Synchronous Double Primary Combined Hepatocellular-cholangiocarcinoma and Cholangiolocarcinoma in a Cirrhotic Liver.

Both combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and cholangiolocarcinoma are rare primary liver cancers. cHCC-CCA is believed to originate from transformed hepatocellular carcinoma or liver stem/progenitor cells. Cholangiolocarcinoma is characterized by ductular reaction-like anastomosing cords and glands resembling cholangioles or canals containing hepatocellular carcinoma components and adenocarcinoma cells. According to the 2019 revision of the World Health Organization criteria, a subtype with stem cell features as a subclassification of cHCC-CCA was abolished for lack of conclusive evidence of the stem cell origin theory. That led to the classification of cholangiolocarcinoma with hepatocytic differentiation as cHCC-CCA. Consequently, cholangiolocarcinoma without hepatocytic differentiation is classified as a subtype of small-duct cholangiocarcinoma and is assumed to originate from the bile duct. Herein, we report the first case of double primary cHCC-CCA and cholangiolocarcinoma without hepatocytic differentiation in different hepatic segments of a cirrhotic liver. We believe this case supports the validity of the new World Health Organization criteria because the pathological finding of cHCC-CCA in this case shows the transformation of hepatocellular carcinoma to cholangiocarcinoma. Furthermore, this case may demonstrate that immature ductular cell stemness and mature hepatocyte cell stemness in hepatocarcinogenesis can coexist in the same environment. The results provide valuable insights into the mechanisms of growth, differentiation, and regulation of liver cancers.

Various associations of aging and long-term HIV infection with different neurocognitive functions: detailed analysis of a Japanese nationwide multicenter study.

Detailed information of the effects of age and long-term HIV infection on various neurocognitive function have not been fully evaluated yet. In a prospective Japanese nationwide multicenter study of 17 facilities (J-HAND study), 728 HIV-infected individuals completed 14 neuropsychological (NP) tests; Verbal Fluency (VF; category and letter), Digit Span (DS; forward and backward), Trail Making Test (TMT) A-B, Rey-Osterrieth Complex Figure Test (ROCFT; copy, immediate and delayed recall), Story Memory Test (SMT; immediate and delayed recall), Digit Symbol Subset (DSS), and the Grooved Pegboard (GP; dominant and non-dominant). Multivariate analysis identified older age (≥ 50 years) to be associated with lower scores in all three ROCFT and GP dominant [odds ratio (OR) [95% confidence interval (CI)] 1.801 (1.217-2.664), 2402 (1.366-3.055), 2.691 (1.720-4.211), and 2.302 (1.145-4.628), respectively], whereas longer time since diagnosis was associated with a lower score in ROCFT (delayed recall) (OR 1.224, 95%CI 1.045-1.434). In VF letter, older age and longer time since diagnosis were associated with a better score [OR (95%CI) 0.449 (0.234-0.861) and 0.831 (0.692-0.997)]. In DSS and TMT-A, longer time since diagnosis was associated with a better score [OR (95%CI): 0.808 (0.670-0.973) and 0.795 (0.665-0.949), respectively]. Older patients in later years since diagnosis are at higher risk of visuospatial and motor impairments despite ART, whereas they are less likely to develop verbal impairment, suggesting that verbal function is relatively resistant to aging and long history of HIV infection under ART. These findings suggest that customtailored supports should be established based on the individual background.

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development.

AIM: To investigate factors that accurately predict hepatocellular carcinoma (HCC) development after antiviral therapy in chronic hepatitis C (CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein (AFP) to predict HCC development after interferon (IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response (SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/mL before therapy and in non-SVR patients showing AFP ≥ 5 ng/mL before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/mL before therapy and no decrease in AFP to < 5 ng/mL 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/mL before therapy and decreased AFP (P = 0.043). AFP ≥ 5 ng/mL before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase (ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/mL before therapy than in those showing AFP ≥ 5 ng/mL. CONCLUSION: The criteria of AFP < 5 ng/mL before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

Follow up of the 987 blood donors found with hepatitis C virus infection over 9-18 years.

AIM: To follow up blood donors found with hepatitis C virus (HCV) infection, to improve the outcome by antiviral treatments. METHODS: Between 1991 and 2001, 3377 of the 1 925 860 donors (0.18%) were found to have HCV infection at the Hiroshima Red Cross Blood Center in Japan. Of them, 987 were able to be followed regularly over 9-18 years until 2009, and received antiviral treatments as required. RESULTS: At the start, chronic hepatitis was diagnosed in 541 (54.8%), cirrhosis in five (0.5%) and hepatocellular carcinoma (HCC) in one (0.1%), whereas the remaining 439 (44.5%) had persistently normal aminotransferase levels (PNAL). Hospital visits were terminated voluntarily in 24.3% within the first year, 46.8% by 10 years and 50.9% by 17 years. Liver disease improved in 178 (18.0%), remained stable in 606 (61.4%) and aggravated in 170 (17.2%). Of the 541 donors with chronic hepatitis, HCC developed in 28 (5.2%) and cirrhosis in 11 (2.0%), whereas HCV infection was cleared in 107 (19.8%) by antiviral treatments. In addition, HCV infection resolved in 54 of the 439 donors (12.3%) with PNAL after they had developed chronic hepatitis and received treatments. In donors with chronic hepatitis, the cumulative incidence of HCC was 4.1% at 10 years. By multivariate analysis, age and diagnosis of chronic hepatitis at the entry were found to be independent risk factors for the development of HCC. CONCLUSION: Individuals with undiagnosed HCV infection need to be identified and receive medical care. They have to be motivated to merit from this health-care program.

Efficacy and cost-effectiveness of consensus interferon monotherapy with high-dose induction for hepatitis C patients with genotype 2.

OBJECTIVE: Several treatment strategies for patients with chronic hepatitis C have been compared mainly in terms of their efficacy, and it has been found that pegylated interferon (IFN) plus ribavirin has become the standard therapy, but aged patients may not tolerate ribavirin and the cost-effectiveness of treatment should also be further considered. We conducted a study to evaluate the efficacy, safety, and cost-effectiveness of consensus IFN monotherapy with high-dose induction for patients with chronic hepatitis C in clinical practice. MATERIAL AND METHODS: We consecutively enrolled 104 patients with chronic hepatitis C. Patients were scheduled to receive 12 or 18 µg of consensus IFN daily for 2 weeks, then three times a week for 22 weeks. Efficacy, safety, and cost-effectiveness were assessed. A Markov model was developed to investigate cost-effectiveness in patients with chronic hepatitis C treated by different IFN-based treatment strategies. RESULTS: Of the 104 study patients, a sustained virological response (SVR) was achieved in 66 (63%). Logistic regression analysis revealed that genotype 2, lower hepatitis C virus RNA levels, and patient age were independently associated with SVR. The response rate was significantly higher in patients with genotype 2 (51/66, 77%) versus genotype 1 (15/38, 40%). Cost-effectiveness analysis in patients with genotype 2 revealed that high-dose induction with consensus IFN monotherapy was as highly cost-effective as pegylated IFN plus ribavirin. CONCLUSION: Consensus IFN monotherapy with high-dose induction shows high efficacy and cost-effectiveness in chronic hepatitis C patients with genotype 2 infection. Thus, it may be a reliable alternative in aged patients and for those excluded from standard combination therapy.