Background: Vitamin D, through its role in antimicrobial peptide (AMP) expression, may influence innate immunity and inflammation in urinary tract infections (UTIs). This study evaluated its role in patients with vesicoureteral reflux (VUR) and its contribution to the pathophysiology of reflux nephropathy (RN). Methods: We conducted a cross-sectional observational study of 25 pediatric patients with VUR, representing a subgroup analysis of a larger cohort examined in a previous study. We determined patients' vitamin D status, correlated it with recurrent UTIs and RS, and explored its relationship with urinary LL-37, NGAL, and IL-6 levels as markers of innate immune function. Results: Serum vitamin D levels ranged from 10.7 to 123.2 ng/mL (mean 39.5 ng/mL); 12% had deficiency and 20% had insufficient levels. Low vitamin D levels were detected in patients with more than five acute pyelonephritis (APNs), with a mean value classified as insufficient (27.3 ng/mL). Patients with RS had a lower mean vitamin D level compared to those without (30.51 ng/mL vs. 41.23 ng/mL), though the difference was not statistically significant (p = 0.39). No significant associations were found between vitamin D and urinary IL-6 or NGAL levels. A strong positive correlation was observed between vitamin D and urinary LL-37/creatinine (r = 0.78, r2 = 0.61). Conclusions: Vitamin D appears to influence the frequency of UTIs and the development of RS, primarily by modulating LL-37 secretion, suggesting a possible role in the pathophysiology of RN.

Background/Objectives: Pediatric acute pancreatitis (AP) is increasingly recognized as a clinically significant disease, yet Central and Eastern European cohort data remain limited. Acute recurrent pancreatitis (ARP) affects a substantial proportion of these children and may reflect distinct underlying etiologies. This study aimed to characterize the etiological spectrum, disease severity, and hospitalization outcomes of AP and ARP in a pediatric tertiary referral population, and to identify early clinical predictors of severity. Methods: We retrospectively analyzed 63 children hospitalized between 2018 and 2025 with 77 documented episodes of AP. Diagnosis followed INSPPIRE criteria, and severity was graded using the 2017 NASPGHAN classification. Etiologies, clinical presentation, laboratory parameters, imaging findings, and hospitalization length were compared between AP and ARP groups, across severity and etiological complexity categories using appropriate non-parametric and permutation-based methods. Results: Genetic etiologies predominated in ARP (37.0%), whereas idiopathic and infectious causes were more common in first-episode AP (24.0% and 14.0%, respectively; overall p < 0.001). Severity distribution did not differ between AP and ARP, with mild disease accounting for the majority of episodes in both groups. Serum albumin was significantly lower in moderate/severe episodes (p = 0.030). Within the single-episode subgroup, etiological complexity emerged as a significant predictor of prolonged hospitalization, with complex multifactorial or systemic etiologies associated with markedly longer stays than idiopathic or single-factor disease (Welch ANOVA p = 0.007). Conclusions: In this Romanian pediatric cohort, genetic causes dominate ARP, while idiopathic and infectious etiologies characterize first-episode AP, supporting a stepwise approach in which comprehensive etiological work-up, including genetic testing, is prioritized after recurrence. The predominance of genetic causes in ARP should be interpreted with caution, as genetic testing was applied selectively, predominantly after recurrence. Recurrence status alone does not predict severity, whereas etiological complexity at first presentation and hypoalbuminemia represent practical, accessible early markers for clinically assessing more severe disease.

Autoimmune hepatitis (AIH) is a progressive inflammatory liver disease characterized by hypergammaglobulinemia, circulating antibodies, and distinctive histological features, with a higher prevalence in females. Immune responses targeting hepatic antigens are considered the main mechanism behind AIH. Many cytokines are involved in the inflammatory response typical of this disease. Interleukin 17 (IL-17) is a powerful pro-inflammatory protein that serves as a key link between the innate and adaptive immune systems. It plays an important role in regulating the inflammatory response in various tissues, including the liver. Several studies have shown that increased IL-17 levels are associated with the severity and progression of AIH. This review explores IL-17’s role in the AIH inflammatory pathway and summarizes existing evidence linking it to liver damage. We also highlight the potential of future therapies targeting this cytokine.

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support.

Cholestasis in children is characterized by impaired bile flow that disrupts hepatic metabolism, nutrient homeostasis, and effects trace element balance. This narrative review summarizes current evidence on the metabolism, biological functions, and clinical implications of key trace elements-zinc, selenium, copper, and manganese-in pediatric cholestatic liver disease. The liver regulates trace element absorption, intracellular trafficking, storage, and biliary excretion; cholestasis alters these processes, leading to deficiencies or toxic accumulation. Zinc and selenium deficiencies are common and contribute to impaired growth, immune dysfunction, oxidative stress, and delayed hepatic regeneration. Conversely, reduced biliary excretion promotes copper and manganese accumulation, potentially exacerbating liver injury and causing manganese-related neurotoxicity. Recent advances in understanding metal-specific hepatic transporters and trafficking pathways have provided mechanistic insight into these alterations. Management strategies emphasize individualized supplementation, monitoring during enteral and parenteral nutrition, and prevention of deficiency and toxicity. Precision-based nutritional approaches may improve outcomes in pediatric cholestatic liver disease.

Background: Chronic liver disease (CLD) in children requires long-term monitoring. Liver biopsy and transient elastography (TE) are resource-intensive methods that require specialized equipment and trained personnel. Simple indirect fibrosis scores based on routine laboratory parameters offer a potentially cost-effective alternative but have not been systematically evaluated in pediatric populations with diverse CLD etiologies. Objectives: This study aimed to assess the performance of several indirect fibrosis and cirrhosis scores in predicting significant (≥F2) and advanced (≥F3) fibrosis and cirrhosis (F4) in children with CLD using TE as a comparator. Methods: We retrospectively reviewed medical records of children with CLD evaluated at a tertiary center between January 2023 and June 2025. TE results and routine laboratory data were used to calculate fibrosis scores, including APRI, FIB-4, FibroIndex, FORNS, GPR, GUCI, King’s score, and Lok’s index. ROC analyses were performed to assess each score’s ability to discriminate significant fibrosis, advanced fibrosis and cirrhosis. Optimal cut-offs were established using the Youden index. Results: GPR showed the strongest concordance with TE-based fibrosis classification across both fibrosis thresholds, achieving an AUROC of 0.835 for significant fibrosis and a superior 0.917 for advanced fibrosis. FibroIndex and APRI also demonstrated good discriminatory power for advanced disease. Utilizing mathematically optimized cut-offs, GPR (0.45) and APRI (0.84) achieved good negative predictive values (100% and 95%) and sensitivities (100% and 85%) for advanced fibrosis, establishing them as potentially valuable screening tools. For cirrhosis detection (F4), Lok’s Index performed best (AUROC 0.854). Conclusions: In this diverse pediatric cohort, simple indirect scores—particularly GPR, APRI, and FibroIndex—demonstrated the highest concordance relative to TE findings, with negative predictive values up to 100% for GPR. This indicates that they can serve as reliable first-line screening tools when TE is unavailable. While their good negative predictive values allow for the confident exclusion of severe disease—potentially sparing many children from invasive testing—their low positive predictive values limit their role in definitive diagnosis. The systematic failure of adult-derived, age-dependent formulas in this cohort underscores the critical need for specialized pediatric biomarkers.

Drug-induced liver injury (DILI) remains one of the most challenging adverse drug reactions in clinical practice, particularly in its idiosyncratic form, which is not dose-dependent and is largely driven by host-specific immune and genetic factors. Recent genomic studies have revealed strong associations between certain human leukocyte antigen (HLA) alleles and susceptibility to DILI, supporting an immunogenetic mechanism in which drug or metabolite-protein adducts act as neoantigens, triggering aberrant T-cell activation and hepatocellular injury. This review summarizes current evidence on the contribution of HLA polymorphisms to the pathogenesis of idiosyncratic DILI, highlighting allele-specific risk patterns, such as HLA-B*57:01 associated with flucloxacillin, HLA-DRB1*15:01-DQB1*06:02 in amoxicillin-clavulanate, and HLA-B*35:02 in minocycline-induced liver injury. Furthermore, ethnic variability and allele-haplotype interactions are discussed as potential modulators of susceptibility and clinical phenotype. By integrating genetic and immunological insights, the identification of HLA signatures offers promising tools for precision medicine, enabling earlier identification of at-risk individuals and improved prevention of severe hepatotoxic reactions.

Background & Aims: Accurate assessment of liver fibrosis is important for the management of pediatric chronic liver disease (CLD). Transient Elastography (TE) has emerged as a validated non-invasive method for accurately assessing hepatic fibrosis, yet it remains available only in specialized centers and requires specialized equipment. We aimed to develop and internally validate a novel, simple, blood-based scoring system—the pediatric-adapted liver score (PAL score)—to predict advanced fibrosis as defined by liver stiffness, measured using TE across diverse etiologies. Methods: A retrospective study was conducted on 107 pediatric patients with CLD who underwent liver stiffness measurement through TE. Advanced fibrosis was defined as a liver stiffness measurement corresponding to the F3 METAVIR stage or above. Independent predictors of advanced fibrosis were identified using multivariable logistic regression with manual backward elimination. To facilitate bedside utility, the regression model was simplified into a ratio-based index. Performance was assessed via the area under the receiver operating characteristic curve (AUROC) and validated using bootstrap resampling (10,000 iterations). Results: Gamma-glutamyl transferase (GGT), platelets, and albumin were identified as independent predictors of fibrosis. The simplified PAL score demonstrated good discrimination with an AUROC of 0.901 (95% CI: 0.84–0.95). While statistically equivalent to the adult-derived GGT-to-platelet ratio (GPR) and S-Index, the PAL score incorporates parameters of hepatic synthesis and portal hypertension that are absent from other ratios and is easier to calculate at the patient’s bedside. At a clinically practical integer cut-off of 5.0, the score achieved a sensitivity of 95.5% and a negative likelihood ratio of 0.06, effectively ruling out advanced fibrosis. Bootstrap validation confirmed the stability of the model (bootstrap-corrected AUC 0.901). Conclusions: The PAL score is the first simple fibrosis index derived for a diverse pediatric population. Highlighting its primary strength as a highly effective screening tool, the score achieves a sensitivity of 95.5% and a negative likelihood ratio of 0.06 at a user-friendly cut-off of 5. These robust metrics allow clinicians to confidently rule out advanced fibrosis, offering an accessible triage alternative in primary care settings where transient elastography is unavailable.

Biliary atresia (BA) is the leading indication for pediatric liver transplantation. In the absence of surgical treatment, BA progresses rapidly toward hepatic fibrosis and cirrhosis. Although liver biopsy remains the gold standard for histological evaluation, its utility is limited by invasiveness, associated risks, and sampling variability. These limitations have spurred the development and validation of noninvasive tools to evaluate liver fibrosis in this patient population. Multiple imaging techniques have been developed to assess liver fibrosis and cirrhosis. In recent years, additional BA-related biomarkers have been identified, showing significant potential for diagnosis, assessment of fibrosis severity, and prediction of native liver survival outcomes. This article reviews the roles and potential clinical applications of the following biomarkers: matrix metalloproteinase-7 (MMP-7), fibroblast growth factor 19 (FGF-19), interleukin-33 (IL-33), clusterin, and osteopontin. Further research is needed to confirm the utility of these prognostic biomarkers in predicting and improving outcomes in BA.

Background: Hemangiomatosis is a rare condition characterized by the presence of multiple benign vascular tumors that may affect various organs, including the skin, liver, and spleen. Complications are closely linked to the location and size of the lesions. Case Presentation: We describe a rare presentation of infantile hemangiomatosis with widespread cutaneous and oral mucosal lesions, further complicated by splenic and hepatic involvement and secondary cholestasis. The initial progression was unfavorable, with an increase in both the number and size of the lesions. Cardiologic evaluation identified minor valvular insufficiencies, but no secondary cardiac failure. Treatment with propranolol and prednisone was initiated, with a slow favorable evolution. There were no new hemangiomas developed, and those on the face and limbs decreased in size, some disappearing entirely. Hepatic and splenic hemangiomas regressed more slowly, but their reduction and the improvement of cholestasis were progressive. Due to significant iatrogenic Cushing’s syndrome, prednisone was gradually tapered. Transient subclinical hypothyroidism occurred during treatment, resolving spontaneously. Conclusions: The present case illustrates the rarity and complexity of multifocal infantile haemangiomatosis and highlights the importance of early diagnosis, comprehensive organ evaluation, and tailored multidisciplinary management. It clearly demonstrates that prompt intervention and careful therapy adjustment can lead to favorable outcomes even in the setting of extensive visceral involvement.

Background: Biliary atresia (BA) is a rare, immune-mediated cholangiopathy in children and a leading cause of neonatal cholestasis and pediatric liver transplantation (LT). Gamma-glutamyl transpeptidase (GGT) is commonly elevated in BA and is used as a diagnostic marker; however, recent studies have suggested that a subset of BA patients present with normal or low GGT levels, potentially indicating a more severe disease course. Methods: This retrospective study evaluated the prognostic value of serum GGT levels in 47 children diagnosed with BA at a single center over 15 years. Patients were stratified by GGT levels at diagnosis, and outcomes were compared, including survival with native liver, need for LT, and mortality. GGT thresholds of 200 U/L and 300 U/L were used to define normal and elevated levels. Results: The study found that 12% of patients had normal or low GGT at diagnosis. Still, there were no statistically significant differences in age at diagnosis, severity of liver fibrosis, age at Kasai portoenterostomy (KPE), or overall outcomes between low and high GGT groups. Although patients with lower GGT tended to require LT at a younger age, this difference was not significant. Receiver operating characteristic (ROC) curve analysis showed that GGT levels at diagnosis, before, and after KPE were not reliable predictors of outcome. Conclusions: The findings contrast with some previous reports suggesting that low GGT is associated with a worse prognosis. Low GGT level alone should not delay diagnosis or surgical intervention in suspected BA. Early referral for KPE remains critical, and patients with low GGT may benefit from earlier LT evaluation. Larger, multicenter studies are needed to clarify the prognostic role of GGT in BA.

Acute pancreatitis (AP) is an acute-onset gastrointestinal disease characterized by a significant inflammation of the pancreas. Most of the time, AP does not leave substantial changes in the pancreas after the resolution of the symptoms but the severe forms are associated with local or systemic complications. The pathogenesis of AP has long been investigated and, lately, the importance of intracellular mechanisms and the immune system has been described. The initial modifications in AP take place in the acinar cell. There are multiple mechanisms by which cellular homeostasis is impaired, one of the most important being calcium overload. Necrotic pancreatic cells initiate the inflammatory response by secreting inflammatory mediators and attracting immune cells. From this point on, the inflammation is sustained by the involvement of innate and adaptive immune systems. Multiple studies have demonstrated the importance of the first 48 h for identifying patients at risk for developing severe forms. For this reason, there is a need to find new, easy-to-use and reliable markers for accurate predictions of these forms. This review provides an overview of the main pathogenetic mechanisms involved in AP development and the most promising biomarkers for severity stratification.

Acute pancreatitis (AP) is a significant cause of morbidity, even in children, and is frequently associated with systemic manifestations. There are many cytokines involved in the inflammatory response characteristic of this disease. Interleukin 6 (IL-6) is one of the most important cytokines involved in AP, beginning from cellular injury and continuing to the systemic inflammatory response and distant organ involvement. IL-6 is a multifunctional cytokine that regulates acute-phase response and inflammation. It is produced by various cells and exerts its biological role on many cells through its high-affinity complex receptor. IL-6 has been investigated as a predicting maker for severe forms of AP. Many studies have validated the use of IL-6 serum levels in the first 48 h as a reliable marker for severe evolution and multisystemic involvement. Still, it has not been used in daily practice until now. This review discusses the main binding mechanisms by which IL-6 triggers cellular response and the AP pathogenetic mechanisms in which IL-6 is involved. We then emphasize the promising role of IL-6 as a prognostic marker, which could be added as a routine marker at admission in children with AP.

Introduction: Deoxyguanosine Kinase (DGUOK) deficiency is a very rare disorder characterized by liver dysfunction, neurological manifestations, and metabolic disorders secondary to severely reduced mitochondrial DNA content. These patients develop early-onset liver failure, and their liver transplantation (LT) indication remains debatable due to the possibility of neurological involvement. Case Report: We present the case of a 6-month-old female diagnosed with DGUOK deficiency who developed liver failure. At 9 months, she underwent a living-related LT with an initial favorable evolution under immunosuppression therapy with tacrolimus. Four months after LT, she presented two prolonged bacterial and Rotavirus enteritis episodes. She developed classical post-transplant complications (severe renal tubular acidosis type IV, secondary to the high tacrolimus level, and post-transplant lymphoproliferative disease) during these episodes. Her condition deteriorated progressively, with reversible hypotonia and significant weight loss. However, the neurological evaluation did not reveal any signs suggestive of the progression of the underlying disease. A few months later, her clinical features and laboratory parameters improved considerably. Conclusions: This case highlights the unpredictable evolution of children with LT for liver failure due to DGUOK deficiency.

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution.

Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.

Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). Individuals affected by this disorder have severe hyperglycemia, pancreatic failure, and bone abnormalities and are prone to severe and life-threatening episodes of liver failure. This report illustrates the case of a 2-month-old infant with extreme hyperglycemia and severe diabetic ketoacidosis. Acute management was focused on correcting severe acidosis. Further management aimed to obtain stable blood glucose levels, balancing the patient's need for comfort and lack of distress with the clinicians' need for adequate information regarding the patient's glycemic control. Genetic testing of the patient and his parents confirmed the diagnosis. The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to.

Acute pancreatitis (AP) is an acute inflammatory disease that must be taken into consideration in the differential diagnosis of abdominal pain in children, due to its unpredictable and in some cases severe evolution with systemic complications. The diagnosis is based on the clinical manifestations, laboratory tests and imaging modifications in children and adults, but the symptoms, evolution and prognosis often differ. In recent years, there has been an increasing interest in the identification of etiological factors associated with AP in children, given that they are different from those from the adult population. The main risk factors identified in acute pancreatitis in children are biliary tract pathology, pancreatic malformations, infections, systemic and metabolic diseases, drugs, traumatisms, genetic predisposition, and idiopathic. In an important percentage of children, more than one risk factor is present. The identification of the etiological factors is important for a complete diagnosis but also for the follow-up and management of these patients, given the fact that some of the risk factors are associated with increased severity and others with recurrences and even evolution to chronic pancreatitis. Although important progress has been made recently, more data on children are needed for a better understanding and management of acute pancreatitis.

Secondary biliary cirrhosis represents a particular form of cirrhosis developed secondary to repeated inflammation produced by the obstruction (partial or total) or narrowing of the extrahepatic bile ducts, leading to periportal fibrosis. Biliary cysts are cystic dilations involving the biliary tree at single or multiple segments of the extrahepatic and intrahepatic bile ducts. Although the curative treat­ment is represented by surgery, patients require a long-term follow-up, because there is a permanent risk of de­velop­ing cholangitis and, in time, even malignancies. We re­port the case of a 13-year-old patient with a history of choledochal cyst operated on at the age of 3 years old and with multiple obstructive gallstones operated on two months before presenting to our service for full as­ses­sment and the establishment of supportive treatment. In ad­di­tion, the histopathological examination after surgery re­vealed histopathological liver changes suggestive of chro­nic cholestatic hepatitis with pre-cirrhotic features. The laboratory findings revealed elevated transaminase levels, cholestasis and hyperbilirubinemia, with negative an­ti­bodies for Ebstein-Barr virus, cytomegalovirus, he­pa­ti­tis C and hepatitis B viruses. Ultrasound examination re­vealed a liver with a micronodular structure, and the tran­sient elastography revealed a rigidity equivalent to stage F4 (METAVIR). We initiated supportive treatment with antibiotics, choleretics and vitamins, with nutritional sup­port and monthly evaluations. The evolution has been pro­gres­sively favorable, with transaminase levels almost in the normal range and cholestasis gradually reducing, with a spectacular return of the weight curve.

Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels.