Seven centimeters as an optimal cutoff value for prognosis stratification in large monofocal hepatocellular carcinoma.

PURPOSE: Barcelona Clinic Liver Cancer (BCLC) guidelines designate monofocal hepatocellular carcinoma (HCC) > 2 cm as BCLC A, and large monofocal HCC is defined at > 5 cm. We aimed to evaluate the optimal cutoff value for large monofocal HCC based on prognosis stratification. METHODS: From 2011 to 2018, 3055 patients with newly diagnosed HCC, who were managed in our institution, including 868 patients with monofocal HCC > 2 cm and 330 patients with BCLC B, were enrolled in this retrospective study. RESULTS: Monofocal HCC > 5 cm patients had worse overall survival (OS) than monofocal HCC 2-5 cm patients (5-year OS: 54% vs. 57%; p = 0.047), confirmed by multivariate analysis (hazard ratio (HR): 1.492, 95% confidence interval (CI): 1.055-2.110; p = 0.024). Monofocal HCC > 5 cm patients had better OS than BCLC B HCC patients (5-year OS: 54% vs. 25%; p < 0.001), confirmed by multivariate analysis (HR: 0.670, 95% CI: 0.481-0.934; p = 0.018). Using 7 cm as the monofocal HCC cutoff value resulted in worse OS than monofocal HCC 2-7 cm (5-year OS: 50% vs. 57%; p = 0.02), confirmed by multivariate analysis (HR: 1.625, 95% CI: 1.039-2.540; p = 0.033). Monofocal HCC > 7 cm patients had better OS than BCLC B patients (p = 0.006). However, no significant difference was identified in the multivariate analysis (HR: 0.726; 95% CI: 0.473-1.115; p = 0.144). CONCLUSIONS: The prognosis of monofocal HCC > 7 cm was similar to that of BCLC B, indicating that 7 cm represents an optimal cutoff value for prognosis stratification in large monofocal HCC.

The characteristics of patients with macrovascular invasion in hepatocellular carcinoma: when East meets West.

PURPOSE: To evaluate the prevalence and extension of macrovascular invasion (MaVI) in a large cohort of hepatocellular carcinoma (HCC) patients and analyze the association between MaVI and overall survival (OS). METHODS: From 2011 to 2018, 2540 patients with newly diagnosed HCC who were managed in our institution were enrolled in this retrospective study. Tumor invasion of the intrahepatic branches of the portal or hepatic veins was defined as peripheral MaVI. Tumor invasion of the main portal vein or inferior vena cava was defined as central MaVI. RESULTS: MaVI prevalence was 16.2% (n = 411). Among patients with Barcelona Clinic Liver Cancer (BCLC) stage C and Child-Pugh class A, 165 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 13.2 months (95% confidence interval [CI]: 11.4-15.4) in the peripheral MaVI group and 6.6 months (95% CI: 3.6-9.5) in the central MaVI group (p < 0.001). In patients with BCLC stage C and Child-Pugh class B or BCLC stage D, 68 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 3.6 months (95% CI: 3.1-4.2) in the peripheral MaVI group and 2.8 months (95% CI: 2.1-3.4) in the central MaVI group (p = 0.674). CONCLUSION: The extension of MaVI significantly affected patient survival only in those with BCLC stage C and Child-Pugh class A. In patients with BCLC stage C and Child-Pugh class B or BCLC stage D, survival was poor irrespective of MaVI status.

Community-based screening by Anti-HCV reflex HCV Ag test and accessible post-screening care toward elimination of hepatitis C in two hyperendemic townships.

BACKGROUND: Hyperendemic townships of hepatitis C virus (HCV) infection should devote extra efforts to eliminate HCV. We aimed to evaluate efficacy of the screening and linkage to care in two HCV hyperendemic townships. METHODS: Village-to-village HCV screening using anti-HCV reflex HCV Ag test was conducted in two HCV hyperendemic rural townships (Lioujiao and Yijhu). All residents aged 30 years or older were invited. Those patients detected as infected were referred to nearby hospitals or clinics in Lioujiao and to an accessible outreach hepatology clinic in Yijhu. RESULTS: The populations of Lioujiao and Yijhu townships at time of survey were 18,389 and 14,787 with 6086 (33.1%) and 4604 (31.1%) having ever been previously screened, and 1517 and 1071 responded to this screening respectively. Their crude screening coverage rates were 41.5% and 38.5%, and adjusted screening coverage rates were 54.3% and 94.6% respectively. The prevalence rates of anti-HCV and HCV Ag were 17.9% and 11.9% in Lioujiao, and 9.2% and 5.6% in Yijhu respectively, with their rates of antigenemia (HCV Ag/anti-HCV) being 62.1% and 60.6% respectively. Numbers needed to test (NNT) to find a candidate for anti-viral treatment were 9 and 18. For linkage to care, treatment rate by referral (Lioujiao) was slightly lower than by accessible outreach hepatology clinic (Yijhu) (84.9% vs. 93.3%, p = 0.093). Overall successful sustained virological response rate at week 12 was 98.2% (161/164) in outreach hepatology clinic. CONCLUSION: Since NNT was low, it was worthwhile conducting intensive screening in these hyperendemic townships. For high treatment rate, accessible outreach hepatology clinic is feasible especially in areas without adequate medical resources.

Incorporating albumin-bilirubin grade and up-to-seven criteria to predict outcomes of patients with intermediate stage hepatocellular carcinoma after transarterial (chemo)embolization.

BACKGROUND/PURPOSE: This study is to use albumin-bilirubin (ALBI) grade and up-to-7 (UT7) criteria to assess outcomes of patients with intermediate stage hepatocellular carcinoma (HCC) after transarterial (chemo)embolization (TA(C)E). METHODS: Between January 2012 and January 2019, newly diagnosed intermediate HCC patients underwent TA(C)E were enrolled and analyzed. The demographics, clinical characteristics and survival were obtained from medical chart reviews. RESULTS: A total of 359 patients were enrolled and 30.4% of them were within UT7 criteria (UT7 (-)). There were 36.5%, 59.3%, and 4.2% of the patients with ALBI grade I, II, and III, respectively. Beyond UT7 (UT7 (+)) and ALBI grade II/III were associated with overall mortality in multivariate analysis. Based on ALBI grade I/II/III and UT7 -/+, patients were classified into six groups as ALBI grade I plus UT7 (-), II plus UT7 (-), III plus UT7 (-), I plus UT7 (+), II plus UT7 (+), and III plus UT7(+). Distributions of median survival were 47.5, 32.9, 15, 34.3, 16.7 and 14.3 months, respectively. Patients with statistically insignificant survivals were further combined. Patients with ALBI grade I plus UT7 (-) were reclassified as ALBI-U class I, whereas ALBI grade II plus UT7 (-) and I plus UT7 (+) were ALBI-U class II, and the others were ALBI-U class III. There were 8.4%, 48.7%, and 42.9% of patients in ALBI-U class I, II, and III, respectively. The 5-year survival rate was 48.8%, 22.5%, and 13.7% in ALBI-U class I, II, and III, respectively (p < 0.01). CONCLUSION: ALBI-U classification was useful in predicting outcomes of patient with intermediate stage HCC after TA(C)E.

Reappraisal of the roles of alpha-fetoprotein in hepatocellular carcinoma surveillance using large-scale nationwide database and hospital-based information.

BACKGROUND/PURPOSE: Controversies over the use of alpha-fetoprotein (AFP) for detection of hepatocellular carcinoma (HCC) existed from guidelines. Using large-scale database and hospital-based information, we aimed to reappraise the role of AFP in HCC surveillance, including proportion of AFP elevation by stage of HCC, additional benefit of AFP in combination of ultrasonography (US) in the detection of early HCC, and survival in early HCC with high AFP levels. METHODS: This retrospective study enrolled 43,437 patients from database of the Taiwan Cancer Registry (TCR) and 4250 patients from Kaohsiung Chang Gung Memorial Hospital (KCGMH) between January 2011 and December 2017. RESULTS: The HCC cases in KCGMH accounted for 9.8% of the total cases in the TCR. Among both nationwide database and hospital-based information, the proportion of early HCC patients with an AFP level of ≥20 ng/mL was approximately 40%. In KCGMH, the proportion of patients with an AFP level of ≥20 ng/mL and a virus-related (hepatitis B and C) etiology was around 41.7%; furthermore, among patients with early HCC, those with an AFP level of ≥20 ng/mL had 4.7 years of median survival and 48.3% of the 5-year overall survival rate. By hospital electronic medical records review of early HCC cohort in KCGMH, approximately 10.9% of patients with AFP levels ≥20 ng/mL had US-undetectable early HCC. CONCLUSION: This study suggested that AFP in combination with US would add an additional benefit as being a prompted role for detection of early HCC in patients with US-undetectable HCC.

The influence of direct-acting antivirals in hepatitis C virus related hepatocellular carcinoma after curative treatment.

This study was done to elucidate the influence of direct-acting antiviral (DAA) agents on the recurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC (HCV-HCC) after curative therapies. HCV-HCC patients who received curative therapies and obtained a complete response were analyzed. From January 2017 to September 2017, 112 HCV-HCC patients received DAA and obtained a sustained virological response (SVR). From January 2006 to December 2014, another 345 HCV-HCC patients received peg-interferon-based treatment and 118 obtained SVR. From January 2012 to December 2016, 248 HCV-HCC patients had complete HCC response and did not receive antiviral treatment. Patients were divided into DAA, IFN, and Untreated groups based on what antiviral treatment they received. There were 82 patients in the DAA group, 80 patients in the IFN group, and 160 patients in the Untreated group. During the follow-up period, the DAA group had 22 (26.8%) recurrent cases, whereas the IFN group had 46 (56.8%) cases after antiviral treatment. Among the 22 recurrent cases in the DAA group, 19 (86.9%) experienced HCC recurrence during 1 year after DAA initiation. Compared with the IFN group, the DAA group had poorer one-year recurrence-free survival (75.4% vs. 95%, p < 0.001), even after adjustment with propensity score matching (81.4% vs. 93.9%, p = 0.034). However, DAA was an improving factor for HCC recurrence compared with the Untreated group in the multivariate analysis. Among HCV-HCC patients with complete treatment, those with DAA-induced SVR had a higher one-year recurrence rate than those who received IFN-based antiviral therapy, but DAA did not seem to increase HCC recurrence compared to untreated patients.

Clinical characteristics and prognosis of HCC occurrence after antiviral therapy for HCV patients between sustained and non-sustained responders.

BACKGROUND: Hepatitis C virus (HCV)-infected patients who achieved sustained virologic response (SVR) may still develop hepatocellular carcinoma (HCC). The characteristic of HCC and the prognosis between SVR and non-SVR patients were not well known. METHODS: Among 1884 HCV-infected patients who were treated with pegylated IFN plus ribavirin therapies, 122 patients developed HCC during follow-up were enrolled in this study. Laboratory data were collected before and at least 1 year after IFN-based therapy, as well as the latest follow-up. RESULTS: Both SVR and non-SVR patients had similar risk factors to develop HCC, but with a little difference. Liver cirrhosis plays a key role in HCC occurrence in both groups. Among the patients who developed HCC, non-SVR patients had significantly higher total bilirubin, higher FIB-4, lower pre-treatment platelet count, higher pre-treatment AFP levels and higher proportion of cirrhosis than SVR patients before occurrence of HCC. After curative treatment, SVR patients had lower recurrence and longer overall survival than non-SVR patients by Kaplan-Meier analysis. Multivariate analysis revealed that APRI ≥0.7 was the independent risk factor for HCC recurrence; and AFP ≥20 ng/ml post IFN therapy, as well as HCC recurrence were the independent risk factors of mortality. CONCLUSION: Liver cirrhosis plays a key role in HCC occurrence after antiviral therapies. SVR patients may have lower HCC recurrence and longer survival rates than non-SVR patients. Only APRI was associated with HCC recurrence; and post-IFN AFP and HCC recurrence were predictive of subsequent mortality independently.

The outcome of sorafenib monotherapy on hepatocellular carcinoma with portal vein tumor thrombosis.

Sorafenib is not recommended for advanced hepatocellular carcinoma (HCC) patients with Vp4 (portal invasion at the main trunk) by the Japan Society of Hepatology (JSH) due to a risk of hepatic failure. This study aimed to elucidate the safety and efficacy of sorafenib monotherapy on HCC with macro-vascular invasion (MVI). A total of 415 consecutive advanced HCC patients received sorafenib in our hospital. Patients with only MVI and sorafenib monotherapy were retrospectively enrolled. We enrolled 113 (27.2%) patients, including 56 (49.5%) Vp3 (portal invasion at the first branch) and 57 (50.5%) Vp4. Their median intervals of follow-up and sorafenib-use were 7.8 months and 2.7 months respectively. Using sorafenib, more Vp4 had hepatic decompensation (HD) (37% VS 18.2%, p = 0.028) than Vp3 patients. The multivariate analysis showed Vp4 (Odds ratio: 2.91; 95% CI: 1.02-8.3, p = 0.041) and baseline alpha-fetoprotein (AFP) ≥ 200 ng/ml were associated with HD. Dividing our patients into four subgroups as Vp3 + AFP < 200 ng/ml, Vp3 + AFP ≥ 200 ng/ml, Vp4 + AFP < 200 ng/ml and Vp4 + AFP ≥ 200 ng/ml, the proportions of HD were 16.7%, 19.4%, 16.7% and 55.2% respectively (p = 0.002). The overall survival rates were distributed with a significant decreasing trend as 10.2 ± 4.4 months, 6.5 ± 1.0 months, 6.0 ± 1.3 months and 2.5 ± 0.5 months (p = 0.001). We found only Vp4 plus AFP ≥ 200 ng/ml could induce more HD and a poorer prognosis than Vp3 patients. Hence, in Vp4 patients with higher AFP, sorafenib should not be the first-line treatment due to its limited survival benefit.

Association between PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma in Asian chronic hepatitis C patients: A longitudinal study.

BACKGROUND/PURPOSE: Prdevious meta-analyses assess whether or not patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409 C > G) was associated with increased risk of hepatocellular carcinoma (HCC) in Caucasians patients with hepatitis C virus (HCV)-related cirrhosis, these meta-analyses did not provide firm conclusions. Only one cross-sectional study involving Asian patients has previously been conducted to explore this issue. We aim to investigate this in a longitudinal cohort of Asian chronic hepatitis C (CHC) patients. METHODS: We consecutively enrolled 1011 CHC patients who underwent liver biopsy before initiating interferon-based therapy. These patients were followed-up and screened for HCC up to a median of 6.9 years. The influence of rs738409 (GG) genotype on the occurrence of HCC was assessed using the Kaplan-Meier method, then according to the multivariate Cox model. RESULTS: During follow-up, 143 (14.1%) patients developed HCC. rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.634). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.12). Among 261 patients with liver cirrhosis, rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.737). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.72). CONCLUSION: In this longitudinal study with liver biopsy to stage liver fibrosis, we affirm there is no influence of the rs738409 (GG) genotype on the occurrence of HCC in Asian CHC patients, including cirrhotic patients.

Albumin-Bilirubin grade predicts prognosis of HCC patients with sorafenib use.

BACKGROUND AND AIM: The Albumin-Bilirubin (ALBI) grade is a new index to assess objectively liver function and prognosis in patients with hepatocellular carcinoma (HCC). This study aimed to elucidate the application of ALBI grade in baseline and sorafenib-end in advanced HCC patients who received sorafenib. METHODS: A total of 415 consecutive advanced HCC patients in Child-Pugh A received sorafenib in our hospital. Sorafenib was terminated when radiologic tumor progression or clinical liver function deterioration (LD) occurred in the reassessment bimonthly. Patients who failed with sorafenib monotherapy were retrospectively analyzed. RESULTS: A total of 260 (62.6%) patients were enrolled, including 98 (37.7%) ALBI grade I and 162 (62.3%) grade II in baseline. More patients in ALBI grade II stopped sorafenib because of LD than in grade I (33.3% vs 14.3%, P < 0.001). Those who in baseline ALBI grade I had a superior overall survival than in grade II (8.5 months vs 4.4 months, P = 0.003). Cox regression analysis confirmed that baseline ALBI grade II (P < 0.001) and ALBI grade increase during treatment (P < 0.001) strongly contributed to the mortality of HCC patients who received sorafenib. After sorafenib failure, those with post-sorafenib treatment had a better post-sorafenib survival than those without (9.3 vs 1.6 months, P < 0.001). Logistic regression analysis indicated that sorafenib-end ALBI grade and LD occurrence were the only two predictors of post-sorafenib treatment after sorafenib failure. CONCLUSIONS: In clinical practice, we firstly demonstrated that not only ALBI grade in baseline but also ALBI grade change during treatment could predict the prognosis of advanced HCC patients who received sorafenib.

Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-naïve and nucleos(t)ide analog-experienced chronic hepatitis B patients.

BACKGROUND AND AIMS: This study compared the efficacy and safety of tenofovir disoproxil fumarate (TDF) up to 3 years of innucleos(t)ide analog (NA)-naïve and NA-experienced chronic hepatitis B (CHB) patients. METHODS: Tenofovir disoproxil fumarate-treated NA-naïve and NA-experienced CHB patients were retrospectively analyzed. RESULTS: After 3 years of TDF therapy, 97.7%, 71%, and 45.5% NA-naïve patients achieved a virological response, alanine aminotransferase normalization, and hepatitis B e antigen seroconversion, respectively. Compared with NA-naïve patients, NA-experienced patients without drug resistance and infected with lamivudine/telbivudine-resistant mutants showed similar results. In contrast, patients previously infected with adefovir-resistant mutants and with a suboptimal entecavir response showed significantly lower rates of virological response and hepatitis B e antigen loss/seroconverion than NA-naïve patients. Mean estimated glomerular filtration rate markedly reduced within 12 months of TDF therapy; however, it did not decrease significantly during 12-36 months of treatment. Diabetes mellitus was an independent predictor of a ≥ 0.5 mg/dL increase above baseline in serum creatinine level, and age, hypertension, diabetes mellitus, and baseline creatinine level were independent factors for > 20% decline in estimated glomerular filtration rate from baseline. Liver stiffness measurements improved significantly, but bone mineral density did not change significantly during treatment. Hepatocellular carcinoma incidence was low at 36 months. Age of > 60 years, cirrhosis, a low baseline platelet count and a high α-fetoprotein level at 12 months were significant predictors of hepatocellular carcinoma development. CONCLUSIONS: Tenofovir disoproxil fumarate is effective and safe for NA-naïve and NA-experienced CHB patients and should be used cautiously in patients with comorbidities because of a renal dysfunction risk.

Tenofovir versus entecavir in treatment of chronic hepatitis B virus with severe acute exacerbation.

Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are effective antivirals recommended as first-line monotherapies for treatment of chronic hepatitis B (CHB) infection. This study aimed to compare the short-term efficacies of TDF and ETV in the treatment of CHB with severe acute exacerbation. From 2008 to 2013, 189 consecutive treatment-naive CHB patients receiving TDF (n = 41) or ETV (n = 148) for severe acute exacerbation were enrolled. The primary endpoint was overall mortality or receipt of liver transplantation by week 24. The baseline characteristics were comparable between these two groups. By week 24, 8 (19% [95% confidence interval {CI}, 7% to 32%]) patients in the TDF group and 26 (18% [95% CI, 11 to 24%]) patients in the ETV group died (n = 30) or received liver transplantation (n = 4) (P = 0.749). The two groups of patients developed similar rates of liver-related complications and achieved comparable biochemical and virological responses at week 24. Cox regression analysis showed that baseline viral DNA level (P = 0.002), hypertension (P = 0.002), model for end-stage liver disease (MELD) score (P = 0.01), platelet count (P = 0.005), early presence (within 4 weeks) of ascites (P = 0.005), hepatic encephalopathy (P = 0.002), and hepatorenal syndrome (P < 0.001) were independent factors for mortality or liver transplantation. Among the patients who survived by week 24, there was no difference between the two groups in the percentage of patients who had a serum creatinine increase of ≥0.5 mg/dl from baseline (6.7% [95% CI, 0% to 16%] versus 2.0% [95% CI, 0% to 4.8%] in the TDF and ETV groups, respectively; P = 0.231), whereas a significant reduction in the estimated glomerular filtration rate (eGFR) was found in the two groups (P = 0.001 for both). In conclusion, TDF and ETV produce a similar treatment response and clinical outcome in patients with severe acute exacerbation of CHB.

Validation and modification of a proposed substaging system for patients with intermediate hepatocellular carcinoma.

BACKGROUND AND AIM: Based on up-to-seven criteria and Child-Pugh score, four substages of Barcelona Clinic Liver Cancer (BCLC) intermediate hepatocellular carcinoma (HCC) were proposed. The purpose of this study was to validate and modify this proposal. METHODS: Between January 2002 and February 2011, newly diagnosed intermediate HCC patients underwent transarterial embolization (TAE) were enrolled. Patients were stratified into four (B1-B4) substages and followed up until death or end of 2012. Patients' survivals and discriminatory ability of substaging systems were compared. RESULTS: Five-hundred and eighty patients were enrolled. There were 56.6%, 33.8%, 7.4%, and 2.2% in substage B1, B2, B3, and B4. The 5-year survival rate was 21.4%, 13.9%, 7.4%, and 7.7% with median survival time of 2.4, 1.3, 0.5, and 0.8 years (P < 0.001). In addition to substage B1-B4, α-fetoprotein (AFP) level was an independent factor associated with survival in multivariate analysis. According to AFP < or > 200 ng/mL, B1 was classified into B1a and B1b, and B2 into B2a and B2b. There were no differences in survivals between B1b and B2a (P = 0.174), and B2b and B3 (P = 0.785). Patients were re-classified into modified (m)B1 (B1a), mB2 (B1b + B2a), mB3 (B2b + B3). The modified substages (mB1-mB3) showed a more desirable substaging system. CONCLUSIONS: For BCLC intermediate HCC patients, substages B1-B4 were useful in predicting survival after TAE. However, modified substaging system provided better prognostic prediction.

Serum proteome predicts virological response in chronic hepatitis C genotype 1b patients treated with pegylated interferon plus ribavirin.

BACKGROUND/PURPOSE: Whether serum proteome changes can predict treatment response in chronic hepatitis C remains unclear. We investigated the association between serum proteome changes and virological responses in chronic hepatitis C virus genotype 1b (HCV-1b) patients treated with pegylated interferon (PegIFN) plus ribavirin (RBV). METHODS: One hundred and thirty-six HCV-1b patients who had completed a course of PegIFN plus RBV for 24 weeks, had a 24-week follow-up, and had pretreatment serum available were enrolled. These patients were divided into training and validation groups. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) for peptide profiling and ClinPro Tools version 2.0 bioinformatics software for data analysis. RESULTS: Seventy-four patients (54%) had a sustained virological response (SVR), whereas 62 did not. We identified three protein peaks in pretreatment sera where the expression levels significantly differed between SVR and non-SVR (p < 0.05). Using the class prediction tool composed of the three protein peaks, we were able to correctly predict SVR in 95% of validation group patients with sensitivity = 95%, specificity = 56.3%, positive predictive value = 73.1%, and negative predictive value = 90%. We also identified a set of 20 protein peaks where the expression levels significantly differed in pretreatment sera between patients with nonresponse (NR) and virological response (SVR plus relapse; p < 0.05). Using the class prediction tool composed of these 20 protein peaks, we were able to correctly predict virological NR in 82% of validation group patients with sensitivity = 100%, specificity = 82%, positive predictive value = 92.6%, and negative predictive value = 100%. CONCLUSION: Pretreatment serum proteome allows prediction of SVR and NR to PegIFN plus RBV treatment in HCV-1b patients.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

BACKGROUND: Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. MATERIALS AND METHODS: Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. RESULTS: Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). CONCLUSION: Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Hepatocellular carcinoma surveillance at 4- vs. 12-month intervals for patients with chronic viral hepatitis: a randomized study in community.

OBJECTIVES: To compare the efficacy of hepatocellular carcinoma (HCC) surveillance at 4- and 12-month intervals in a community for patients with chronic viral hepatitis and thrombocytopenia. METHODS: In 10 townships, adults (≥ 40 years) with platelet ≤ 150 (× 10(9))/l, positive hepatitis B surface antigen, or antibody to hepatitis C virus were invited to this study. These townships were randomized into 4- (group A) and 12-month (group B) interval surveillance groups. Seven hundred and eighty-five and 796 residents met the study criteria in groups A and B. Ultrasonography (US) was the surveillance method. RESULTS: A total of 744 residents (group A: 387; group B: 357) were enrolled. In the study period, HCC was diagnosed in 39 residents (group A: 24; group B: 15). There was no difference in cumulative 3-year HCC incidence between the two groups. The tumors were smaller in group A than in group B, though group A had more patients with tumor ≤ 2 cm (P = 0.003) who were in Barcelona Clinic Liver Cancer (BCLC) very-early stage (P = 0.017) and had undergone curative treatments (P = 0.049). Male gender, cirrhosis, and platelet ≤ 100 (× 10(9))/l were associated factors of HCC occurrence. There was no difference in 4-year overall survival between the two groups. Patients undergoing recommended treatments had better 4-year survival rates. CONCLUSIONS: Compared with 12-month interval, US surveillance at 4-month interval detected more patients with HCC ≤ 2 cm who were in BCLC very-early stage and were fit for curative treatments. Up to 4-year follow-up, however, the overall survival was not different.

Improvement of thrombocytopenia in hepatitis C-related advanced fibrosis patients after sustained virological response.

BACKGROUND: The long-term trend of platelet count in chronic hepatitis C virus patients with sustained virological response (SVR) has rarely been investigated. AIMS: To elucidate changes of thrombocytopenia after SVR, trajectory patterns of platelet count over time and their associated factors. METHODS: From May 1999 to July 2005, a total of 135 patients (mean age 50.2 ± 11.1 years) that received interferon-α based regimen plus ribavirin were enrolled. Platelet counts were followed every 6 months prospectively. The patterns of platelet counts over time were identified by trajectory analysis. RESULTS: Mean follow-up duration was 4.4 ± 1.7 years (median 4.5; range 1.0-8.5 years). Baseline platelet count in all and thrombocytopenic patients increase significantly at the end of follow-up, from 172 ± 56 × 10(9)/l and 115 ± 21 × 10(9)/l to 196 ± 57 × 10(9)/l and 148 ± 37 × 10(9)/l, respectively (all p < 0.001). In patients with advanced fibrosis (n = 50), pretreatment platelet count also increased significantly (146 ± 45 × 10(9)/l vs. 173 ± 51 × 10(9)/l, p < 0.001). Twenty-six of 37 (69.2 %) patients with pretreatment mild thrombocytopenia (100-150 × 10(9)/l) had normalization of platelet count, while seven of 13 (53.8 %) patients with pretreatment moderate to severe thrombocytopenia (<100 × 10(9)/l) had elevation of platelet count up to 100-150 × 10(9)/l. Three trajectory groups were identified, i.e., elevation (n = 43, 31.9 %), stationary (n = 79, 58.5 %), and decrease (n = 13, 9.6 %) groups. Multiple logistic regression showed pretreatment thrombocytopenia was the factor in elevation of platelet count (OR = 2.28, 95 % confidence interval = 1.01-5.11, p = 0.046). CONCLUSIONS: Platelet count increased significantly in patients with SVR after long-term follow-up. Patients with low baseline platelet count benefit more from SVR with respect to increased platelet count, compared to those with higher platelet count at baseline.

Validation of the 7th edition TNM staging system for hepatocellular carcinoma: an analysis of 8,828 patients in a single medical center.

BACKGROUND: Major modification of the 7th tumor-node-metastasis (TNM) staging system for hepatocellular carcinoma (HCC) was divided into 6th stage IIIA to 7th IIIA (multiple tumors, any>5 cm) and IIIB (tumors involving a major vessel). This study aimed to validate 6th and 7th TNM systems in prognostic prediction, then analyze the impact of time, Child-Pugh classification and treatment modalities in survival. METHODS: A total of 5,611 and 3,217 HCC patients were enrolled between 1986-2002 (past period) and 2003-2010 (recent period), respectively. The Akaike information criteria (AIC) within a Cox proportional hazard regression model were used to demonstrate the discriminatory ability for staging systems. RESULTS: The 1-, 3-, and 5-year survival rates of past and recent periods were 44.8, 24.9, 17.1%, and 65.5, 44.5, 34.6%, respectively (p<0.001). Rates of smaller HCC detection and received curative treatment were significantly higher in the recent period than in the past period (p<0.001). Survival rates were different in each Child-Pugh class (all p<0.001). Patients receiving curative treatment had highest survival rates, followed by non-curative treatment, and untreated patients (p<0.05). In both periods, significant differences in survival curves existed between each of the stages in the 6th and 7th TNM staging (all p<0.05), and also between IIIA and IIIB in the 7th TNM (p<0.001). The AIC of two periods in the 6th and 7th TNM systems were decreased, with 77,895 and 77,630, and 19,162 and 19,135, respectively. CONCLUSION: The 7th TNM provided better prognostic prediction than the 6th TNM after dividing into IIIA and IIIB. Survival rates of HCC have been improving in recent decades.

Stationary Trend in Elevated Serum Alpha-Fetoprotein Level in Hepatocellular Carcinoma Patients.

A recent study from the US showed a decreasing trend in the elevated serum alpha-fetoprotein (AFP) level (i.e., ≥20 ng/mL) in hepatocellular carcinoma (HCC) patients at the time of diagnosis. Furthermore, advanced tumor stage and severe underlying liver disease were associated with elevated AFP levels. We aimed to evaluate this issue in an area endemic for hepatitis B virus (HBV). Between 2011 and 2020, 4031 patients were newly diagnosed with HCC at our institution. After excluding 54 patients with unknown AFP data, the remaining 3977 patients were enrolled in this study. Elevated AFP level was defined as ≥20 ng/mL. Overall, 51.2% of HCC patients had elevated AFP levels; this proportion remained stationary between 2011 and 2020 (51.8% vs. 51.1%). Multivariate analysis showed that female gender (odds ratio (OR) = 1.462; p < 0.001), tumor size per 10 mm increase (OR = 1.155; p < 0.001), multiple tumors (OR = 1.406; p < 0.001), Barcelona Clinic Liver Cancer stages B-D (OR = 1.247; p = 0.019), cirrhosis (OR = 1.288; p = 0.02), total bilirubin > 1.4 mg/dL (OR = 1.218; p = 0.030), and HBV- or hepatitis C virus (HCV)-positive status (OR = 1.720; p < 0.001) were associated with elevated AFP levels. In conclusion, a stationary trend in elevated serum AFP level in HCC patients has been noted in the past 10 years. Advanced tumor stage, severe underlying liver disease, viral etiology, and female gender are associated with elevated AFP levels in HCC patients.

Causes of Death among Patients with Hepatocellular Carcinoma According to Chronic Liver Disease Etiology.

This study was conducted to determine whether the causes of death among patients with hepatocellular carcinoma (HCC) differ according to chronic liver disease (CLD) etiology. Between 2011 and 2020, 3977 patients who were newly diagnosed with HCC at our institution were enrolled in this study. We determined whether the cause of death was HCC-related and non-HCC-related. For patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related causes > all negative. All negative was defined as negative for HCV, HBV, and alcohol-related causes. Among 3977 patients, 1415 patients were classified as HCV-related, 1691 patients were HBV-related, 145 patients were alcohol-related, and 725 patients were all negative. HCC-related mortality was the leading cause of death, irrespective of etiology. Among patients who underwent curative treatment, HCC-related mortality was the leading cause of death for patients in the HCV, HBV, and all-negative groups, but not for patients in the alcohol-related group. Among patients 75 years and older who underwent curative treatment, HCC-related mortality was the leading cause of death in the HCV but not HBV or all-negative groups. In conclusion, although most patients with HCC die due to HCC-related causes, non-HCC-related mortality represents a competing event in certain patient subgroups. The current study results underscore the importance of assessing and managing underlying comorbidities, particularly among patients with HCC at risk of non-HCC-related mortality.