Differentiation of clinical patterns and survival outcomes of hepatocellular carcinoma on hepatitis B and nonalcoholic fatty liver disease.

BACKGROUND: The main etiologies of hepatocellular carcinoma (HCC) were often hepatitis B virus (HBV) or C and alcohol, rarely autoimmune and biliary diseases. Nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis, cirrhosis, and eventually HCC in recent years. The aim of our study is to investigate and compare the clinical features of HCC in patients with NAFLD and HBV, including age, gender, cirrhosis, liver function tests, largest tumor size, and cancer stage at the time of diagnosis. The survival outcome was compared between the two groups and the significant predictors of mortality were also analyzed in all patients with HCC. METHODS: Most patients with HCC were recruited from the database of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017; and the other patients consecutively from the HCC multidisciplinary conference between January 2018 and December 2019. NAFLD was defined as nonviral hepatitis B (negative HBsAg and either positive anti-HBs or negative anti-HBc), nonviral hepatitis C (negative antihepatitis C virus [HCV]), nonalcoholic (alcohol consumption of <30 g/d for men and <20 g/d for women) liver disease, or present or past histological or ultrasonographic evidence of fatty liver. Totally, 23 NAFLD-related and 156 HBV-related HCC patients were enrolled in our study for further analysis. RESULTS: NAFLD-related HCC patients were significantly older (median age: 70.0 [61.0-79.0] years vs. 63.0 [56.0-72.0] years, p = 0.012) and heavier (median body mass index [BMI]: 26.6 [24.2-30] kg/m2 vs. 24.8 [22.0-27.1] kg/m2, p = 0.044) than those with HBV-related HCC. They were also more susceptible to diabetes mellitus (DM), and 60.9% (14 of 23) of them had this comorbidity compared with 29.5% (46 of 156) of those with HBV-related HCC (p = 0.003). Only 34.8% (8 of 23) and 71.2% (111 of 156) of patients with NAFLD- and HBV-related HCC were cirrhotic, respectively (p = 0.001). However, gender, tobacco use, international normalized ratio, albumin, creatinine, and cholesterol levels were not significantly different between the two groups. Tumor characteristics such as the Barcelona clinic liver cancer stage, largest tumor size, tumor number, extrahepatic metastasis, and treatment modalities had no significant difference between such groups.According to the Kaplan-Meier method analysis, the overall survival was not significantly different between these two patient groups (log-rank test, p = 0.101). To evaluate which patient group would lead to poor prognosis, we analyzed the survival of all patients through multivariate Cox proportional hazard regression after controlling other factors that may influence the hazard ratio. The analysis revealed that NAFLD and HBV infection as the cause of HCC are not risk factors of poor prognosis. CONCLUSION: In conclusion, our study showed NAFLD-related HCC patients were older, heavier, and more had DM than HBV-related. In addition, more NAFLD-related HCC patients were noncirrhotic than HBV-related. The survival rate was similar between NAFLD and HBV-related HCC patients.

Teriparatide in East Asian Postmenopausal Women with Osteoporosis in a Real-World Setting: A Baseline Analysis of the Asia and Latin America Fracture Observational Study (ALAFOS).

PURPOSE: The aim of this analysis is to describe the baseline characteristics of patients who are prescribed teriparatide for the treatment of postmenopausal osteoporosis in a real-world setting in East Asia. PATIENTS AND METHODS: The Asia and Latin America Fracture Observational Study (ALAFOS) is a prospective, multinational, observational study designed to evaluate real-world use of teriparatide in the treatment of postmenopausal osteoporosis in 20 countries across Asia, Latin America, the Middle East, and Russia. This subregional analysis focuses on the East Asian subpopulation of the ALAFOS study. Here we report baseline clinical characteristics, details regarding the history of fractures, risk factors for osteoporosis, comorbidities, osteoporosis treatment, and health-related quality of life in patients enrolled in China, Hong Kong, South Korea, and Taiwan. RESULTS: The East Asian subgroup of ALAFOS included 1136 postmenopausal women, constituting 37.5% (1136/3031) of the overall ALAFOS patient population. The mean (SD) age was 75.0 (9.6) years. The mean (SD) bone mineral density T-scores were -3.11 (1.54), -2.58 (1.11), and -2.86 (1.09) at the lumbar spine, total hip, and femoral neck, respectively; 69.6% of patients had experienced at least one fragility fracture and 40.4% had experienced ≥2 fragility fractures after 40 years of age. Overall, 63.3% of patients had used medications for osteoporosis in the past. The mean (SD) EQ-5D-5L Visual Analog Scale (VAS) score at baseline was 59.7 (20.8); the mean (SD) back pain numeric rating scale score for worst pain in the last 24 hrs was 5.2 (3.2). CONCLUSION: Our results indicate that patients who are prescribed teriparatide in East Asia were elderly women with severe osteoporosis, low bone mineral density, high prevalence of fractures, back pain and poor health-related quality of life. Most of the patients received teriparatide as a second-line treatment.

Quantification of Protein Levels in Single Living Cells.

Accurate measurement of the amount of specific protein a cell produces is important for investigating basic molecular processes. We have developed a technique that allows for quantitation of protein levels in single cells in vivo. This protein quantitation ratioing (PQR) technique uses a genetic tag that produces a stoichiometric ratio of a fluorescent protein reporter and the protein of interest during protein translation. The fluorescence intensity is proportional to the number of molecules produced of the protein of interest and is used to determine the relative amount of protein within the cell. We use PQR to quantify protein expression of different genes using quantitative imaging, electrophysiology, and phenotype. We use genome editing to insert Protein Quantitation Reporters into endogenous genomic loci in three different genomes for quantitation of endogenous protein levels. The PQR technique will allow for a wide range of quantitative experiments examining gene-to-phenotype relationships with greater accuracy.

Serum prohepcidin levels correlate with hepatic iron stores in chronic hepatitis C patients.

BACKGROUND/AIMS: Increased serum iron indices and hepatic iron stores are frequent in patients with chronic hepatitis C (CHC). The antimicrobial peptide hepdicin produced in the liver plays a pivotal role in iron homeostasis. METHODOLOGY: To determine the expression of hepcidin, the serum levels of prohepcidin were measured in 58 CHC patients and 144 healthy controls. The hepatic iron stores were scored by Perls' stain on liver biopsy specimens in 39 CHC patients. The serum prohepcidin levels were correlated with biochemical inflammation markers, histological necroinflammation grades, hemoglobin levels and iron status in CHC patients. RESULTS: The concentrations of serum prohepcidin were significantly higher in CHC patients than in healthy controls (142.07 +/- 67.06 vs. 89.07 +/- 37.32 ng/mL, p < 0.001). The CHC patients with positive hepatic iron stains had significantly higher serum prohepcidin levels than the CHC patients without (221.20 +/- 117.74 vs. 123.81 +/- 60.53 ng/mL, p = 0.037). The serum prohepdicin levels were not significantly correlated with the ages (r = -0.041, p = 0.760), hemoglobin (r = 0.127, p = 0.346), alanine aminotransferase (r = -0.032, p = 0.813), transferrin saturation (r = 0.025, p = 0.862), ferritin levels (r = 0.211, p = 0.133) and hepatic inflammation grades (r = 0.153, p = 0.352) in CHC patients. CONCLUSIONS: The expression of serum prohepcidin is independent of the degree of hepatic inflammation as measured by the histological activity or aminotransferase level. The serum prohepcidin levels are associated with hepatic iron stains and significantly higher in CHC patients than in healthy controls. Our results suggest that CHC may induce the expression of hepcidin possibly by increased hepatic iron stores.

Hepatic iron influences responses to combination therapy with peginterferon alfa and ribavirin in chronic hepatitis C.

BACKGROUND/AIMS: Mild to moderate iron overload is common in chronic hepatitis C (CHC) and may influence the response to antiviral therapy. The aim of this study was to assess the association among serum iron indices, hepatic iron stores and sustained virological response (SVR) rates of combination therapy with peginterferon alfa and ribavirin in patients with CHC. METHODOLOGY: A total of 36 CHC patients were treated with peginterferon and ribavirin for 6 months. The SVR was defined as undetectable hepatitis C virus RNA by qualitative assay 6 months after the end of therapy. The serum iron indices including ferritin, iron and transferrin saturation were measured. The hepatic iron deposition was graded on Perls' stain. RESULTS: The SVR was obtained in 25/36 (69.44%) patients. The serum iron indices including transferrin saturation and ferritin were not significantly different between patients with the SVR and without. In multivariate logistic regression analysis, cirrhosis (P = 0.010, odds ratio = 0.020) and a positive hepatic iron stain (P = 0.046, odds ratio = 0.065) were both significantly independent predictors of non-SVR. CONCLUSIONS: The findings suggest that the positive hepatic iron stain is an independent predictor of non-response to combination therapy with peginterferon alfa and ribavirin for patients with CHC. Liver cirrhosis also predicts non-responses to the combination therapy.

Influence of iron on the severity of hepatic fibrosis in patients with chronic hepatitis C.

AIM: To evaluate the association among hepatic fibrosis, serum iron indices, and hepatic iron stores in patients with Chronic Hepatitis C (CHC). METHODS: Thirty-two CHC patients were included in our study. The histological degree of fibrosis and inflammation activity was assessed according to the Metavir system. The serum iron indices including ferritin, iron and transferrin saturation were measured. Hepatic iron deposition was graded by Perls' stain. RESULTS: The CHC patients with severe hepatic fibrosis (n = 16) were significantly older than CHC patients with mild fibrosis (n = 16) (P = 0.024). The serum iron indices, increased serum iron store and positive hepatic iron stain were not significantly different between the two groups. In multivariate logistic regression analysis, the age at biopsy was an independent predictor of severe hepatic fibrosis (Odds ratio = 1.312; P = 0.035). The positive hepatic iron stain was significantly associated with the values of alanine aminotransferase (ALT) (P = 0.017), ferritin (P = 0.008), serum iron (P = 0.019) and transferrin saturation (P = 0.003). The ferritin level showed significant correlation with the value of ALT (r = 0.531; P = 0.003), iron (r = 0.467; P = 0.011) and transferrin saturation (r = 0.556; P = 0.002). CONCLUSION: Our findings suggest that the severity of hepatitis C virus (HCV)-related liver injury is associated with patient age at biopsy. Both serum iron indices and hepatic iron deposition show correlation with serum indices of chronic liver disease but are not related to grade and stage of liver histology.

Usefulness of serum des-gamma-carboxy prothrombin in detection of hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) has been reported to be more sensitive and specific in diagnosing hepatocellular carcinoma (HCC) when compared with alpha-fetoprotein (AFP). However, its ability to identify small HCC still remains unclear. Thus, we conducted a cross-sectional case control study to evaluate whether DCP is better than AFP for differentiating HCC from nonmalignant liver disease and further evaluate the usefulness of DCP in early diagnosis of small HCC. METHODS: Serum DCP and AFP levels were determined in 127 patients. Among these patients, 32 were with non-cirrhotic chronic hepatitis, 34 were with compensated cirrhosis, and 61 were with HCC. The cut-off value for the DCP and AFP were set as 40 mAU/mL and 20 ng/mL, respectively. To compare the diagnostic value of DCP and AFP in distinguishing HCC from nonmalignant chronic liver disease, receiver operating characteristic (ROC) curves were constructed for each assay. RESULTS: The accuracy, sensitivity and specificity of DCP were higher than AFP in detecting HCC (81.9%, 77% and 86.4% vs 68.5%, 59% and 77.3%, respectively). The area under the ROC (AUROC) curves revealed that DCP had a better accuracy than AFP in diagnosis of HCC (0.85 [95%CI, 0.78-0.91] vs 0.73 [95%CI, 0.65-0.81], P = 0.013). In 39 patients with solitary HCC, the positive rates of DCP were 100% in patients with tumor size larger than 3 cm, 66.7% in patients with tumor size 2-3 cm and 50% in patients with tumor size less than 2 cm. The positive rates of AFP in patients with tumor size larger than 3 cm, 2-3 cm and less than 2 cm were 55.6%, 50%, and 33.3%, respectively. The median level of DCP in HCC patients with tumor size larger than 3 cm was significantly higher than those with tumor size 2-3 cm and those with the size of less than 2 cm. CONCLUSION: Our study indicates that DCP has a better diagnostic value than AFP in differentiating HCC from nonmalignant chronic liver disease. DCP has not only a stronger correlation with HCC than AFP in tumor size but also more effectiveness than AFP in detecting small size of HCC.

Prevalence of HFE mutations and relation to serum iron status in patients with chronic hepatitis C and patients with nonalcoholic fatty liver disease in Taiwan.

AIM: To assess the prevalence of the two mutations, C282Y and H63D of HFE gene, in healthy subjects, patients with chronic hepatitis C (CHC), and patients with nonalcoholic fatty liver disease (NAFLD) in Taiwan and to explore the contribution of the HFE mutation on serum iron stores in CHC and NAFLD groups. METHODS: We examined C282Y and H63D mutations of HFE gene in 125 healthy subjects, 29 patients with CHC, and 33 patients with NAFLD. The serum iron markers, including ferritin, iron, and total iron binding capacity (TIBC), were assessed in all patients. RESULTS: All of the healthy subjects and patients were free from C282Y mutation. The prevalence of H63D heter-ozygosity was 4/125 (3.20%) in healthy subjects, 2/29 (6.90%) in CHC group, and 1/33 (3.03%) in NAFLD group. The healthy subjects showed no significant difference in the prevalence of H63D mutation as compared with the CHC or NAFLD group. Increased serum iron store was found in 34.48% of CHC patients and 36.36% of NAFLD patients. In three patients of H63D heterozygosity, only one CHC patient had increased serum iron store. There was no significant difference in the prevalence of HFE mutations between patients with increased serum iron store and those without in CHC or NAFLD group. CONCLUSION: The HFE mutations may not contribute to iron accumulation in the CHC or NAFLD group even when serum iron overload is observed in more than one-third of these patients in Taiwan.

Spontaneous regression of hepatocellular carcinoma: a case report and literature review.

A case of spontaneous regression of hepatocellular carcinoma is reported and compared with the reports published in the English literature. Spontaneous regression of a histologically proven hepatocellular carcinoma was observed in a 42-year-old male patient with chronic hepatitis B. The patient refused to receive any medical therapy. The tumor subsequently regressed without specific treatment, as demonstrated radiologically by computed tomography 22 months and ultrasonography 24 months after initial diagnosis. We review 27 case reports of apparently spontaneous regression of hepatocellular carcinoma that have been published in the English literature from 1982 to 2002. In this report, we present our unusual case and discuss possible causes of spontaneous total necrosis or regression of hepatocellular carcinoma.