Wilson Disease in Children in the Eastern Region of Morocco: Analysis of 24 Cases.

Wilson's disease (WD), or "hepato-lenticular degeneration," is a rare genetic disorder of autosomal recessive inheritance causing toxic tissue accumulation of copper, mainly in the liver, brain, and cornea. Its phenotypic and genotypic heterogeneity characterizes it. This study aimed to clarify the clinical features and spectrum of Wilson's disease in children from the eastern region of Morocco and to study the evolutionary profile and survival in this population while discussing and highlighting the various diagnostic and therapeutic difficulties encountered in the management of WD in our context. This retrospective study encompassed 24 children diagnosed with Wilson's disease, selected from the gastroenterology-hepatology and pediatric nutrition units at Mohamed VI University Hospital in Oujda, Morocco, over a span of nine years, from January 2015 to November 2023. Our series results show 14 boys and 10 girls; the median age of discovery was 11 years, with extremes ranging from 18 months to 15 years. The consanguinity was found in 13 patients. Clinically, the edemato-ascitic syndrome was noted in 14 patients with an alteration of the general state; icterus was found in 13 patients; signs of portal hypertension were present in six patients; and neurological signs in seven cases. Skin manifestations occurred in three cases, and arthralgia in three cases. Six children were diagnosed on the occasion of a family screening. Biologically, hepatic cytolysis was found in 20 patients, with signs of hepatocellular failure in 15 cases. Hemolytic anemia was present in nine patients. Ceruloplasminemia was decreased in 21 patients and cupremia in 19 patients. Cupruria was increased in 22 cases. The Kayser-Fleicher ring was found in 10 cases. Abdominal ultrasound showed ascites in 16 patients, hepatomegaly in 1, splenomegaly in two cases, hepatosplenomegaly in five cases, and cirrhosis in two. MRI showed signal abnormalities in 11 patients. Therapeutically, D-penicillamine was initially introduced in 18 patients and zinc acetate in 6 patients. The evolution was favorable for 15 patients still followed up in the department. Three patients died of hepatocellular failure, and two died of hepatic encephalopathy. Four patients were lost to follow-up.

A Meta-Analysis of Cumulative Incidence of Hepatocellular Carcinoma After the Fontan Operation.

BACKGROUND: Hepatic complications are increasingly recognized after the Fontan operation. The development of hepatocellular carcinoma (HCC) is associated with high mortality when diagnosed, but its incidence and risk factors are poorly understood. We conducted a systematic review and meta-analysis of the cumulative incidence of HCC after Fontan and associated risk factors. METHODS: We searched PubMed, CINAHL, and MEDLINE databases for articles reporting the cumulative incidence of HCC after Fontan operation on March 21, 2023. A single-arm random effects meta-analysis was conducted to assess cumulative incidence at 10, 20, and 30 years after Fontan. Meta-analysis of the difference of the medians was used to assess the influence of risk factors on the development of HCC. RESULTS: Four studies including a total of 1320 patients reported cumulative incidence. The cumulative incidence of HCC at 10, 20, and 30 years after Fontan was 0% (95% CI 0.00-0.01), 2% (0.01-0.06), and 7% (0.03-0.17) respectively. Seven studies including 6,250 patients reported overall incidence of HCC and associated risk factors. At a median 18.4 (IQR 11.9-24.9) years of follow-up, incidence of HCC was 2% (0.01-0.04). Only use of anticoagulation was associated with a lower risk of HCC (RR 0.3, 95% CI 0.1-0.88). DISCUSSION: By 30 years after Fontan, cumulative incidence of HCC is high (7%). Risk of HCC development prior to 10 years post-Fontan is low (0%), though the decision to defer HCC surveillance in this period may require future investigation based on larger studies. Screening with ultrasound every 6 months starting 20 years post-Fontan is reasonable, however, further research regarding timing, cost-effectiveness, additional risk factors associated with HCC risk, and different screening modalities is required.

Phenotypic and Genotypic Features of the FAN1 Mutation-Related Disease in a Large Hungarian Family.

Pathogenic variants in the FAN1 gene lead to a systemic disease with karyomegalic interstitial nephritis (KIN) at the forefront clinically. The phenotypic-genotypic features of a FAN1 mutation-related disease involving five members of a Hungarian Caucasian family are presented. Each had adult-onset chronic kidney disease of unknown cause treated with renal replacement therapy and elevated liver enzymes. Short stature, emaciation, latte-colored skin, freckles, and a hawk-like nose in four patients, a limited intellect in two patients, and chronic restrictive lung disease in one patient completed the phenotype. Severe infections occurred in four patients. All five patients had ceased. Four patients underwent autopsy. KIN and extrarenal karyomegaly were observed histologically; the livers showed no specific abnormality. The genotyping using formalin-fixed tissue samples detected a hitherto undescribed homozygous FAN1 mutation (c.1673_1674insT/p.Met558lfs*4; exon 5) in three of these patients and a heterozygous FAN1 mutation in one patient. The reason for the heterozygosity is discussed. In addition, 56 family members consented to the screening for FAN1 mutation from which 17 individuals proved to be heterozygous carriers; a blood chemistry evaluation of their kidney and liver function did not find any abnormality. The clinical presentation of FAN1-related disease was multifaceted, and not yet described manifestations were observed besides kidney and liver disease. Mutation in this gene should be suspected in adults with small kidneys of unknown cause, elevated liver enzymes, and recurrent infections, even without a family history.

A Case of Type 1 Diabetes Mellitus with Diabetic Ketoacidosis Presenting with Transient Severe Fatty Liver and Subsequent Liver Dysfunction.

Patients often present with severe fatty liver (FL) due to insulin deficiency at the onset of diabetic ketoacidosis (DKA). On the other hand, glycogenic hepatopathy (GH) is a possible cause of liver dysfunction in patients with DKA. We herein report a case of type 1 diabetes mellitus with severe FL at the onset of DKA, who demonstrated subsequent marked liver dysfunction after achieving an improvement of FL. As liver dysfunction persisted even after the FL improved, GH was suspected to be the cause of liver dysfunction. FL and GH have different prognoses and should therefore be differentiated using imaging studies and biopsies.

Congestive Hepatopathy: A Review of the Literature.

Congestive hepatopathy (CH), stemming from compromised hepatic venous flow or heightened intrahepatic pressure, represents a significant consequence of cardiovascular conditions like congestive heart failure (CHF). This review of literature encapsulates the core aspects of this condition, characterized by hepatic congestion, cellular injury, and impaired liver function. Diagnostic challenges arise due to symptoms mirroring primary liver diseases. Management revolves around addressing the underlying cause and mitigating fluid retention. This review of literature provides a snapshot of CH's complexity, emphasizing its clinical implications and the need for comprehensive understanding in clinical practice.

Treatment of Francisella philomiragia bacteremia in a dog.

To describe the diagnosis and successful treatment of systemic francisellosis in a dog. An 11-year-old female spayed Labrador retriever presented for progressive lethargy, hyporexia, and cough. The dog was febrile with a neutrophilia, nonregenerative anemia, thrombocytopenia, and had increased activity in serum of liver-derived enzymes. Francisella philomiragia was isolated from aerobic blood culture. The dog was treated for 6 weeks with enrofloxacin orally. Repeated aerobic blood cultures after 2 and 6 weeks of antibiotic therapy were negative. The dog was clinically normal 7 months after diagnosis with no evidence of relapse.

Hepatic insufficiency in two juvenile dogs with histoplasmosis.

A 9-month-old female intact toy poodle and a 1-year-old female intact Labrador retriever mix presented to separate teaching hospitals for chronic histories of malaise and clinicopathologic evidence of hepatic dysfunction. The signalment and clinical histories of these dogs prompted consideration of a congenital portosystemic shunt as a primary differential. However, microscopic evaluation of peritoneal effusion, pleural effusion, and peripheral blood samples from the dogs revealed round to ovoid yeast organisms morphologically most compatible with Histoplasma capsulatum. Additional testing confirmed histoplasmosis in each case. The poodle underwent a computed tomography (CT) study, which showed hepatomegaly with a spleno-gonadal shunt, pancreatic and gastric wall edema, and marked peritoneal effusion, findings compatible with portal hypertension and secondary acquired shunt formation. The dog was later humanely euthanized due to clinical deterioration, and on necropsy hepatic histoplasmosis was verified, with additional affected tissues comprising lungs and spleen. The Labrador Retriever mix responded clinically and clinicopathologically to antifungal therapy, though no abdominal imaging was performed to definitively exclude the possibility of a congenital portosystemic shunt. In retrospect, several features were more compatible with histoplasmosis than portosystemic shunt in these cases, including hyperbilirubinemia, effusion, and hepatomegaly. These findings serve as a reminder of the need to interpret serum biochemical findings in the context of the totality of the clinicopathologic data and imaging findings, as well as the diagnostic value of microscopy in the evaluation of hematologic and body cavity fluid samples.

Congestive Hepatopathy Diagnosed by Venous Excess Ultrasound Score.

Accurate and rapid detection of venous organ congestion, especially congestive hepatopathy, is essential to reduce morbidity and mortality. The Venous Excess Ultrasound Score is an emerging point-of-care ultrasound examination that can grade severity of venous organ congestion using spectral Doppler evaluation of the hepatic, portal, and intrarenal veins, but its utility in congestive hepatopathy is unknown. We report a case of acute liver injury where Venous Excess Ultrasound Score supported a diagnosis of congestive hepatopathy and guided management, leading to a favorable outcome.

Copper hepatopathies in Australian dogs.

INTRODUCTION: To evaluate hepatopathies in Australian dogs according to the World Small Animal Veterinary Association (WSAVA) guidelines. Specifically, to describe the prevalence and survival of dogs with copper-associated hepatopathy. MATERIALS AND METHODS: Medical records from the Small Animal Specialist Hospital were reviewed to identify dogs with liver disease and liver biopsy between November 2008 and November 2021. Liver histopathology reports were reviewed with a board-certified veterinary pathologist and classified according to the WSAVA guidelines. Histopathology reports and clinical records were reviewed to ascertain the most important histological process for statistical analysis. Copper-associated hepatopathy was defined as (i) histological evidence of copper accumulation in centrilobular areas (Zone 3) associated with hepatocyte necrosis, inflammation with copper-laden macrophages and chronic hepatitis (ii) histochemical copper staining showing hepatocyte copper accumulation in the centrilobular areas and iii) hepatic copper measurement with concentrations greater than 600 µg/g dry weight of liver. Dogs with primary inflammatory parenchymal disease included dogs with copper-associated hepatopathy, idiopathic chronic hepatitis, non-specific reactive hepatitis, chronic bacterial hepatitis and immune-mediated chronic hepatitis. Descriptive statistics were performed for all dogs. Age, weight and clinicopathologic data were compared between dogs with copper-associated hepatopathy and dogs with other causes of chronic primary inflammatory parenchymal liver disease (Kruskal-Wallis test). Survival times were calculated and compared (Kaplan-Meier curves and log rank test) between dogs with copper-associated hepatopathy and dogs with other chronic primary inflammatory parenchymal liver diseases. Breed was evaluated to determine the breed most commonly affected with copper-associated hepatopathy and identify any breed in which this disease has not previously been described. RESULTS: Sixty-seven (43 female, 24 male) dogs with a median age of 7.8 years (quartile [Q] Q1-Q3 4.5-9.6 years) were included. Thirteen dogs had copper-associated hepatopathy, eight dogs had idiopathic chronic hepatitis, eight dogs had non-specific reactive hepatitis, seven dogs had disorders associated with portal hypertension, five dogs had chronic bacterial hepatitis and four dogs had immune-mediated chronic hepatitis. Compared with dogs with other causes of chronic primary inflammatory parenchymal liver disease, dogs with copper-associated hepatopathy tended to be younger (6.73 vs. 8.01 years, P = 0.057) and heavier (19.8 vs. 9.6 kg, P = 0.052) than dogs with other causes of primary chronic inflammatory parenchymal diseases. There was no statistically significant difference when ALT (P = 0.30), ALP (P = 0.18) and total bilirubin (P = 0.13) were compared between the two groups. The median survival time for all dogs after liver biopsy was 2010 days (CI 1321 days - not reached). There was no significant difference in survival between dogs with copper-associated hepatopathy and dogs with other causes of chronic primary inflammatory parenchymal liver disease (P = 0.5). CONCLUSIONS: Copper-associated hepatopathy was common among Australian dogs with chronic hepatopathies, occurring in younger and heavier dogs than other causes of primary inflammatory parenchymal liver disease. Clinical pathology is not useful for differentiating between copper-associated hepatopathy and other causes of chronic primary inflammatory parenchymal liver disease. When copper-associated hepatopathy is treated, the prognosis can be good. This is the first report of copper-associated hepatopathy in Australian Cavalier King Charles Spaniels.

Leflunomide with prednisone or nonsteroidal anti-inflammatory drug therapy is safe and tolerated for long-term treatment of immune-mediated polyarthritis in 27 dogs.

OBJECTIVE: To retrospectively evaluate safety and tolerance of leflunomide for long-term treatment of canine idiopathic immune-mediated polyarthritis (IMPA). ANIMALS: 27 dogs with clinical signs and synovial fluid cytology supportive of IMPA with ≥ 6 months' follow-up after starting leflunomide. METHODS: Medical records were reviewed to identify dogs prescribed leflunomide for treatment of IMPA from February 2012 to May 2022. Initial leflunomide doses of 2 to 4 mg/kg once daily were prescribed and were titrated to the lowest effective dose with concurrent anti-inflammatory therapy. Complete blood count, serum chemistry, and clinical signs were monitored throughout the course of treatment. RESULTS: Adverse effects potentially attributable to leflunomide noted in 9 of 27 dogs (33%) included vomiting, diarrhea, lethargy, decreased or absent appetite, polyuria and polydipsia, and secondary antibiotic responsive infection and were self-limiting or resolved with outpatient therapy. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) elevation were documented in all dogs prescribed leflunomide plus prednisone, with persistent liver enzyme elevation in 6 of 9 dogs (67%) and normalization after antibiotic therapy in 3 of 9 dogs (33%). The majority of dogs prescribed leflunomide plus NSAID (11/17 [65%] dogs) did not experience liver enzyme elevation; 2 of 17 (12%) dogs developed transient antibiotic-responsive liver enzyme elevations, and 4 of 17 (23%) dogs had persistent liver enzyme elevation. CLINICAL RELEVANCE: Leflunomide was well tolerated for long-term management of IMPA. A significant difference in liver enzyme elevation was identified between dogs prescribed prednisone versus NSAID in combination with leflunomide. Leflunomide with NSAID therapy resulted in less hepatotoxicity compared with leflunomide with prednisone.

Case report: Severe hepatopathy following rivaroxaban administration in a dog.

Rivaroxaban, a specific factor Xa inhibitor and commonly utilized anticoagulant, has been known to cause hepatotoxicity and liver failure in humans. Although rivaroxaban is frequently used in veterinary medicine, hepatotoxicity has not been previously reported in dogs. The current case report describes a dog that developed severe hepatopathy following rivaroxaban administration for a large right pulmonary artery thrombus. An estimated 6-year-old spayed female mixed-breed dog developed anorexia and lethargy 9 days after rivaroxaban administration began. Subsequent labwork revealed severe hepatocellular hepatopathy, and rivaroxaban was discontinued. Additional diagnostics did not reveal an underlying etiology, although hepatic cytology could be consistent with a toxic injury. The hepatopathy and clinical signs improved after rivaroxaban was discontinued. The time to onset, type of hepatopathy, and time to resolution were all similar to those reported for human cases. This case provides precedence to advocate for improved and closer monitoring of dogs receiving factor Xa inhibitors. In cases of suspected hepatotoxicity with no other identifiable cause, a risk-benefit analysis should be performed, and discontinuation of rivaroxaban administration or alternative anticoagulant medications should be considered.

Diagnosis and classification of portosystemic shunts: a machine learning retrospective case-control study.

Diagnosis of portosystemic shunts (PSS) in dogs often requires multiple diagnostic tests, and available clinicopathologic tests have limitations in sensitivity and specificity. The objective of this study was to train and validate a machine learning model (MLM) that can accurately predict the presence of a PSS utilizing routinely collected demographic data and clinicopathologic features. Dogs diagnosed with PSS or control dogs tested for PSS but had the condition ruled out (non-PSS) were identified. Dogs were included if a complete blood count and serum chemistry panel were available from PSS diagnostic testing. Dogs with a PSS were subcategorized as having a single intrahepatic PSS, a single extrahepatic PSS, or multiple extrahepatic PSS. An extreme gradient boosting (XGboost) MLM was trained with data from 70% of the cases, and MLM performance was determined on the test set, comprising the remaining 30% of the case data. Two MLMs were created. The first was designed to predict the presence of any PSS (PSS MLM), and the second to predict the PSS subcategory (PSS SubCat MLM). The trained PSS MLM had a sensitivity of 94.3% (95% CI 90.1-96.8%) and specificity of 90.5% (95% CI 85.32-94.0%) for dogs in the test set. The area under the receiver operator characteristic curve (AUC) was 0.976 (95% CI; 0.964-0.989). The mean corpuscular hemoglobin, lymphocyte count, and serum globulin concentration were most important in prediction classification. The PSS SubCat MLM had an accuracy of 85.7% in determining the subtype of PSS of dogs in the test set, with variable sensitivity and specificity depending on PSS subtype. These MLMs have a high accuracy for diagnosing PSS; however, the prediction of PSS subclassification is less accurate. The MLMs can be used as a screening tool to increase or decrease the index of suspicion for PSS before confirmatory diagnostics such as advanced imaging are pursued.

RETRACTED: Sixteen years of canine hepatic copper concentrations within normal reference ranges in dogs fed a broad range of commercial diets.

OBJECTIVE: To examine the effects of age, sex, breed, liver histopathology, and year of death/sample collection on liver copper concentrations in dogs fed various commercial dog foods throughout their lives. SAMPLE: During necropsy, 336 samples were collected between the years 2006 and 2022 from dogs that were fed a variety of commercial dog foods on the market. This study utilized all liver samples available and did not require specific criteria for sample selection. METHODS: Liver samples (n = 336) were analyzed as dry weight for copper concentration by inductively coupled plasma-optical emission spectrometry. The potential effects of animal age and year of death/collection (scatterplots and linear regression), sex, liver histopathology (t test), and breed (ANOVA) on liver copper concentration were assessed. RESULTS: Labrador Retrievers had lower liver copper concentrations than Beagles, but mixed breeds did not differ from Beagles or Labrador Retrievers. Analysis of year of death showed that liver copper concentrations decreased from 2006 through 2011, increased in 2012, decreased in 2013, and peaked in 2016, decreasing thereafter. Mean copper concentration of abnormal liver histopathology samples was lower than mean copper concentrations of normal liver histopathology samples. Age (12.9 ± 2.6 years) and sex had no effect on liver copper concentrations. Of note, some samples showed abnormal hepatic pathology. CLINICAL RELEVANCE: Liver copper concentrations varied significantly with breed and year of death; however, average liver copper concentrations of each year were within normal. However, this was a retrospective population study and diet histories of the dogs were unknown, requiring further investigation.

Acute renal failure and hepatopathy consequent upon ingestion of cooked gallbladder of Indian carp: A case report.

Among freshwater fishes, the Indian Carp (Labeo rohita, "ROHU") is one of the most chosen species for Indian diets, but reports of toxicity are rare. This report is of a middle-aged healthy female who developed pain in the abdomen, vomiting, and diarrhea within hours of ingestion of a cooked portion of Indian carp's intestines and gallbladder. There was an inadvertent delay in diagnosis over 1 week due to the rarity of incidence and non-availability of a definite diagnostic indicator coupled with the lack of awareness and high index of suspicion. However, the patient could finally be diagnosed and treated appropriately after roving around many hospitals and then had life-threatening complications such as acute renal failure and hepatopathy, requiring repeated hemodialysis and supportive treatment before being fit for discharge. In this report, a detailed discussion of the clinical course and toxicological aspects are enumerated with a cautious note to spread awareness to facilitate prompt diagnosis.

Cannabidiol may prevent the development of congestive hepatopathy secondary to right ventricular hypertrophy associated with pulmonary hypertension in rats.

BACKGROUND: Pulmonary hypertension (PH) can cause right ventricular (RV) failure and subsequent cardiohepatic syndrome referred to as congestive hepatopathy (CH). Passive blood stasis in the liver can affect inflammation, fibrosis, and ultimately cirrhosis. Cannabidiol (CBD) has many beneficial properties including anti-inflammatory and reduces RV systolic pressure and RV hypertrophy in monocrotaline (MCT)-induced PH in rats. Thus, it suggests that CBD may have the potential to limit CH development secondary to RV failure. The present study aimed to determine whether chronic administration of CBD can inhibit the CH secondary to RV hypertrophy associated with MCT-induced PH. METHODS: The experiments involved rats with and without MCT-induced PH. CBD (10 mg/kg) or its vehicle was administered once daily for 3 weeks after MCT injection (60 mg/kg). RESULTS: Monocrotaline administration increased the liver/body weight ratio. In histology examinations, we observed necrosis and vacuolar degeneration of hepatocytes as well as sinusoidal congestion. In biochemical studies, we observed increased levels of nuclear factor-κappa B (NF-κB), tumour necrosis factor-alpha (TNA-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6). CBD administration to PH rats reduced the liver/body weight ratio, improved the architecture of the liver, and inhibited the formation of necrosis. Cannabidiol also decreased the level of NF-κB, TNF-α, IL-1ß and IL-6. CONCLUSIONS: The studies show that CBD can protect the liver from CH probably through attenuating PH, protective effects on the RV, and possibly direct anti-inflammatory effects on liver tissue through regulation of the NF-κB pathway.

Acute sickle cell hepatopathy: A case report and literature review.

Sickle cell disease (SCD) is an inherited hemoglobinopathy with protean clinical manifestations. The liver could be affected by various SCD-associated complications of an overlapping nature. The clinical presentations of "sickle cell hepatopathy" range from clinically asymptomatic patients to those with life-threatening complications. Herein we report an SCD patient who presented with right upper quadrant abdominal pain and jaundice, eventually diagnosed as a self-limited form of acute sickle cell hepatopathy with overlapping features of acute hepatic crisis and benign intrahepatic cholestasis. Using this patient as an illustration, we will review the spectrum of hepatobiliary presentations in the SCD population.

IgA-Dominant Staphylococcus-Associated Glomerulonephritis: An Uncommon Complication of Intravenous Drug Use.

A 24-year-old female with a history of intravenous heroin use presented with two weeks of chills, myalgias, and cough and was found to be in acute hypoxemic respiratory failure. Subsequent workup revealed the presence of bilateral septic pulmonary emboli and tricuspid valve endocarditis. Several weeks into her hospitalization, she developed periorbital edema and laboratory testing revealed she had developed acute renal failure and nephrotic range proteinuria. A renal biopsy confirmed the diagnosis of IgA-dominant Staphylococcus-associated glomerulonephritis (IgA-SAGN). Early recognition of this newly recognized variant of glomerulonephritis is paramount, as improper treatment may lead to catastrophic consequences.

Hepatopathy in Scrub Typhus: Clinical Presentation, Association With Morbidity and Impact on Outcome.

INTRODUCTION: Acute liver injury accompanies tropical fevers like scrub typhus. This study was undertaken to evaluate liver injury in scrub typhus and its association with the disease severity. METHODS: This was a single-centre prospective, observational study on in-patients of scrub typhus from north India. All patients were categorized on basis of elevation of transaminases as having normal or abnormal liver function. Those with hepatopathy were sub-categorized as having mild, moderate, severe or very severe liver injury. RESULTS: Liver dysfunction was present in 76/109 of the patients and was significantly associated with eschar, clinically discernible hepatomegaly and splenomegaly. Shock, renal and respiratory insufficiency, need for intensive care and oxygen supplementation were also significantly associated with hepatopathy. Duration of hospitalization and mortality were comparable in patients with/without liver injury; however delayed defervescence (6.2+3.8 vs. 4.5+2.5 days; p=0.025) was observed with hepatopathy. Icterus (p=0.001), hepatomegaly (p=0.015), thrombocytopenia (p<0.001) and raised erythrocyte sedimentation rate (ESR) (p=0.003) were significantly observed with increasing grade of liver injury.  Conclusion: Liver dysfunction and its increased severity in scrub typhus did not translate into increased morbidity and/or poor outcomes.

Mimickers of immunoglobulin G4-related hepatobiliary disease on biopsy.

With the growing recognition of IgG4-related hepatobiliary disease, establishing a definitive diagnosis relies mainly on a combination of clinical findings, serological markers, and imaging modalities. However, the role of histopathological evaluation remains indispensable, particularly in cases necessitating differential diagnosis or malignancy exclusion. While diagnosing IgG4-related hepatobiliary disease through surgical resection specimens is often straightforward, pathologists encounter substantial challenges when evaluating biopsies. The increasing rarity of surgical interventions exacerbates this due to improved disease recognition and suspicion. Numerous confounding factors, including the absence of the characteristic histologic features, limited tissue sample size, biopsy artifacts, and the limited value of IgG4 counts, further complicate the diagnostic process. Additionally, many other disorders exhibit clinical and histological features that overlap with IgG4-related disease, intensifying the complexity of interpreting biopsy specimens. This article explores the clinical and histomorphologic features of IgG4-related hepatobiliary disease and its potential mimickers. It offers valuable insights for pathologists and clinicians when confronted with biopsy specimens from hepatobiliary organs.

Perioperative Characteristics and Outcomes of Fontan Versus Non-Fontan Patients Undergoing Combined Heart-Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Combined heart-liver transplantation (CHLT) is becoming increasingly frequent as a maturing population of patients with Fontan-palliated congenital heart disease develop advanced liver fibrosis or cirrhosis. The authors present their experience with CHLT for congenital and noncongenital indications, and identify characteristics associated with poor outcomes that may guide intervention in high-risk patients. DESIGN: This was a single-center retrospective cohort study. SETTING: This study was conducted at Vanderbilt University Medical Center in Nashville, Tennessee. PARTICIPANTS: The study included 16 consecutive adult recipients of CHLT at the authors' institution between April 2017 and February 2022. INTERVENTIONS: Eleven patients underwent transplantation for Fontan indications, and 5 were transplanted for non-Fontan indications. MEASUREMENTS AND MAIN RESULTS: Compared with non-Fontan patients, Fontan recipients had longer cardiopulmonary bypass duration (199 v 119 minutes, p =m0.002), operative times (786 v 599 minutes, p = 0.01), and larger blood product transfusions (15.4 v 6.3 L, p = 0.18). Six of 16 patients required extracorporeal membrane oxygenation (ECMO), of whom 4 were Fontan patients who subsequently died. Patients who required ECMO had lower 5-hour lactate clearance (0.0 v 3.5 mmol/L, p = 0.001), higher number of vasoactive infusions, lower pulmonary artery pulsatility indices (0.58 v 1.77, p = 0.03), and higher peak inspiratory pressures (28.0 v 18.5 mmHg, p = 0.01) after liver reperfusion. CONCLUSIONS: Combined heart-liver transplantation in patients with Fontan-associated end-organ disease is particularly challenging and associated with higher recipient morbidity compared with non-Fontan-related CHLT. Early hemodynamic intervention for signs of ventricular dysfunction may improve outcomes in this growing high-risk population.