Background and Aim
It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new‐onset liver cirrhosis (LC) in ...patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis.
Methods
Taiwanese chronic hepatitis C cohort (T‐COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new‐onset LC and liver‐related complications (DLD or HCC).
Results
Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow‐up duration was 4.38 ± 2.79 years, with overall 46 798 person‐years. The 10‐year cumulative incidence rates of new‐onset LC were 5.0% (95% confidence interval CI: 3.2–7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4–32.4) in those without SVR (hazard ratio HR: 0.22, P < 0.001). The 10‐year cumulative incidence rates of liver‐related complications were 21.4% (95% CI: 11.1–37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1–86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0.001).
Conclusions
Hepatitis C virus eradication with PR therapy decreased the incidence of new‐onset LC in noncirrhotic patients and the incidence of liver‐related complications in cirrhotic patients with CHC.
Background & Aims Host and viral factors interplay in the spontaneous clearance of hepatitis C virus (HCV) infection. We aimed to explore the roles of IL28B genotypes and hepatitis B virus (HBV) ...infections in spontaneous HCV seroclearance. Methods IL28B rs8099917 genotypes, HCV and HBV markers were determined in 290 patients who were seropositive for HCV antibodies from 1681 total uremic patients on maintenance hemodialysis. Results Persistent HCV viremia was observed in 74.6% (214/287) of patients. Logistic regression revealed that the strongest factors associated with spontaneous HCV seroclearance were carriage of rs8099917 TT-type (odds ratio/95% confidence intervals OR/CI: 6.22/1.41–27.35, p = 0.016), followed by concurrent hepatitis B surface antigen (HBsAg) seropositivity (OR/CI: 2.37/1.06–5.26, p = 0.035). The clearance rate was highest among patients with both positive HBsAg/rs8099917 TT-type (44.8%, OR/CI: 20.88/3.5–402.5), followed by positive HBsAg/rs8099917 non-TT-type (28.6%, OR/CI: 8.86/1.8–160.8), and negative HBsAg/rs8099917 TT-type (26.7%, OR/CI: 12.75/1.0–319.4), compared to 4% of negative HBsAg/rs8099917 non-TT-type (trend p = 0.0002). HBsAg levels, but not HBV DNA levels, were significantly associated with spontaneous HCV seroclearance. Spontaneous HCV seroclearance rate was 58.3% in patients with HBsAg >200 IU/ml/rs8099917 TT-type (OR/CI: 42.54/5.7–908.4), 28.0% in patients with HBsAg <200 IU/ml/rs8099917 TT-type or HBsAg >200 IU/ml/rs8099917 non-TT-type (OR/CI: 11.12/2.3–201.0), compared to only 3.3% in those with HBsAg <200 IU/ml/rs8099917 non-TT-type (trend p = 0.0004). Five of 214 (2.3%) HCV viremic patients at enrollment had spontaneous HCV seroclearance during one-year follow-up, which was associated with baseline HCV RNA and HBsAg levels. Conclusions High HBsAg levels and favorable IL28B genotype were additively associated with spontaneous HCV seroclearance in uremic patients.
Background and Aim
Chronic hepatitis C virus (HCV) infection is associated with impaired renal function. The aim of this study is to explore the risk of and factors associated with end‐stage renal ...diseases (ESRD) under maintenance dialysis among HCV patients after anti‐HCV therapy.
Methods
A total of 12 696 HCV‐infected patients with interferon‐based therapy, including 9679 (76.2%) achieving sustained virological response (SVR), were enrolled from 23 hospitals in Taiwan.
Results
During a mean follow‐up period of 5.3 years (67 554 person‐years), the annual incidence of 4.1/10 000 person‐years, 4.0/10 000 and 4.7/10 000 person‐years among SVR patients and non‐SVR patients, respectively. History of diabetes and baseline estimated glomerular filtration rate < 60 mL/min/m2, instead of SVR, were the significant risk factors for developing ESRD with maintenance dialysis after anti‐HCV therapy (adjusted hazard ratio 7.75 and 9.78).
Conclusion
Diabetes and baseline impaired renal function were strongly associated with progression to ESRD with maintenance dialysis among chronic HCV‐infected patients after antiviral therapy.
Abstract
Mixed neuroendocrine‐non‐neuroendocrine neoplasms (MiNENs) of the ampulla of Vater are extremely rare. We present a case of a MiNEN of the ampulla of Vater and review the literature related ...to management and treatment recommendations. A 72‐year‐old woman presented with Charcot's triad for a week. Computed tomography revealed a periampullary tumor. Endoscopic retrograde cholangiopancreatography with internal drainage and sphincterotomy with biopsy revealed mixed adenocarcinoma‐neuroendocrine carcinoma. Ampullary MiNEN with an American Joint Committee on Cancer (8th edition) TNM classification of Stage IIIA T3bN1M0 was diagnosed, and the Whipple procedure was performed. Both components of the tumor were of high grade, each component accounting for approximately 50% of the tumor. FOLFOX (oxaliplatin + de Gramont) was prescribed as adjuvant chemotherapy. No recurrence was noted at the 3‐month follow‐up. Diagnosis of MiNENs through biopsies is challenging, and core biopsies should be suggested when a surgical sample is unavailable. Although heterogeneous, MiNENs are usually highly aggressive neoplasms, contributing to the dissemination of metastases and poor prognosis. In conclusion, radical resection is the optimal treatment choice for almost all potentially curable cases. In addition, treatment strategies for patients with a new diagnosis of MiNENs of the ampulla of Vater should be formulated after discussions in multidisciplinary meetings and should be based on the most aggressive and predominant component in the diagnostic sample.
Lymphocyte-rich hepatocellular carcinoma (HCC) represents the rarest subtype among the various subgroups of HCC, and limited clinical data are available for this particular subtype. It is commonly ...observed as a solitary lesion and tends to present at an early stage. Histopathological examination typically reveals tumor cells infiltrated by a lymphocyte-rich background, leading to its designation as lymphoepithelioma-like HCC. Unlike other lymphoepithelioma-like tumors associated with the Epstein–Barr virus (EBV), lymphocyte-rich HCC is predominantly negative for EBV. This subtype is characterized by more favorable clinical outcomes and prognosis compared to conventional HCC. Here, we present a case of lymphocyte-rich hepatocellular carcinoma (HCC) characterized by the presence of bilateral hepatic tumors and concurrent multiple lymphadenopathy. Interestingly, contrary to previous literature, the examination for the Epstein–Barr virus (EBV) revealed a positive result in this particular case.
Abstract Primary hepatic angiosarcoma (PHA) accounts for 0.5% to 2% of all primary hepatic malignancies, and histopathology findings are required to diagnose PHA accurately. This study investigated ...12 patients with PHA at a single medical center in southern Taiwan. We analyzed the clinical characteristics, imaging features, histopathology findings, and survival outcomes of patients with PHA. Of the 12 patients, abdominal pain and fullness were the most common symptoms, and their liver biochemistry data and tumor markers were mostly within the normal limits. The liver tumors tended to present as multifocal or diffuse nodules with bilobar involvement. The median overall survival (OS) of the 12 patients after diagnosis was 9 months. Improved OS was observed in the surgery group compared with the nonsurgery group (15 vs. 2 months, p = .003). The median OS of patients in the surgery ± systemic therapy group was superior to that of patients in the systemic therapy group and in the no‐therapy groups (15 vs. 5 vs. 2 months, respectively; p = .012). Complete surgical resection remains the optimal treatment choice, and combined surgery and systemic therapy seem beneficial but require further investigation.
Autoimmune hepatitis (AIH) is rare in Asian countries compared to the West, and an exceptionally low prevalence was noted previously in Taiwan. Using the revised criteria of the IAIHG, 48 cases of ...AIH patients were diagnosed. All patients were consecutively diagnosed over a period of 5 years. Detailed medical histories including disease onset, hepatitis B and C, alcohol, drugs, blood transfusion, and family history of autoimmune disease were recorded. Clinical manifestations, result of steroid therapy, outcome, and survival rate were investigated and analyzed. Clinical data on AIH patients with cirrhosis and without cirrhosis were compared and analyzed for their outcome. The statistical methods used were Fisher's exact test, Wilcoxon rank sum test, and Kaplan-Meier curve. Forty-eight patients were diagnosed as AIH type 1, with a median age of 58 years and a female:male ratio of 37:11. The most common clinical features at presentation were fatigue, jaundice, and anorexia. Ninety-eight percent of patients were ANA positive, and most of the patients showed elevated values of AST, ALT, serum globulin, and bilirubin. A substantial proportion of patients presented with poor liver function at entry and 35% of patients had liver cirrhosis, with relatively prolonged PT (P=0.001) and poorer outcome (P=0.005) compared to the noncirrhotics. As a whole there was a favorable treatment response and the overall survival rate was 85%. We conclude that the incidence of AIH in Taiwan is much higher than previously presumed and AIH type 1 is the predominant type of the disease. Although a substantial proportion of AIH patients presented with poor hepatic function at entry, as a whole there was a favorable clinical outcome.
Extracellular signal-regulated kinase (ERK1/2) is implicated in the malignant behavior of breast cancer cells. However, previous clinical-pathological studies have shown that expression of ...activated/phosphorylated ERK1/2 is not associated with enhanced proliferation and invasion of mammary carcinomas. ERK1/2 is expressed in the cytoplasm, and activated/phosphorylated ERK1/2 translocates to the nucleus. The aim of this study is to evaluate nuclear phosphorylated ERK1/2 as a biomarker for breast cancer prognosis. The clinical-pathological relation of cytoplasmic/nuclear phosphorylated ERK1/2 was analyzed in 105 surgically resected breast cancer specimens by immunohistochemistry with tissue microarray. The results showed that non-neoplastic breast tissue mainly showed faint phosphorylated ERK1/2 staining. No statistically significant association was found between the level of cytoplasmic phosphorylated ERK1/2 expression and the clinical features of the disease. High nuclear phosphorylated ERK1/2 expression was associated with high grade (poor differentiation, p = = 0.010), high T status (larger tumor size, p = 0.033), and an advanced stage (p = 0.018) of the disease. Thus, nuclear phosphorylated ERK1/2 is associated with enhanced proliferation and invasion of mammary carcinomas and may be a biomarker for breast cancer prognosis and the determination of therapeutic strategies.
Sporadic cases of acute hepatitis E virus (HEV) infection with production of anti-HEV IgM have been reported occasionally in Taiwan despite no reported outbreaks in the past. This study was ...undertaken to determine whether serological markers correlated with virus detection. From 2002 to 2006, 72 reported cases of acute hepatitis E seropositive for anti-HEV IgM in Taiwan were enrolled for investigation. Acute phase serum samples were collected for detection of HEV RNA, HBV DNA, HCV RNA, and GBV-C RNA by PCR. The results showed that viral sequences of HEV, HBV, HCV and GBV-C were detected in 54 (75%), 21 (29.2%), 9 (12.5%), and 22 (30.6%) of cases, respectively. Acute hepatitis A co-infection was excluded in all patients because none were seropositive for anti-HAV IgM and, nine patients (12.5%) did not seroconvert to anti-HEV IgG. These results suggest that serum markers did not correlate completely with viremia in the diagnosis of acute HEV infection. Multiple viruses may co-infect with acute hepatitis E virus in Taiwan. Detection of hepatitis E viremia together with seropositivity for anti-HEV IgM and followed by seroconversion to anti-HEV IgG should be included in the diagnostic criteria for HEV infection. J. Med. Virol. 81:1734-1742, 2009.
Hepatitis after transarterial chemoembolization (TACE) is common. Stronger Neo‐Minophagen C (SNMC) has demonstrated benefits in patients with hepatitis. We aimed to determine its usefulness in ...post‐TACE hepatitis in patients with hepatomas. Overall, 60 patients with hepatomas who were treated with TACE were prospectively analyzed; of these, 30 patients underwent SNMC treatment after TACE. Daily serial changes in the liver function tests (serum levels of aspartate aminotransferase AST, alanine aminotransferase ALT, total bilirubin, prolonged prothrombin time, and international normalized ratio PT/INR) were compared between the two groups. Common complications, such as fever, nausea, and emesis, were also compared. There were no significant differences in baseline characteristics between the groups (P > .05). Although the absolute value of AST/ALT was lower in the SNMC treatment group, differences between the groups were nonsignificant. Total bilirubin and PT/INR levels were significantly different between the groups (P = .03 and .02, respectively), thus indicating potential SNMC effects on hepatocyte regeneration. Significant differences were also observed between the groups with respect to fever and nausea/emesis (both P = .002). Side effects of SNMC, such as hyperkalemia or hypertension, were not significantly different between the groups. SNMC demonstrated some benefits in patients with hepatomas after TACE.
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