Exercise and diet modification in non-obese non-alcoholic fatty liver disease: analysis of biopsies of living liver donors

Background and Aims: We evaluated efficacy of exercise and diet modification for steatosis improvement of non‐obese non‐alcoholic fatty liver disease (NAFLD) patients. Methods: We analyzed retrospectively the clinical and histological parameters of consecutive living liver donors, who experienced repeated liver biopsies due to steatosis and were treated using exercise and diet modification. Results: From 1995 to 2009, among a total of 1365 potential living liver donors with NAFLD seen on the initial liver biopsy, 120 consecutive donors with steatosis ≥ 30% or an estimated donor‐recipient weight ratio < 0.8, underwent exercise and diet modification and received follow‐up liver biopsy at our institution. Median age was 33 years, and median interval between the two consecutive biopsies was 10 weeks (range, 1–39). At the time of initial biopsy, the number of normal body mass index, overweight, and obese donors was 49 (40.8%), 65 (54.2%), and 6 (5.0%), respectively. After lifestyle modification, weight reduction and steatosis improvement were observed in 92 (76.7%) and 103 (85.8%) donors, respectively, at the time of follow‐up biopsy. On multivariate analysis, initially higher steatosis (hazard ratio [HR] 1.03, P = 0.02), total cholesterol reduction ≥ 10% (HR 5.59, P = 0.02), and weight reduction ≥ 5% (HR 6.63, P = 0.03) were significantly associated with ≥ 20% steatosis improvement in 120 donors with NAFLD, after exercise and diet modification. Conclusions: Exercise and diet modification were effective in reducing steatosis in potential living liver donors with non‐obese NAFLD. Total cholesterol reduction ≥ 10% could be used as a non‐invasive predictor for steatosis improvement in liver donors with NAFLD, after exercise and diet modification.     

Day-of-surgery rejection of donors in living donor liver transplantation

AIM: To study diagnostic laparoscopy as a tool for excluding donors on the day of surgery in living donor liver transplantation (LDLT).METHODS: This study analyzed prospectively collected data from all potential donors for LDLT. All of the donors were subjected to a three-step donor evaluation protocol at our institution. Step one consisted of a clinical and social evaluation, including a liver profile, hepatitis markers, a renal profile, a complete blood count, and an abdominal ultrasound with Doppler. Step two involved tests to exclude liver diseases and to evaluate the donor’s serological status. This step also included a radiological evaluation of the biliary anatomy and liver vascular anatomy using magnetic resonance cholan-giopanc reatography and a computed tomography (CT) angiogram, respectively. A CT volumetric study was used to calculate the volume of the liver parenchyma. Step three included an ultrasound-guided liver biopsy. Between November 2002 and May 2009, sixty-nine potential living donors were assessed by open exploration prior to harvesting the planned part of the liver. Between the end of May 2009 and October 2010, 30 potential living donors were assessed laparoscopically to determine whether to proceed with the abdominal incision to harvest part of the liver for donation. RESULTS: Ninety-nine living donor liver transplants were attempted at our center between November 2002 and October 2010. Twelve of these procedures were aborted on the day of surgery (12.1%) due to donor findings, and eighty-seven were completed (87.9%). These 87 liver transplants were divided into the following groups: Group A, which included 65 transplants that were performed between November 2002 and May 2009, and Group B, which included 22 transplants that were performed between the end of May 2009 and October 2010. The demographic data for the two groups of donors were found to match; moreover, no significant difference was observed between the two groups of donors with respect to hospital stay, nar-cotic and non-narcotic analgesia requirements or the incidence of complications. Regarding the recipients, our study clearly revealed that there was no significant difference in either the incidence of different complications or the incidence of retransplantation between the two groups. Day-of-surgery donor assessment for LDLT procedures at our center has passed through two eras,open and laparoscopic. In the first era, sixty-nine LDLT procedures were attempted between November 2002 and May 2009. Upon open exploration of the donors on the day of surgery, sixty-five donors were found to have livers with a grossly normal appearance. Four donors out of 69 (5.7%) were rejected on the day of surgery because their livers were grossly fatty and pale. In the laparoscopic era, thirty LDLT procedures were attempted between the end of May 2009 and October 2010. After the laparoscopic assessment on the day of surgery, twenty-two transplantation procedures were completed (73.4%), and eight were aborted (26.6%). Our data showed that the levels of steatosis in the rejected donors were in the acceptable range. Moreover, the results of the liver biopsies of rejected donors were comparable between the group A and group B donors. The laparoscopic assessment of donors presents many advantages relative to the assessment of donors through open exploration; in particular, the laparo-scopic assessment causes less pain, requires a shorter hospital stay and leads to far superior cosmetic results. CONCLUSION: The laparoscopic assessment of donors in LDLT is a safe and acceptable procedure that avoids unnecessary large abdominal incisions and increases the chance of achieving donor safety.     

PNPLA3 as a liver steatosis risk factor following living‐donor liver transplantation for hepatitis C

Aim

Liver steatosis frequently occurs following liver transplantation (LT) and can affect patient outcome. Here, we aimed to clarify the steatosis and steatohepatitis risk factors that apply after living‐donor LT for chronic hepatitis C.

Methods

We retrospectively examined 43 transplant recipients and donors, and tested for single nucleotide polymorphisms in the PNPLA3 gene. Liver biopsies taken 1 year after transplantation and yearly thereafter, or when abnormal liver enzyme levels were detected, were examined by histopathology.

Results

Liver steatosis (>5% steatotic hepatocytes) was evident in 13 of 43 cases (30%), and steatohepatitis in 3 (7.0%). The average time to steatosis after LT was 2.74 ± 1.55 years. The PNPLA3 rs738409 GG genotype, a steatosis risk factor, was identified in 13 recipients and 10 donors. Steatosis prevalence did not differ according to recipient genotype. However, this condition was significantly more common among patients who received tissue from donors carrying the rs738409 GG genotype compared to those with grafts from donors of the CC or CG genotype (60, 7, and 26%, respectively; P < 0.05). All 3 steatohepatitis cases were associated with the GG donor genotype.

Conclusion

The PNPLA3 rs738409 GG donor genotype affects liver steatosis and steatohepatitis risk following living‐donor LT.     

Weight loss interventions in living donor liver transplantation as a tool in expanding the donor pool: A systematic review and meta-analysis

BACKGROUNDWith increasing rates of liver transplantation and a stagnant donor pool, the annual wait list removals have remained high. Living donor liver transplantation (LDLT) is an established modality in expanding the donor pool and is the primary method of liver donation in large parts of the world. Marginal living donors, including those with hepatic steatosis, have been used to expand the donor pool. However, due to negative effects of steatosis on graft and recipient outcomes, current practice excludes overweight or obese donors with more than 10% macro vesicular steatosis. This has limited a potentially important source to help expand the donor pool. Weight loss is known to improve or resolve steatosis and rapid weight loss with short-term interventions have been used to convert marginal donors to low-risk donors in a small series of studies. There is, however, a lack of a consensus driven standardized approach to such interventions. AIMTo assess the available data on using weight loss interventions in potential living liver donors with steatotic livers and investigated the feasibility, efficacy, and safety of using such donors on the donor, graft and recipient outcomes. The principal objective was to assess if using such treated donor livers, could help expand the donor pool.METHODSWe performed a comprehensive literature review and meta-analysis on studies examining the role of short-term weight loss interventions in potential living liver donors with hepatic steatosis with the aim of increasing liver donation rates and improving donor, graft, and recipient outcomes. RESULTSA total of 6 studies with 102 potential donors were included. Most subjects were males (71). All studies showed a significant reduction in body mass index post-intervention with a mean difference of -2.08 (-3.06, 1.10, I² = 78%). A significant reduction or resolution of hepatic steatosis was seen in 93 of the 102 (91.2%). Comparison of pre- and post-intervention liver biopsies showed a significant reduction in steatosis with a mean difference of -21.22 (-27.02, -15.43, I² = 56%). The liver donation rates post-intervention was 88.5 (74.5, 95.3, I² = 42%). All donors who did not undergo LDLT had either recipient reasons or had fibrosis/steatohepatitis on post intervention biopsies. Post-operative biliary complications in the intervention group were not significantly different compared to controls with an odds ratio of 0.96 [(0.14, 6.69), I² = 0]. The overall post-operative donor, graft, and recipient outcomes in treated donors were not significantly different compared to donors with no steatosis. CONCLUSIONUse of appropriate short term weight loss interventions in living liver donors is an effective tool in turning marginal donors to low-risk donors and therefore in expanding the donor pool. It is feasible and safe, with comparable donor, graft, and recipient outcomes, to non-obese donors. Larger future prospective studies are needed.     

Comparison of clinical features and liver histology in hepatitis C-positive dialysis patients and renal transplant recipients

Objective: Liver biopsies in hepatitis C virus (HCV)-positive end stage renal disease (ESRD) patients before or after renal transplantation were compared to study the effect of transplant-related immunosuppression. Methods: In this prospective study all patients on the active transplant list and all patients with functioning renal transplants at our hospital were tested for HCV antibody (ELISA-2) over a 30-month period. HCV infection was confirmed by polymerase chain reaction in most patients. All HCV-positive patients were asked to undergo liver biopsy without regard to serum transaminase levels. Patients were interviewed, examined, and had detailed chart review. By protocol, liver histology was evaluated according to stage and inflammatory activity in a blinded fashion. Results: There were 129 HCV-antibody–positive patients, of 795 tested. Sixty-seven agreed to liver biopsy. Of these, 22 patients had never been transplanted and 45 had received transplants. Mean transplant duration before biopsy was 41.2 months (range, 1–204 months). Transplant patients had significantly longer duration of ESRD and estimated duration of HCV infection than patients not transplanted. Dialysis patients had significantly more portal inflammatory activity and lymphoid follicles on biopsy whereas transplant patients had more piecemeal necrosis and steatosis. However, the total histological activity score and stage were similar between groups. Multivariate analysis confirmed the association between transplant and steatosis. But independent variables including transplant duration, HCV infection duration, and ESRD duration were not correlated with histological findings. Conclusion: Renal transplantation may not be associated with an increased risk of progressive liver disease in HCV-positive patients, compared with ESRD patients receiving chronic dialysis. Long-term studies with serial liver biopsies are needed to resolve this issue.     

Alcoholic liver disease. An update

The prevalence and incidence of alcoholic liver disease are constantly evolving. Alcoholic liver disease has a wide clinical spectrum. It may progress to cirrhosis and to end-stage liver disease requiring liver transplantation. The histological manifestations range from steatosis without inflammation to liver cell injury and ultimately to fibrosis and cirrhosis. In some cases, the histological manifestation is steatohepatitis, morphologically characterized by inflammation and necrosis. Currently, although there are no specific tests to establish a diagnosis of steatohepatitis, some serological, radiological, or laboratory tests may be useful. Liver biopsy is useful in confirming a suspected diagnosis and in assessing the extent of parenchymal damage. This review synthesizes the main aspects of the epidemiology, pathogenesis, morphological characteristics, diagnosis, treatment, and prognosis of alcoholic liver disease.     

Radiologic evaluation of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is a frequent cause of chronic liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH)-related liver cirrhosis. Although liver biopsy is still the gold standard for the diagnosis of NAFLD, especially for the diagnosis of NASH, imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy. Ultrasonography is a well-established and cost-effective imaging technique for the diagnosis of hepatic steatosis, especially for screening a large population at risk of NAFLD. Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis, operator-dependent, and rather qualitative. Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard. However, computed tomography may be effective in specific clinical situations, such as evaluation of donor candidates for hepatic transplantation. Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice, especially for longitudinal follow-up of patients with NAFLD. Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis. This article will review current imaging methods used to evaluate hepatic steatosis, including the diagnostic accuracy, limitations, and practical applicability of each method. It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD.     

Impairment of hepatic microcirculation in fatty liver

Fatty liver or hepatic steatosis, which is the result of the abnormal accumulation of triacylglycerol within the cytoplasm of hepatocytes, is a common histological finding in human liver biopsy specimens that is attributed to the effects of alcohol excess, obesity, diabetes, or drugs. There is a general consensus that fatty liver compromises hepatic microcirculation, the common exchange network upon which hepatic arterial and portal inflows converge, regardless of underlying etiology. A significant reduction in hepatic microcirculation has been observed in human fatty donor livers and in experimental models of hepatic steatosis. There is an inverse correlation between the degree of fat infiltration and both total hepatic blood flow and flow in microcirculation. Fatty accumulation in the cytoplasm of the hepatocytes is associated with an increase in the cell volume that reduces the size of the hepatic sinusoid space by 50% compared with a normal liver and may result in partial or complete obstruction of the hepatic sinusoid space. As a result of impaired hepatic microcirculation, the hepatocytes of the fatty liver have reduced tolerance against ischemia-reperfusion injury, which affects about 25% of the donors for liver transplantation because severe steatosis is associated with a high risk of primary nonfunction after liver transplantation.     

Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation

BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation. METHODS: Ninety-four patients undergoing liver transplan-tation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis (MiS): MiS<30% (n=27), MiS 30%-60% (n=41) and MiS >60% (n=26). The outcomes after liver transplantation were evaluated, in-cluding the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction (EAD) and primary nonfunction (PNF). RESULTS: The incidences of EAD and PNF did not difter significantly between the groups. We observed 5 cases of PNF, one occurred in the MiS <30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not dif-fer signiftcantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS <30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS >60% group.CONCLUSION: Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.     

Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss

The effect of significant weight loss on nonalcoholic fatty liver disease remains unclear. In this case series of 36 selected obese patients, we examined the effect of weight loss on nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis (NASH) and hepatic fibrosis. These 36 patients (11 males, 25 females) had paired liver biopsies, the first at the time of laparoscopic adjustable gastric band placement and the second after weight loss. Second biopsies were obtained from two groups: those requiring a subsequent laparoscopic procedure (n = 19) and those with index biopsy score of 2 or greater for zone 3-centric hepatic fibrosis (n = 17). All biopsies were scored, blinded to the patient's identity and clinical condition, for individual histological features and for NASH stage and grade. Initial biopsies demonstrated NASH in 23 patients and steatosis in 12 patients. Repeat biopsies were taken at 25.6 +/- 10 months (range, 9-51 months) after band placement. Mean weight loss was 34.0 +/- 17 kg, and percentage of excess weight loss was 52 +/- 17%. There were major improvements in lobular steatosis, necroinflammatory changes, and fibrosis at the second biopsy (P <.001 for all). Portal abnormalities remained unchanged. Only four of the repeat biopsies fulfilled the criteria for NASH. There were 18 patients with an initial fibrosis score of 2 or more compared with 3 patients at follow-up (P <.001). Those with the metabolic syndrome (n = 23) had more extensive changes before surgery and greater improvement with weight loss. In conclusion, weight loss after surgery provides major improvement or resolution of obesity and metabolic syndrome-associated abnormal liver histological features in severely obese subjects.     

Effect of steatosis and inflammation on liver fibrosis in chronic hepatitis C

Background/Aims: The role of liver biopsy has been questioned in the management of patients with hepatitis C viral (HCV) infection. The aims of this study were to determine the impact of clinical parameters and degree of inflammation and steatosis on liver fibrosis. Patients/Methods: Clinical data and liver histology findings in 510 HCV patients were analysed. Results: Hepatitis C virus genotype 1 (GT‐1) was found in 38%, GT‐2 in 15% and GT‐3 in 45% of patients. In liver biopsy specimens, inflammation activity was present in 68%, increased fibrosis in 19% and marked steatosis in 17% of patients. Independent clinical risk factors for the increased fibrosis were patients' age at biopsy, body mass index (BMI) and duration of HCV. Steatosis and inflammation activity were independent histological risk factors for fibrosis only in GT‐1; in GT‐3, only inflammation correlated independently with fibrosis. Conclusions: Age at liver biopsy, BMI and duration of HCV were independent risk factors for increased fibrosis in HCV patients. Steatosis as a risk factor for fibrosis is evident in GT‐1. When scoring liver biopsies of HCV patients, the degree of steatosis should be included in addition to fibrosis and inflammation activity.     

The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease

BACKGROUND:

Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy.

OBJECTIVE:

To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD.

METHODS:

From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists.

RESULTS:

NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively.

CONCLUSION:

Xe-133 liver scan proved to be a safe, reliable, non-invasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.     

Applicability of adult-to-adult living donor liver transplantation

BACKGROUND/AIMS: The applicability of adult-to-adult living donor liver transplantation has not been established yet. We report the first data in a European center of the process leading to this procedure from the first moment the patients were informed about it. METHODS: In phase 1 of the process, 121 adult patients enlisted for cadaveric liver transplantation and their relatives were informed of the technical aspects, advantages and risks of living donor liver transplantation, and the essential criteria for living donation. In phase 2, potential donors identified in phase 1 were evaluated in depth. RESULTS: Twenty-one (17%) patients underwent living donor liver transplantation. This procedure was not performed in 60 patients (50%) for reasons concerning the patients themselves, especially their refusal to receive living donor liver transplantation from a relative (30%). Forty patients (33%) did not undergo living donor liver transplantation for reasons concerning potential donors: donors were not identified (14%), declined the donation (13%), or were refused for technical reasons (6%). The expected waiting time to transplantation was longer in patients who underwent living donor liver transplantation than in those who did not. CONCLUSIONS: The applicability of adult-to-adult living donor liver transplantation is low, mainly because of reasons related to potential recipients.     

Live donors in liver transplantation

Living donor liver transplantation (LDLT) has been controversial since its inception. Begun in response to deceased donor organ shortage and waiting list mortality, LDLT was initiated in 1989 in children, grew rapidly after its first general application in adults in the United States in 1998, and has declined since 2001. There are significant risks to the living donor, including the risk of death and substantial morbidity, and 2 highly publicized donor deaths are thought to have contributed to decreased enthusiasm for LDLT. Significant improvements in outcomes have been seen over recent years, and data, including from the National Institutes of Health-funded Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL), have established a survival benefit from pursuing LDLT. Despite this, LDLT still composes less than 5% of adult liver transplants, significantly less than in kidney transplantation where living donors compose approximately 40% of all transplantations performed. The ethics, optimal utility, and application of LDLT remain to be defined. In addition, most studies to date have focused on posttransplantation outcomes and have not included the effect of the learning curve on outcome or the potential impact of LDLT on waiting list mortality. Further growth of LDLT will depend on defining the optimal recipient and donor characteristics for this procedure as well as broader acceptance and experience in the public and in transplant centers.     

Artificial intelligence for prediction of donor liver allograft steatosis and early post-transplantation graft failure

BackgroundDonor livers undergo subjective pathologist review of steatosis before transplantation to mitigate the risk for early allograft dysfunction (EAD). We developed an objective, computer vision artificial intelligence (CVAI) platform to score donor liver steatosis and compared its capability for predicting EAD against pathologist steatosis scores.MethodsTwo pathologists scored digitized donor liver biopsy slides from 2014 to 2019. We trained four CVAI platforms with 1:99 training:prediction split. Mean intersection-over-union (IU) characterized CVAI model accuracy. We defined EAD using liver function tests within 1 week of transplantation. We calculated separate EAD logistic regression models with CVAI and pathologist steatosis and compared the models’ discrimination and internal calibration.ResultsFrom 90 liver biopsies, 25,494 images trained CVAI models yielding peak mean IU = 0.80. CVAI steatosis scores were lower than pathologist scores (median 3% vs 20%, P < 0.001). Among 41 transplanted grafts, 46% developed EAD. The median CVAI steatosis score was higher for those with EAD (2.9% vs 1.9%, P = 0.02). CVAI steatosis was independently associated with EAD after adjusting for donor age, donor diabetes, and MELD score (aOR = 1.34, 95%CI = 1.03–1.75, P = 0.03).ConclusionThe CVAI steatosis EAD model demonstrated slightly better calibration than pathologist steatosis, meriting further investigation into which modality most accurately and reliably predicts post-transplantation outcomes.     

Utility of liver biopsy in bone marrow transplant patients

Background and Aim: Hepatic dysfunction is a common cause of morbidity and mortality in bone marrow transplant recipients. During the complex clinical management of these patients, liver biopsies may be obtained during evaluation of abnormal liver tests. The purpose of our study was to assess the safety and use of liver biopsy in this patient population. Methods: In total, 1700 bone marrow transplants were performed at our institution from June 1982 to December 2002. Data from patients who underwent liver biopsy after their transplant were reviewed once they were identified through a computerized medical index system. Impact of the histological diagnosis on subsequent patient management was obtained from clinical records. The histological diagnosis made by dedicated hepatopathologists was used as the ‘gold standard’ to assess the reliability of clinical diagnosis. Results: Sixty‐one patients, comprising 39 males and 22 females, had a liver biopsy performed (27 transjugular, 29 percutaneous, four laparoscopic, one not specified). As a result of liver biopsy, management was changed in 37% of patients and included addition of medical therapy in 11 and cessation of therapy in five patients. Complications from the liver biopsy were observed in 15 (25%) patients and involved 10 cases of pain or bleeding at the biopsy site, four subcapsular hemorrhages, and one arrhythmia leading to death. Conclusion: Liver biopsy, although infrequently obtained during the assessment of hepatic dysfunction in the bone marrow transplant population, can serve as an important diagnostic tool with a significant impact on the clinical management of these patients. Although we observed a higher complication rate, the majority of them were minor.     

Influence of donor post-reperfusion changes on graft evolution after liver transplant.

INTRODUCTION: The increase in indications for liver transplantation has meant that waiting lists are growing ever longer. For this reason, broadening the donor pool is a priority for most groups. OBJECTIVE: The objective of this study was to analyze the predictive value of post-reperfusion biopsy in the evolution of graft function after liver transplantation. PATIENTS: One hundred and forty-eight liver biopsies, obtained after graft reperfusion, were analyzed. Eight pathological variables and thirty-seven clinical variables of the donors were recorded. Risk factors for presenting primary graft non-function or dysfunction were studied with logistic regression models. Factors associated to the long-term graft failure were studied using Cox analysis and actuarial survival curves. RESULTS: Microvesicular steatosis greater than 50% was the only risk factor associated to graft dysfunction in the multivariate logistic regression model. Microvesicular steatosis greater than 30%, severe hepatocyte necrosis and presence of abundant neutrophilic leukocytes were risk factors associated to graft failure in the univariate study. Only steatosis remained as an independent risk factor in the multivariate study. These grafts also presented poorer long-term survival. Abundant polymorphonuclear infiltrate was associated to a higher frequency of biliary complications. CONCLUSIONS: Microvesicular steatosis implies a better evolution than macrovesicular steatosis. Neutrophilic infiltrate and hepatocellular necrosis lead to poorer initial graft function and reduced long-term survival.     

Effect of maintenance therapy with low-dose peginterferon for recurrent hepatitis C after living donor liver transplantation

Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n =17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.     

Effects of donor steatosis on liver biochemistry and significance of body mass index in predicting steatosis

Background

Hepatic steatosis is a major concern in living donor liver transplantation. Factors affecting hepatic functional status after a donor right hepatectomy (with the middle hepatic vein included in the graft) with a focus on changes owing to steatosis were retrospectively studied.

Methods

Donors (n= 325) were categorized into three groups: G0 (no steatosis, n= 178), G1 (< = 10% steatosis, n= 128) and G2 (>10% steatosis, n= 19). Donors with >20% steatosis were excluded. Changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin levels and prothrombin time (PT) were assessed. Factors predicting steatosis were also assessed. A liver biopsy was performed on selected donors.

Results

The ALT level rose until day 3 in G1 and day 6 in G2 (P < 0.05). The AST level rose until day 7 in G2 (P < 0.05) but stayed unchanged in G1. The bilirubin level was higher only on day 1 in G2 (P < 0.05). By day 30, no significant difference between any groups was noted. Receiver-operating characteristic (ROC) area under the curve for body mass index (BMI) on predicting steatosis was 0.75 [confidence interval (CI) = 69–80]. Among donors with a BMI > 23.5 kg/m², 75% had steatosis. Five donors had >20% steatosis and were not assessed.

Conclusion

Using a liver with up to 20% steatosis in right liver donation, even if the middle hepatic vein is included in the graft, is safe. For Asian donors, a BMI > 23.5 kg/m² is a guide in deciding whether to perform a liver biopsy for steatosis.     

Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies

BACKGROUND AND AIMS: Steatosis, a frequent histological finding in patients with chronic hepatitis C (CHC), has been suggested to influence liver fibrosis progression. The aim of the present study was to evaluate in patients with CHC and paired liver biopsies the relationship between the evolution of steatosis and that of fibrosis between the two biopsies. METHODS: Ninety six patients were selected according to the following criteria: absence of treatment; absence of cirrhosis at initial biopsy; and serum hepatitis B surface antigen and human immunodeficiency virus antibody negativity. Degrees of necroinflammatory activity, fibrosis, and steatosis grades were assessed in the two biopsies. In addition to histological lesions, parameters studied included the source of infection, duration of infection, body mass index, alcohol intake, alanine aminotransferase levels, hepatitis C virus genotype, and viral load. RESULTS: The mean interval between the two biopsies was 48 (32) months. Steatosis was found in 54% of patients at first biopsy, and was severe in 9%. Worsening of steatosis was observed in 34% of patients, stability in 50%, and improvement in 16%. Worsening of steatosis was significantly associated with hepatic fibrosis progression in patients with (p=0.03) or without (p<0.03) steatosis at diagnosis. Overall, fibrosis progression was observed in 31% of patients and stability in 69%. In a univariate analysis, fibrosis progression was associated with male sex (p=0.05), worsening of histological activity (p=0.04), and worsening of steatosis (p=0.0003). In a multivariate analysis, the only factor independently associated with fibrosis progression was worsening of steatosis (worsening v improvement/stability: odds ratio 4.7 (95% confidence interval 1.3-10.8); p=0.0001). CONCLUSIONS: Our results suggest that in untreated patients with CHC and serial liver biopsies, fibrosis progression is strongly associated with worsening of steatosis.