Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%‐8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long‐term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis‐related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow‐up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow‐up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow‐up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942‐2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407‐3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333‐1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.     

Risk factors for hepatocellular carcinoma in patients with liver cirrhosis.

OBJECTIVE: Although cirrhosis is known to predispose toward hepatocellular carcinoma (HCC), there is no agreement on the factors that can influence the risk for HCC in patients with cirrhosis. This study was designed to identify differences in cirrhosis-related risk factors for developing HCC in relation to epidemiological characteristics, stage of the disease and etiology. METHODS: 512 patients from southwestern Spain with Child-Pugh stage A or B cirrhosis were examined periodically by ultrasonography, and alpha-fetoprotein (AFP) concentration was measured. RESULTS: The average length of follow-up was 37 months. A total of 52 cases of HCC were detected, which represented a risk of 17% after 5 years of follow-up. The Cox model showed that the risk of HCC increased by 8% per year of increasing age. Male sex (relative risk: 3.4), hepatitis C virus infection (relative risk: 4.6), hepatitis B virus infection (relative risk: 2.9) and AFP levels higher than 15 ng/ml (relative risk: 2.5) were also shown to be risk factors. Among alcoholic patients, only age (risk increased by 15% per year), and hepatitis C virus infection (relative risk: 5.4) were risk factors for HCC. However, in patients infected by hepatitis C virus, the main risk factors were age (relative risk increased by 8% per year), male sex (relative risk: 3.9), co-infection with hepatitis B virus (relative risk: 4.9), and increased AFP (relative risk: 2.8). Of the patients with HCC, 71% were infected with hepatitis C virus. Alcoholism, Child-Pugh stage and duration of cirrhosis did not increase the risk of the appearance of HCC. CONCLUSIONS: The risk of HCC increased to 17% after 5 years of follow-up in patients with Child-Pugh stage A or B cirrhosis. Hepatitis C virus infection was the main risk factor in patients with cirrhosis. Other risk factors were age, male sex, hepatitis B virus infection and altered AFP level.     

Des-gamma-carboxyprothrombin, alpha-fetoprotein and AFP-L3 in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma

Background and Aim: Hepatocellular carcinoma (HCC) is a common complication in patients with chronic viral hepatitis. Detection of HCC at an early stage is critical for a favorable clinical outcome. The study aim was to: (i) compare the levels of des‐γ‐carboxyprothrombin (DCP), α‐fetoprotein (AFP) and AFP‐L3 in HCC patients and in chronic viral hepatitis patients without HCC; (ii) define the level of each tumor marker with the best sensitivity and specificity for HCC diagnosis; and (iii) to correlate the levels of these markers with respect to size and tumor burden. Methods: Two hundred and forty patients with either hepatitis B virus (HBV) or hepatitis C virus (HCV) infection were studied. These included 144 with HCC, 47 with chronic hepatitis (fibrosis stage I–III on liver biopsy) and 49 with cirrhosis. Results: Levels of DCP, AFP and AFP L‐3 were significantly higher in patients with HCC than in those without HCC (P ≤ 0.0001). Receiver–operating curves (ROC) indicated that the cut‐off value with the best sensitivity and specificity for each test was ≥84 mAU/mL for DCP, ≥25 ng/mL for AFP and ≥10% for AFP‐L3. The sensitivity, specificity and positive predictive value (PPV) for DCP was 87%, 85% and 86.8%, for AFP 69%, 87% and 69.8%, and for AFP‐L3 56%, 90% and 56.1%, respectively. DCP levels were below the ROC cut‐off in all patients without HCC. In patients with single lesions, there was a direct correlation of DCP to tumor size. High levels of AFP correlated with diffuse type of HCC. All three markers were significantly elevated in the presence of metastatic HCC. No advantage was observed by combining two or three markers for HCC diagnosis. Conclusion: DCP had the highest sensitivity and PPV for HCC diagnosis, had a direct correlation with tumor size, and was not elevated in any patients without HCC. DCP should be used as the main serum test for HCC detection.     

Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low‐endemic area

Abstract: Aims/Background: This study was undertaken in order to assess the main features of hepatocellular carcinoma in Germany, a country with low incidences of this tumor. Methods: Two hundred and eighty consecutive patients with hepatocellular carcinomas admitted to the Medical School Hannover between 1993–1997 were retrospectively studied. Results: Reliable data for the assessment of the etiology and the tumor stage of HCC were available for 268 patients. The female/male ratio was 1/4. In 51.9% of the patients, HCC was associated with hepatitis virus B or C (HBV, HCV) infection: 35.1% with HBV, 26.9% with HCV and 10% coinfection with HBV/HCV. This result emphasizes the major impact of HBV and HCV infection in liver cancer in Germany. Of all patients with HCC 74.6% had liver cirrhosis. The predominant majority of the HCC (87%) were restricted to the liver: in only 5.9% could regional lymph node metastases as well as 8.5% metastases in other organs be clinically diagnosed by chest X‐ray, computed tomography scan or sonography. Data to asses the Okuda tumor stage were available for 166 patients: 47% were classified as stage I, 47% as stage II and only 6% as stage III. Serum AFP were determined in 195 patients. In 66% of the patients, the AFP value was elevated, but only in 30% did the AFP level reach the value of 500 μg/l, which is considered to be significant for HCC diagnosis in patients with liver cirrhosis. The proportion of liver cirrhosis was higher in HCV (97.8%) versus HBV (80.6%) associated HCC, which was the only significant (p<0.05) difference in the characteristics of HCC according to the etiology. Conclusion: Our study shows that liver cirrhosis is the prime risk factor for hepatocarcinogenesis in Germany. However, the very high proportion of hepatitis virus related HCC, in particular the high proportion of HBV infections, contradicts the common view that alcohol is by far the most important etiological factor for hepatocarcinogenesis in low hepatitis virus endemic areas such as Germany.     

Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low-endemic area

AIMS/BACKGROUND: This study was undertaken in order to assess the main features of hepatocellular carcinoma in Germany, a country with low incidences of this tumor. METHODS: Two hundred and eighty consecutive patients with hepatocellular carcinomas admitted to the Medical School Hannover between 1993-1997 were retrospectively studied. RESULTS: Reliable data for the assessment of the etiology and the tumor stage of HCC were available for 268 patients. The female/male ratio was 1/4. In 51.9% of the patients, HCC was associated with hepatitis virus B or C (HBV, HCV) infection: 35.1% with HBV, 26.9%) with HCV and 10% coinfection with HBV/HCV This result emphasizes the major impact of HBV and HCV infection in liver cancer in Germany. Of all patients with HCC 74.6%) had liver cirrhosis. The predominant majority of the HCC (87%) were restricted to the liver: in only 5.9% could regional lymph node metastases as well as 8.5%) metastases in other organs be clinically diagnosed by chest X-ray, computed tomography scan or sonography. Data to asses the Okuda tumor stage were available for 166 patients: 47% were classified as stage I, 47% as stage II and only 6% as stage III. Serum AFP were determined in 195 patients. In 66% of the patients, the AFP value was elevated, but only in 30% did the AFP level reach the value of 500 microg/l, which is considered to be significant for HCC diagnosis in patients with liver cirrhosis. The proportion of liver cirrhosis was higher in HCV (97.8%) versus HBV (80.6%) associated HCC, which was the only significant (p<0.05) difference in the characteristics of HCC according to the etiology. CONCLUSION: Our study shows that liver cirrhosis is the prime risk factor for hepatocarcinogenesis in Germany. However, the very high proportion of hepatitis virus related HCC, in particular the high proportion of HBV infections, contradicts the common view that alcohol is by far the most important etiological factor for hepatocarcinogenesis in low hepatitis virus endemic areas such as Germany.     

Efficacy of ultrasonography and alpha-fetoprotein on early detection of hepatocellular carcinoma

AIM: To evaluate the effectiveness of ultrasonographic screening for early detection of hepatocellular carcinoma (HCC). METHODS: The data of 14968 patients who had ultrasonography (US) for chronic liver diseases were collected into a database program from June 1995 to June 2005. The risk factors for HCC were also studied. A total of 6089 patients who had repeated US were enrolled, 264 patients were diagnosed with HCC during follow-up (mean, 39 mo). RESULTS: The detection rate of small HCC (≤3 cm in diameter) was 67.7%. The tumor size detected by screening at the intervals of 6 mo was significantly smaller than that at longer intervals. Only 29.3% of HCC patients had an elevated serum alpha fetoprotein (AFP) level above 400 ng/mL. The risk of HCC development during follow-up was higher in patients with liver cirrhosis (10.9%) and hepatitis C (9.0%) than in patients with chronic hepatitis (4.2%), hepatitis B (4.9%) and non-B, non-C hepatitis (NBNC, 3.9%). CONCLUSION: US screening at a interval of 6 mo is beneficial to high-risk patients over 40 years old and the early detection of HCC prolongs survival.     

A prospective study of blood alpha-fetoprotein messenger RNA as a predictor of hepatocellular carcinoma in patients with cirrhosis

Summary. Blood alpha-fetoprotein messenger RNA (AFP mRNA) is thought to be a marker of hepatocellular carcinoma (HCC). Its value as a predictor of HCC in patients at risk is not known. A series of 201 patients with compensated cirrhosis (114 men, mean age 58 years) underwent surveillance with semi-annual ultrasound and serum alpha-fetoprotein measurements. Total RNA was extracted from peripheral blood mononuclear cells collected at different intervals and AFP mRNA was retrotranscribed and amplified by nested polymerase chain reaction. Ten patients with HCC and 30 blood donors were used as controls. Three patients with HCC, 39 with cirrhosis under surveillance and four blood donors circulated AFP mRNA (30, 20 and 13%, NS). During 50 months of surveillance, 27 patients with cirrhosis developed HCC: the tumour was detected more often in patients with higher than normal baseline serum AFP (≥7 IU/L) than in those with normal AFP levels (21% vs 9%, P  = 0.02). The incidence of HCC was the same in patients with and without AFP mRNA at baseline (15% vs 14%). In 53 patients, AFP mRNA was re-tested after 6–25 months of surveillance. HCC developed in two of 11 (18%) who were initially AFP mRNA positive and later became negative, in none of those who were initially negative and later became positive and in two of 39 (5%) who remained persistently negative. In conclusion, blood AFP mRNA is not a sensitive predictor of HCC in patients with compensated cirrhosis.     

Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C

Objective: The clinical and morphological significance of a raised alpha-fetoprotein (AFP) level in patients with chronic hepatitis C is undefined. We sought to determine the relation between serum AFP level and liver histology in this population.
Methods: We reviewed the clinical and histological records of 200 consecutively evaluated patients with chronic hepatitis C whose serum AFP levels were recorded. Two groups were studied: group I = 125/200 (62%) patients with normal AFP, < 10 ng/ml; and group II = 75/200 (38%) patients with raised AFP, > 10 ng/ml. The groups were compared according to age, gender, duration of disease, histology, and history of alcohol abuse.
Results: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration. Significant histological differences were observed: cirrhosis was present in 57 (45%) patients in group I versus 51 (68%) in group II (   p < 0.001  ). Hepatocellular carcinoma was more frequent in group II (14/75 [19%]) than in group I (1/125 [1%]) (   p < 0.001  ). Ten of 77 (13%) noncirrhotic patients and 51/108 (47%) cirrhotic patients had a raised AFP (   p < 0.002  ; relative risk, 3.262; confidence interval [C.I.], 1.912–5.564). A derived AFP level of 17.8 ng/ml maximized specificity for predicting histological outcome: one of 76 (1.3%), 29/108 (26.8%), and 14/15 (93.3%) patients were noncirrhotic, cirrhotic, or had HCC, respectively. This derived AFP value is 35% sensitive and 98.6% specific for cirrhosis, with a positive predictive value of 97.7%.
Conclusions: A serum AFP level >17.8 ng/ml strongly suggests the diagnosis of cirrhosis in a population of patients with chronic hepatitis C.     

Screening for hepatocellular carcinoma in patients with hepatitis C cirrhosis: a cost-utility analysis

OBJECTIVES: Screening for hepatocellular carcinoma (HCC) is advocated in cirrhotic patients to optimize early detection and treatment. However, the cost-effectiveness is not well defined. Our objective was to perform a cost-utility analysis from a third-party payer's perspective of no screening, alpha-fetoprotein (AFP) concentration measurement alone, abdominal ultrasound (US) and AFP, abdominal three-phase CT and AFP, and abdominal magnetic resonance imaging (MRI) and AFP. METHODS: A Markov model was constructed simulating the natural history of hepatitis C-related cirrhosis in a cohort of patients age 50 yr over a time horizon of their remaining life expectancy. Transition probabilities were obtained from published data and U.S. vital statistics. Costs represented Medicare reimbursement data. Costs and health effects were discounted at a 3% annual rate. RESULTS: Screening with ultrasonography and AFP concentration measurement was associated with an incremental cost-utility ratio of 26,689 US dollars per quality-adjusted life year, whereas screening with abdominal three-phase CT and AFP concentration measurement was associated with an incremental cost-utility ratio of 25,232 US dollars per quality-adjusted life year compared with no screening. Compared with three-phase CT and AFP, magnetic resonance and AFP imaging costs 118,000 US dollars per quality-adjusted life year. Sensitivity analysis demonstrated that the results are most sensitive to the annual incidence of HCC, proportion of tumors amenable to treatment, and to transplant candidacy, whereas the choice of screening strategy is most sensitive to the test characteristics and cost. CONCLUSIONS: Screening for HCC with CT is a cost-effective strategy in transplant-eligible patients with cirrhosis secondary to chronic hepatitis C viral (HCV) infection, comparable with other commonly accepted screening interventions such as mammography and colonoscopy.     

Epidemiology and outcomes of hepatitis C infection in elderly US Veterans

The chronic hepatitis C (CHC) cohort in the United States is getting older. Elderly patients with CHC may be at a high risk of cirrhosis and hepatocellular carcinoma (HCC), but also other nonhepatic comorbidities that negatively impact their likelihood of receiving or responding to antiviral treatment. There is little information on the clinical epidemiology or outcomes of CHC and its treatment in the elderly. We conducted a retrospective cohort study of 1 61 744 patients with a positive Hepatitis C virus RNA in the Veterans Health Administration Hepatitis C Clinical Case Registry to examine the association between age subgroups (20–49, 50–64, 65–85 years) and risk of cirrhosis, HCC or death using Cox proportional hazards models. We also examined the effect of treatment with a sustained viral response (SVR) on these outcomes in each age subgroup. The age distribution was 36.8% 20‐ to 49‐year‐olds, 57.6% 50‐ to 64‐year‐olds and 5.6% 65‐ to 85‐year‐olds (i.e. elderly). Risk of cirrhosis, HCC and death was significantly elevated in elderly patients [HR cirrhosis = 1.14 (1.00–1.29), HR HCC = 2.44 (1.99–2.99); HR death 2.09 (1.98–2.22)] compared with younger patients. The incidence of HCC was than 8.4 per 1000 PY in the elderly compared with 2.6 per 1000 PY and 5.7 per 1000 PY, among the 20–49 and 50–64 age groups, respectively. Elderly patients were significantly less likely to receive antiviral treatment (3.8% vs 14.8% and 19.1%, P < 0.0001), but among those who received treatment SVR was not different among the age groups (33.5% vs 33.2% and 32.1%). In an analysis limited to those who received treatment, SVR compared to treatment receipt with no SVR was associated with a reduction in risk of developing cirrhosis (HR = 0.34; 0.18–0.66) and HCC (HR = 0.60; 0.22–1.61) and all‐cause mortality risk (HR = 0.52, 0.33–0.82). Elderly patients with CHC are more likely to develop HCC than younger patients but have traditionally received less antiviral treatment than younger patients. However, receipt of curative treatment is associated with a benefit in reducing cirrhosis, HCC and overall mortality, irrespective of age.     

Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers

Background and Aims:  The role of glypican-3 (GPC3), a novel serum marker, in differentiating hepatocellular carcinoma (HCC) from non-malignant chronic liver disease and other malignant space-occupying lesions in the liver is largely unknown. The aims of this study were to evaluate its diagnostic role and clinical correlations in patients with HCC.
Methods:  Six groups were studied which included 40 healthy subjects, 50 patients with chronic hepatitis (CH), 50 patients with liver cirrhosis (LC), 100 patients with HCC, 50 patients with intrahepatic cholangiocarcinoma (ICC) and 50 patients with metastatic carcinoma (MCA). Serum GPC3 levels were measured by using a sandwich enzyme-linked immunosorbent assay method.
Results:  Fifty-three percent of HCC patients had elevated serum GPC3 levels with values ranging 35.5–7826.6 ng/mL. The serum marker was undetectable in other groups except one patient (2%) with LC and another patient (2%) with MCA. In most cases of HCC, elevated GPC3 values did not correlate with α-fetoprotein (AFP) levels. Detectable GPC3 was significantly correlated with the presence of viral hepatitis markers but was not correlated with tumor size and stage of HCC. Serum GPC3 was superior to AFP in detecting small HCC (56.3% and 31.3%, respectively). A combination of serum GPC3 and AFP yielded an improved sensitivity for detecting small HCC to 75%.
Conclusion:  Serum GPC3 is highly specific for detecting HCC. The combined use of serum GPC3 and AFP provides a potentially promising tool to better differentiate HCC from benign liver disorders, as well as from other liver cancers.     

Evaluation of serum clusterin as a surveillance tool for human hepatocellular carcinoma with hepatitis B virus related cirrhosis

Background and Aim: Hepatocellular carcinoma (HCC) is a common human cancer worldwide. The levels of serum clusterin in HCC patients and its potential diagnostic significance is not clear. We aimed to evaluate the clinical use of serum clusterin levels as a surveillance tool for HCC with hepatitis B virus (HBV) related cirrhosis. Methods: Twenty‐two cases of healthy subjects, 31 cases of HBV carriers, 26 patients with chronic hepatitis B, 29 patients with cirrhosis, and 76 patients with HCC were enrolled in this study. Serum levels of clusterin were measured by a sandwich enzyme‐linked immunosorbent assay. Results: The serum clusterin levels in HCC patients were significantly lower than that in healthy, HBV carriers and chronic hepatitis B, but statistically higher than in cirrhosis patients. Receiver operator characteristic (ROC) curve indicated that a serum clusterin value of 50 µg/mL yielded the best sensitivity (91%) and specificity (83%) for differentiating HCC patients with HBV‐related cirrhosis from those with HBV‐related cirrhosis. The optimal alpha fetoprotein (AFP) cutoff value was 15 ng/mL and was inferior to the clusterin value of 50 µg/mL, the area under the ROC curves being 0.937 versus 0.781, respectively (P < 0.05). Conclusions: Serum clusterin was more sensitive and specific than serum AFP for differentiating HCC patients with HBV‐related cirrhosis from those with HBV‐related liver cirrhosis, and may be a useful surveillance tool of HCC based on HBV‐related cirrhosis.     

Risk and outcome of hepatocellular carcinoma in liver cirrhosis in Southern Sweden: a population-based study

Background and aims: Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC). While the HCC risk is thought to be highest in hepatitis B and hepatitis C, the risk in other cirrhosis etiologies is not fully established. Therefore, we aimed to study the risk and outcome of HCC in alcoholic cirrhosis compared to cirrhosis of other etiologies, in Sweden.

Material and methods: We used population-based medical registries to identify patients diagnosed with cirrhosis in the Scania region in southern Sweden between 2001 and 2010. Medical records were reviewed to identify all HCC cases and to register clinical parameters. All patients were followed until death, emigration or December 2017.

Results: The cohort comprised 1317 patients with cirrhosis. A total of 200 patient developed HCC, including 75 with prevalent HCC. The annual incidence of HCC after six months was 1.5% in alcoholic cirrhosis and 4.7% in hepatitis C cirrhosis. In alcoholic cirrhosis, 40 patients were diagnosed with HCC during follow-up, of which 15 patients fulfilled the Milan criteria and 10 received treatment, curative or palliative. The overall median survival after HCC diagnosis was 7.7 months, with 4.5, 11 and 9.3 months, in cirrhosis due to alcohol, hepatitis C or remaining causes, respectively.

Conclusion: We find an annual incidence of HCC in alcoholic cirrhosis of 1.5% indicating need for surveillance in these patients. Survival after HCC diagnosis was worst in alcoholic cirrhosis due to more advanced stage at diagnosis with few patients eligible for treatment.     

Long‐term outcome and hepatocellular carcinoma development in chronic hepatitis B or cirrhosis patients after nucleoside analog treatment with entecavir or lamivudine

Aim: We conducted this prospective study to elucidate the long‐term outcome and incidence of hepatocellular carcinoma (HCC) development after nucleos(t)ide analog (NA) treatment in patients with chronic hepatitis B (CHB) or cirrhosis. Methods: CHB or cirrhosis patients without past NA treatment or HCC were started on entecavir (ETV) or lamivudine (LVD), and prospectively followed up with monthly blood tests, and with abdominal imaging every 6 months in CHB and every 3 months in cirrhosis patients. Results: A total of 256 subjects with CHB (n = 194) or cirrhosis (n = 62) received ETV (n = 129) or LVD (n = 127) for 4.25 years (range: 0.41–10.0). After NA treatment, serum HBV DNA, alanine aminotransferase and α‐fetoprotein (AFP) dropped significantly, along with significant increases in serum albumin and prothrombin time. Drug‐resistance developed in 60 cases in the LVD group and in only one case in the ETV group. HCC developed in 35 patients, and the incidence at years 1, 3, 5, 7 and 10 was significantly higher in patients with cirrhosis (8.1%, 17.5%, 43.2%, 46.7% and 53.4%, respectively) than chronic hepatitis (1.6%, 3.5%, 3.5%, 7.1% and 29.6%, respectively), with no difference between ETV and LVD. After NA treatment, the sensitivity/specificity for HCC of AFP and des‐γ‐carboxy prothrombin (DCP) was 45.7%/97.3% and 33.3%/96.2%, respectively, with the specificity of AFP being higher than at baseline (64.4%), at the cut‐off of 10 ng/mL. Conclusion: NA exerted a long‐term efficacy and improved hepatic reservation in CHB and cirrhosis. After NA treatment, AFP dropped to lower than 10 ng/mL with marked elevation of specificity, leading to an earlier detection of HCC.     

Long‐term outcome of hepatitis B virus‐related Chronic Hepatitis under protracted nucleos(t)ide analogues

Long‐term outcome of patients with chronic hepatitis B virus (HBV) infection under continuous nucleos(t)ide analogues (NUCs) has been poorly elucidated. We enrolled 121 anti‐HBe‐positive patients into a prospective surveillance programme while on (>36 months) NUCs therapy. HBV‐DNA clearance, add‐on therapy and safety were evaluated. Development of cirrhosis, events of liver decompensation and hepatocellular carcinoma (HCC) during the follow‐up were the main endpoints, as the complication‐free survival. At baseline, 74 patients (61%) had chronic hepatitis, the remainders a cirrhotic liver. HBV‐DNA levels >38 000 IU/mL were discovered in 103 patients. At enrolment, 79 patients were naïve to NUCs treatment. Lamivudine monotherapy (n = 70) or a different NUC (n = 51) was administered. At month 6 of therapy, HBV‐DNA clearance was documented in 88 patients (73%). Treatment schedule was modified in 52 patients due to breakthrough or suboptimal response. During a mean follow‐up of 6 ± 3 years, viral clearance was achieved in the majority of patients. Ten of 74 patients (13.5%) with chronic hepatitis progressed to cirrhosis, 1 patient developed a HCC. In the 47 patients with cirrhosis at presentation, HCC occurred in 14 (30%) and liver decompensation in 5 (11%). The 5 and 10‐year event‐free survivals were, respectively, 89.3% (95% CI, 81.7 ?96.9) and 75.6% (95% CI, 61.5 ?89.7) for patients with chronic hepatitis, and 70.2% (95% CI, 56.3 ?84.1) and 40.4% (95% CI, 16.9 ?63.9) for those with cirrhosis. Protracted, effective treatment with oral NUCs affects the natural history of chronic HBV infection by reducing the incidence of cirrhosis and risk of complications, but does not guarantee against the development of HCC in cirrhosis at presentation.     

Ultrasonography and alpha-fetoprotein in diagnosis of hepatocellular carcinoma in cirrhosis

The accuracy of ultrasound (US) and alpha-fetoprotein (AFP) in the diagnosis of hepatocellular carcinoma (HCC) in 363 patients with cirrhosis (C) and a clinical suspicion of HCC was assessed. The ultrasonographic patterns of HCC and their relationship with AFP values were analyzed. Echographic patterns were distributed as follows: 47 patients had sonodense lesions; 30 patients had hypoechoic lesions; 47 had mixed-pattern lesions, and in four patients focal dilated intrahepatic bile ducts were demonstrated. The sensitivity of US was 90%; specificity was 93.3%. Serum AFP level 500 ng/ml (RIA) was the first clue to the diagnosis in 71 patients (48.6%); specificity was 100%. In 28 patients AFP levels became significantly elevated during follow-up after US detection of HCC. No relationship between echo pattern and serum AFP levels was demonstrated. An algorithm for diagnosis of HCC is proposed.     

Data mining reveals complex interactions of risk factors and clinical feature profiling associated with the staging of non‐hepatitis B virus/non‐hepatitis C virus‐related hepatocellular carcinoma

Aim: Non‐hepatitis B virus/non‐hepatitis C virus‐related hepatocellular carcinoma (NBNC‐HCC) is often detected at an advanced stage, and the pathology associated with the staging of NBNC‐HCC remains unclear. Data mining is a set of statistical techniques which uncovers interactions and meaningful patterns of factors from a large data collection. The aims of this study were to reveal complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC‐HCC using data mining techniques. Methods: A database was created from 663 patients with NBNC‐HCC at 20 institutions. The Milan criteria were used as staging of HCC. Complex associations of variables and clinical feature profiling with the Milan criteria were analyzed by graphical modeling and decision tree algorithm methods, respectively. Results: Graphical modeling identified six factors independently associated with the Milan criteria: diagnostic year of HCC; diagnosis of liver cirrhosis; serum aspartate aminotransferase (AST); alanine aminotransferase (ALT); α‐fetoprotein (AFP); and des‐γ‐carboxy prothrombin (DCP) levels. The decision trees were created with five variables to classify six groups of patients. Sixty‐nine percent of the patients were within the Milan criteria, when patients showed an AFP level of 200 ng/mL or less, diagnosis of liver cirrhosis and an AST level of less than 93 IU/mL. On the other hand, 18% of the patients were within the Milan criteria, when patients showed an AFP level of more than 200 ng/mL and ALT level of 20 IU/mL or more. Conclusion: Data mining disclosed complex interactions of the risk factors and clinical feature profiling associated with the staging of NBNC‐HCC.     

Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study

Background

Increasing evidence suggests the efficacy of interferon therapy for hepatitis C in reducing the risk of hepatocellular carcinoma (HCC). The aim of this study was to identify predictive markers for the risk of HCC incidence in chronic hepatitis C patients receiving interferon therapy.

Methods

A total of 382 patients were treated with standard interferon or pegylated interferon in combination with ribavirin for chronic hepatitis C in a single center and evaluated for variables predictive of HCC incidence.

Results

Incidence rates of HCC after interferon therapy were 6.6% at 5?years and 13.4% at 8?years. Non-sustained virological response (non-SVR) to antiviral therapy was an independent predictor for incidence of HCC in the total study population. Among 197 non-SVR patients, independent predictive factors were an average alpha-fetoprotein (AFP) integration value ≥10?ng/mL and male gender. Even in patients whose AFP levels before interferon therapy were ≥10?ng/mL, reduction of average AFP integration value to <10?ng/mL by treatment was strongly associated with a reduced incidence of HCC. This was significant compared to patients with average AFP integration values of ≥10?ng/mL (P?=?0.009).

Conclusions

Achieving sustained virological response (SVR) by interferon therapy reduces the incidence of HCC in hepatitis C patients treated with interferon. Among non-SVR patients, a decrease in the AFP integration value by interferon therapy closely correlates with reduced risk of HCC incidence after treatment.     

Incidence of hepatocellular carcinoma among Indian patients with cirrhosis of liver: an experience from a tertiary care center in northern India.

BACKGROUND/AIM: Despite bearing the main burden of HCC, prospective studies from developing countries are lacking. This prospective observational study was designed to estimate the incidence of HCC among Indian patients with hepatic cirrhosis. METHODS: Between April 2001 and November 2004, we enrolled 301 patients with liver cirrhosis. Patients found to be free of HCC using baseline abdominal ultrasound, triple-phase computed tomography (TPCT) and serum alpha-fetoprotein (AFP) levels were followed up prospectively for detection of HCC using ultrasound and AFP every 6 months, and TPCT annually. RESULTS: Among the 194 patients (mean age [SD] 45.1 [+/-13.1] years; male:female 6.1:1.0) followed up, 154 had Child's A and 40 had Child's B disease. The causes of cirrhosis were: hepatitis B-71 (36.6%), hepatitis C-54 (27.8%), dual infection with hepatitis B and C-12 (6.2%) and others including autoimmune, alcoholic and cryptogenic cirrhosis 57 (29.4%). During a cumulative follow up period of 563.4 person-years, 9 cases of HCC were detected, with an incidence rate of 1.60 per 100 person-years. CONCLUSION: In our study, the incidence of HCC among patients with liver cirrhosis was intermediate, being lower than that in Japan but higher than that reported from Europe.     

中国北方地区321例乙型肝炎病毒相关肝细胞癌患者的流行病学和临床特征分析

背景:我国是肝细胞癌(HCC)高发区,其中大部分HCC与乙型肝炎病毒(HBV)感染相关,有必要对其自然史和临床进程作大样本调查研究。目的:了解中国北方地区HBV相关HCC患者的流行病学和临床特征。方法:对中国北方地区321例HBV相关HCC患者作流行病学问卷调查,行肝功能、甲胎蛋白(AFP)、HBV血清标志物和HBV DNA水平检测,并进行统计分析。结果:321例HBV相关HCC患者中,仅7.2%接受过抗病毒治疗;46.4%和25.5%分别有肝硬化和肝癌家族史;38.3%有饮酒史。21.0%的患者乙型肝炎e抗原(HBeAg)阳性,62.3%乙型肝炎e抗体(HBeAb)阳性,HBeAg阳性者合并肝硬化的比例和HBV DNA水平较高。84.5%的患者HBV DNA阳性,但其中仅42.6%HBV DNA≥5.0log10,HBV DNA高水平者合并肝硬化的比例显著高于HBV DNA低水平者。无症状HBV感染、慢性乙型肝炎、代偿性和失代偿性肝硬化患者分别占4.1%、24.1%、39.0%和32.9%。71.0%的患者AFP升高,但其中仅33.8?P≥400ng/ml。结论:本组HBV相关HCC患者中,HBeAg阳性和高HBV DNA水平者不多,但病情常较重。肝硬化是HCC的重要危险因素,饮酒和肝癌家族史对HCC的发生有一定影响。血清AFP筛查有助于HCC的诊断。