Clinical Characteristics, Genetic Features, and Long-Term Outcome of Wilson’s Disease in a Taiwanese Population: An 11-Year Follow-Up Study

Objective@#aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort. @*Methods@#aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes. @*Results@#aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations. @*Conclusion@#aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Taiwan perspective

Hepatocellular carcinoma (HCC) is the fourth most common cancer and the second leading cause of cancer-related death in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan developed and updated the guidelines for HCC management in 2020. In clinical practice, we follow these guidelines and the reimbursement policy of the government. In Taiwan, abdominal ultrasonography, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) tests are performed for HCC surveillance every 6 months or every 3 months for high-risk patients. Dynamic computed tomography, magnetic resonance imaging, and contrast-enhanced ultrasound have been recommended for HCC surveillance in extremely high-risk patients or those with poor ultrasonographic visualization results. HCC is usually diagnosed through dynamic imaging, and pathological diagnosis is recommended. Staging of HCC is based on a modified version of the Barcelona Clinic Liver Cancer (BCLC) system, and the HCC management guidelines in Taiwan actively promote curative treatments including surgery and locoregional therapy for BCLC stage B or C patients. Transarterial chemoembolization (TACE), drug-eluting bead TACE, transarterial radioembolization, and hepatic artery infusion chemotherapy may be administered for patients with BCLC stage B or C HCC. Sorafenib and lenvatinib are reimbursed as systemic therapies, and regorafenib and ramucirumab may be reimbursed in cases of sorafenib failure. First-line atezolizumab with bevacizumab is not yet reimbursed but may be administered in clinical practice. Systemic therapy and external beam radiation therapy may be used in specific patients. Early switching to systemic therapy in TACE-refractory patients is a recent paradigm shift in HCC management.

Clinical and Histologic Features of Patients with Biopsy-Proven Metabolic Dysfunction-Associated Fatty Liver Disease

Background/Aims@#Fatty liver disease is defined as a cluster of diseases with heterogeneous etiologies, and its definition continues to evolve. The novel conceptional criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) were proposed in 2020 to avoid the exclusion of a certain subpopulation, but their evaluations have been limited. We aimed to examine and compare the clinical as well as histologic features of MAFLD versus nonalcoholic fatty liver disease (NAFLD) in patients with biopsy-proven hepatic steatosis. @*Methods@#From January 2009 to December 2019, 175 patients with histology-proven hepatic steatosis and 10 with cryptogenic cirrhosis who were treated at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. Patients were classified into different groups according to the diagnostic criteria of MAFLD and NAFLD. The clinical and histologic features were then analyzed and compared. @*Results@#In total, 76 patients (41.1%) were diagnosed with both MAFLD and NAFLD, 81 patients (43.8%) were diagnosed with MAFLD alone, nine patients (4.9%) were diagnosed with NAFLD alone, and 19 patients (10.3%) were diagnosed with neither. Those with MAFLD alone exhibited a higher degree of disease severity regarding histology and laboratory data than those with NAFLD alone. Advanced fibrosis was associated with the presences of hepatitis B virus infection and metabolic diseases. @*Conclusions@#The novel diagnostic criteria for MAFLD include an additional 38.9% of patients with hepatic steatosis and can better help identify those with a high degree of disease severity for early intervention than can the previous NAFLD criteria.

Clinical and Histologic Features of Patients with Biopsy-Proven Metabolic Dysfunction-Associated Fatty Liver Disease

Background/Aims@#Fatty liver disease is defined as a cluster of diseases with heterogeneous etiologies, and its definition continues to evolve. The novel conceptional criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) were proposed in 2020 to avoid the exclusion of a certain subpopulation, but their evaluations have been limited. We aimed to examine and compare the clinical as well as histologic features of MAFLD versus nonalcoholic fatty liver disease (NAFLD) in patients with biopsy-proven hepatic steatosis. @*Methods@#From January 2009 to December 2019, 175 patients with histology-proven hepatic steatosis and 10 with cryptogenic cirrhosis who were treated at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. Patients were classified into different groups according to the diagnostic criteria of MAFLD and NAFLD. The clinical and histologic features were then analyzed and compared. @*Results@#In total, 76 patients (41.1%) were diagnosed with both MAFLD and NAFLD, 81 patients (43.8%) were diagnosed with MAFLD alone, nine patients (4.9%) were diagnosed with NAFLD alone, and 19 patients (10.3%) were diagnosed with neither. Those with MAFLD alone exhibited a higher degree of disease severity regarding histology and laboratory data than those with NAFLD alone. Advanced fibrosis was associated with the presences of hepatitis B virus infection and metabolic diseases. @*Conclusions@#The novel diagnostic criteria for MAFLD include an additional 38.9% of patients with hepatic steatosis and can better help identify those with a high degree of disease severity for early intervention than can the previous NAFLD criteria.

Combination Therapy for Chronic Hepatitis B: Current Updates and Perspectives

Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; however, the therapeutic response remains unsatisfactory. Although NUC therapy exhibits potent on-treatment viral suppression, frequent off-therapy virological relapses suggest an indefinite treatment course. Interferon modulates the innate and adaptive antiviral immune responses and thus increases the chance of viral eradication. Interferon therapy has the advantage of a finite duration, absence of drug resistance, and durable posttreatment responses. Therefore, the combination of NUCs and interferon can theoretically facilitate a synergistic therapeutic effect. This paper summarizes the current strategies of various combination therapies into three categories: the simultaneous “dual” strategy, sequential combination “add-on” strategy, and “switch” strategy. Generally, dual therapy exhibits greater on-treatment and off-therapy viral suppression and lower drug resistance compared with NUC monotherapy. Compared with interferon monotherapy, dual therapy has greater on-treatment viral suppression but shows no difference in off-therapy sustained virological responses. Specific add-on or switch strategies provide promising on-treatment efficacy in select patients. Pretreatment or on-treatment quantitative hepatitis B surface antigen and e antigen are predictive for the treatment efficacy of combination therapy. The optimal schedule of combination regimens and individualized therapy remain to be comprehensively evaluated.

Combination Therapy for Chronic Hepatitis B: Current Updates and Perspectives

Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; however, the therapeutic response remains unsatisfactory. Although NUC therapy exhibits potent on-treatment viral suppression, frequent off-therapy virological relapses suggest an indefinite treatment course. Interferon modulates the innate and adaptive antiviral immune responses and thus increases the chance of viral eradication. Interferon therapy has the advantage of a finite duration, absence of drug resistance, and durable posttreatment responses. Therefore, the combination of NUCs and interferon can theoretically facilitate a synergistic therapeutic effect. This paper summarizes the current strategies of various combination therapies into three categories: the simultaneous “dual” strategy, sequential combination “add-on” strategy, and “switch” strategy. Generally, dual therapy exhibits greater on-treatment and off-therapy viral suppression and lower drug resistance compared with NUC monotherapy. Compared with interferon monotherapy, dual therapy has greater on-treatment viral suppression but shows no difference in off-therapy sustained virological responses. Specific add-on or switch strategies provide promising on-treatment efficacy in select patients. Pretreatment or on-treatment quantitative hepatitis B surface antigen and e antigen are predictive for the treatment efficacy of combination therapy. The optimal schedule of combination regimens and individualized therapy remain to be comprehensively evaluated.