Canadian liver journal最新文献

Background: Liver transplantation is a life-saving treatment for end-stage liver disease, significantly improving survival. In Canada, the number of liver transplants has increased, with British Columbia performing 107 transplants in 2023. One-year survival rates have risen from 74.8% in 1990 to 93.2% in 2021 due to advancements in surgical and immunosuppressive methods. However, long-term survival remains suboptimal, with malignancy, graft failure, and cardiovascular disease being key contributors to mortality. This study analyzed causes of mortality among liver transplant recipients in British Columbia to identify strategies for improving outcomes.

Methods: This retrospective study included 314 deceased liver transplant recipients (age ≥18 years) in British Columbia between 2013 and 2023, using the BC Transplant database. Statistical analyses included descriptive statistics, Kruskal-Wallis survival analysis, and linear regression, with significance set at p < 0.05.

Results: Malignancy was the leading cause of death (24.8%), followed by unknown causes (19.4%) and multi-organ failure (13.1%). One-year survival rates varied significantly by cause of death (p = 0.018), with malignancy having the highest 1-year survival (94.9%) and septicemia the lowest (73.5%). Younger recipients had longer survival times (r = -0.321, p < 0.001), while multiple transplants were associated with poorer outcomes (ρ = -0.252, p < 0.001).

Conclusions: Malignancy remains the most frequent cause of death post-transplant, requiring enhanced surveillance. The significant variability in 1-year survival by cause of death highlights the need for tailored interventions, particularly to reduce sepsis-related mortality. Improved documentation of unknown causes is critical to optimizing long-term strategies.

Background: Whether the incidence of autoimmune hepatitis (AIH) is higher in women prescribed antibiotics during pregnancy remains to be determined.

Methods: Administrative databases and hospital abstracts were reviewed to identify all pregnant women in the province of Manitoba from 1996 to 2001 who were prescribed antibiotics during pregnancy and subsequently diagnosed with AIH until 2020.

Results: In this study, 70,666 pregnant women were identified during the 5-year period. Antibiotics were prescribed in 11,654 (16.5%). AIH was subsequently diagnosed in more mothers who were prescribed antibiotics than in those who were not (82/11,654 [0.7%] versus 166/58,975 [0.28%], p <0.0001). The number of antibiotic prescriptions was higher in mothers who subsequently developed AIH than in those who were prescribed antibiotics but did not develop AIH (0.56 [SD 1.09] versus 0.24 [SD 0.67], p <0.0001) as were the prescribed durations of treatment (4.19 [SD 7.72] versus 2.03 [SD 7.55] days, p <0.0001). The mean ages (25.9 [SD 6.0] and 26.8 [SD 5.8]; years) and times to AIH diagnosis (10.6 [SD 4.9] and 10.8 [SD 4.8] years) were similar in mothers who were prescribed and not prescribed antibiotics and developed AIH. The relative risk of developing AIH in antibiotic recipients was 2.5 (95% CI 1.92-3.25, p <0.0001), and the hazard ratio was 2.58 (95% CI 1.98-3.36, p <0.001).

Conclusions: These results describe an association between mothers prescribed antibiotics during pregnancy and the subsequent development of AIH.

Background: Chronic hepatitis C (HCV) in children is primarily acquired through vertical transmission from an HCV-infected mother. The primary risk factor for chronic HCV in mothers is intravenous drug use, which, in pregnancy, is associated with increased risk of neurodevelopmental disorders in children. We explored the prevalence of neurodevelopmental disorders among children with chronic HCV in British Columbia.

Methods: Retrospective chart review was conducted for children actively followed for HCV at our centre between December 2020 and April 2024. Data were collected on demographic and clinical information including diagnoses of neurodevelopmental disorders and other learning difficulties.

Results: We identified 29 children under 18 years of age (13 male, 16 female); 28 had HCV due to vertical transmission and 1 for unknown reasons, potentially due to the patient's own substance use. Forty-eight percent (n = 14) of patients had attention deficit hyperactivity disorder (ADHD). Among these, 43% (n = 6) had fetal alcohol spectrum disorder, 21% (n = 3) had autism spectrum disorder, and 14% (n = 2) had other learning and developmental difficulties including speech delay and sensory processing issues. In total, 62% (n = 18) of patients had some neurodevelopmental disorder or learning difficulty.

Conclusions: In our study population of children with chronic HCV, a majority had at least one documented neurodevelopmental disorder, representing a previously undescribed issue among pediatric patients with chronic HCV. We suggest practitioners who care for children with chronic HCV may have a role in proactively identifying patients with neurodevelopmental difficulties and linking them with appropriate resources.

Colorectal cancer has a high global prevalence and is one of the leading causes of cancer-related death. Approximately one quarter of patients with colorectal cancer will develop metastases, most commonly to the liver, with the majority of liver metastases being unresectable and carrying a poor prognosis. Initial results from trials examining liver transplantation as a potentially curative option for isolated liver metastases from colorectal cancer have yielded promising survival outcomes as compared with standard chemotherapy. However, many of the studies are small and non-randomized with highly selected patient cohorts. This treatment option also raises numerous ethical issues, most notably regarding its feasibility in settings with limited liver donor availability. In this review, current evidence examining outcomes following liver transplantation for liver-only colorectal metastases is outlined, along with details surrounding ongoing trials. Ethical and practical considerations surrounding its implementation as a treatment option are also explored.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator widely used in patients with cystic fibrosis (CF), typically associated with mild, early onset liver enzyme elevations.

Methods: We report a case of a 35-year-old man with CF who developed a marked hepatic transaminitis, with an alanine aminotransferase peaking at >1,000 IU/L after 30 months of stable ETI therapy. The patient was asymptomatic, and an extensive workup excluded viral, autoimmune, and metabolic liver disease. Various imaging modalities excluded other secondary causes, such as portal venous or arterial thromboses.

Results: Using the Roussel Uclaf Causality Assessment Method (RUCAM), a score of 8 indicated a probable link to drug-induced liver injury (DILI), which was further supported by World Health Organization-Uppsala Monitoring Centre (WHO-UMC) causality assessment.

Conclusions: This case highlights the potential for delayed-onset hepatotoxicity with ETI and emphasizes the need for continued liver monitoring during long-term therapy.

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disorder caused by mutations in the LIPA gene, leading to accumulation of cholesterol esters and triglycerides, particularly in the liver and spleen. The disease manifests as either severe infantile Wolman disease or the milder chronic cholesteryl ester storage disease (CESD). Enzyme replacement therapy (ERT) with sebelipase alfa (Kanuma) has shown potential in reducing hepatic and lipid abnormalities.

Methods: We present a case of a 41-year-old female with biopsy-confirmed CESD and cirrhosis, diagnosed in childhood. She was enrolled in the 2015 phase 3 clinical trial for Kanuma and continued on biweekly ERT thereafter. Serial liver imaging and biopsies were performed between 2002 and 2023 to monitor fibrosis progression or regression.

Results: Initial fibrosis staging progressed to cirrhosis (Metavir F4) by 2016. Despite persistently elevated lipid levels (LDL 3.81 mmol/L in 2025), MR elastography and liver biopsy in 2023 demonstrated regression of fibrosis to stage 1-2 and histologic signs of cirrhosis reversal while she was taking Kanuma. This occurred in the absence of significant hepatic steatosis or iron overload.

Conclusions: This case highlights the potential for long-term Kanuma therapy to reverse liver fibrosis in LAL-D, even with ongoing dyslipidemia. While early initiation of ERT may optimize outcomes, this case supports its continued use in advanced disease stages. Further research is needed to assess the long-term metabolic and histologic benefits of ERT in LAL-D patients.

Background: Hepatitis B virus (HBV) antiviral treatment is guided by HBV DNA levels, liver enzyme values, and fibrosis score. Quantitative hepatitis B surface antigen (qHBsAg) may represent a more cost-effective and less labour-intensive surrogate for HBV DNA. The influence of HBV genotype on qHBsAg has not been well considered. We explored the relationship between HBV DNA and qHBsAg as well as the influence of genotype.

Methods: Genotype, HBV DNA, and qHBsAg levels for 138 non-HBV antiviral-treated patients followed at The Ottawa Hospital Viral Hepatitis Program were assessed. Correlations between HBV DNA and qHBsAg as a function of HBV genotype were evaluated.

Results: Mean age was 44.5 years; 52.2% were male, 52.3% Asian, and 34.9% Black. Overall median HBV DNA was 2,557 IU/mL. Highest median HBV DNA was in genotypes B (7,899 IU/mL) and C (39,900 IU/mL) and the lowest in genotype E (684 IU/mL). Median qHBsAg overall was 2,000 IU/mL. Highest median qHBsAg was in genotype E (9665 IU/mL) and lowest in genotypes B (300 IU/mL) and C (1,913 IU/mL). HBV DNA-to-qHBsAg ratio differed in direction and magnitude by genotype. HBV DNA and qHBsAg were positively correlated for genotypes A, B, and D but not correlated for genotypes C and E. Age, HBeAg status, and genotype independently predicted HBsAg level and log10 HBV DNA-to-log10 qHBsAg ratio by multi-variable median regression analysis.

Conclusions: Median amounts and correlations between HBV DNA and qHBsAg differ in magnitude and direction depending on genotype. This knowledge may be relevant to HBV antiviral treatment guideline development.

Background: Albumin platelet product (APP) is a novel blood-based biomarker for liver fibrosis staging. This study evaluates APP's performance against Fibrosis-4 index (FIB-4), AST-platelet ratio index (APRI), and aspartate aminotransferase-alanine aminotransferase (AST/ALT) ratio in diagnosing advanced fibrosis and cirrhosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients with and without diabetes (DM).

Method: Adults with MASLD/metabolic dysfunction-associated steatohepatitis (MASH) in 2010-2023 and available fibrosis staging biomarkers were included. Clinical fibrosis staging was confirmed by liver biopsy, transient elastography (FibroScan), and/or magnetic resonance elastography. Fibrosis staging-matched fibrosis biomarkers were calculated and analyzed.

Results: A total of 570 patients (48.6% male) with available clinical staging and biomarkers were analyzed. DM was present in 38% of the cohort with a significantly higher prevalence among those with advanced fibrosis or cirrhosis (p < 0.001). APP and FIB-4 showed comparable diagnostic performance with areas under the curve (AUCs) of 0.85 (95% CI 0.82-0.88) and 0.84 (95% CI 0.81-0.87), both significantly outperforming APRI and AST/ALT ratio (AUC 0.76, p < 0.05). Importantly, all AUCs were significantly lower in the DM cohort. In patients with DM, APP outperformed FIB-4 in detecting cirrhosis (AUC 0.80 versus 0.76, p = 0.04) and was comparable for advanced fibrosis. In the non-DM cohort, APP and FIB4 performed similarly (AUCs 0.84-0.89, p > 0.05).

Conclusion: APP outperformed FIB4 in detecting cirrhosis or advanced fibrosis among patients with DM and was comparable in non-DM patients. Revised FIB-4 thresholds may be needed in MASLD/MASH patients with DM to improve its diagnostic accuracy.