Hepatology Forum最新文献

Background and aim: Although there are a few studies reporting transplantation for celiac disease (CD), there are no studies reporting long-term outcomes after transplantation in CD patients. Therefore, we aimed to report the long-term outcomes of patients who underwent liver transplantation (LT) for CD in our high-volume liver transplantation center.

Materials and methods: Our study was a single-center, retrospective study and included 28 CD patients who underwent LT at Inonu University. CD diagnosis was made based on anti-tissue transglutaminase or anti-endomysium antibody positivity and/or duodenal biopsy results.

Results: The 1-, 3-, 5-, and 10-year survival rates after transplantation were 92.9%, 92.9%, 84.4%, and 75%, respectively. The most striking finding in the study was the high frequency of biliary complications. Another important finding was the significant difference in body mass index (BMI) between pre-transplant and post-transplant (p<0.001). The incidence of rejection and recurrence was 39.1% and 25%, respectively. The number of patients with high anti-tissue transglutaminase (anti-TTG) levels after transplantation decreased significantly (p<0.001).

Conclusion: Our study suggests that the frequency of post-transplant biliary complications is very high in CD patients and that LT had positive effects on BMI and anti-tissue transglutaminase levels.

Background and aim: Pneumocystis jirovecii (PJ) can be seen in solid organ transplant (SOT) recipients. Despite guidelines recommending PJP prophylaxis for 6-12 months post-transplantation, the necessity for liver transplant patients remains controversial, with conflicting evidence on PJP rates. This study examined PJP occurrence in 242 liver transplant patients at a single center who received no PJP prophylaxis.

Materials and methods: A retrospective study examined the clinical and microbiological data of 242 liver transplant (LTx) patients to evaluate PJP incidence within one year post-transplant. PJP was diagnosed microbiologically and/or radiologically in cases of clinical suspicion, without systematic screening. The study investigated PJP infection risk factors reported previously, including cytomegalovirus (CMV) infection, bolus steroid therapy, age >65, prolonged neutropenia, and anti-thymocyte globulin (ATG) usage.

Results: The study involved 242 liver transplant recipients, with an average age of 56 years, predominantly male (71%), and a mean Model for End-Stage Liver Disease (MELD) score of 16. No PJP cases were reported. Among PJP risk factors, none had prolonged neutropenia, though two developed CMV infection. Empirical steroid bolus treatment for suspected acute cellular rejection was given to 62 patients (26%). The cohort included 22 (9%) individuals over 65 years old, and none received ATG.

Conclusion: This pioneering study examines a substantial living liver donor transplantation (LDLT) cohort without PJP prophylaxis, suggesting it may be unnecessary in centers with low immunosuppression and a low percentage of risk factors. Prospective studies are essential to establish targeted prophylactic approaches due to variations in PJP incidence across centers.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a public health problem, given its increasing incidence worldwide and strong association with metabolic syndrome components such as obesity, insulin resistance, and systemic inflammation. Recent studies have shown the relevance of microRNAs (miRNAs) as potential biomarkers and therapeutic targets in MASLD. This bibliometric review aimed to evaluate the scientific production of the last decade on miRNAs involved in the pathophysiology and diagnosis of MASLD. A total of 775 articles were initially retrieved from the PubMed database, with 51 meeting the inclusion criteria after a systematic screening process. Bibliometric analysis showed that China and the United States had the highest number of publications, with studies published mainly by the International Journal of Molecular Sciences and Hepatology. Among the most studied miRNAs were miR-122, miR-29a, miR-34a, and miR-223, which participate in lipid metabolism, inflammation, fibrosis, and insulin sensitivity. Co-authorship network analysis identified Gao Bin as the most influential author in the field. Keyword co-occurrence analysis showed growing interest in miRNAs in general, miR-29a, miR-34a, miR-122, miR-223, nonalcoholic fatty liver disease, lipogenesis, and mitochondrial stress in recent years. This review emphasizes the increasing scientific attention on miRNAs involved in MASLD and highlights their diagnostic and therapeutic potential. However, further studies are still needed for the identification and clinical validation of therapeutic targets that modulate miRNAs. Future perspectives include the integration of omics approaches and the exploration of nutritional or pharmacological strategies for miRNA modulation.

Hepatotoxicity represents one of the significant and challenging health concerns at the worldwide level. To overcome this condition, essential oil can act as a natural therapeutic in alleviating hepatic disorders caused by toxins, drugs, alcohol, or infections. Various aromatic plants such as Citrus species, Allium species, spices, and rosemary species contain bioactive compounds-mainly terpenes, phenolics, flavonoids, and sulfur-containing compounds. These bioactive compounds possess excellent antioxidant potential to neutralize free radicals and promote the endogenous antioxidant defense system, such as SOD, catalase, Gpx, and others as well. In addition to this, they exhibit anti-inflammatory potential to regulate inflammatory cascades and cytokine levels, while their detoxification mechanism stimulates the liver's capacity to eradicate harmful substances. Although previous research has documented that essential oil exhibits the ability to protect the liver from chronic diseases-mainly fibrosis, non-alcoholic fatty liver disease (NAFLD), and drug-induced hepatotoxicity-by modulating lipid metabolism, hepatocyte integrity, the antioxidant defense system, and pathological factors, future research is still required to evaluate its efficacy, bioavailability, safe doses, and explore synergistic formulations. Keeping these perspectives in mind, the current review is planned to highlight the hepatoprotective properties of essential oils, their underlying mechanisms, and their prospective contribution to the development of natural therapeutics for liver health.

Background and aim: Metabolic-dysfunction-associated steatotic liver disease and its related mortality are increasing worldwide. This study evaluated the potential of rifaximin in preventing and treating steatohepatitis induced by a high-fructose diet by modulating intestinal pathology.

Materials and methods: Forty-two rats were randomly divided into six groups: one group received a normal diet, another was fed a fructose diet, two groups received rifaximin (once or three times weekly) along with a fructose diet, and the remaining two groups were given rifaximin (once or three times weekly) with a normal diet. After eight weeks, liver tissues were examined for malondialdehyde, tumor necrosis factor-α, nuclear factor-κB, and nuclear factor erythroid 2-related factor 2 using Western blot analysis, while blood samples were analyzed for uric acid, liver enzymes, triglycerides, and cholesterol; plasma tumor necrosis factor-α was measured by ELISA.

Results: The fructose diet group showed significant increases in body and liver weights, ballooning degeneration, lobular inflammation, and macrovesicular steatosis. Metabolic dysfunction-associated steatotic liver disease developed in 21 rats, yet steatohepatitis was observed only in the fructose-only group. Biochemical markers, including liver enzymes, triglycerides, and cholesterol, were significantly elevated in the fructose group. Moreover, plasma and tissue tumor necrosis factor-α and nuclear factor-κB levels were higher in the fructose group (p=0.03), while Nrf-2 levels were elevated in the rifaximin-treated groups (p=0.043). Additionally, MDA levels were markedly increased in the fructose-only group (p=0.033) and decreased dose-dependently with rifaximin treatment (p=0.029).

Conclusion: These findings suggest that rifaximin's anti-inflammatory and antioxidant effects may alleviate fructose-induced steatohepatitis, although further clinical studies are warranted.

Hepatitis C virus (HCV) infection can cause various manifestations, including rare biliary complications. This case details a 44-year-old Thai woman with severe biliary pain but normal blood counts, liver function, and amylase levels. Abdominal MRI, MRCP, and endoscopic ultrasound ruled out mechanical obstruction but revealed diffuse thickening of the intrahepatic and common hepatic bile duct walls, and soft tissue thickening surrounding the left portal vein branch, suggestive of an inflammatory process. Further investigation confirmed positive HCV RNA. Serology revealed low complement levels, suggesting immune-mediated inflammation, though ANA, ANCA, and cryoglobulin were negative. Serum IgG4 levels were also normal. This led to a diagnosis of small vessel vasculitis of the biliary tract secondary to chronic HCV infection. Treatment with antiviral therapy and a short course of prednisolone resulted in significant symptom improvement. This case underscores the need for increased awareness of biliary complications associated with chronic HCV infection.

Liver re-transplantations (re-LTx) have been documented as high-risk operations considering technical and immunological challenges. However, improvements over the last two decades have increased success rates, bringing them closer to those of primary liver transplantations (LTx). At present, deceased organ shortage is a critical issue, and even potential live donors may not be suitable regarding vascular and biliary challenges, volume discrepancies, and ABO incompatibility for both primary and re-LTx. The hospital records of a patient who underwent two liver transplantations in our institution were evaluated retrospectively. A twelve-year-old girl with Progressive Familial Intrahepatic Cholestasis Type 3 underwent live-donor LTx with a graft from her mother. The patient required emergency re-LTx due to primary non-function of the graft, and there were no suitable deceased or live donors during that critical period. The patient was introduced to the liver paired exchange system and underwent a lifesaving re-LTx from an altruistic paired exchange donor. As a developing strategy, liver paired exchange transplantation is a reasonable solution to achieve the most suitable liver graft when it is most needed, especially in populations with very low deceased organ donation rates. There is a need for large studies to analyze the role and success of liver paired exchange transplantation in pediatric patients in urgent and elective situations.

Rhabdomyosarcoma (RMS) comprises approximately 5% of all pediatric malignancies, and the biliary system is considered one of the rarest RMS locations. Awareness, knowledge, and early recognition of the disease are essential for accurate diagnosis and proper treatment of biliary RMS in a child with obstructive jaundice and suspicious radiological findings. We present two pediatric biliary RMS cases requiring different managements because of their primary evaluations at their referring facilities. A four-and-a-half-year-old boy was referred to our institution for liver transplantation following neoadjuvant chemotherapy for centrally located unresectable biliary RMS. The patient received a left lateral segment graft from a living donor with no complications during the post-transplant period. The second patient was a seven-year-old foreign boy with obstructive jaundice and a history of choledochal cyst resection. A tumoral mass was revealed during exploration, and macroscopic total resection of the lesion was performed. The final pathology result of the resected material was biliary RMS with microscopic residue on the bile duct margin and lymph node involvement. The patient was transferred to the Pediatric Oncology Division for systemic treatment following surgical recovery. Biliary RMS presents distinct challenges in terms of accurate diagnosis and successful management. A multidisciplinary approach is indispensable for effective treatment. Complete surgical resection has been proven to be the mainstay strategy in feasible cases. Contributions of pre- and postoperative chemotherapy and radiotherapy are crucial in extensive disease. Liver transplantation should be considered, with reasonable success rates, in persistent unresectable and non-metastatic cases.

Wilson's disease (WD) is a genetic disease of autosomal recessive inheritance resulting in the mutation of the adenosine triphosphate 7B (ATP7B) gene. The estimated prevalence of WD is one in 30,000 to 100,000, with a wide age of presentation between 3 to 55 years. Initial manifestations of WD are mainly neurologic, hepatic, or a combination of both. Proximal myopathy, however, is a rare presenting feature, with only a limited number of cases described in the literature. Presenting features such as rhabdomyolysis, hypokalemic muscle paralysis, and spasmodic contractions have been documented, but, as per our knowledge, only one case of proximal myopathy as the initial complaint has been reported. The underlying mechanism of this phenomenon in untreated cases remains unclear and warrants further investigation. We report the case of a 9-year-old female who presented with difficulty in walking, difficulty standing from a sitting position, and jaundice, subsequently diagnosed as WD with proximal myopathy.

Background and aim: Resmetirom received conditional Food and Drug Administration (FDA) approval in 2024 for metabolic dysfunction-associated steatotic liver disease (MASLD) based on its promising liver-targeted therapy. Clinical trials required a histological diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) with F2-F3 fibrosis, excluding cirrhosis, while real-world prescribing relies on non-invasive tests (NITs). This study evaluates their efficacy in identifying the target population within a biopsy-proven Turkish MASLD cohort.

Materials and methods: We analyzed 266 patients with biopsy-proven MASLD from the Turkish NAFLD Biobank. Inclusion required AST >17 U/L (females) or >20 U/L (males), and CAP ≥280 dB/m. Eligibility was defined by liver stiffness measurement (LSM) of 10-19.9 kPa (excluding cirrhosis or low platelet count) or a FAST score ≥0.67.

Results: Among the study population, 130 patients (48.9%) had histologically confirmed MASH with F2-F3 fibrosis. Based on LSM criteria applied to histologically eligible patients, 81 patients (62.3%) were underdiagnosed, compared to 95 patients (73.1%) when using the FAST score. Additionally, among patients who corresponded to NIT, 34 patients (41.0%) were overprescribed using LSM, while 23 patients (39.7%) were overprescribed using the FAST score. The kappa value as a measure of agreement showed poor compatibility for both LSM and FAST with liver biopsy (0.128 and 0.101, respectively). When treatment decisions were guided by either of the NITs, 44 patients (44.0%) received unnecessary prescriptions, and 74 patients (44.6%) had missed diagnoses.

Conclusion: The NITs defined for identifying the target population for resmetirom demonstrated poor performance in accurately detecting or excluding eligible patients. Therefore, performing a liver biopsy before starting resmetirom treatment will prevent unnecessary increases in cost and significantly reduce the economic burden of the treatment.

Keywords: Fibrosis; MASLD; MASH; non-invasive test; resmetirom.