Pretransplant hepatomegaly is linked to relapse in patients with leukemia and myelodysplastic syndrome not in remission.

Hepatomegaly is an extramedullary disease (EMD) manifestation of hematological malignancy. Although EMD before allogeneic hematopoietic stem cell transplantation (allo-HCT) is a risk factor for relapse in patients not in complete remission (NonCR) patients, the significance of hepatomegaly to allo-HCT is unclear. We conducted a single-center retrospective observational study of 140 patients with acute leukemia and myelodysplastic syndrome who underwent allo-HCT at our institution from 2014 to 2019. Hepatomegaly was assessed by ultrasonography using the liver index (LI). In the univariable analysis, the LI/height ratio was significantly associated with relapse (hazard ratio [HR] per standard deviation [sd]: 1.51, 95% confidence interval [CI] 1.18-1.93, p = 0.001, sd = 13.8) in NonCR patients (n = 62), but showed no significant association in CR patients (n = 78) (HR per sd: 0.95, 95% CI 0.64-1.39, p = 0.780, sd = 8.7). In multivariable analysis, the LI/height ratio was significantly associated with relapse (HR per sd: 1.34, 95% CI 1.02-1.78, p = 0.037) after adjusting for the refined disease risk index and conditioning intensity. Interaction analysis showed a noteworthy but not statistically significant association between the LI/height ratio and CR status (p = 0.110). In conclusion, our findings suggest that the LI may be a risk factor for relapse in NonCR patients after allo-HCT.

Liver damage and hepatomegaly in COVID-19 patients.

INTRODUCTION: The aim of this study was to evaluate the patients with high liver function test results detected at admission to the hospital diagnosed with COVID-19. METHODOLOGY: Patients diagnosed with COVID-19 by a nasopharyngeal RT-PCR (+) test in the emergency department were included in the study. CRP, liver function tests, and abdominal ultrasonography (US) findings of the patients were recorded. RESULTS: A total of 367 COVID-19 patients, 254 (69.2%) males and 113 (30.8%) females, with a mean age of 60.39 (16.81) years, were included in the study. It was seen that 236 (68.7%) patients were treated without complications, 131 (35.7%) patients needed intensive care, and 81 (22.1%) patients died. The frequency of hepatomegaly was significantly higher in patients with severe course and mortality (p < 0.001). When COVID-19 patients who developed mortality were compared with other patients with a diagnosis of COVID-19, no additional risk factors affecting mortality were detected, except LDH [OR: 1.009, (1.006-1.012); p < 0.001] and high CK [OR: 1.001 CI: 95%, (1.000-1.001); p = 0.032]. CONCLUSIONS: Patients who need to be hospitalized with COVID-19 and who do not have acute and/or chronic liver disease, elevated liver function test results, and an increase in liver sizes at presentation, it was seen that these did not have an effect on the clinical outcome. However, in addition to the presence of advanced age and comorbidity, the presence of hepatomegaly measured by CT at admission, and high LDH and CK levels were associated with poor clinical outcomes.

Combined liver-kidney transplant in polycystic diseases: a case report.

Polycystic liver disease, a hereditary pathology, usually manifests as autosomal dominant polycystic kidney disease. The many cysts in the liver cause massive hepatomegaly, majorly affecting the patient's quality of life. In cases of refractory symptoms, liver transplantation is the only treatment choice. A 43-year-old woman was followed up as a hepatology outpatient in August 2020, with a progressive increase in abdominal volume, lower limb edema, and cachexia. The patient was diagnosed with polycystic renal and liver disease with massive hepatomegaly in March 2021, a combined kidney-liver transplant. Liver size represented 13% of the patient's corporal composition, weighing 8.6kg. The patient was discharged on the 7th postoperative day with no complications. Only 10-20% of patients with polycystic liver disease have clinical manifestations, most of which result from hepatomegaly. An increase in liver volume deteriorates liver function until the condition becomes end-stage liver disease, as kidney function is already compromised; liver-kidney transplantation remains the only treatment choice. The case described drew significant attention to the massive hepatomegaly presented in the patient, with the liver representing over 10% of the patient's body weight, approximately five to six times larger than a normal-sized liver.

Hemophagocytic lymphohistiocytosis as a rare complication of dengue haemorrhagic fever: a case report.

BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is an uncommon systemic inflammatory syndrome that can happen secondary to numerous conditions. It rarely occurs due to dengue infection causing significant mortality and morbidity even with appropriate treatment. The outcome is further poor if the diagnosis of HLH is delayed or left untreated. Therefore, a high degree of clinical suspicion is paramount in diagnosing HLH. CASE PRESENTATION: A 17-year-old Sinhalese boy was admitted to a tertiary care hospital in Sri Lanka with a 4-day history of fever, headache, nausea, vomiting, and diarrhea. He was hemodynamically stable, and the serological investigation confirmed a dengue infection. On the fifth day of fever, he entered the critical phase of dengue infection, confirmed by ultrasound evidence of plasma leaking. However, he had ongoing high fever spikes during the critical phase, and even after the critical phase was over, the fever spikes continued. Simultaneously, hepatosplenomegaly was noticed, and he showed persistent thrombocytopenia, neutropenia, and anemia despite the resolution of the critical phase. Further, the workup revealed a serum ferritin level of > 3000 ng/mL triglyceride level of 314 mg/dL, and the bone marrow biopsy revealed an increased haemophagocytic activity. Secondary HLH was diagnosed on the basis of criteria used in the HLH-2004 trial and successfully managed with intravenous dexamethasone 10 mg/body surface area/day for the first 2 weeks, followed by a tapering regimen over 8 weeks. CONCLUSION: This case emphasizes the need to consider HLH as a potential complication when persistent fever and cytopenias are present after recovering from dengue fever, particularly in patients with unusual clinical features like hepatosplenomegaly. Early recognition and prompt treatment with appropriate immunosuppressive therapy, such as intravenous dexamethasone, can lead to a successful response and good prognosis.

Lysosomal acid lipase deficiency manifestations in children and adults: Baseline data from an international registry.

BACKGROUND AND AIMS: Lysosomal acid lipase deficiency (LAL-D) is a rare, autosomal recessive disease involving lysosomal accumulation of cholesteryl esters and triglycerides. The International Lysosomal Acid Lipase Deficiency Registry (NCT01633489), established in 2013 to understand LAL-D natural history and long-term outcomes, is accessible to centres caring for patients diagnosed by deficient LAL activity and/or biallelic pathogenic LIPA variants. We describe the registry population enrolled through 2 May 2022. METHODS: In this prospective observational study, we analysed demographic and baseline clinical characteristics of children (ages ≥6 months to <18 years) and adults diagnosed with LAL-D. RESULTS: Of 228 patients with confirmed disease, 61% were children; 202/220 (92%) with data on race were white. Median age was 5.5 years at sign/symptom onset and 10.5 years at diagnosis; median time from sign/symptom onset to diagnostic testing was 3.3 years. The most common manifestations raising suspicion of disease were elevated alanine (70%) and aspartate aminotransferase levels (67%) and hepatomegaly (63%). Among 157 with reported LIPA mutations, 70 were homozygous and 45 were compound heterozygous for the common exon 8 splice junction pathogenic variant (E8SJM-1). Seventy percent (159/228) of patients had dyslipidaemia. Among 118 with liver biopsies, 63% had microvesicular steatosis exclusively, 23% had mixed micro- and macrovesicular steatosis and 47% had lobular inflammation. Of 78 patients with fibrosis-stage data, 37% had bridging fibrosis and 14% had cirrhosis. CONCLUSIONS: Although LAL-D signs/symptoms occur early, diagnosis is often delayed. Abnormal transaminase levels associated with hepatomegaly and dyslipidaemia should raise suspicion and prompt earlier diagnosis of LAL-D. TRIAL REGISTRATION NUMBER: NCT01633489.

Hepatopathy of Mauriac syndrome. The importance of therapeutic adherence.

The Pierre Mauriac syndrome described in the year 1930, is characterized by growth failure, cushingoid appearance, hepatomegaly and hypertransaminasemia, in a patient with chronic uncontrolled DM1. The most common age of presentation is usually in adolescence, although cases have been described in both children and adults. The hallmark of this syndrome is extreme liver enlargement from massive acucumulation of glycogen. The diagnosis of hepatopathy requires high clinical suspicion and the presence of glycogen accumulation must be corroborated with a liver biopsy. The accumulation of glycogen in hepatocytes is partly caused by long periods of hyperglycemia, in which glucose enters the hepatocyte independently of insulin and is converted to glycogen. Mauriac syndrome is currently a rare cause of liver disease, due to improvements in control and treatment of patients with DM1. However, some cases are described in people with complicated social situations or without therapeutic compliance. This is a reversible condition after improvement in glycemic control with adequate insulinization. For this reason, we believe it convenient to suspect this clinical picture in patients with poor glycemic control and symptoms of pain and abdominal distension.

Simultaneous portal and hepatic vein embolization is better than portal embolization or ALPPS for hypertrophy of future liver remnant before major hepatectomy: A systematic review and network meta-analysis.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is the Achilles' heel of hepatic resection for colorectal liver metastases. The most commonly used procedure to generate hypertrophy of the functional liver remnant (FLR) is portal vein embolization (PVE), which does not always lead to successful hypertrophy. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has been proposed to overcome the limitations of PVE. Liver venous deprivation (LVD), a technique that includes simultaneous portal and hepatic vein embolization, has also been proposed as an alternative to ALPPS. The present study aimed to conduct a systematic review as the first network meta-analysis to compare the efficacy, effectiveness, and safety of the three regenerative techniques. DATA SOURCES: A systematic search for literature was conducted using the electronic databases Embase, PubMed (MEDLINE), Google Scholar and Cochrane. RESULTS: The time to operation was significantly shorter in the ALPPS cohort than in the PVE and LVD cohorts by 27 and 22 days, respectively. Intraoperative parameters of blood loss and the Pringle maneuver demonstrated non-significant differences between the PVE and LVD cohorts. There was evidence of a significantly higher FLR hypertrophy rate in the ALPPS cohort when compared to the PVE cohort, but non-significant differences were observed when compared to the LVD cohort. Notably, the LVD cohort demonstrated a significantly better FLR/body weight (BW) ratio compared to both the ALPPS and PVE cohorts. Both the PVE and LVD cohorts demonstrated significantly lower major morbidity rates compared to the ALPPS cohort. The LVD cohort also demonstrated a significantly lower 90-day mortality rate compared to both the PVE and ALPPS cohorts. CONCLUSIONS: LVD in adequately selected patients may induce adequate and profound FLR hypertrophy before major hepatectomy. Present evidence demonstrated significantly lower major morbidity and mortality rates in the LVD cohort than in the ALPPS and PVE cohorts.

A Retrospective Multicentric Study of 34 Patients with Niemann-Pick Type C Disease and Early Liver Involvement in France.

OBJECTIVE: To describe the clinical features and course of liver involvement in a cohort of patients with Niemann-Pick type C disease (NP-C), a severe lysosomal storage disorder. STUDY DESIGN: Patients with genetically confirmed NP-C (NPC1, n = 31; NPC2, n = 3) and liver involvement before age 6 months were retrospectively included. Clinical, laboratory test, and imaging data were collected until the last follow-up or death; available liver biopsy specimens were studied using anti-CD68 immunostaining. RESULTS: At initial evaluation (median age, 17 days of life), all patients had hepatomegaly, 33 had splenomegaly, and 30 had neonatal cholestasis. Portal hypertension and liver failure developed in 9 and 4 patients, respectively. Liver biopsy studies, performed in 16 patients, revealed significant fibrosis in all 16 and CD68+ storage cells in 15. Serum alpha-fetoprotein concentration measured in 21 patients was elevated in 17. Plasma oxysterol concentrations were increased in the 16 patients tested. Four patients died within 6 months of life, including 3 from liver involvement. In patients who survived beyond age 6 months (median follow-up, 6.1 years), cholestasis regressed in all, and portal hypertension regressed in all but 1; 25 patients developed neurologic involvement, which was fatal in 16 patients. CONCLUSIONS: Liver involvement in NP-C consisted of transient neonatal cholestasis with hepatosplenomegaly, was associated with liver fibrosis, and was responsible for death in 9% of patients. The combination of liver anti-CD68 immunostaining, serum alpha-fetoprotein measurement, and studies of plasma biomarkers should facilitate early identification of NP-C.

Predictors of early death risk among untransplanted patients with combined immunodeficiencies affecting cellular and humoral immunity: A multicenter report.

BACKGROUND: There is an increased demand for hematopoietic stem cell transplant (HSCT) to treat various diseases including combined immunodeficiencies (CID), with limited worldwide availability. Variables affecting the decision regarding CID patients' prioritization for HSCT are not known. We aimed to determine general, clinical, and immunologic factors associated with the higher risk of early death (≤6 months after diagnosis) in untransplanted CID patients. METHODS: Data collection was done retrospectively from five centers and included general patients' information, and clinical and laboratory variables. Inclusion criteria were untransplanted patients who are either dead or alive with a follow-up period ≥6 months after diagnosis. RESULTS: Two hundred and thirty-six CID patients were reported by participating centers, of whom 111 were included in the study with a cumulative follow-up period of 278.6 years. Seventy-two patients died with the median age of death of 10.5 months. 35.1% of the patients succumbed within 6 months after the diagnosis. Having a history of Candida infections, sepsis or hepatomegaly was associated with an increased risk of early death. None of the other general or clinical variables was associated with such risk. Bivariate analysis of lymphocyte subsets showed that patients with the following counts: CD3+  < 100, CD4+  < 200, CD8+  < 50, or CD16+ CD56+ <200 cells/µl had increased risk of early death. In adjusted analysis, increased risk of early death was observed among patients with CD3+ count <100 cells/µl. CONCLUSION: Combined immunodeficiencies patients with a history of Candida infections, sepsis, hepatomegaly, or severe T-lymphopenia should be given priority for HSCT to avoid early death.