High prevalence of multinodular hepatocellular carcinoma in patients with cirrhosis attributable to multiple risk factors.

To see whether or not there is an association between the cause of cirrhosis and the number of hepatocellular carcinoma (HCC) nodules, we analyzed 178 consecutive patients in whom HCC was detected during a prospective screening by abdominal ultrasound (US). The relevant information was obtained from the database of the screening programs operating at four hospitals in the Milan area. One hundred twenty-nine (72%) patients had a single tumor nodule detected by US and 49 (28%) patients had multinodular disease. Ninety-eight (55%) patients had normal serum values of alpha-fetoprotein (AFP). Tumor staging with biphasic computed tomography (CT) scan or hepatic arteriography with lipiodol revealed that 101 (57%) patients had single tumor nodules and 77 (43%) patients had more than one HCC nodule. After staging, multinodular HCC was more common in patients with multiple risk factors than in the hepatitis C virus (HCV) carriers (56% vs. 38%, P =.05). Interestingly, single tumors were as common in the 126 patients undergoing 6-month interval screening as in the 52 patients who were studied at yearly intervals. The former patients, however, had more small tumors than the latter ones (91% vs. 74%, P =.04). The 22 patients who were alcohol abusers had normal levels of serum AFP more often than the hepatitis B virus (HBV) or HCV carriers or those with multiple risk factors (86% vs. 57%, P <.04; vs. 47%, P <.002; vs. 52%, P <.006, respectively). We concluded that multinodular HCC was underdetected by real time US; it prevailed among patients with multiple risk factors. In these patients, screening with US exams every 6 months may be inadequate for early detection of liver cancer.     

Efficacy and cost of a hepatocellular carcinoma screening program at an Australian teaching hospital

Background and Aim: Western countries are seeing an increasing prevalence of chronic viral hepatitis and a subsequent rise in the incidence of hepatocellular carcinoma (HCC). Screening patients at high risk of HCC has become standard practice. The aim of this study was to assess the efficacy and cost of screening high‐risk individuals for HCC in an Australian tertiary hospital. Methods: A retrospective review was performed of all patients who underwent HCC screening at the Austin Hospital in Melbourne between 1 October 1998 and 31 August 2004. HCC screening was carried out in all cirrhotic patients and male non‐cirrhotic patients with chronic hepatitis B virus. Screening consisted of 6‐monthly alpha fetoprotein (AFP) measurements and ultrasounds (US). Outcomes of those who had HCC detected were followed up until 15 February 2007. Patients who had HCC satisfying the Milan criteria for liver transplantation were considered to have potentially curable tumor. Costs for the diagnostic tests were obtained from the 2004 Australian Medicare Benefits Schedule. Results: A total of 268 patient records were reviewed as part of the study. Chronic viral hepatitis accounted for 63% of the patients (n = 167). US screening was carried out at a median of 6.5 months and AFP measurements at a median of 4.0 months. HCC was detected in 22 patients (8.2%) at an incidence of 2.7% per year. These patients had a mean follow up of approximately 5.0 years after tumor detection. At the time of diagnosis, 17 patients had potentially curable tumor and 10 were alive at the conclusion of follow up. Of these 10 patients, six were successfully transplanted, three were successfully treated with radiological therapies and one was awaiting transplantation. The total cost of the screening program over the study period, including secondary investigations, was $A300 568. The cost per HCC detected was $13 662 and cost per potentially curable HCC was $17 680. Conclusion: An effective HCC screening program can be provided through a multi‐disciplinary outpatient facility in an Australian teaching hospital. Further stratification of the high risk patient cohort may improve the cost effectiveness of this screening program.     

Mass screening for hepatocellular carcinoma: Experience in Hokkaido, Japan

Abstract Mass screening for liver cancer based mainly on abdominal ultrasound was begun in major cities of Hokkaido, Japan, in November 1981, to enable early detection and treatment of hepatocellular carcinoma (HCC). Serum alpha-fetoprotein levels were also measured to minimize false negative studies. Examinees included those who sought liver disease screening as well as high risk individuals: hepatitis B surface antigen carriers and those with a past or current liver disease, history of blood transfusion, family history of liver cancer, and more recently those with positive anti-hepatitis C antibodies. The examination was carried out on each Saturday and Sunday as one round, and by February 1992 48 rounds had been performed. A total of 8090 individuals were investigated, and HCC was detected in 91 with a detection rate of 1.12%. This rate was 1.6% among 5684 individuals who were selected for high risk. Cumulative rates of survival among these patients were 79.0% at 1 year, 43.8% at 3 years, 19.3% at 5 years and 15.4% at 7 years. These survival rates were comparable with those for the patients with HCC diagnosed during follow-up of chronic liver disease and treated at our hospital. The cost for detecting one HCC patient in this programme was ¥ 2 660 000 (∼US$25 000), which was less than those for some other types of cancer in a similar setting. Considering the high detection rate in this programme, we feel that similar programmes should be encouraged and supported.     

A Prospective Study of Hepatocellular Carcinoma Incidence in Thalassemia

Hepatocellular carcinoma (HCC) is a complication of cirrhosis. Due to blood transfusions, patients with β-thalassemia (thal) are often infected with either hepatitis C virus (HCV) or hepatitis B virus (HBV). In the past, many patients did not survive long enough to develop HCC. The recent improvements in prognosis have helped in the diagnosis of HCC that has developed. The aim of this study was to evaluate HCC incidence in β-thal. We performed liver ultrasound (US) on all adults without a previous diagnosis of HCC. Risk factors (iron overload, HCV infection, HBV infection, cirrhosis) were evaluated. One hundred and eight thalassemia patients have been evaluated; of whom three were excluded (two patients as they were under the age of 18 years and one patient because he had a previous history of HCC). Seventy-two patients [31 had thalassemia major (TM), 41 had thalassemia intermedia (TI)] with risk factors (iron overload in 72, HCV infection in 46, HBV infection in two, cirrhosis in 10) and 33 (four with TM and 29 with TI) without risk factors underwent liver US. Overall, two patients were found to have a newly developed HCC. Of these two patients, one was treated with surgery and the other with percutaneous radiofrequency. Further follow-up did not show any evidence of recurrence after 23 and 15 months, respectively. Ultrasound screening can allow early detection and treatment of HCC in thalassemia patients.     

Outcome of screening for hepatitis C virus infection based on risk factors

OBJECTIVES: Screening for hepatitis C virus (HCV) infection in individuals at increased risk is currently recommended by most, but not all, health authorities. This study identifies outcomes of individuals diagnosed through a screening program targeting high-risk patients. METHODS: Veterans presenting for care in VA facilities are assessed for HCV risk factors by a questionnaire. Those with a risk factor are offered anti-HCV testing. Between October 1998 and May 2004, 25,701 patients were assessed and 8,471 patients had a risk factor for HCV. Patients diagnosed through the screening program were assessed per study protocol. RESULTS: The prevalence of a positive HCV antibody in veterans who identified a risk factor was 7.3% (95% CI 6.6-8.0%). Among those diagnosed through the screening program (N = 260), 47% had chronic hepatitis C. Among patients with chronic HCV, 18% had evidence of advanced liver disease (stage III/IV on biopsy or clinical cirrhosis) while 34% had persistently normal alanine aminotransferase (ALT). Two-thirds of individuals who underwent liver biopsy had minimal or no fibrosis. About half (47%) of the screen-detected patients with chronic HCV were treatment candidates. Forty-four percent were not immediate candidates secondary to medical or psychiatric comorbidities or active substance abuse. Twenty-two patients (8%) had died after a median follow-up of 911 days. Two were liver-related deaths. CONCLUSION: Screening for hepatitis C in persons at high risk can lead to early identification of individuals at risk for progressive liver disease who may benefit from antiviral therapy and counseling to reduce HCV-related liver injury.     

A prospective study of hepatocellular carcinoma incidence in thalassemia

Hepatocellular carcinoma (HCC) is a complication of cirrhosis. Due to blood transfusions, patients with beta-thalassemia (thal) are often infected with either hepatitis C virus (HCV) or hepatitis B virus (HBV). In the past, many patients did not survive long enough to develop HCC. The recent improvements in prognosis have helped in the diagnosis of HCC that has developed. The aim of this study was to evaluate HCC incidence in beta-thal. We performed liver ultrasound (US) on all adults without a previous diagnosis of HCC. Risk factors (iron overload, HCV infection, HBV infection, cirrhosis) were evaluated. One hundred and eight thalassemia patients have been evaluated; of whom three were excluded (two patients as they were under the age of 18 years and one patient because he had a previous history of HCC). Seventy-two patients [31 had thalassemia major (TM), 41 had thalassemia intermedia (TI)] with risk factors (iron overload in 72, HCV infection in 46, HBV infection in two, cirrhosis in 10) and 33 (four with TM and 29 with TI) without risk factors underwent liver US. Overall, two patients were found to have a newly developed HCC. Of these two patients, one was treated with surgery and the other with percutaneous radiofrequency. Further follow-up did not show any evidence of recurrence after 23 and 15 months, respectively. Ultrasound screening can allow early detection and treatment of HCC in thalassemia patients.     

Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study

A prospective surveillance of hepatocellular carcinoma (HCC) using serum alpha-fetoprotein and high-resolution, linear-array, real-time ultrasonography was carried out in 432 patients with clinicopathologically proven chronic type B hepatitis. During a follow-up period of 6-85 mo (median 23, mean 26.9 +/- 16.8 mo), asymptomatic HCC was identified in 8 patients, with a calculated annual incidence of 826/100,000, and 2768/100,000 for patients over age 35 yr. The relative risk of developing HCC in hepatitis B surface antigen-positive chronic hepatitis patients was 2 when compared to those that were hepatitis B surface antigen-negative, and was 5 when compared in patients over age 35 yr. Hepatocellular carcinomas detected by these methods were in a relatively early stage as most tumors were small, only 50% were associated with cirrhosis, 37.5% were positive for hepatitis B e antibody, and most were still resectable. We, therefore, recommend a combination of alpha-fetoprotein and ultrasonography surveillance in patients with chronic hepatitis in order to improve the chance of early HCC detection as well as the chance for successful resection. In addition, the low incidence of cirrhosis and hepatitis B e antibody in these patients with "early" HCCs and the occurrence of hepatitis B e antigen/hepatitis B e antibody seroconversion after HCC had developed suggest that the development of HCC and progression from hepatitis to cirrhosis were two independent (though related) sequelae of chronic hepatitis B virus infection.     

Hepatocellular Carcinoma in a β-Thalassemia Intermedia Patient: Yet Another Case in the Expanding Epidemic

The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is increasing, the two well recognized HCC risk factors in thalassemia being iron overload and chronic hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, whereas chronic hepatitis leads to necroinflammation that can accelerate progression to HCC. We hereby report the case of a non transfused, hepatitis C-negative, β-thalassemia intermedia (β-TI) patient from our practice who had evidence of significant iron overload, suggesting the importance of increased iron burden as a HCC risk factor in this patient population. As such, screening thalassemia patients using magnetic resonance imaging (MRI)-based liver iron concentration (LIC) measurement and liver ultrasound is strongly recommended for early detection of iron overload and HCC, respectively. Data appears to be lacking on HCC treatment outcomes in patients who have thalassemia, but an approach tailored to each patient’s comorbidities is key to treatment success. The prognosis of these patients can be improved by multicenter studies investigating novel HCC therapeutic targets in the thalassemia realm.     

Long-term follow-up of HCV patients with sustained virological response after treatment with pegylated interferon plus ribavirin

Background: The progress of liver diseases may not stop after viral eradication. This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV) infection who underwent pegylated interferon plus ribavirin(PR) regimen and achieved a sustained virological response 24 weeks post-treatment(SVR24). Methods: Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up. Baseline characteristics were profiled. The incidence of hepatocellular carcinoma(HCC), progression of liver disease(increase in liver stiffness or occurrence of decompensated complication), and HCV recurrence was all monitored. The accumulative and annualized incidence rates(AIRs) of these adverse events were analyzed, and the risk factors were also examined. Results: In total, 151 patients reached a median follow-up time of 103 weeks. Among them, two had an incidence of HCC during the surveillance with AIR of 0.68%(95% CI: 0.00-1.63%). Six patients showed progression of liver disease with AIR of 2.05%(95% CI: 0.42%-3.68%). Three patients who had risky behaviors encountered HCV reinfection. The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients, including HCC and progression of liver disease(AIR: 6.17% vs. 1.42%, P = 0.039). Conclusions: The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period, but the risk level was low. Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones. HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.     

Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America

BACKGROUND: Measurement of serum alpha-fetoprotein (AFP) and abdominal ultrasound (US) examination are used for the early detection of hepatocellular carcinoma (HCC) in chronic liver disease patients. However, the accuracy and usefulness of these tests in a clinical setting in the United States of America have not been clarified. METHODS: We conducted a 7-year prospective surveillance study by using both AFP and US to detect HCC in 602 patients with chronic viral hepatitis. Our main goal was to determine the optimal test for detection of early HCC. We also assessed the clinical outcome of HCC patients identified during this time period. RESULTS: Thirty-one cases of HCC were detected. Serum AFP levels were elevated in 74% of HCC patients, but was also high in 10% of patients who did not develop HCC. The positive predictive value for AFP to detect HCC was only 12% or less for all AFP cut-off values, and the maximum joint sensitivity and specificity as determined by receiver operator characteristic analysis was approximately 65 and 90%, respectively. Abdominal US identified all 31 cases of HCC. The positive predictive value for US examinations to detect HCC was 78%, while the sensitivity and specificity was 100 and 98%, respectively. After detection of HCC, 24 (77%) patients died within a mean of 16.7 +/- 19.4 months. CONCLUSIONS: Our study indicates that US examination was more accurate in detecting HCC. Because of its poor predictive value and low sensitivity, serum AFP should not be used as the only test for screening and surveillance for HCC.     

Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status

OBJECTIVES: The incidence of hepatocellular carcinoma (HCC) seems to be rising in the United States (US), and considerable variability in the incidence and etiology of HCC has been noted among different racial and ethnic groups in this country. The aim of this study was to evaluate the influence of racial and ethnic status in the viral etiology of HCC in the US. METHODS: Retrospective surveys were conducted at liver transplantation centers in the US. Respondents were asked to review the charts of all patients with HCC seen at their institution for the 2-yr period between July, 1997, and June, 1999, and provide information about the racial and ethnic distribution of cases and their serological status with regard to hepatitis B and C markers. RESULTS: Complete information was available on 691 patients who formed the basis of this study, comprising 59% whites, 14% blacks, 16% Asians, and 11% other racial groups. Of the patients, 107 patients (15.4%) were positive for hepatitis B surface antigen (HBsAg), 322 had antibodies to hepatitis C virus (anti-HCV) (46.5%), 33 (4.7%) had both HBsAg and anti-HCV), and 229 (33.1%) had neither marker present. Clear differences were seen among racial groups. Anti-HCV positivity was the most frequent risk factor in both blacks and whites, whereas HBsAg positivity was the most frequent etiological factor in Asians with HCC. CONCLUSIONS: HCV infection seems to be the major risk factor for HCC in the US, particularly among individuals of white and black ethnicity, whereas hepatitis B remains the main risk factor among patients of Asian ethnicity. These preliminary findings indicate the need for a more detailed study of ethnic variability in the pathogenesis of HCC.     

Metformin does not improve survival in patients with hepatocellular carcinoma

AIM: To assess whether metformin, which has a chemopreventive effect in chronic liver disease, has any chemotherapeutic effect in hepatocellular carcinoma.METHODS: This was a retrospective study of 701 patients with newly diagnosed hepatocellular carcinoma (HCC) seen between January 2005 and June 2011 at Mayo Clinic, Rochester, Minnesota. This patient cohort was a part of the global HCC BRIDGE study, which is a large longitudinal study of HCC determining the real-world experience of HCC characteristics, management and patient outcomes. We defined significant metformin exposure as continuation of this agent at least 90 d beyond diagnosis of HCC, and compared survival of diabetic patients on metformin to diabetic patients not on metformin and non-diabetics.RESULTS: Our cohort was 72.9% male, with a mean ± SD age of 62.6 ± 12.3 years. The most common etiologies of liver disease were hepatitis C (34%), alcoholic liver disease (29%), fatty liver disease (15%) and hepatitis B (9%). By univariate analysis, using diabetics not on metformin as the reference group, diabetic patients with HCC on metformin had no survival advantage, with a HR (95%CI) of 1.0 (0.8-1.3). Non-diabetic HCC patients also did not appear to have a survival advantage as compared to diabetic HCC patients not on metformin, as demonstrated by a HR (95%CI) of 1.1 (0.7-1.7). Diabetics on metformin beyond 90 d after HCC diagnosis had a longer median survival at 34.2 mo, as compared to 25.5 mo among diabetic patients who were not on metformin or had discontinued metformin within 90 d after HCC diagnosis. This finding was likely due to potential survival bias among those who lived long enough to receive metformin.CONCLUSION: Although the literature suggests a chemotherapeutic effect in other malignancies, our study demonstrates no survival benefit to the use of metformin in diabetic patients with HCC.     

Clinical prognostic variables in young patients (under 40 years) with hepatitis B virus-associated hepatocellular carcinoma

OBJECTIVE: The aim of this study was to determine the impact of hepatocelluar carcinoma (HCC) screening in chronic hepatitis B patients who did not meet the current screening recommendations. METHODS: Patients who were admitted to Bellevue Hospital Center with HCC were assessed for risk factors, cirrhosis and tumor‐specific factors. Eligibility for liver transplantation or resection with favorable outcome was determined by applying Milan criteria. RESULTS: In all 93 patients were diagnosed with hepatitis B virus (HBV)‐associated HCC, 18 of whom were under 40 years. Cirrhosis was infrequently associated with HCC in this group, with most cancers occurring in non‐cirrhotic patients (12/18, 66.7%). No patient developed HCC outside the American Association for the Study of Liver Diseases (AASLD) cancer screening recommendations (young age, non‐cirrhotic) were eligible for liver transplantation or resection with favorable outcomes (within Milan criteria). However, HCC patients who were diagnosed within AASLD screening recommendations did meet Milan criteria in 17.3% (14/81) patients. CONCLUSIONS: Current guidelines for HCC screening in patients with HBV may lead to a delay in diagnosis in non‐cirrhotic patients under 40 years. Consideration should be given to modifying current recommendations to advocate entering HBV patients into a cancer‐screening program at young age.     

Utility of alpha-fetoprotein (AFP) in the screening of patients with virus-related chronic liver disease: does different viral etiology influence AFP levels in HCC? A study in 350 western patients

BACKGROUND/AIMS: Dosage of serum AFP (alpha-fetoprotein) is widely used for HCC screening in patients with chronic liver disease. Virus-related chronic liver disease is the main cause of cirrhosis and HCC in Western and Far Eastern countries, but the relationship between viral etiology and AFP levels in HCC is still unclear. The aim of this study was to verify, in Western patients with post-viral chronic liver disease, the usefulness of AFP dosage for the detection of HCC, and the influence of viral etiology on AFP levels in HCC. METHODOLOGY: The study population included 350 patients with post viral chronic liver disease that underwent liver biopsy, serum AFP determination and ultrasound liver evaluation. Seven patients had normal liver histology, 197 had chronic hepatitis, 72 had cirrhosis, and 74 had cirrhosis and HCC. ROC (receiver operating characteristic) analysis was used to assess the best diagnostic AFP threshold value for HCC detection. Logistic regression analysis was performed to individuate independent predictors of HCC diagnosis. RESULTS: No difference was observed in AFP levels between HCV- and HBV-positive patients, neither in the whole population nor in the HCC patients only. ROC area under curve for AFP was 0.801 (95% CI: 0.721-0.867). The analysis individuated a best accurate AFP threshold value for HCC diagnosis of 50 ng/mL. HCC was detected with specificity > or = 95% only for AFP > 100 ng/mL. The sensitivity however was poor (25%). Male sex, age > 60, and AFP were independent predictors of HCC diagnosis. CONCLUSIONS: Serum AFP levels in HCC patients are not influenced by virus B or C hepatitis pattern. AFP dosage should not be used for HCC diagnosis in non-cirrhotic patients. Male patients with cirrhosis should be regarded with a more "aggressive" screening program compared to females.     

Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients.

BACKGROUND: Interferon (IFN) improves hepatic inflammation/fibrosis and reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CH-C). However, HCC develops in some patients who have a sustained virological response (SVR) to IFN therapy. We designed this study to establish a follow-up protocol for patients with CH-C who have SVR to IFN therapy. METHODS: We retrospectively studied 1124 patients with CH-C who received IFN. RESULTS: HCC developed in 3.5% of patients with SVR to IFN. As compared with SVR patients without HCC, SVR patients with HCC were predominantly male (P=0.003), older at the initiation of IFN therapy (P=0.002), and at a more advanced histologic stage of disease (P<0.001). However, three of the 13 SVR HCC patients had mild fibrosis. The mean interval from IFN therapy to the detection of HCC in SVR HCC patients was 5.8 years and did not differ significantly from that in non-SVR HCC patients (P=0.304). Although most patients with HCC received curative therapy, the prognosis of some SVR HCC patients was poor, probably because of insufficient follow-up, resulting in delayed detection of HCC. CONCLUSIONS: SVR patients with CH-C who are elderly, male, or have an advanced histologic stage are at a high risk for the development of HCC after IFN therapy. We recommend that SVR patients should be observed carefully for more than 10 years after the completion of IFN therapy, even if they only have early fibrosis.     

Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients

BACKGROUND Reliable biomarkers of cirrhosis, hepatocellular carcinoma(HCC), or progression of chronic liver diseases are missing. In this context, Golgi protein-73(GP73) also called Golgi phosphoprotein-2, was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells. As a result, GP73 expression was found primarily in biliary epithelial cells, with only slight detection in hepatocytes. However, in patients with acute or chronic liver diseases and especially in HCC, the expression of GP73 is significantly up-regulated in hepatocytes. So far, few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA (QUANTA Lite~? GP73, Inova Diagnostics, Inc., Research Use Only) in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa, Greece(n = 366) and Debrecen, Hungary(n = 266). Aspartate aminotransferase(AST)/Platelets(PLT) ratio index(APRI) was also calculated at the relevant time points in all patients. Two hundred and three patients had chronic hepatitis B, 183 chronic hepatitis C, 198 alcoholic liver disease, 28 autoimmune cholestatic liver diseases, 15 autoimmune hepatitis, and 5 with other liver-related disorders. The duration of follow-up was 50(57) mo [median(interquartile range)]. The development of cirrhosis, liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines. In particular, the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP) determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73( 20 units) were detected at initial evaluation in 277 out of 632 patients(43.8%). GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4% vs 51.5%, P 0.001), decompensation of cirrhosis(60.3% vs 35.5%, P 0.001), presence of HCC(18.4% vs 7.9%, P 0.001) and advanced HCC stage(52.9% vs 14.8%, P = 0.002). GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score [Area under the curve(AUC)(95%CI): 0.909(0.885-0.934) vs 0.849(0.813-0.886), P = 0.003]. Combination of GP73 with APRI improved further the accuracy(AUC: 0.925) compared to GP73(AUC: 0.909, P = 0.005) or APRI alone(AUC: 0.849, P 0.001). GP73 levels were significantly higher in HCC patients compared to non-HCC [22.5(29.2) vs 16(20.3) units, P 0.001) and positively associated with BCLC stage [stage 0: 13.9(10.8); stage A: 17.1(16.8); stage B: 19.6(22.3); stage C: 32.2(30.8); stage D: 45.3(86.6) units, P 0.001] and tumor dimensions [very early: 13.9(10.8); intermediate: 19.6(18.4); advanced: 29.1(33.6) units, P = 0.004]. However, the discriminative ability for HCC diagnosis was relatively low [AUC(95%CI): 0.623(0.570-0.675)]. Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline, was prognostic of higher rates of decompensation(P = 0.036), HCC development(P = 0.08), and liver-related deaths(P 0.001) during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination. In combination with APRI, its diagnostic performance can be further improved. Most importantly, the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases.     

Hepatocellular carcinoma surveillance:An evidence-based approach

Hepatocellular carcinoma(HCC) makes up 75%-85% of all primary liver cancers and is the fourth most common cause of cancer related death worldwide. Chronic liver disease is the most significant risk factor for HCC with 80%-90% of new cases occurring in the background of cirrhosis. Studies have shown that early diagnosis of HCC through surveillance programs improve prognosis and availability of curative therapies. All patients with cirrhosis and high-risk hepatitis B patients are at risk for HCC and should undergo surveillance. The recommended surveillance modality is abdominal ultrasound(US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with non-alcoholic fatty liver disease(NAFLD). With the current obesity epidemic and rise in the prevalence of NAFLD, abdominal computed tomography or magnetic resonance imaging may be indicated as the primary screening modality in these patients. The addition of alpha-fetoprotein to a surveillance regimen is thought to improve the sensitivity of HCC detection.Further investigation of serum biomarkers is needed. Semiannual screening is the suggested surveillance interval. Surveillance for HCC is underutilized and low adherence disproportionately affects certain demographics such as nonCaucasian race and low socioeconomic status.     

Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence

Abstract: Thirty-eight patients with porphyria cutanea tarda (PCT) have been seen in the last 18 years. Five of these patients (13%) developed hepatocellular carcinoma (HCC) during follow-up. We analyzed the differences in clinical, laboratory and liver histology findings at presentation, between patients who developed HCC during follow-up (HCC-group, n = 5) and those who did not (PCT-group, n = 33). Of the clinical features the duration of skin-symptoms was longer in the HCC-group (mean: 10.4±1.1 years) than in the PCT-group (mean: 1.4±1 years) (p > 0.001). No differences in routine laboratory findings were found. Although 11/38 (29%) patients had serologic evidence of a past hepatitis B virus infection and 7/38 (18%) patients had antibodies against hepatitis C virus, no differences in these parameters were found between the PCT-group and the HCC-group. In all 34 liver biopsies a variable degree of siderosis was found (PCT-group vs. HCC-group: NS). Only piecemeal necrosis (p>0.01) and advanced fibrosis or cirrhosis (p>0.001) were more common in liver biopsies in the HCC-group. In conclusion, factors related to an increased risk of HCC in PCT are: a) a long symptomatic period before start of treatment and b) the presence of chronic active hepatitis and/or advanced fibrosis or cirrhosis in liver biopsies.     

Hepatocellular carcinoma in porphyria cutanea tarda: frequency and factors related to its occurrence.

Thirty-eight patients with porphyria cutanea tarda (PCT) have been seen in the last 18 years. Five of these patients (13%) developed hepatocellular carcinoma (HCC) during follow-up. We analyzed the differences in clinical, laboratory and liver histology findings at presentation, between patients who developed HCC during follow-up (HCC-group, n = 5) and those who did not (PCT-group, n = 33). Of the clinical features the duration of skin-symptoms was longer in the HCC-group (mean: 10.4 +/- 1.1 years) than in the PCT-group (mean: 1.4 +/- 1 years) (p less than 0.001). No differences in routine laboratory findings were found. Although 11/38 (29%) patients had serologic evidence of a past hepatitis B virus infection and 7/38 (18%) patients had antibodies against hepatitis C virus, no differences in these parameters were found between the PCT-group and the HCC-group. In all 34 liver biopsies a variable degree of siderosis was found (PCT-group vs. HCC-group: NS). Only piecemeal necrosis (p less than 0.01) and advanced fibrosis or cirrhosis (p less than 0.001) were more common in liver biopsies in the HCC-group. In conclusion, factors related to an increased risk of HCC in PCT are: a) a long symptomatic period before start of treatment and b) the presence of chronic active hepatitis and/or advanced fibrosis or cirrhosis in liver biopsies.     

HCV HBV感染与肝细胞性肝癌

调查了肝癌高发地区不同肝病患者中丙型肝炎病毒(HCV)感染率。慢性肝病患者绝大多数已被乙型肝炎病毒(HBV)感染。HCV第二代抗体阳性率,肝癌7.3％,肝硬化6.6％,慢性肝炎6.6％和急性肝炎3.4％。两种病毒的复合感染率,肝癌5.1％,肝硬化1.7％,慢性肝炎3.9％和急性肝炎1.1％。在38例HCV抗体阳性的慢性肝病患者中,ALT异常84.2％,有输血史者占57.9％,HCV-RNA阳性率为71.1％。本研究的资料分析提示,在肝癌高发地区尽管HCV抗体阳性率较低,但HCV感染也是肝癌发生的重要病因之一。