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.

Background and aim: The present study aimed to determine the effect of hepatic steatosis, as detected by liver biopsy, on Hepatitis B surface antigen (HbsAg) seroclearance and disease progression in patients infected with hepatitis B virus (HBV).

Materials and methods: Patients with chronic HBV infection and chronic hepatitis B (CHB) from an existing cohort of HBV-infected patients were enrolled.

Results: This study included 296 patients: 186 with chronic HBV infection and 110 with CHB. Patients with chronic HBV infection were older (p=0.006), and exhibited a higher prevalence of wild-type mutants (p<0.001). At the baseline liver biopsy, 31% of the patients had hepatosteatosis. Thirty-two patients (11%) achieved HBsAg loss during the follow-up period; 72% had HBsAg seroconversion to anti-HBs. Multivariable Cox regression showed that the stage of HBV disease (chronic HBV infection vs. CHB) (Hazard ratio [HR]: 6.385, Confidence interval [CI]: 1.513-26.941, p=0.012) and grading of hepatosteatosis at baseline liver biopsy (HR: 4.699, CI: 1.662-13.286, p=0.004) were predictors of HBsAg seroclearance.

Conclusion: Hepatic steatosis was associated with a functional cure for chronic HBV infection; however, it also causes disease progression in HBV-infected patients.

Hepatocellular carcinoma (HCC) is one of the most common and deadly forms of liver cancer worldwide. Recent research suggests that the insulin-like growth factor (IGF) system, including insulin-like growth factor-1, insulin-like growth factor-2, and their receptors, may play a critical role in the pathogenesis and progression of HCC. However, the precise mechanisms through which IGFs contribute to HCC development remain unclear. The objective of this review is to explore the association between IGF signaling and HCC, with a focus on understanding the molecular pathways through which the IGF axis influences the pathophysiology of HCC. The review also examines the potential of utilizing the IGF pathway as a therapeutic target for HCC. IGF-1R overexpression, elevated IGF-2 levels, and decreased IGF-1 levels are seen in HCC and are linked to a poor prognosis. The IGF-1R signaling pathway leads to activation of PI3K/AKT/mTOR and RAS/RAF/MEK/ERK, which increases cell growth and proliferation and inhibits apoptosis, resulting in HCC. Also, in diabetic conditions, low levels of IGF-1 contribute to a higher risk of HCC due to hyperinsulinemia, chronic inflammation, and diseases like non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH).

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) encompass a group of rare autoimmune diseases characterized by granuloma formation and/or inflammation of small vessels. The clinical spectrum of AAV varies widely. Liver involvement is exceptional, posing diagnostic challenges. Moreover, AAV can co-exist with other systemic diseases, further complicating the diagnosis. We herein present a unique case of AAV overlapping with Sjögren's syndrome (SS) with an uncommon onset of the disease. A 47-year-old female was admitted for hiatal hernia surgery. During the intervention, nodular hepatomegaly was observed. A liver biopsy was performed, showing non-necrotizing epithelioid and central giant cell granulomas. Computed tomography (CT) scan showed perilymphatic pulmonary micronodules with bilateral hilar lymphadenopathies, raising the suspicion of sarcoidosis. Minor salivary gland biopsy revealed Chisholm grade 3 sialadenitis, which, along with the patient's dry eye and mouth symptoms, confirmed SS. Immunological workup showed negative antinuclear antibodies and positive anti-myeloperoxidase (MPO) antibodies. A year later, the patient presented with asthma flare-ups and ear, nose, and throat (ENT) symptoms. A nasal biopsy showed signs of eosinophilic leukocytoclastic vasculitis, confirming the diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA). Oral steroid therapy was initiated, which resulted in clinical improvement. We present a case highlighting that EGPA is a protean disease, possibly mimicking or co-occurring with other autoimmune disorders. Thus, it is important to consider the differential diagnoses and carefully monitor for any new symptom or organ dysfunction.

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.