Previous History Of Hepatocellular Carcinoma Research Articles

Abstract 5925: Albumin-bilirubin score as a marker for predicting occurrence of hepatocellular carcinoma in patients with liver cirrhosis

Abstract Background: The newly developed albumin-bilirubin (ALBI) score has been proved to be a simple and useful marker for predicting prognosis in patients with hepatocellular carcinoma (HCC). However, evidence is scarce regarding the use of ALBI score to predict occurrence of HCC in patients with chronic liver disease. In the current study, we examined the usefulness of ALBI score to predict occurrence of HCC in patients with liver cirrhosis. Methods: In this retrospective study, we included only cirrhotic patients without previous history of HCC. A total of 68 cirrhotic patients (median age, 68 years old; 36 males and 32 females; 42 compensated and 26 decompensated cirrhosis) were included. Using a Cox proportional hazard model, we identified the risk factors for HCC occurrence and mortality. The potential factors were age, gender, causes of cirrhosis (hepatitis virus infection vs others), platelet count, serum alpha-fetoprotein (AFP) level, serum endocan level, ALBI score, and successful treatment for cirrhosis (yes vs no). Results: The leading cause of cirrhosis was hepatitis virus infection (9 HBV- and 20 HCV-infected patients), followed by alcohol-related liver disease (23 patients), nonalcoholic steatohepatitis (5 patients), and other causes (2 patients). The median follow-up period was 10 years. During the study period, 16 patients had HCC and 22 patients died (12 liver failure, 3 HCC, 2 variceal rupture, 2 bacterial infection, and 3 other causes). Cumulative survival rates were 92%, 72%, and 59%, at 5, 10, and 15 years, respectively. Regarding risk factors for HCC occurrence, univariate analysis identified a low platelet count and an increased ALBI score as significant factors. However, on multivariate analysis, an increased ALBI score was the only significant factor [hazard ratio, 7.49 (1.65−34.04); p = 0.009]. Regarding risk factors for mortality, univariate analysis identified older age as the only significant factor; male gender and hepatitis virus infection tended to be significant. However, on multivariate analysis, older age, male gender, and hepatitis virus infection were significant factors. Conclusion: The results indicate that an increased ALBI score is a useful factor to predict occurrence of HCC in patients with liver cirrhosis. Citation Format: Nobuyuki Toshikuni, Mutsumi Tsuchishima, Mikihiro Tsutsumi, Joseph George. Albumin-bilirubin score as a marker for predicting occurrence of hepatocellular carcinoma in patients with liver cirrhosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5925.

A Novel Standard for Hepatocellular Carcinoma Screening Intensity After Hepatitis C Elimination.

PurposeTo investigate long-term incidence of hepatocellular carcinoma (HCC) and the factors associated with HCC occurrence after achieving sustained virological response (SVR) by direct-acting antiviral agent (DAA) treatment for hepatitis C virus (HCV).MethodsA total of 476 patients (male 227, female 249; median age 68) with chronic HCV infection who were treated with DAAs and achieved SVR were analyzed. The incidence of HCC and factors related to the development of HCC after HCV elimination were evaluated.ResultsThe median observation period was 46.4 months. During this period, 40 patients developed HCC. The incidence rates of HCC were 3.7%, 6.0%, 7.1%, 9.3%, and 10.6% at 1, 2, 3, 4, and 5 years post-SVR12, respectively. Multivariate analysis with pre-treatment factors revealed that platelet count, α-fetoprotein, fibrosis-4 (Fib-4) index, and previous HCC history were independent factors that contributed to development of HCC post-SVR following DAA treatment. Of these factors, previous HCC history was the most significant, followed by Fib-4 index. Using these two factors, a novel scoring system was established. The presence of previous HCC history was scored as 2, and then, the absence of previous HCC history was stratified by Fib-4 index (≥3.07, 1; <3.07, 0). The HCC occurrence rate at 5 years was 0.4% in the 0-point group, 6.8% in the 1-point group, and 55.6% in the 2-point group, respectively.ConclusionFib-4 index and previous HCC history were independent predictors for development of HCC after DAA treatment. Patients with these risk factors require careful observation.

Hepatocellular Carcinoma in Hepatitis C Virus Cirrhosis After Treatment with Direct Acting Antiviral Therapy

Aim: this study aimed to clarify the possible effect of direct acting antivirals (DAAs) treatment on development of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. , Methods: this study was conducted on 400 chronic hepatitis C cirrhotic patients, divided into two groups according to treatment with DAAs, group I including (200 Patients with chronic HCV cirrhosis treated with DAAs), and group II including (200 patients with chronic HCV cirrhosis without DAAs treatment), all patients were recruited from the Gastroenterology and Hepatology department Kobry Elkobba Military Hospital, all patients were males with no previous history of HCC, human immunodeficiency virus (HIV) or hepatitis B virus (HBV) infection or history of liver transplantation. After one year of follow up all patients were divided into further two subgroups according HCC development, group III ( 11 HCV cirrhotic patients treated with DAAs (sofosbuvir and daclatasvir) and developed HCC) and group IV (22 HCV cirrhotic patients not treated and developed HCC). Results: HCC developed more in not treated group with a significant difference as 11% of not treated group developed HCC compared to 5.5% only of treated group (P=0.046). using univariate cox regression, it was shown that no treatment was an independent risk factor of getting hepatocellular carcinoma (HCC), as cases not receiving the study treatment are at higher risk for developing HCC (HR=3.4, P=0.002). conclusion: DAA treatment is not associated with a higher risk of HCC in cirrhotic patients with chronic HCV infection in the short-term. The occurrence of HCC is significantly decreased in patients treated with DAAs.

Serum PreS1 and HBsAg ratio reflects liver fibrosis and predicts the development of hepatocellular carcinoma in chronic hepatitis B patients.

While the preS1 region of the large hepatitis B surface protein plays an essential role in hepatitis B virus (HBV) infection, the effect of preS1 on liver fibrosis and hepatocarcinogenesis in chronic hepatitis B (CHB) patients is not well known. In this study, we measured serum preS1levels by chemiluminescent immunoassay technology in 690 CHB patients and evaluated the correlation between serum preS1levels and HBV, liver function markers and liver inflammation, fibrosis assessed by histological findings. Predictive factors for hepatocellular carcinoma (HCC) development in patients who had no previous history of HCC at the time of preS1level measurement were also analysed. Median hepatitis B surface antigen (HBsAg) and preS1levels were 3.08log IU/mL and 98ng/mL, respectively. PreS1values were significantly correlated with serum HBsAg (p <0.001), hepatitis B core-related antigen (HBcrAg) (p <0.001) and HBV DNA levels (p <0.01). PreS1values were also significantly correlated with serum alanine aminotransferase levels (p <0.001) and were significantly higher in patients who had higher grading of liver inflammatory activity (p <0.05). HBsAg level was correlated, but preS1/HBsAg ratio reflected liver fibrosis staging more directly than HBsAg alone. Multivariate analysis identified age ≥53years (hazard ratio [HR], 18.360 for <53years; p = 0.021) and preS1/HBsAg ratio ≥0.12 (HR, 6.205 for <0.12; p = 0.040) as significant and independent factors for HCC development in CHB patients. The preS1/HBsAg ratio directly reflects liver fibrosis, and the ratio might be a predictive marker for HCC development in CHB patients.

AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

BackgroundAn unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment.MethodsOf 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated.ResultsNinety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase.ConclusionPatients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

Risk Factors for Hypervascularization in Hepatobiliary Phase Hypointense Nodules without Arterial Phase Hyperenhancement: A Systematic Review and Meta-analysis

To perform a systematic review and meta-analysis to determine risk factors for hypervascularization in hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) in patients with hepatocellular carcinoma (HCC). Pubmed and EMBASE databases were searched up to May 7, 2020. Studies which evaluated radiologic and clinical risk factors for hypervascularization in HBP hypointense nodules without APHE were included. Hazard ratios were meta-analytically pooled using random-effects model. Methodological quality of included studies was assessed using Quality in Prognostic Studies (QUIPS) tool. Sixteen studies with 934 patients were included. HBP hypointense nodules without APHE with baseline size greater than 10 mm, T2 hyperintensity, and restricted diffusion showed risk for hypervascularization with pooled HRs of 2.95 (95% confidence interval [CI], 1.94-4.20), 4.21 (95% CI, 1.15-15.40), 5.83 (95% CI, 1.42-23.95), respectively. Previous HCC history contributed to hypervascularization of the nodules with hazard ratio of 2.06 (95% CI, 1.23-3.44). T1 hyperintensity, intralesional fat, Child-Pugh Class B, sex, alfa-fetoprotein, hepatitis B or C infection were not significant risk factors for hypervascularization (p ≥0.05). Study quality was generally moderate. HBP hypointense nodules without APHE on gadoxetic acid-enhanced MRI with baseline size greater than 10 mm, T2 hyperintensity, restricted diffusion and previous hepatocellular carcinoma history pose higher risk for hypervascularization. Proper patient management in patients with HBP hypointense nodules without APHE on gadoxetic acid-enhanced MRI may need to be tailored according to these risk factors.

Follow-up Results of HCV GT2 Patients After Sofosbuvir/Ribavirin Therapy: Careful Attention to Occurrence of HCC.

We examined treatment the efficacy and data on long-term outcomes in real-world Japanese patients infected with hepatitis C virus (HCV) genotype 2 treated with 12-week sofosbuvir/ribavirin combination therapy. In a total of 86 patients who were treated with sofosbuvir/ribavirin, sustained virological response (SVR) rates and long-term-outcomes were retrospectively analyzed. The adherence to this combination therapy was 98.8%. The rates of SVR at week 24 (SVR24) achieved with this treatment according to the 'intention-to-treat' and 'per-protocol' analyses were 89.5% and 96.2%, respectively. Two patients who experienced relapse did not have any previously reported resistance-associated substitutions in the HCV non-structural protein 5B (NS5B) polymerase region. We did not observe any patients who experienced late relapse but did observe that 50% and 1.3% of patients with and without a previous history of hepatocellular carcinoma (HCC), respectively, developed HCC after achieving SVR24 (with a mean follow-up period of 2.7±0.8 years). Patients with SVR should be carefully followed-up to screen for the occurrence of HCC, although it is infrequent.

The predictors of sustained virological response with sofosbuvir and ribavirin in patients with chronic hepatitis C genotype 2.

Background/AimsReal-world, clinical practice data are lacking about sofosbuvir/ribavirin (SOF/RBV) treatment of Korean patients with hepatitis C virus genotype 2 (HCV GT2) infection. This study investigated the efficacy and safety of SOF/RBV in Korean patients with HCV GT2 infection and clinical factors predicting sustained virological response 12 weeks (SVR12) after the end of SOF/RBV treatment.MethodsA total of 181 patients with HCV GT2 with/without cirrhosis were treated with SOF/RBV for 16/12 weeks. Rapid virological response (RVR) was defined as non-detectable HCV RNA at 4 weeks.ResultsThe RVR rate was 80.7% (146/181), the end of treatment response rate was 97.8% (177/181) and the SVR12 rate was 92.8% (168/181). Of eight patients with relapse, four did not achieve RVR. Three patients had a history of hepatocellular carcinoma (HCC). Multivariable analysis showed that RVR (p = 0.015) and no previous history of HCC (p = 0.007) were associated with SVR12. Factors significantly contributing to RVR included cirrhosis, creatinine concentration, and pre-treatment HCV RNA level. SVR12 rate was significantly higher in RVR (+) than RVR (–) patients (95.2% vs. 82.9%, p = 0.011) and also significantly higher in patients without than with a history of HCC (94.1% vs. 72.7%, p = 0.008). During treatment, 80/181 patients (44.2%) experienced mild to moderate adverse events, with 32 (17.7%) requiring RBV dose reductions due to anemia.ConclusionsSOF/RBV treatment was effective and tolerable in HCV GT2 patients. RVR and no previous history of HCC were positive predictors of SVR12.

Clinicopathological features and differential diagnosis of hepatocellular carcinoma in extrahepatic metastases.

Extrahepatic metastasis of hepatocellular carcinoma (HCC) may cause a diagnostic problem. All 195 cases of histologic and immunostained sections were reviewed retrospectively in one center. The expression of arginase-1 (Arg-1), hepatocyte paraffin-1 (HepPar-1), glypican-3 (GPC-3), and α-Fetoprotein (AFP) was evaluated. Eighty cases of metastatic tumors of the liver were also collected to verify their effectiveness. Totally 151 cases had previous history of HCC, in whom 49 had history of liver transplantation. Forty-four cases were diagnosed as metastatic HCC at initial presentation. The most common extrahepatic metastatic sites were bone (57%), followed by lung, lymph node, etc. Around 19 cases were positive for 1 marker, 22 were positive for 2 markers, 95 were positive for 3 markers, and 59 were positive for 4 markers. With the number of antibody increased in the panel, the negative cases decreased. The sensitivity of ARG, GPC-3, HepPar-1, and AFP was 82.6%, 89.2%, 83.6% and 53.8%, and the specificity was 98.3%, 94.8%, 96.2% and 100%, respectively. These data suggest that the panel of ARG-1, GPC-3, HepPar-1 and AFP has a high sensitivity and specificity to differentiate HCC from non-HCC. This study indicated that HCC should be considered when diagnosing metastasis of unclear origin. It is recommended to use the panel of ARG-1, GPC-3, HepPar-1 and AFP to differentiate HCC from non-HCC in extrahepatic metastasis, because of their sensitivity and specificity, especially in poorly differentiated lesions.

Predictors of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals

BackgroundDespite the dramatic improvement in viral eradication rates that has been reached with direct antiviral agents (DAAs), the real benefit of viral eradication after DAAs on hepatocellular carcinoma (HCC) development is still controversial. AimTo prospectively assess the risk of HCC occurrence and early recurrence in a large cohort of DAA-treated HCV-cirrhotic patients and to identify potential predictors of HCC development. MethodsWe analyzed data prospectively collected from 1927 consecutive HCV-infected cirrhotic patients treated with DAA from January to December 2015 in 10 tertiary liver centers in Italy and followed-up for one year after therapy. 161 patients had a previous HCC. Results38/161 subjects developed tumor recurrence during the follow-up (recurrence rate = 24.8 per 100-year), patients with SVR had a significantly lower rate of recurrence. Lack of SVR and alpha-fetoprotein (AFP) were independent predictors of HCC recurrence. 50/1766 patients without a previous HCC history developed HCC during follow-up (incidence rate = 2.4 per 100-year). Lack of SVR was the strongest predictor of HCC development. Furthermore, patients with SVR and no stigmata of portal hypertension have a lower incidence rate of HCC (1.0 per 100-year). ConclusionsSVR is associated with a significant decrease of recurrent or de novo HCC. Baseline AFP and signs of portal hypertension can help to stratify the risk of HCC.

Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts early occurrence of hepatocellular carcinoma after sustained virologic response by direct-acting antivirals for hepatitis C virus.

The aim of this study is to clarify the value of serum Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) for predicting hepatocellular carcinoma (HCC) in chronic hepatitis C patients who achieved sustained virologic response (SVR) by therapy with interferon-free, direct-acting antivirals (DAAs). This is a retrospective cohort study that included 567 patients who underwent antiviral therapy with an interferon-free DAA regimen and achieved SVR. Serum WFA+ -M2BP was measured after SVR. Factors predictive of HCC occurrence and recurrence were analyzed in the patients after stratification by previous treatment history of HCC. Among 518 patients who had no history of HCC, 13 developed HCC. Post-SVR WFA+ -M2BP ≥1.75 cut-off index (C.O.I., P < 0.001) and α-fetoprotein (AFP) level ≥6ng/mL (P = 0.01) were significant predictors of HCC development. Multivariate analysis showed that post-SVR WFA+ -M2BP ≥1.75 C.O.I. was an independent factor significantly associated with the development of HCC (hazard ratio [HR] 6.0; 95% confidence interval (CI), 1.8-19.4; P = 0.003). Among 49 patients who had a previous history of HCC, 22 had recurrence after SVR. Post-SVR AFP ≥6ng/mL was the only factor associated with recurrence-free survival (HR 3.1; 95% CI, 1.3-7.5; P = 0.01). Post-SVR WFA+ -M2BP is a predictive factor for the development of HCC in patients with no previous HCC history and treated with DAAs. Post-SVR AFP was predictive for HCC recurrence after DAA therapy.

Impact of direct-acting antiviral agents on the development of hepatocellular carcinoma: evidence and pathophysiological issues.

Hepatitis C virus (HCV) infection is currently one of the main causes of cirrhosis and hepatocellular carcinoma (HCC) at a global level. Recently, a new generation of direct-acting antiviral agents (DAAs) has entered the HCV treatment landscape, providing impressively high rates of sustained virological response (SVR), and is expected to lead to an eventual decrease in HCV-related cirrhosis, liver transplantation and mortality. However, during the first years of their use, several studies reported a possible correlation between DAA treatment and an increased risk of HCC. Following the publication of larger prospective studies, the risk of de novo HCC occurrence has clearly been proven to be lower after the achievement of SVR, regardless of antiviral treatment. On the other hand, the risk of HCC recurrence following treatment with DAAs is debatable; existing data remain controversial, possibly because of the lack of large, well designed cohorts with more homogeneous patient populations. With regard to the pathophysiology behind the above observations, especially in patients with previous HCC history, HCC development could possibly be favored by the changes in the immunological milieu and the different cellular behavior after eradication of HCV infection with DAA treatment.

Short article: Management of ruptured hepatocellular carcinoma in a European tertiary care center.

Spontaneous rupture is a rare complication of hepatocellular carcinoma (HCC). Treatment options consist of transcatheter arterial embolization (TAE), hepatic resection, and conservative therapy. The best approach is under debate. This study presents a review of clinical data of patients with a ruptured HCC admitted to a European tertiary care center. Eleven patients were included; six (55%) had underlying cirrhosis. The majority of patients (73%) had no previous history of HCC. Spontaneous HCC rupture was diagnosed using abdominal computed tomography with or without a diagnostic paracentesis. Computed tomography showed one or two tumors in eight (73%) patients; the other patients had multiple tumors or diffuse infiltrative HCC. Seven (64%) patients were initially treated by TAE and one (9%) patient underwent hepatic resection. The remaining three (27%) patients, all of whom had liver cirrhosis, received conservative therapy. Two patients initially treated by TAE underwent a delayed resection and ultimately received systemic therapy. Overall, at the end of the follow-up period, three patients were still alive at 84, 991, and 1026 days after the initial presentation. Eight (73%) patients had died after a median of 88 days (range 7-417). One year after presentation, none of the conservatively treated patients was alive compared with three out of seven (43%) patients treated with TAE with or without delayed resection. Patients with a spontaneously ruptured HCC have a poor prognosis. In selected patients, however, prolonged survival is possible using TAE as initial therapy with or without a delayed resection and systemic therapy.

Orbital Metastasis From Hepatocellular Carcinoma

A series of 6 consecutive cases of orbital metastasis from hepatocellular carcinoma (HCC) were reported in the last 5 years. All patients were men. The age of patients ranged between 47 and 70 years. Four patients presented with recent onset of unilateral proptosis, 1 patient presented with inflammatory manifestations, and 1 patient presented with unilateral ptosis. Pain was present in 4 patients. Three patients had a previous history of HCC, while the orbital affection was the first manifestation of the disease in 3 cases. All patients had chronic hepatitis C. CT scan of 5 patients showed a mass in upper lateral orbital quadrant, and 1 patient had the mass in the upper central orbit. Bone changes (thinning, notching, or erosion) were detected in all patients. Diagnosis was confirmed by incision biopsy in all cases. Life span of 5 patients in the study had a mean of 10.2 (±2.3) months.

Obesity Is an Independent Risk Factor for Hepatocellular Carcinoma Development in Chronic Hepatitis C Patients

It is not fully elucidated whether obesity enhances hepatocarcinogenesis in patients with chronic hepatitis C. The aim of this study was to investigate the relationship between body weight and risk of hepatocarcinogenesis in chronic hepatitis C patients. We enrolled 1431 patients with chronic hepatitis C who visited our liver clinic between 1994 and 2004, excluding those with hepatocellular carcinoma (HCC) at their visit or with a previous history of HCC. They were divided into 4 groups according to body mass index (BMI): underweight (< or =18.5 kg/m(2), N = 112); normal (18.5 to less than 25 kg/m(2), N = 1023); overweight (25 to less than 30 kg/m(2), N = 265); and obese (>30 kg/m(2), N = 31). We assessed the impact of obesity on the hepatocarcinogenesis adjusted by multivariate Cox proportional hazard regression with other risk factors found significant in univariate analysis. During the follow-up period (mean, 6.1 y), HCC developed in 340 patients, showing cumulative incidence rates of 10.5%, 19.7%, and 36.8% at 3, 5, and 10 years, respectively. The incidence differed significantly among the BMI groups (P = .007). Adjusting for other significant factors, overweight and obesity were shown to be an independent risk factor of HCC, with a hazard ratio of 1.86 (95% confidence interval, 1.09-3.16; P = .022) and 3.10 (95% confidence interval, 1.41-6.81; P = .005) as compared with the underweight patients. The risk of HCC in patients with chronic hepatitis C increases in proportion to BMI in a wide range of its values, from underweight to obese.

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.

Contrast-enhanced doppler ultrasonography in the diagnosis of hepatocellular carcinoma and premalignant lesions in patients with cirrhosis

Hepatocellular carcinogenesis in cirrhosis is a multistage process that includes large regenerative nodules, dysplastic nodules, and hepatocarcinoma. The aim of this study was to establish whether contrast-enhanced Doppler ultrasonography (US) is able to distinguish between early hepatocellular carcinoma (HCC) and small nonmalignant nodules in cirrhosis. Between January 1998 and December 1999, 500 cirrhotic patients with no previous history of HCC or evidence of hepatic focal lesions were enrolled and prospectively followed-up with US every 6 months until December 2000. Sixty-one patients developed focal lesions, 12 multifocal, and 49 monofocal. Biopsy of focal lesions, contrast-enhanced Doppler US, and spiral computed tomography (CT) were performed in 41 consecutive patients with small ([lt ]3 cm) monofocal lesions. Twenty nodules were diagnosed as HCC and 21 as nonmalignant (14 large regenerative nodules, 3 low-grade, and 4 high-grade dysplastic nodules) by liver biopsy. Intratumoral arterial blood flow was detected in 19 of 20 (95%) HCC and 6 of 21 (28%) nonmalignant nodules by contrast-enhanced Doppler US (P[lt ].0001). The mean peak resistance and pulsatility indices were 0.82 [plusmn] 0.09 and 1.56 [plusmn] 0.2 in HCC and 0.62 [plusmn] 0.08 and 0.82 [plusmn] 0.08 in dysplastic lesions (P = .002 and .0001), respectively. Spiral CT revealed arterial perfusion in 19 of 20 HCC and in 4 of 21 nonmalignant nodules (high-grade dysplastic nodules). Four of the apparently false-positive nodules at enhanced Doppler US were high-grade dysplastic nodules and 2 evolved to HCC during follow-up. In conclusion, contrast-enhanced Doppler US is a noninvasive, very sensitive technique in differentiating malignant and premalignant lesions from nonmalignant focal lesions in the liver. (HEPATOLOGY 2001;34:1109-1112.)

Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus–related chronic liver diseases

Three-hundred forty-one HBsAg-positive family members of 152 patients with chronic hepatitis B virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis B virus infection in the family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseases. Most of the family members had no history of acute hepatitis, were asymptomatic and were unaware of their carrier status. However, 5.3% had stigmata of chronic liver disease, 6% had serum ALT levels that exceeded two times the upper limit of normal and 78% of those who had biopsies had chronic hepatitis with or without cirrhosis. During a follow-up period of 12 to 90 mo (median = 39 mo), 3% had symptoms of chronic liver disease; 24% had transient, recurrent or persistent elevation in serum ALT levels, 1.4% had cirrhosis and 1% had hepatocellular carcinoma. Neither hepatocellular carcinoma in the index patient nor a previous history of hepatocellular carcinoma in the family was associated with an increase in the morbidity and mortality from chronic hepatitis B virus infection in the HBsAg-positive family members.