Received Liver Transplantation Research Articles

Outcomes of Liver Transplant for Hepatic Epithelioid Hemangioendothelioma.

Hepatic epithelioid hemangioendothelioma (HEH) is a rare indication of liver transplant with limited evidence. Adult recipients undergoing first-time liver-only transplant from 2002 to 2021 in the United States were identified using the UNOS/OPTN database. We compared post-transplant outcomes of recipients receiving liver transplant for HEH versus other diagnoses. Survival was visualized using Kaplan-Meier curves and compared using log-rank test and multivariable Cox regression. Propensity score matching for recipient age, sex, and MELD was performed, with baseline characteristics and survival compared between groups. Of 111 558 liver transplant recipients identified, 121 (0.1%) underwent transplant for HEH. Donors to HEH recipients were more often living donors. Recipients with HEH were younger, more likely to be female, and had lower BMI. Recipients with HEH had higher albumin, lower bilirubin, lower INR, and lower serum creatinine, as well as lower MELD scores and rates of ascites and encephalopathy. Similar post-transplant survival was observed for recipients with HEH (16.6 [lower 95% CI 14.9] years) and non-HEH diagnoses (13.8 [95% CI 13.6-13.9] years, log-rank p = 0.28), even after adjusting for baseline donor and recipient characteristics (aHR 1.28 [95% CI 0.94-1.74], p = 0.12). The propensity score matched cohort also had similar post-LT survival. This national study represents the largest known report on liver transplant for HEH. The survival of recipients with HEH was similar to other etiologies, supporting the use of liver transplantation (LT) in advanced HEH.

Cell-cell communications in the brain of hepatic encephalopathy: The neurovascular unit.

Many patients with liver diseases are exposed to the risk of hepatic encephalopathy (HE). The incidence of HE in liver patients is high, showing various symptoms ranging from mild symptoms to coma. Liver transplantation is one of the ways to overcome HE. However, not all patients can receive liver transplantation. Moreover, patients who have received liver transplantation have limitations in that they are vulnerable to hepatocellular carcinoma, allograft rejection, and infection. To find other therapeutic strategies, it is important to understand pathological factors and mechanisms that lead to HE after liver disease. Oxidative stress, inflammatory response, hyperammonaemia and metabolic disorders seen after liver diseases have been reported as risk factors of HE. These are known to affect the brain and cause HE. These peripheral pathological factors can impair the blood-brain barrier, cause it to collapse and damage the neurovascular unit component of multiple cells, including vascular endothelial cells, astrocytes, microglia, and neurons, leading to HE. Many previous studies on HE have suggested the impairment of neurovascular unit and cell-cell communication in the pathogenesis of HE. This review focuses on pathological factors that appear in HE, cell type-specific pathological mechanisms, miscommunication/incorrect relationships, and therapeutic candidates between brain cells in HE. This review suggests that regulating communications and interactions between cells may be important in overcoming HE.

Long-term outcomes of pediatric hepatoblastoma patients who present with metastasis and receive liver transplantation

Long-term outcomes of pediatric hepatoblastoma patients who present with metastasis and receive liver transplantation

HOPE treatment prior to organ transplant alters key immune modulators in patients receiving liver transplantation

HOPE treatment prior to organ transplant alters key immune modulators in patients receiving liver transplantation

How to Predict Recurrence After Resection of Hepatocellular Carcinoma.

Predictors of recurrence following resection of hepatocellular carcinoma (HCC) are not fully established. This study investigated potential risk factors and prognostic scores for this situation. In 297 patients undergoing resection of HCC between 2000 and 2021, risk scores and potential additional risk factors for intrahepatic and extrahepatic recurrence were assessed. Median overall survival was 48.4 months, median time to recurrence 25.1 months. The Alpha-Fetoprotein (AFP)-score differentiated between low and high-risk groups (21.8 vs. 8.3 months, p=0.001), as did the Risk Estimation of Tumor Recurrence After Transplant (RETREAT)-score (16 vs. 9 months, p=0.004) and the Clinical Risk Score (CRS) (14.9 vs. 3.9 months, p=0.002). Advanced T-stage, multiple lesions, and vessel infiltration were significantly associated with any type of recurrence, advanced T-stage, and multiple lesions with intrahepatic recurrence. Predictors of recurrence following resection of HCC were identified. Prognostic scores traditionally used for patients receiving liver transplantation (AFP-score, RETREAT-score, CRS) were predictive also of recurrence after resection of HCC.

Effect of Transplanted Liver Fat Percentage on Organ Survival: A Retrospective Review.

Liver transplant is the most effective therapeutic option for patients with end-stage liver disease, nonalcoholic steatohepatitis, and acute liver failure. We evaluated whether the percentage of hepatic fat percentage affected transplant outcomes to determine whether livers with varying severity of macrosteatosis should be considered suitable for donation. We analyzed data from 381 patients with liver failure who received liver transplant at Montaseriyeh Hospital in Mashhad, Iran, between 2013 and 2022. Clinical and demographical data were collected, and we examined frozen-section slides of pretransplant biopsy specimens from donor livers. Liver allograft macrosteatosis was categorized into 4 groups according to severity of steatosis: <10%, 10% to 20%, 20% to 30%, and >30%. The mean age of recipients was 49 years; mean age of donors was 37 years. The mean liver survival rate was approximately 56 months. A total of 115 recipients (30%) died after liver transplant, with graft rejection as the leading cause of death (38%). Grafts with hepatic macrosteatosis <10% contributed to the largest share (87%). No significant differences were observed in the indication for liver transplant, life outcome, cause of death after liver transplant, or mean rate of liver survival among the 4 groups. Also, there was no significant correlation between the severity of liver macrosteatosis and graft or patient survival. Our findings suggest that livers with varying degrees of macrosteatosis are safe for transplant and should not be excluded from the donor pool.

Outcomes of Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation Utilizing Extended Criteria Donor Grafts

Background: The deceased donor shortage in the United States has led to increased utilization extended criteria donor (ECD) liver grafts. Centers often utilize ECD grafts in patients with low Model for End-Stage Liver Disease scores, like patients with hepatocellular carcinoma (HCC). However, few studies have directly examined outcomes of using ECD grafts in HCC patients. Methods: Adults receiving liver transplantation (LT) for HCC between 2010-2020 were identified in the Organ Procurement and Transplantation Network database. Recipients were categorized according to donor type: standard criteria (SCD), extended criteria, donation after brain death (ECD-DBD), and donation after circulatory death (DCD). Multivariable Cox regression analysis identified variables associated with overall or graft survival at 3 years post-LT. Results: Most patients received ECD-DBD grafts (51.4%); only 8.3% received DCD grafts. Time on waitlist was similar for ECD and SCD recipients (p=0.79). SCD recipients had higher 5-year overall survival post-LT than ECD-DBD or DCD recipients (79.1%, 77.1%, and 76.8%, respectively, p<0.001). Similarly, 5-year graft survival was also highest in SCD recipients (SCD, 77.8%; ECD-DBD, 75.7%; DCD, 72,.2%; p<0.001). In multivariable analysis, DCD grafts increased mortality risk (HR, 1.33; 95% CI, 1.12-1.57; p=0.001), but ECD-DBD grafts did not (HR, 1.10; 95% CI, 1.00-1.22; p=0.052). Conclusions: DCD and ECD-DBD recipients had significantly lower overall and graft survival. However, the survival benefit of liver transplantation for HCC patients greatly outweighs the small differences in patient and graft survival from using ECD grafts. Further research should investigate whether treatment of ECD grafts with machine perfusion may ameliorate this discrepancy.

An Effective Treatment of Fulminant Hepatic Failure: A Single-Center Retrospective Study.

Fulminant hepatic failure is a critical condition with a high mortality rate. Currently, liver transplantation is considered one of the most effective treatment methods, but the shortage of organ resources has presented a major obstacle. The use of marginal donor livers, including those from syphilis-positive donors, offers new opportunities. This study reviewed and analyzed data from our center to summarize the management experience of using syphilis-positive donor livers to treat fulminant hepatic failure. From January 2016 to December 2021, 17 adult patients with fulminant hepatic failure received liver transplants from syphilis-positive donors at our center. Given the imbalance in several baseline variables, propensity score matching was used. We compared outcomes, including complications, hospital stay, recovery of liver function, and survival rates between groups of patients with syphilis-positive and syphilis-negative grafts. We also reviewed treatment of recipients of syphilis-positive livers. No significant differences were shown in complications and hospital stays between recipients of syphilis-positive and syphilis-negative grafts. Both groups showed similar trends in liver function recovery. Patient and graft survival rates were comparable between the groups. Benzathine penicillin effectively protected recipients from syphilis. Use of liver grafts from syphilis-positive donors did not increase morbidity and mortality in recipients. Liver transplant can effectively treat patients with fulminant hepatic failure. In addition, prophylactic use of benzathine penicillin was beneficial.

A retrospective multicenter study of WHO 2021 classification-diagnosed solitary fibrous tumor of the CNS in a population from Lombardy, Italy.

In this retrospective, multicenter study, we collected patients withsolitary fibrous tumor-SFT-of the CNS followed in eight hospitals in Lombardia from 2004 to 2019, revising the diagnosis according to the WHO 2021 classification. Clinical data were analyzed at diagnosis and during follow-up. Overall, 57 patients were enrolled, of whom 52.6% female. Median age was 54, 91% had an intracranial tumor and 9% a spinal location. 49% patients had grade 1, 31.5% grade 2 and 19% grade 3 tumor. After a median follow-up of84months, 49% of the patients had progressed and 8.7% had died. Gross tumor resection was obtained in 70%, subtotal in 26.3%, partial in 1.7% and biopsy in 1.7%.15.7% (n = 9) of patients developed extra-CNS metastases, mainly involving bone, lung and liver, six of these were grade 3 and 3 were grade 2 at first diagnosis. 14 patients (24.5%) underwent radiation therapy, 3 chemotherapy and one received liver transplant. The 14 radiation-treated patients included all grade 3 and 3 grade 2 with partial or subtotal resection. Only tumor grade had a prognostically significant impact on PFS at univariate analysis, while age had not. All but one case displayed nuclear expression for STAT6, the remaining case showed diffuse expression of CD34. Whereas grade 3 was confirmed as a prognostically relevant factor, partially overlapping behaviours were detected in patients usually considered at low (all grade 1 and grade 2 with gross total resection) versus moderate risk (grade 2 with biopsy or non-gross total resection).

Incidence and risk factors of de novo hepatitis E virus infection after receiving liver transplantation.

Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.

High bone fracture risk in a large modern cohort of liver transplant recipients.

Liver transplantation (LT) has historically been associated with a high prevalence of osteoporosis, but most of the available data date back to late 1990s-early 2000s with limited sample size. Our aim was to assess the prevalence of bone fragility fractures and contributing factors in a large modern cohort of liver transplant recipients. Retrospective study of 429 consecutive patients receiving liver transplantation from 1/1/2010 to 31/12/2015. Final cohort included 366 patients. Electronic radiological images (lateral views of spine X-rays or Scout CT abdominal scans) performed within 6months from LT, were blinded reviewed to screen for morphometric vertebral fractures. Symptomatic clinical fragility fractures were recorded from the medical records. Patients with fragility fractures in the cohort were 155/366 (42.3%), with no significant differences between sexes. Most sustained vertebral fractures (145/155, 93.5%), mild or moderate wedges, with severe fractures more frequently observed in women. Multiple vertebral fractures were common (41.3%). Fracture rates were similar across different etiologies of cirrhosis and independent of diabetes or glucocorticoids exposure. Kidney function was significantly worse in women with fractures. Independently of age, sex, alcohol use, eGFR, and etiology of liver disease, low BMI was significantly associated with an increased risk for fractures (adjusted OR 1.058, 95%CI 1.001-1.118, P = 0.046). Our study shows a considerable fracture burden in a large and modern cohort of liver transplant recipients. Given the very high prevalence of bone fractures, a metabolic bone disease screening should be implemented in patients awaiting liver transplantation.

Clinical and Histopathologic Characteristics of Acute Severe Hepatitis Associated With Human Herpesvirus 6 Infection.

Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 ( P =0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 ( P <0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8 + T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process.

Natural history of deoxyguanosine kinase deficiency

Background and objectivesDeoxyguanosine kinase deficiency is one genetic cause of mtDNA depletion syndrome. Its major phenotypes include neonatal/infantile-onset hepatocerebral disease, isolated hepatic disease and myopathic disease. In this retrospective study, we seek to describe the natural history of deoxyguanosine kinase deficiency and identify any genotype-phenotype correlations. MethodsRetrospective literature search and collation of data from genetically confirmed cases of deoxyguanosine kinase deficiency. Results173 cases of DGUOK deficiency were identified. Neonatal/infantile-onset hepatocerebral disease accounted for 128 (74%) of cases. Isolated liver disease was seen in 36 (21%) and myopathic disease in 9 (5%) of cases. The most frequently involved systems were liver (98%), brain (75%), growth (46%) and gastrointestinal tract (26%). Infantile-onset disease typically presented with cholestatic jaundice and lactic acidosis. Neurological involvement included hypotonia, nystagmus and developmental delay with MRI brain abnormalities in about half of cases. Missense variants accounted for 48% of all pathogenic variants while variants resulting in truncated transcripts accounted for 39%. Prognosis was poor, especially for neonatal/ infantile-onset hepatocerebral disease for which 1 year survival was 11%. Twenty-three patients received liver transplants, of whom 12 died within 2 years of transplant. Patients with two truncating variants had a higher risk of death and were more likely to have the neonatal/infantile-onset hepatocerebral disease phenotype. No blood biomarker predictive of neurological involvement was identified. Earlier onset correlated with increased mortality. ConclusionsThere is a narrow window for therapeutic intervention. For the hepatocerebral disease phenotype, median age of onset was 1 month while the median age of death was 6.5 months implying rapid disease progression.

Long-term Outcomes of Liver Transplantation for Inborn Errors of Metabolism in Children

BackgroundLiver transplantation for inborn errors of metabolism is increasingly common and has historically had positive outcomes. However, this therapeutic modality is not without risks, and patient post-transplant quality of life should be part of the consideration. MethodsThis retrospective, observational cohort study included all pediatric patients receiving liver transplant from 2010 through 2020 at a single center. Recipients were split into 2 groups based on metabolic or non-metabolic indications for liver transplant. Ten-year patient survival and graft survival were analyzed. The PedsQL Transplant Module and RAND 36-Item Health Survey 1.0 were administered prospectively to those recipients with metabolic indications. ResultsTen-year patient survival was statistically significantly higher in the metabolic group than in the non-metabolic (p < .05), and there was no difference in 10-year graft survival between groups. Of the 12 patients in the metabolic group who completed the PedsQL Transplant Module or RAND 36-Item Health Survey 1.0, the median score was 88, similar to the score seen in healthy children. ConclusionsLiver transplantation for inborn errors of metabolism provides excellent long-term outcomes in terms of patient and graft survival, while maintaining a high quality of life.

Impact of Donor Age on Liver Transplant Outcomes in Patients with Acute-on-Chronic Liver Failure: A Cohort Study.

Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age into group I (donor age ≤17 years, n=647); group II (donor age 18-59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were compared among the three age groups and the four ACLF grades. Cox regression was also analyzed. The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001). When we analyzed the different effects of donor age on OS with different ACLF grades, in groups II and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Donor age is related to OS and graft survival of ACLF patients after transplantation, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Intensive locoregional therapy before liver transplantation for colorectal cancer liver metastasis: A novel pretransplant protocol.

We describe a novel pre-liver transplant (LT) approach in colorectal liver metastasis, allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. Patients undergoing LT for colorectal liver metastasis at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by positron emission tomography scan and carcinoembryonic Ag. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. Nine patients received liver transplant out of 27 who were evaluated (33.3%). The median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease, and 4 had treatment-induced cirrhosis. Pretransplant management included chemotherapy (n = 9) +/- bevacizumab (n = 6) and/or anti-EGFR (n = 6). The median number of pre-LT cycles of chemotherapy was 16 (range 10-40). Liver-directed therapy included Yttrium-90 (n = 5), ablation (n = 4), resection (n = 4), and hepatic artery infusion pump (n = 3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n = 6/8) and 60% (n = 3/5). Recurrence occurred in the lungs (n = 1), liver graft (n = 1), and lungs+para-aortic nodes (n = 1). Patients with pre-LT detectable disease had reduced RFS ( p = 0.04). All patients with recurrence had histologically viable tumors in the liver explant. Patients treated in our protocol (n = 16) demonstrated improved survival versus those who were not candidates (n = 11) regardless of transplant status ( p = 0.01). A protocol defined by aggressive pretransplant liver-directed treatment and transplant for patients with the undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.

Prognostic significance of real-world (RW) recurrence patterns after resection or ablation of early-stage hepatocellular carcinoma (HCC): Insights from the US Medicare population.

e16241 Background: The prognosis after curative-intent resection or ablation of early-stage HCC remains poor, largely due to high rates of recurrence. We aimed to characterize real-world recurrence patterns and determine whether the timing of recurrence was associated with overall survival (OS). Methods: Patients (pts) with early-stage HCC who underwent resection and/or ablation were identified from the SEER-Medicare database (2010-2019). Pts who received liver transplant were excluded. A proxy for recurrence was defined as the receipt of new HCC treatments (surgery, locoregional therapy, systemic therapy) or a secondary malignant neoplasm claim (excluding liver). Pseudo-recurrence dates were assigned to pts without recurrence to match the distribution of time between initial resection/ablation and recurrence in the recurrence cohort, to avoid immortal time bias. Early vs late recurrence was defined as occurring within 1 year vs after 1 year of initial resection/ablation. Primary outcome was OS as measured both from the time of recurrence/pseudo-recurrence and initial resection/ablation. Results: 1,146 eligible pts with early-stage HCC were identified. 63% were male, mean age was 74 yrs, and initial therapy was resection (39%), ablation (50%), or both (11%). 736 (64%) experienced recurrence. Among them, 53% received ablation, 37% surgery, and 11% received both. Median OS from recurrence or pseudo-recurrence was 22 months (mo) vs 67 mo (p &lt; 0.001) for pts with vs without recurrence, respectively. When measured from resection/ablation date, median OS was 39 mo vs 83 mo (p &lt; 0.001). After adjusting for relevant demographic and clinico-pathologic factors, including type of index therapy, in a multivariable Cox regression model, recurrence remained significantly associated with an increased risk of death (hazard ratio [HR]: 2.24; 95% CI: 1.85-2.71; p &lt; 0.001). Among pts who recurred, 380 (52%) had early recurrence and 356 (48%) had late recurrence. Median OS from recurrence was 17 mo vs 30 mo (p &lt; 0.001) for early vs late recurrence, respectively, and 23 mo vs 63 mo when measured from resection/ablation The adjusted HR for the risk of death associated with early recurrence was 1.39 (95% CI: 1.14-1.68; p &lt; 0.001) compared to late recurrence. Other significant prognostic factors associated with reduced OS included larger tumor size ( &gt; = 5cm), greater extent of disease, and poor differentiation (grade III and above). Conclusions: In this study among US Medicare pts, early recurrence within one year after curative-intent treatment of early-stage HCC was significantly associated with decreased OS compared to pts who recur later or without recurrence. This highlights the need for developing and utilizing effective adjuvant therapy regimens to delay or avoid recurrence.

Investigation of Post-Transplant Mental Well-Being in Liver Transplant Recipients with Hepatic Encephalopathy.

Objective: In this study, we aimed to examine the healing trend of hepatic encephalopathy after transplantation surgery in patients with liver failure. Method: We conducted this descriptive and cross-sectional study with the participation of liver transplant recipients. A personal information form, the West Haven Criteria (WHC), the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS), and the Richmond Agitation Sedation Scale (RASS) were used for data collection. The data were analyzed using Chi-squared tests, ANOVA, and paired-samples t-tests. Results: As time progressed after liver transplantation, hepatic encephalopathy stages regressed (p < 0.01). We found that liver transplant recipients with end-stage hepatic encephalopathy were mostly within the first 6 months after transplantation, while patients with first-stage hepatic encephalopathy had received liver transplants more than 2 years ago (p < 0.01). Conclusions: The results of our study revealed that hepatic encephalopathy stages regressed after transplantation, but there was no complete recovery. This highlights the need to develop new treatment strategies other than liver transplantation for the treatment of hepatic encephalopathy.

A case study of a liver transplant-treated patient with glycogen storage disease type Ia presenting with multiple inflammatory hepatic adenomas: an analysis of clinicopathologic and genetic data

BackgroundGlycogen storage disease (GSD) is a disease caused by excessive deposition of glycogen in tissues due to genetic disorders in glycogen metabolism. Glycogen storage disease type I (GSD-I) is also known as VonGeirk disease and glucose-6-phosphatase deficiency. This disease is inherited in an autosomal recessive manner, and both sexes can be affected. The main symptoms include hypoglycaemia, hepatomegaly, acidosis, hyperlipidaemia, hyperuricaemia, hyperlactataemia, coagulopathy and developmental delay.Case presentationHere, we present the case of a 13-year-old female patient with GSD Ia complicated with multiple inflammatory hepatic adenomas. She presented to the hospital with hepatomegaly, hypoglycaemia, and epistaxis. By clinical manifestations and imaging and laboratory examinations, we suspected that the patient suffered from GSD I. Finally, the diagnosis was confirmed by liver pathology and whole-exome sequencing (WES).WES revealed a synonymous mutation, c.648 G > T (p.L216 = , NM_000151.4), in exon 5 and a frameshift mutation, c.262delG (p.Val88Phefs*14, NM_000151.4), in exon 2 of the G6PC gene. According to the pedigree analysis results of first-generation sequencing, heterozygous mutations of c.648 G > T and c.262delG were obtained from the patient's father and mother.Liver pathology revealed that the solid nodules were hepatocellular hyperplastic lesions, and immunohistochemical (IHC) results revealed positive expression of CD34 (incomplete vascularization), liver fatty acid binding protein (L-FABP) and C-reactive protein (CRP) in nodule hepatocytes and negative expression of β-catenin and glutamine synthetase (GS). These findings suggest multiple inflammatory hepatocellular adenomas. PAS-stained peripheral hepatocytes that were mostly digested by PAS-D were strongly positive.This patient was finally diagnosed with GSD-Ia complicated with multiple inflammatory hepatic adenomas, briefly treated with nutritional therapy after diagnosis and then underwent living-donor liver allotransplantation.After 14 months of follow-up, the patient recovered well, liver function and blood glucose levels remained normal, and no complications occurred.ConclusionThe patient was diagnosed with GSD-Ia combined with multiple inflammatory hepatic adenomas and received liver transplant treatment. For childhood patients who present with hepatomegaly, growth retardation, and laboratory test abnormalities, including hypoglycaemia, hyperuricaemia, and hyperlipidaemia, a diagnosis of GSD should be considered. Gene sequencing and liver pathology play important roles in the diagnosis and typing of GSD.

Opioid use and risks in candidates and recipients of liver transplant.

Opioid use is extremely prevalent among patients with cirrhosis and those who received liver transplant (LT), despite concerns regarding opioid-related risks in this population. While there are many theoretical risks of opioids in patients with hepatic dysfunction, there is limited evidence on the effect of opioid use on clinical outcomes in cirrhosis and patients before and after LT specifically. As a result, there is significant center-level variability in opioid-related practices and policies. The existing data-largely based on retrospective observational studies-do suggest that opioids are associated with increased health resource utilization pre-LT and post-LT and that they may precipitate HE in patients with cirrhosis and increase the risk of graft loss and death after LT. The strongest predictor of opioid use after LT is opioid use before transplant; thus, a focus on safe opioid use in the pretransplant and peritransplant periods is essential for minimizing opioid-related harms. We describe 3 strategies to guide LT providers including (1) improved characterization of pain, mental health symptoms, and opioid and polysubstance use; (2) minimization of opioid prescriptions for those at highest risk of adverse events; and (3) safe prescribing strategies for those who do use opioids and for the management of opioid use disorder. Ultimately, our goal is to improve the quality of life and transplant outcomes among patients with cirrhosis and those who received LT, particularly those living with concurrent pain, mental health, and substance use disorders.