver resections or liver injuries, still maintain their popularity. In our study, the effects of agents were identified in three different ways. Ischemia-reperfusion injury-reducing effect of pentoxifylline gave parallel results with three methods.

Epidemiological characteristics and access to end-stage liver disease care for HIV-positive patients with HCV and/or HBV coinfections in Central/Eastern European and neighboring countries – data from the ECEE network

There is currently an urgent need to harmonize hepatitis standards of care for HIV-positive patients across Europe. The HIV epidemic in Central and Eastern Europe has often been driven by injecting drug use, therefore a higher rate of co-infection with HCV and HBV is expected in this region. We have investigated the epidemiological prevalence and treatment availability for end-stage liver disease in HIV/HCV/HBV coinfections in countries represented in the ECEE Network Group. The Euroguidelines in Central and Eastern Europe (ECEE) Network Group was initiated in February 2016 to compare standards of care regarding HIV infection in the region. Information about HIV/HCV/HBV co-infections and the availability for end-stage liver disease treatment for HIV-positive patients were collected through on-line surveys. The respondents were ECEE members from 16 countries of the region. The information on co-infection prevalence was sourced from WHO, national HIV programmes, articles published in international journals, single clinic reports, and personal information in ten of the participating countries (62.5%). The HIV/HCV co-infection rate was from 3% to 99%. The range of reported of HIV/HBV coinfection percentages was 2.3% to 40%. HIV/HCV/HBV co-infection ranged from 0% to 9%. Regarding treatment for end-stage liver disease, liver transplantation was an available option for HIV-positive patients in only three countries (19%). Our findings revealed only a limited number of treatment options for the end-stage liver disease in HIV-positive patients for the vast majority of Central and Eastern European countries. There are gaps in epidemiological surveillance in this region. It appears there are many differences in the number of co-infected patients among Central and Eastern European and neighboring countries, but there is no unification of information sources.

Patients with hepatorenal syndrome may have better renal outcome after living donor liver transplantation comparing with patients with chronic kidney disease

Introduction: Hepatorenal syndrome (HRS) is one of the most severe complications of liver cirrhosis. Liver transplantation (LT), the ultimate curative treatment for end-stage liver disease, is needed to completely reverse HRS. However, risk of renal function deterioration after LT has been associated with pre-LT renal dysfunction. Several studies have reported outcome comparisons between patients with or without HRS. Here we compare the outcomes between LT patients with HRS or with chronic kidney disease (CKD). Method: Medical records of adult patients receiving living donor liver transplantation (LDLT) at Kaohsiung Chang Gung Memorial Hospital from July 2008 to September 2017 were reviewed. Patients with renal function impairment were enrolled. According to the diagnostic criteria of HRS, 12 patients were type 1, 19 patients were type 2, and 44 patients were CKD, respectively. And 67 patients with normal renal function were chosen for comparison. Result: The serum creatinine levels of the 3 groups with renal dysfunction at initial presentation had no significant differences. At the time of liver transplantation, the serum creatinine level of HRS type 2 group was better than CKD group (1.46mg/dL vs 2.32mg/dL, p = 0.002). There were no significant differences in creatinine level between HRS type 1 and 2, neither between HRS type 1 and CKD group. However, model for end-stage liver disease (MELD) score in HRS type 1 group was significantly higher than in CKD group. Two years later after LDLT, patients in CKD group had the highest serum creatinine level than in HRS type 1 and type 2 group (2.30mg/dL vs. 1.95mg/dL and 1.49mg/dL, p = 0.152 and 0.084, respectively). Conclusion: Despite higher pre-LT disease severity, patients with HRS still had slightly better renal outcome at two years after LDLT than patients with CKD.

The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study

BackgroundLiver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure.Patient and methodsWe propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test.DiscussionThis trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes.Trial registrationISRCTN27083228.

Innate Immune Cells in Immune Tolerance After Liver Transplantation.

Currently, liver transplantation is the most effective treatment for end-stage liver disease. Immunosuppressive agents are required to be taken after the operations, which have significantly reduced rejection rates and improved the short-term (<1 year) survival rates. However, post-transplant complications related to the immunosuppressive therapy have led to the development of new protocols aimed at protecting renal function and preventing de novo cancer and dysmetabolic syndrome. Donor specific immune tolerance, which means the mature immune systems of recipients will not attack the grafts under the conditions without any immunosuppression therapies, is considered the optimal state after liver transplantation. There have been studies that have shown that some patients can reach this immune tolerance state after liver transplantation. The intrahepatic immune system is quite different from that in other solid organs, especially the innate immune system. It contains a variety of liver specific cells, such as liver-derived dendritic cells, Kupffer cells, liver sinusoidal endothelial cells, liver-derived natural killer (NK) cells, natural killer T (NKT) cells, and so on. Depending on their specific structures and functions, these intrahepatic innate immune cells play important roles in the development of intrahepatic immune tolerance. In this article, in order to have a deeper understanding of the tolerogenic functions of liver, we summarized the molecular mechanisms of immune tolerance induced by intrahepatic innate immune cells after liver transplantation.

Clinical use of an immune monitoring panel in liver transplant recipients: A prospective, observational study

Immunosuppressive therapy greatly contributed to making liver transplantation the standard treatment for end-stage liver diseases. However, it remains difficult to predict and measure the efficacy of pharmacological immunosuppression. Therefore, we used a panel of standardized, commonly available, biomarkers with the aim to describe their changes in the first 3 weeks after the transplant procedure and assess if they may help therapeutic drug monitoring in better tailoring the dose of the immunosuppressive drugs.We prospectively studied 72 consecutive patients from the day of liver transplant (post-operative day #0) until the post-operative day #21. Leukocytes, neutrophils, lymphocytes (CD4+, CD8+), natural killer cells, monocytes, immunoglobulins and tacrolimus serum levels were measured on peripheral blood (at day 0, 3, 7, 14, 21 after surgery). Patients who developed infections showed significantly higher CD64+ monocytes on post operative day #7. IgG levels were lower on post operative day #3 among patients who later developed infections. We also found that a sharp decrease in IgA from post operative day #0 to 3 (−226 mg/dL in the ROC curve analysis) strongly correlates with the onset of infections among HCV− patients. No specific markers of rejection emerged from the tested panel of markers. Our results show that some early changes in peripheral blood white cells and immunoglobulins may predict the onset of infections and may be useful in modulating the immunosuppressive therapy. However, a panel of commonly available, standardized biomarkers do not support in improving therapeutic drug monitoring ability to individualize immunosuppressive drugs dosing.

Factors influencing health self-management in adherence to care and treatment among the recipients of liver transplantation.

IntroductionLiver transplantation is the global treatment of end-stage liver diseases. Since the patients’ survival rate has been improved, the patient may experience reductions in physical, cognitive, and psychosocial functions after liver transplantation influencing their adherence to care and treatment. The transplant survival is complex and patients’ adherence to care and treatment should be considered when health care providers make decisions regarding treatment. This qualitative study aimed to explore factors influencing health self-management in adherence to care and treatment among the recipients of care and treatment.MethodsIn this study, 23 interview sessions were carried out with a total 18 patients, 2 family members and 3 transplantation team members from May to November 2017. The patients were selected using the purposive method from both genders, with a various age range and initial diseases leading to liver transplantation, and time passed from liver transplantation. A semi-structured interview guide was developed based on literature review and pilot interviews. The participants were asked to describe their experiences of self-management behaviors in adherence to treatment and care. The data were analyzed using a conventional content analysis method and managing via the MAXQDA-10 software.ResultsTwo themes were developed during data analysis as “self-regulation” and “self-care”. “Self-regulation” consisted of “intentionally changing”, “positively thinking”, “information seeking”, “problem-solving”, “past knowledge transferring”, and “self-controlling”. “Self-care” had three sub-themes “shift to independence”, “vigilance”, and “self-care support”.ConclusionThe participants perceived the health self-management in adherence to care as a set of factors related to “self-regulation” and “self-care” behaviors. “Self-regulation” is required to create a balance in life. Also, “self-care” efforts can help with maintaining and improving patients’ health.