Clinical outcomes of patients with hepatic insufficiency undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is currently a common treatment in high-risk aortic stenosis patients, but the impact of hepatic insufficiency on prognosis after TAVI is debatable and whether TAVI is superior to surgical aortic valve replacement (SAVR) in patients with hepatic insufficiency is uncertain. OBJECTIVE: To investigate the effect of abnormal liver function on the outcome and safety after TAVI and whether TAVI is superior to SAVR in patients with hepatic insufficiency. METHODS: PubMed, Embase, the Cochrane Library and Web of Science were systematically searched from inception up to 26 November 2021. Studies were eligible if mortality and complications after TAVI in patients with and without hepatic insufficiency, or mortality and complications for TAVI versus SAVR in patients with hepatic insufficiency were reported. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of each study. This meta-analysis was registered with PROSPERO (CRD42021253423) and was carried out by using RevMan 5.3 and Stata 14.0. RESULTS: This meta-analysis of 21 studies assessed a total of 222,694 patients. Hepatic insufficiency was associated with higher short-term (in-hospital or 30-day) mortality [OR = 1.62, 95% CI (1.18 to 2.21), P = 0.003] and 1-2 years mortality [HR = 1.64, 95% CI (1.42 to 1.89), P < 0.00001] after TAVI. Between TAVI and SAVR in patients with hepatic insufficiency, there was a statistically significant difference in in-hospital mortality [OR = 0.46, 95% CI (0.27 to 0.81), P = 0.007], the occurrence rate of blood transfusions [OR = 0.29, 95% CI (0.22 to 0.38), P < 0.00001] and the occurrence rate of acute kidney injury [OR = 0.55, 95% CI (0.33 to 0.91), P = 0.02]. CONCLUSIONS: TAVI patients with hepatic insufficiency may have negative impact both on short-term (in-hospital or 30-day) and 1-2-years mortality. For patients with hepatic insufficiency, TAVI could be a better option than SAVR.

Fulminant hepatic failure after simultaneous kidney-pancreas transplantation: a case report / Insuficiência hepática fulminante após transplante simultâneo de rim-pâncreas: um relato de caso

Abstract We describe an unusual case of hyperacute hepatic failure following general anesthesia in a patient receiving a simultaneous kidney-pancreas transplant. Despite an aggressive evaluation of structural, immunological, viral, and toxicological causes, a definitive cause could not be elucidated. The patient required a liver transplant and suffered a protracted hospital course. We discuss the potential causes of fulminant hepatic failure and the perioperative anesthesia management of her subsequent liver transplantation.

Resumo Descrevemos um caso incomum de insuficiência hepática hiperaguda após a anestesia geral em uma paciente que recebeu um transplante simultâneo de rim-pâncreas. Apesar de uma avaliação agressiva das causas estruturais, imunológicas, virais e toxicológicas, uma causa definitiva não pôde ser identificada. A paciente precisou de um transplante de fígado que resultou em prolongamento da internação hospitalar. Discutimos as potenciais causas da insuficiência hepática fulminante e o manejo da anestesia no período perioperatório de seu subsequente transplante de fígado.

Rabies Virus Transmission in Solid Organ Transplantation, China, 2015-2016.

We report rabies virus transmission among solid organ transplantation recipients in Changsha, China, in 2016. Two recipients were confirmed to have rabies and died. Our findings suggest that more attention should be paid to the possibility of rabies virus transmission through organ transplantation for clinical and public health reasons.

Paecilomyces variotii Fungemia in a Patient with Lymphoma Needing Liver Transplant.

Paecilomyces sp. are emerging pathogens in immunocompromised patients. We report here a case of Paecilomyces variotii fungemia, cured with amphotericin and anidulafungin, illustrating difficulties of early diagnosis and therapeutic choice in such rare fungal infection.

Alterations of Serum IP-10 and TARC in Patients with Early Acute Rejection after Liver Transplantation.

BACKGROUND/AIMS: To analyze alterations of interferon-γ-induced protein 10 (IP-10) and thymus and activation-regulated chemokine (TARC) levels in early acute liver transplantation rejection. METHODS: Thirty-six patients with early acute liver transplantation rejection were classified as non-, mild, moderate, and severe rejection groups. The levels of serum IP-10 and TARC were determined on days 3, 2, 1, and 0 before biopsy. RESULTS: The IP-10 activities in all rejection groups were significantly higher (p < 0.05) than those in the non-rejection group at all time points and correlated with the extent of rejection (p < 0.05). The differences in TARC among the three rejection groups were significant (p < 0.05), and its highest level was found in the mild rejection group at all observed time points, whereas its lowest level was detected in the severe rejection group. The analysis of the TARC/IP-10 ratio revealed that the volume was correlated with the rejection degree. This ratio in the moderate and severe rejection groups on days 2, 1, and 0 before biopsy were 20% lower than that before transplantation. CONCLUSION: Serum IP-10 showed an increasing trend during early acute liver transplantation rejection. IP-10 increase or TARC/IP-10 ratio decrease combining with abnormal hepatic enzymatic alteration could be a valuable and specific sign for early rejection of the transplanted liver.

Treat chronic hepatitis C virus infection in decompensated cirrhosis - pre- or post-liver transplantation? the ironic conundrum in the era of effective and well-tolerated therapy.

The management of hepatitis C virus (HCV) infection in patients with decompensated cirrhosis has evolved dramatically over the past few years mainly due to the availability of all-oral antiviral regimens. The currently approved all-oral direct-acting antivirals (DAA) containing sofosbuvir, ledipasvir, daclatasvir and ribavirin, in various combinations, have shown to be safe and effective in patients with decompensated cirrhosis with sustained virological response (SVR) rates nearly comparable to those with well-compensated liver disease. Unique issues yet remain such as the challenges with renal insufficiency, tolerability of ribavirin and risk of further hepatic decompensation with a protease inhibitor-based regimen. While most patients who achieve SVR have demonstrated improvement in hepatic synthetic function over the short course of follow, the long-term beneficial effects are unknown. Further, the baseline predictors of improvement in hepatic function have not been well delineated and thus have left us in a quandary as to what we might expect with successful therapy and thus we are at a loss to well educate our patients. The major concern, in potential liver transplant candidates, is of unintended 'harm' by achieving SVR but without improvement in hepatic function to an extent where the patients might function well. As HCV therapies are as effective in liver transplant recipients, there is a growing sentiment in some of the transplant quarters that those with decompensated liver disease and awaiting liver transplant be treated for HCV after liver transplant. This strategy would thus eliminate any concern of leaving a patient in 'no person's' land by treating HCV successfully pretransplant but not to the point of functional normalcy, while also would maintain the risk of HCC. Yet a contrarian view would be that not all patients have access to liver transplantation (LT), cannot bear the cost, have comorbidities or contraindications to LT. While the debate continues, it is essential that we develop robust predictors of improvement in liver function so that we can carefully select our patients for therapy in the context of liver transplantation.

[STATE OF HEPATIC HEMODYNAMICS IN TRANSPLANTATION OF ITS RIGHT PART WITH MEDIAN HEPATIC VEIN].

Peculiarities of regional hemodynamics in transplantation of right hepatic part with median hepatic vein were studied. The blood flow parameters ­ the volume portal blood flow (VPBF), linear speed of blood flow (LSBF), the resistance index (RI) in hepatic artery; phasic structure of the blood flow along hepatic veins were determined in 31 patients in accordance to ultrasonographic flowmetry data. Maximal value of VPBF was observed on a second postoperative day, minimal one ­on the fourth day. Аrterial blood flow have had enhanced immediately after transplantation up to maximal one on the second day, and from second to the fourth day ­ have had reduced to minimal one. Phasic structure of blood flow along hepatic vein have had changed postoperatively in 12 (38%) patients. Changes in the hepatosplanchnic blood flow after transplantation constitutes a consequence of the vascular resistance reduction, the venous outflow and regenerative activity of the transplanted hepatic part improvement.

Differential Effects of Gut-Homing Molecules CC Chemokine Receptor 9 and Integrin-ß7 during Acute Graft-versus-Host Disease of the Liver.

Homing of allogeneic donor T cells to recipient tissue is imperative for the development of acute graft-versus-host disease (GVHD) after bone marrow transplantation (BMT). In this study we show that alteration of T cell homing due to integrin-ß7 deficiency on T cells or its ligand MAdCAM-1 in BMT recipients contributes to the pathophysiology of experimental GVHD. In contrast, lack of CC chemokine receptor 9 on donor T cells alters tissue homing but does not impact GVHD survival. We further demonstrate that MAdCAM-1 is aberrantly expressed in hepatic murine GVHD as well as in patients with active liver GVHD. However, infiltration of donor T cells in gut but not liver was dependent of MAdCAM-1 expression, indicating, that homing and/or retention of donor T cells rests on divergent molecular pathways depending on the GVHD target tissue.

[ROENTGEN-ENDOVASCULAR EMBOLIZATION OF THE PORTAL VEIN BRANCHES AS A PATIENTS CONDITIONING FOR EXTENSIVE HEPATIC RESECTION].

The results of surgical treatment of 316 patients, suffering focal hepatic diseases, in whom for preoperative preparation a portal vein embolization (PVE) was performed, were analyzed. PVE was applied in a small planned hepatic residual volume. The patients have aged from 21 to 77 yrs, (57 ± 10.6) yrs at average. During (22 ± 7) days after the procedure a hypertrophy of a planned postresectional hepatic volume by 58.6% was observed, while a hypertrophy degree have depended on the embolization volume performed: 57.3%--after embolization of branches of C(V)-C(VIII) hepatic segments, 66%--the segments C(V)-C(VIII) + C(IV). In 281 (89%) patients the extensive hepatic resection was performed, a fatal postresection hepatic insufficiency was not observed. A three-year and five-year disease-free survival have constituted 43.8 and 16.4% accordingly. Thus, a PVE constitutes a miniinvasive intervention, permitting to achieve a planned residual hepatic volume, to expand a diapazon of application of radical extensive hepatic resection in patients, suffering focal hepatic diseases while a small planned residual hepatic volume.

Lack of association between CD40 polymorphisms and acute rejection in German liver transplant recipients.

CD40 and its ligand, CD154, are major costimulatory molecules whose interactions are important in alloreactive transplant rejection. The aim of this study was to examine the association of CD40 polymorphisms with the susceptibility to acute rejection episodes in liver transplantation. In total, 112 liver transplant recipients with biopsy proven acute rejections (BPAR), 97 without BPAR (WBPAR), and 112 healthy control individuals were enrolled in the study. Two single nucleotide polymorphisms (SNPs) of CD40 gene (rs1883832 and rs4810485) were genotyped by polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA). Both SNPs has been tested for a recessive and a dominant model. No significant differences were found in the genotype and allele frequencies of the SNPs rs1883832 and rs4810485 between BPAR liver recipients and WBPAR recipients. Our results do not suggest an important role of tested CD40 SNPs in the susceptibility to acute liver transplant rejection in a Caucasian population.

p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic cholestatic liver injury.

BACKGROUND AND AIMS: The cyclin-dependent kinase inhibitor p21 has been implicated as a tumour suppressor. Moreover, recent genetic studies suggest that p21 might be a potential therapeutic target to improve regeneration in chronic diseases. The aim of this study was to delineate the role of p21 in chronic liver injury and to specify its role in hepatocarcinogenesis in a mouse model of chronic cholestatic liver injury. METHODS: The degree of liver injury, regeneration and tumour formation was assessed in Mdr2(-/-) mice and compared with Mdr2/ p21(-/-) mice. Moreover, the role of p21 was evaluated in hepatoma cells in vitro and in human hepatocellular carcinoma (HCC). RESULTS: Mdr2(-/-) mice developed HCCs as a consequence of chronic inflammatory liver injury. In contrast, tumour development was profoundly delayed in Mdr2/ p21(-/-) mice. Delayed tumour development was accompanied by markedly impaired liver regeneration in Mdr2/ p21(-/-) mice. Moreover, the regenerative capacity of the Mdr2/ p21(-/-) livers in response to partial hepatectomy declined with age in these mice. Hepatocyte transplantation experiments revealed that impaired liver regeneration was due to intrinsic factors within the cells and changes in the Mdr2/ p21(-/-) microenvironment. In human HCCs, a subset of tumours expressed p21, which was associated with a significant shorter patient survival. CONCLUSIONS: We provide experimental evidence that p21 is required for sustained liver regeneration and tumour development in chronic liver injury indicating that p21 needs to be tightly regulated in order to balance liver regeneration and cancer risk. Moreover, we identify p21 as a negative prognostic marker in human HCC.

[The role of transjugular hepatic biopsy in preparation of the patients for the large hepatic resection].

The results of transjugular hepatic biopsy (TJHB) were analyzed in 32 patients, in whom the performance of hepatic radical resection was planned for the focal hepatic diseases. The biopsy procedures have had succeeded in 100% of observations. The severe complications were absent. The specimen length have constituted 12 mm at average, fragmentation was noted in 32% of observations. All the specimen were recognized as affordable for histological studying. In 24 patients in terms of 2-4 weeks after biopsy the embolization of lobar branches of portal vein was performed with the objective to enhance the assumed residual hepatic volume. In all the patients in terms of 2-8 weeks the spacious radical hepatic resection was succeeded. The data obtained witness that application of TJHB is expedient in the patients, who are prepared for spacious radical hepatic resection, for estimation of the organ parenchyma state and prognostication of postoperative hepatic insufficiency.

[The clinical experience with hepatocyte transplantation for the treatment of hepatic insufficiency].

Hepatocyte transplantation represents a supplementary strategy for treating liver diseases. Several methods including extracorporeal devices, cell transplantation and implanted tissue-engineered units were proposed as liver support before liver transplantation. The ability to repopulate the liver with healthy and disease-resistant hepatocytes opens up new possibilities for correcting genetic disorders and treating patients with chronic liver diseases. Some results of experimental and clinical therapy of liver diseases are summarized in this review.

Liver transplantation in the 21st century: expanding the donor options.

Over the past decade, use of ECD organs for OLT has allowed many transplant programs to afford patients access to an otherwise scarce resource and to maintain center volume. Although overall posttransplant outcomes are inferior to results with optimal, whole-liver grafts, aggressive utilization of ECD and DCD organs significantly lowers median wait-times for OLT, MELD score at OLT, and death while awaiting transplantation. It is incumbent on the transplant community to provide continued scrutiny of the many factors involved in ECD organ utilization, evaluate the degree of risk and benefit such allografts may impart on particular recipients, and thereby provide suitable "matching" to maximize favorable outcomes. Transplant caregivers need to provide patients with evidence-based care decisions, be good stewards of a scarce resource, and maintain threshold survival results for their programs. This requires balancing the urgency with which a transplant is needed and the utility of such a transplant. There is a clear necessity to pursue additional donor research to improve use of these marginal grafts and assess interventions that enhance the safety of ECD livers.

Long-term management of the liver transplant recipient: pearls for the practicing gastroenterologist.

Liver transplantation is becoming more common and patients are surviving longer after transplantation. Special care must be paid to the long-term management of these patients because they are at increased risk for medical problems, malignancies, and adverse effects from immunosuppression. A stable and continuing relationship must be developed between the physician and the patient to optimize the long-term outcomes for these individuals.

[Therapeutic effect of autologous bone marrow stem cell transplantation in the treatment of severe liver damage].

OBJECTIVE: To evaluate the effect of autologous bone marrow stem cell transplantation in the treatment of severe liver damage. METHODS: Autologous bone marrow (50 ml) was harvested from 6 patients aged 44 to 69 years admitted for severe liver damage. Human bone marrow stem cells (HMSCs) were isolated and transplanted in to the patients' liver. At l, 4, 8, and 12 weeks after the transplantation, the changes in ALT, ALB, Cr, TB, PT and the clinical symptoms of the patients were observed. RESULTS: The transplantation of autologous bone marrow stem cells resulted in obvious improvement of the liver function. At 12 weeks after the transplantation, ALT was reduced from 98.4 IU/L to 41.5 IU/L, TB from 136.5 µmol/L to 78.4 µmol/L, Cr from 112.3 µmol/L to 72.1 µmol/L, and ALB rose from 23.3 g/L to 32.6 g/L. The survival of the patients was 100% at 12 weeks, but one patient died at 7 months after the transplantation. The symptoms of the patients were also alleviated after the transplantation. At 12 weeks after transplantation, 3 patients reported improved appetite, 3 showed recovery of physical strength, and 2 showed lessened abdominal swelling. No serious adverse complications in association with the transplantation were found in the in 4 patients available to the follow-up. CONCLUSION: Autologous bone marrow stem cell transplantation can improve the liver function of patients with severe liver damage without causing serious complications.

Assessing outcomes in liver disease patients: reliability and validity of the Spanish version of the Liver Disease Quality of Life Questionnaire (LDQOL 1.0).

OBJECTIVE: To assess the reliability and validity of a Spanish version of the LDQOL 1.0 (Liver Disease Quality of Life questionnaire). METHODS: Observational, cross-sectional study in Spanish patients awaiting liver transplantation (LT). Feasibility was assessed by analyzing administration times and missing responses. Ceiling and floor effects were calculated and reliability was tested by examining internal consistency (Cronbach's alpha). Convergent validity was tested by examining correlations between LDQOL disease-specific and Short Form health survey with 36 questions (SF-36) dimensions. Known groups' validity was tested by examining the LDQOL's capacity to discriminate between groups defined by etiology and Child-Turcotte-Pugh (CTP) scores. RESULTS: A total of 200 patients were included for analysis. Mean age (SD) was 52.6 (9.8) years and 73% of the sample were male. The most common indication for LT was liver cancer (34%). Mean (SD) time to complete the questionnaire was 35.8 minutes (21.2 minutes). Missing responses were highest on the dimensions of sexual functioning and symptoms of liver disease. Ceiling effects were over 20% on 7 of the LDQOL's 12 disease-specific scales. Cronbach's alpha coefficients were over 0.70 on all but 2 dimensions. Correlations between SF-36 and LDQOL disease-specific dimensions generally fulfilled the hypotheses, with 35 of the 40 highest and lowest correlations (87.5%) being in the expected direction. The LDQOL discriminated well between patients in CTP class A and C, and as hypothesized, hepatocarcinoma and alcoholic cirrhosis patients scored better on most dimensions than patients with hepatitis C virus or other etiologies. CONCLUSIONS: The Spanish version of the LDQOL 1.0 has shown satisfactory reliability and validity.

[Criteria of differential assignment of drugs with sorptive and disintoxication properties to patients with obturative icterus of non-tumoral genesis].

The article defines criteria of differential assignment of drugs with sorptive and disintoxication properties according an analysis of clinical signs of a mechanical icterus, results of biochemical, immunologic, biophysical, crystal optics methods. The results were assessed by points (high--a score 98-65; average--64-32 a point; low--not higher 31 points) that allowed to judge severity level of a patient condition with obturative icterus not tumoral genesis. Positive efficiency of treatment was defined by point estimation which was not lower than 10 times (severe and moderate degrees; moderate and mild degrees). The study has shown that consideration both clinical and laboratory characteristics of the course of obturative icterus allows raising results of the treatment due to individual therapy and to predict its efficiency based on dynamic definition of point assessment of severity level.

Liver and kidney transplantation in HIV-infected patients.

HIV infection has evolved into a chronic condition as a result of improvements in therapeutic options. Chronic exposure with HIV and associated co-pathogens as well as toxicities from prolonged therapy with antiviral medications has resulted in increased morbidity and mortality rates from end-stage liver and kidney disease in the HIV-infected population. Since the definitive treatment for end-stage organ failure is transplantation, demand has increased among HIV-infected patients. Although the transplant community has been slow to recognize HIV as a chronic condition, many transplant centers have eliminated HIV infection as a contraindication to transplantation as a result of better patient management and demand. This review examines the current clinical strategies and issues surrounding liver and kidney transplantation in HIV-infected patients.