HBV-associated Intrahepatic Cholangiocarcinoma Research Articles

High serum gamma-glutamyl transpeptidase concentration associates with poor postoperative prognosis of patients with hepatitis B virus-associated intrahepatic cholangiocarcinoma.

BackgroundIntrahepatic cholangiocarcinoma (ICC) caused by chronic hepatitis B virus (HBV) infection has become prominent. Prospectively stratifying postoperative risk factors is a challenging task.MethodsWe retrospectively assessed the relationship between serum gamma-glutamyl transpeptidase (GGT) concentration and postoperative outcomes in 107 subjects with HBV-associated ICC. Cox proportionate hazard models and subgroup analyses were used to test the hypothesis with adjustment for potential confounders.ResultsSerum GGT concentration was negatively correlated with postoperative outcomes. For a 1-standard deviation (per-SD) (117 µ/L) increase of serum GGT concentration, the relative risk (RR) for overall survival (OS) and time to recurrence (TTR) were 1.72 [95% confidence interval (CI), 1.37 to 2.16] and 1.53 (95% CI, 1.22 to 1.91), respectively. In addition, the RRs of middle and top tertiles of GGT for death were 1.81 (95% CI, 0.98 to 3.32) and 3.56 (95% CI, 1.97 to 6.42), respectively (P for trend <0.001). Similarly, the RRs for recurrence of the corresponding tertiles were 1.70 (95% CI, 0.93 to 3.10) and 3.27 (95% CI, 1.77 to 6.06), respectively (P for trend =0.002). In our study, the negative correlation between serum GGT levels and OS did not differ significantly between groups stratified by age, sex, HBV DNA level, carbohydrate antigen 19-9 (CA19-9) level and liver resection type (all P for interaction >0.05); however, there was a significant interactive effect of serum GGT and adjuvant chemotherapy on OS (RR =0.64 vs. 1.77, P for interaction =0.04).ConclusionsHigh serum GGT concentration is associated with an increased risk of postoperative death and tumor recurrence in patients with HBV-associated ICC. However, this relationship became less significant with the implementation of adjuvant chemotherapy.

The research progress in clinicopathological characteristics and treatment of hepatitis B virus-associated intrahepatic cholangiocarcinoma

Hepatitis B is a common and multiplex disease in China. Recently, epidemiological studies have shown that hepatitis B virus(HBV) infection is a high-risk factor for the development of intrahepatic cholangiocarcinoma(ICC). Based on a retrospective analysis of relevant literature of recent years, this article concludes that HBV-associated ICC is very different from other ICC regarding clinicopathological characteristics and treatment. Distinctive features of patients with HBV-associated ICC included younger age, preponderance of male patients, frequent elevation of alpha fetoprotein, decrease of CA19-9, frequent appearance of cirrhosis, infrequent lymph node metastasis and better prognosis. Because these clinicopathological features are similar to those of HBV-associated hepatocellular carcinoma(HCC), we speculate that the cell origin of HBV-associated ICC and HBV-associated HCC are consistent. In addition, this article also discusses that HBV-associated ICC should be treated with surgery-based comprehensive treatment in order to improve prognosis.

1278 Often a Favorable Prognostic Factor: Unusually Elevated Alpha-Fetoprotein (AFP) in a Case of Hepatitis B Virus (HBV) Associated Intrahepatic Cholangiocarcinoma (ICC)

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC), often an incidental finding is a rare tumor of the epithelial cells of the biliary ducts that originate in the liver and extrahepatic bile ducts. Serum alpha-fetoprotein (AFP), as a tumor marker of hepatocellular carcinoma (HCC), and carbohydrate antigen 19-9 (CA 19-9), as a tumor marker of ICC, have been widely used in clinical practice. Although, a subset of patient with ICC (20-25%) present with elevated AFP levels, usually &gt;100 ng/mL and very rarely &gt;1000 ng/mL, its role remains significant in prognosis of ICC. Herein, we discuss a case of Hepatitis B virus (HBV) associated ICC in a young individual with exceptionally high serum AFP levels. CASE DESCRIPTION/METHODS: A 45-year-old male with no apparent past medical history was seen for complaints of fatigue, nausea, anorexia, and associated 34-lb weight loss of 6-weeks duration. Initial labs revealed a chronic HBV infection and an obstructive pattern on liver function tests. Computerized tomography (CT) scan of the abdomen showed a large heterogeneous mass originating from porta hepatis and invading the left lobe of the liver with multiple liver metastases and metastatic lymphadenopathy of the porta hepatis. CT also revealed a mass in the gallbladder along with thrombosed portal vein and intrahepatic biliary dilation (Figures 1 and 2). Magnetic resonance cholangiopancreatography (MRCP) confirmed initial CT findings. Labs revealed an AFP level of 9,715 ng/mL and CA 19-9 level of 554 units/mL. Percutaneous transhepatic cholangiography (PTC) and tissue biopsy revealed liver parenchymal poorly differentiated adenocarcinoma. Attempted internalization of a biliary stent by interventional radiology (IR) was unsuccessful. Management options were discussed with the patient and family who opted for a palliative approach without chemotherapy. DISCUSSION: Intrahepatic cholangiocarcinoma (ICC) is a rare tumor of the epithelial cells of the biliary ducts originating in the liver and extrahepatic bile ducts. ICC tends to be aggressive due to lymph node involvement at diagnosis with intrahepatic, and peritoneal dissemination. Several factors have been implicated in the pathogenesis of ICC including hepatitis B and C viral infections. Role of AFP, often a marker of HCC, is a significant one in prognostication of ICC. Elevated AFP levels, especially with HBV-associated ICC carries a favorable prognosis. Unfortunately, in the case of our patient, due to the advanced nature of his condition, his prognosis remained poor.

Pre-operative imaging characteristics in hepatitis B – associated, histology-proven resected intrahepatic cholangiocarcinoma

Introduction: Despite being different diseases, intrahepatic cholangiocarcinoma(ICC) can show imaging characteristics similar to hepatocellular carcinoma (HCC) on Computed Tomography scans (CT) and Magnetic Resonance Imaging (MRI). Also, hepatitis B has been associated with both HCC and ICC. The objective of this study is to evaluate the association of specific imaging characteristics (arterial enhancement, portal venous washout) to that of Hepatitis B virus infected (HBV) patients with ICC. Methods: Data on patients with HBV-associated ICC, undergoing surgical resection at the Singapore General Hospital were identified from a prospectively-kept database. Pre-operative cross-sectional imaging characteristics were analyzed. Results: 34 patients with HBV-associated ICC underwent resection between 1 January 2000 to 31 December 2016. The mean age was 60.79 (+/−12.25) years with a total of 20 males, of which 29 were Chinese, 1 was Malay and 4 were foreigners. In addition, the median number of lesion was 1 (range 1 to innumerable), mean maximum size of lesions (mm) was 49.38mm (+/−32.00mm) and mean AFP value was 340.29 (+/−1738.78). Of the 29 patients who did CT, 13 who did MRI and 9 who did both, 23 showed arterial enhancement and 13 showed portal venous washout, while 12 showed both on at least one imaging modality. Conclusions: Many HBV patients with ICC showed imaging characteristics of arterial enhancement and a significant proportion had portal venous washout. In the population of HBV positive patients, ICC can mimic HCC on preoperative imaging, and should be borne in mind as a differential.

Transarterial Chemoembolization: A Favorable Postoperative Management to Improve Prognosis of Hepatitis B Virus-associated Intrahepatic Cholangiocarcinoma after Surgical Resection.

Background: There is no information regarding transarterial chemoembolization (TACE) as a postoperative management after hepatic resection for patients with hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC).Methods: Forty-two patients with pathological confirmation of HBV-associated ICC were enrolled. Prognostic impact of the clinicopathological factors as well as postoperative TACE were evaluated. Computed tomography findings of HBV-associated ICC were assessed.Results: Tumor size of larger than 5 cm (hazard ratio [HR], 5.654; 95% confidence interval [CI], 1.175 to 27.204; P = 0.031), postoperative TACE (HR, 0.123; 95% CI, 0.023 to 0.643; P = 0.013), and lymph node metastasis (HR, 3.284; 95% CI, 1.236 to 8.724; P = 0.017) revealed to be independently associated with survival outcomes of patients with HBV-associated ICC. Application of TACE, as a postoperative management to control early local recurrence on the basis of hepatic arterial phase enhancement, significantly prolonged survival outcomes (1-yr, 88.9%; 3-yr, 77.8%; 5-yr, 66.7%), compared to the patients who did not receive TACE (1-yr, 63.6%; 3-yr, 30.8%; 5-yr, 13.0%). When analyzed according to the status of hepatic arterial phase, arterial phase enhancement demonstrated a favorable trend on prognosis of patients with HBV-associated ICC without statistical significance (HR, 0.435; 95% CI, 0.140 to 1.359; P = 0.141), and TACE independently improved overall survival of patients with arterial phase enhancement (HR, 0.105; 95% CI, 0.014 to 0.774; P = 0.027).Conclusions: Put together, our results indicate that postoperative TACE effectively improves prognosis of HBV-associated ICC with arterial phase enhancement in CT scans. Large-sized trials are required for our results to be applied in clinical medicine.

Hepatitis B virus-associated intrahepatic cholangiocarcinoma: a malignancy of distinctive characteristics between hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

It has been a decade since hepatitis B virus infection was identified as an etiological factor for the development of intrahepatic cholangiocarcinoma (ICC). In recent years, several studies have elucidated the critical impact of hepatitis B virus in ICC that significantly influenced the clinicopathological characteristics of ICC patients with intrahepatic cholangiocarcinoma. Distinctive features of patients with hepatitis B virus-associated ICC included younger age, preponderance of male patients, frequent elevation of alpha-fetoprotein, and infrequent lymph node metastasis. Furthermore, several studies indicated that the presence of hepatitis B virus is a favorable prognostic factor in terms of overall survival and relapse-free survival. However, there are also a few studies demonstrating that hepatitis B virus negatively influenced or showed no significant association with survival outcomes of patients with ICC. At present, there are no consensus on diagnostic procedures and treatments for such population. Therefore, we elucidated current knowledge and recent identifications of HBV-associated ICC to clarify the impact of chronic HBV infection on patients with ICC and to precisely conduct diagnostic procedures and curative treatments for HBV-associated ICC.

Hepatitis B virus is associated with the clinical features and survival rate of patients with intrahepatic cholangiocarcinoma

The pathogenesis and development of intrahepatic cholangiocarcinoma (ICC) may be triggered by hepatitis B virus (HBV). We conducted this retrospective study to explore the potential association between HBV infection and the clinical features and survival rate of patients with ICC. Patients with ICC who had undergone a curative resection were enrolled and divided into three groups according to the seropositivity of the hepatitis B surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). The groups were as follows: group I, HBsAg (+)/anti-HBc (+); group II, HBsAg (-)/anti-HBc (+); group III HBsAg (-)/anti-HBc (-). The symptoms, pathologic findings, and outcome information of all patients were retrospectively reviewed. The patient sera were isolated to detect anti-HCV, HBsAg, and anti-HBc. Surgical specimens were assessed by hematoxylin and eosin (HE) staining. The expression of cytokeratin 7 was evaluated by immunohistochemistry. Finally, the 1-, 3-, and 5-year cumulative survival rates were analyzed. Ninety-seven patients with ICC were enrolled in group I (n=26); group II, (n=50), and group III (n=21). A total of 26.8% (26/97) patients with ICC were positive for HBsAg. Patients with HBV-associated ICC tended to be younger (P=0.018), have lower CA19-9 levels (P=0.000), a higher alpha fetal protein (AFP) level (P=0.012) and prothrombin time (P=0.030), a higher risk of hepatic cirrhosis (P=0.001), and poor differentiation (P=0.028). The 1-, 3-, and 5-year cumulative survival rates for patients within the three groups were as follows: 27.3%, 0%, and 0% for group I, respectively; 62.5%, 30.0%, and 0% for group II, respectively; and 87.5%, 66.7%, and 50.0% for group III, respectively. The results were significantly different in an overall comparison (P=0.000). Patients with HBV-associated ICC showed different clinicopathological features and lower survival rates compared to patients with ICC without HBV infection.

Prognosis after resection for hepatitis B virus-associated intrahepatic cholangiocarcinoma.

To investigate the prognostic factors after resection for hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC) and to assess the impact of different extents of lymphadenectomy on patient survival. A total of 85 patients with HBV-associated ICC who underwent curative resection from January 2005 to December 2006 were analyzed. The patients were classified into groups according to the extent of lymphadenectomy (no lymph node dissection, sampling lymph node dissection and regional lymph node dissection). Clinicopathological characteristics and survival were reviewed retrospectively. The cumulative 1-, 3-, and 5-year survival rates were found to be 60%, 18%, and 13%, respectively. Multivariate analysis revealed that liver cirrhosis (HR = 1.875, 95%CI: 1.197-3.278, P = 0.008) and multiple tumors (HR = 2.653, 95%CI: 1.562-4.508, P < 0.001) were independent prognostic factors for survival. Recurrence occurred in 70 patients. The 1-, 3-, and 5-year disease-free survival rates were 36%, 3% and 0%, respectively. Liver cirrhosis (HR = 1.919, P = 0.012), advanced TNM stage (stage III/IV) (HR = 2.027, P < 0.001), and vascular invasion (HR = 3.779, P = 0.02) were independent prognostic factors for disease-free survival. Patients with regional lymph node dissection demonstrated a similar survival rate to patients with sampling lymph node dissection. Lymphadenectomy did not significantly improve the survival rate of patients with negative lymph node status. The extent of lymphadenectomy does not seem to have influence on the survival of patients with HBV-associated ICC, and routine lymph node dissection is not recommended, particularly for those without lymph node metastasis.

Occult Hepatitis B Virus Infection in Chinese Cryptogenic Intrahepatic Cholangiocarcinoma Patient Population

There is no information available about occult hepatitis B virus (HBV) infection (OBI) in individuals with intrahepatic cholangiocarcinoma (ICC). To investigate the correlation between OBI and ICC. A retrospective case-control study was conducted. The cases were 183 cryptogenic ICC patients (group I), and the controls were 549 healthy individuals (group II). The cases and controls were matched for age, sex, and inhabitancy. Adjusted odds ratios and 95% confidence intervals were calculated. Intrahepatic total HBV DNA in 63 paraffin-embedded samples was collected from patients in group I (n=44), HBV-associated ICC patients (n=3), and hepatic cavernous hemangioma patients with seronegative HBsAg (hepatitis B S antigen) (group III; n=16). We determined the levels of serum and intrahepatic HBV DNA and compared the level of intrahepatic HBV DNA in 44 cryptogenic patients from group I with the level in the patients from group III. Compared with group II, group I had a lower prevalence of anti-HBs (antibody against HBsAg) and a higher prevalence of anti-HBe (antibody against hepatitis B e antigen) and anti-HBc (antibody against hepatitis B c antigen). Multivariate analysis confirmed that anti-HBe and anti-HBc positivity were associated with ICC. The odds ratios and 95% confidence intervals for anti-HBe and anti-HBc were 2.482 and 1.482-4.158, 4.556 and 2.938-7.066, respectively. Compared with group III, cryptogenic ICC cases showed more frequent detection of intrahepatic total HBV DNA (63.64% vs. 18.75%, P=0.002). OBI may represent an important risk factor for ICC. HBsAg seroclearance does not signify eradication of HBV and may not entirely prevent the development of ICC.

Characteristics of intrahepatic cholangiocarcinoma in patients with hepatitis B virus infection: clinicopathologic study of resected tumours

Recent efforts suggest an aetiological role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC). The purpose of this study was to clarify the clinicopathologic characteristics and surgical outcomes of patients with HBV-associated ICC. All patients with chronic HBV infection were identified from a database of patients with ICC that underwent surgical resection between 1 January 2005 and 31 December 2006. Their clinicopathologic and survival characteristics were compared with ICC patients without chronic HBV infection. The age of the HBV-associated ICC patients tend to be younger than that of ICC patients without chronic HBV infection. HBV-associated ICC patients tend to have higher abnormal α-fetoprotein levels and lower abnormal serum carbohydrate antigen19-9 (CA19-9), r-glutamyltransferase (r-GT) and alkaline phosphatase levels. The pathologic features of the resected specimens revealed that HBV-associated ICC patients tended to be of the mass-forming type have a lower prevalence of lymphatic involvement and poorer tumour differentiation, and a higher prevalence of capsule formation and liver cirrhosis. Patients with HBV-associated ICC had a significantly better survival than patients without chronic HBV infection. The clinicopathological features of HBV-associated ICC patients showed significant differences from ICC patients without HBV infection. These tumours are characterized by the mass-forming growth pattern and appeared to have a more favourable prognosis.

Evaluation of Risk Factors and Clinicopathologic Features for Intrahepatic Cholangiocarcinoma in Southern China: A Possible Role of Hepatitis B Virus

Recent efforts suggest an etiologic role of hepatitis B virus (HBV) infection in intrahepatic cholangiocarcinoma (ICC) and the involvement of hepatic progenitor cell in ICC development, without definitive conclusions. This case-control study was undertaken to investigate risk factors for ICC, and clinicopathological features of HBV-associated ICC were analyzed. The report comprised 98 patients with pathologically confirmed ICC and 196 healthy control subjects. Logistic regression was used to determine odds ratios and 95% confidence intervals. The sex and age distributions of HBV-related and unrelated ICC patients were compared respectively with those of 882 HBV-associated hepatocellular carcinoma patients from a random selection, and the clinicopathological data of 62 ICC patients with or without HBV infection undergoing surgical resection were compared. There was an association between ICC and each of HBV infection, liver cirrhosis, hepatolithiasis, and liver fluke infestation with the odds ratios (95% confidence intervals) of 2.75 (1.27-5.95), 8.42 (2.50-28.37), 22.81 (7.16-72.68), and 3.55 (1.60-7.89), respectively, with a marked synergism of cirrhosis and HBV infection (20.67; 5.40-79.06). Compared with HBV-unrelated ICC patients, HBV-related ICC patients were more common in male and younger subjects, had a higher incidence of abnormal serum alfa-fetoprotein level, cirrhosis, and neutrophilic infiltration, and had a lower proportion of elevated carbohydrate antigen 19-9 (CA19-9) values. The independent association of HBV infection with ICC, synergy between cirrhosis and HBV infection, and some clinicopathological similarities between HBV-related ICC and hepatocellular carcinoma suggests that both may share similar or common tumorigenic process and may possibly originate from malignant transformation of hepatic progenitor cell.

Hepatitis B virus-associated intrahepatic cholangiocarcinoma and hepatocellular carcinoma may hold common disease process for carcinogenesis

Aims To evaluate potential risk factors for intrahepatic cholangiocarcinoma (ICC) and analyse clinicopathologic characteristics of ICC patients with seropositive hepatitis B surface antigen (HBsAg). Methods A retrospective case–control study was conducted. Cases were 317 ICC patients referred to the Eastern Hepatobiliary Surgery Hospital in China between 2003 and 2006. Controls were 634 healthy individuals. Adjusted odds ratios (ORs) were calculated in logistic regression analysis. Among 317 consecutively enrolled ICC patients, 154 patients were seropositive HBsAg (48.6%). We compared clinicopathologic characteristics of these patients (group I) with ICC patients seronegative for HBsAg (group II; n = 163) and compared the age and sex distributions of patients in group I with randomly selected hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) (group III; n = 1140). Results Compared with the controls, ICC patients had a high prevalence of seropositive HBsAg, cirrhosis, hepatolithiasis and hepatic schistosomiasis. Compared with seronegative-HBsAg ICC patients, seropositive-HBsAg ICC patients were younger, more frequently male and had a higher proportion of abnormal aminotransferase and serum alpha-fetoprotein (AFP) level, histological inflammation and cirrhosis, right-lobe focus, poor tumour differentiation, tumour encapsulation and microvascular invasion; had a lower proportion of abnormal serum carbohydrate antigen 19-9 (CA19-9) level and lymphatic metastasis. The age and sex distribution profiles were nearly identical between seropositive-HBsAg ICC patients and HBV-associated HCC patients. Conclusions The HBV infection, cirrhosis, hepatolithiasis and hepatic schistosomiasis may be potential risk factors for ICC. HBV-associated ICC shares many clinicopathological similarities with HBV-associated HCC. The result indicated HBV-associated ICC and HBV-associated HCC may hold common disease process for carcinogenesis.