Isatuximab plus atezolizumab in patients with advanced solid tumors: results from a phase I/II, open-label, multicenter study.

BACKGROUND: The anti-CD38 antibody isatuximab is approved for the treatment of relapsed/refractory multiple myeloma, but there are no data on its efficacy in solid tumors. This phase I/II study (NCT03637764) assessed the safety and activity of isatuximab plus atezolizumab (Isa + Atezo), an anti-programmed death-ligand 1 (PD-L1) antibody, in patients with immunotherapy-naive solid tumors: epithelial ovarian cancer (EOC), glioblastoma (GBM), hepatocellular carcinoma (HCC), and squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Phase I assessed safety, tolerability, pharmacokinetics, pharmacodynamics, and the recommended phase II dose (RP2D) of isatuximab 10 mg/kg intravenously (i.v.) every week for 3 weeks followed by once every 3 weeks + atezolizumab 1200 mg i.v. every 3 weeks. Phase II used a Simon's two-stage design to assess the overall response rate or progression-free survival rate at 6 months (GBM cohort). Interim analysis was carried out at 6 months following first dose of the last enrolled patient in each cohort. Pharmacodynamic biomarkers were tested for CD38, PD-L1, tumor-infiltrating immune cells, and FOXP3+ regulatory T cells (Tregs) in the tumor microenvironment (TME). RESULTS: Overall, 107 patients were treated (EOC, n = 18; GBM, n = 33; HCC, n = 27; SCCHN, n = 29). In phase I, Isa + Atezo showed an acceptable safety profile, no dose-limiting toxicities were observed, and RP2D was confirmed. Most patients experienced ≥1 treatment-emergent adverse event (TEAE), with ≤48.5% being grade ≥3. The most frequent TEAE was infusion reactions. The study did not continue to stage 2 based on prespecified targets. Tumor-infiltrating CD38+ immune cells were reduced and almost cleared after treatment. Isa + Atezo did not significantly modulate Tregs or PD-L1 expression in the TME. CONCLUSIONS: Isa + Atezo had acceptable safety and tolerability. Clinical pharmacodynamic evaluation revealed efficient target engagement of isatuximab via treatment-mediated reduction of CD38+ immune cells in the TME. Based on clinical data, CD38 inhibition does not improve responsiveness to PD-L1 blockade in these patients.

Sacral tumours and their mimics: pictorial review and diagnostic strategy.

Sacral tumours encompass an extensive range of differential diagnosis. The clinical presentation is often non-specific, including neurological deficits and low back pain. Accurate diagnosis of sacral lesions is challenging and requires a comprehensive imaging strategy and robust knowledge on the imaging characteristics of different pathological processes. This review will provide an updated overview of the computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)-CT features of some common and rare sacral tumours and their mimics. Several clinical scenarios with specific diagnostic considerations and treatment implications will be described.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

BACKGROUND: Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. METHODS: This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. RESULTS: Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). CONCLUSIONS: Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed.

Potassium contributes to zinc stress tolerance in peach (Prunus persica) seedlings by enhancing photosynthesis and the antioxidant defense system.

Zinc (Zn) is considered to be a major industrial pollutant because excessive amounts can impair plant growth. In this paper, we found that peach 'Yoshihime' seedlings are promising Zn tolerant plants. However, heavy Zn toxicity (2 mM) damaged plant performance by disrupting biochemical processes, including photosynthesis, proline production, and K(+) nutrition. Notably, elevated external K(+) supply (10 mM) alleviated peach seedlings from Zn toxicity, evidenced by enhanced photosynthesis, antioxidant defense systems, and plant K(+) nutritional status. Moreover, the transcript levels of KUP (K(+) uptake) genes involved in K(+) acquisition, transport, and homeostasis were significantly upregulated following supply of sufficient K(+) upon Zn toxicity. In general, K(+) favorably contributes to improvements in internal K(+) homeostasis, via the help of K(+) transporters, further protecting plant photosynthesis and the antioxidative defense system. Our findings further benefit the study of the mechanisms underpinning heavy metal tolerance in woody plants.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

Serum peptide profiles during progression of chronic hepatitis B virus infection to liver failure.

Chronic hepatitis B virus (HBV)-infected patients with liver failure have a poor prognosis, and no satisfactory biomarkers are available for diagnosis before the end-stage. We explored serum peptide profiling for diagnosis and prediction of progression to liver failure in HBV-infected patients. Serum samples (164) from healthy subjects (n = 20), or subjects with chronic hepatitis B without cirrhosis and liver failure [chronic hepatitis B subjects without cirrhosis and liver failure (CHB); n = 33], with compensated liver cirrhosis (compensated liver cirrhosis (LC); n = 35), with acute-on-chronic liver failure [acute-on-chronic liver failure (ACLF); n = 38] or with chronic liver failure [chronic liver failure (CLF), n = 38] were applied to ClinProt magnetic beads, and bound peptides/proteins were analyzed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Our classification diagnostic models of liver disease were generated based on the Genetic Algorithm (GA) and Quick Classifier Algorithm (QC). Differentially expressed peptides were found among all test groups, with patterns of difference that readily distinguished between healthy and various HBV-associated liver disease samples. The model generated seven characteristic peptide peaks at 4053 m/z, 3506 m/z, 4963 m/z, 9289 m/z, 2628 m/z, 3193 m/z and 6432 m/z, giving overall predictive capability of 54.27%. Two-way comparisons of LC, ACLF or CLF vs CHB had predictive capabilities of 79.8%, 91.41% and 97.99%, respectively. Comparisons of ACLF or CLF vs LC were predictive at 87.72% and 82.18%, respectively and ACLF vs CLF was predictive at 75.05%. These classification diagnostic models generated by different peptide peaks were further validated in blinded tests with 67-100% accuracy. Serum peptide patterns vary during progression of chronic HBV infection to liver failure and may be used to distinguish different stages of the disease.

Antinuclear antibody is associated with a more advanced fibrosis and lower RNA levels of hepatitis C virus in patients with chronic hepatitis C.

AIMS: Positive serum antinuclear antibody (ANA) is present in a number of patients with chronic hepatitis C virus (HCV) infection. This study aimed to evaluate the prevalence of ANA in patients with chronic hepatitis C (CHC) and to elucidate its clinical implications in virological and histological characteristics of CHC infection. METHODS: A total of 614 CHC patients were enrolled in this prospective, hospital-based study. The serum levels of aspartate aminotransferase, alanine aminotransferase and ANA, and HCV genotype, HCV RNA level, and histological activity index scores for liver histopathology, were determined. RESULTS: The prevalence of positive ANA (titre >1:40) was 35.0%. Women had a significantly higher prevalence than men (41.2 vs 31.0%; p = 0.012). Patients positive for ANA were significantly older (mean (SD), 53.7 (10.5) vs 49.7 (11.3) years; p<0.001) and had higher mean (SD) alanine aminotransferase levels (186.9 (178.8) vs 155.50 (113.5) IU/l; p<0.001) and lower mean (SD) HCV RNA levels (5.2 (0.9) vs 5.4 (1.0) log IU/ml; p = 0.048) than those without ANA. Among 447 patients undergoing liver biopsy, those positive for ANA had a significantly higher mean (SD) fibrosis score (2.0 (1.3) vs 1.5 (1.1); p<0.001) and a higher frequency of F3-4 (69/187, 36.9% vs 50/260, 19.2%; p<0.001) than those negative for ANA. Multivariate logistic regression analyses showed that advanced fibrosis, lower HCV RNA levels and age were significant factors related to positive ANA. CONCLUSION: ANA is associated with a more advanced liver fibrosis and lower serum HCV RNA level in patients with CHC.

Sustained virological response to interferon reduces cirrhosis in chronic hepatitis C: a 1,386-patient study from Taiwan.

BACKGROUND: The long-term benefits of interferon-based therapy on preventing cirrhosis at non-cirrhotic stage in chronic hepatitis C patients are not fully clarified. AIM: To evaluate the effectiveness of interferon-based therapy regarding to cirrhosis prevention in non-cirrhotic chronic hepatitis C patients. METHODS: A total of 1386 biopsy-proven, non-cirrhotic chronic hepatitis C patients (892 received interferon-based therapy and 494 untreated) were enrolled. RESULTS: Fifty-six untreated and 51 treated (24 sustained virologic responders and 27 non-responders) patients developed cirrhosis during a mean follow-up period of 5.0 (1-16) and 5.1 (1-15.3) years, respectively. The annual incidences of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non-responders: 1.99%, sustained responders: 0.74%), respectively. The 15-year cumulative incidence of cirrhosis was significantly lower in treated (9.9%) than untreated patients (39.8%, P = 0.0008, log-rank test). The 14.5-year cumulative incidence of cirrhosis was significantly lower in sustained responders (4.8%) compared with non-responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001). The difference was not significant between non-responders and untreated controls. Cox proportional hazards regression showed sustained virologic responders and younger age were independent negative factors for cirrhosis development. CONCLUSION: A sustained virologic response secondary to IFN-based therapy could reduce cirrhosis development in chronic hepatitis C patients.

Associations of tumour necrosis factor alpha promoter polymorphisms at position -308 and -238 with clinical characteristics of chronic hepatitis C.

The aim of this study was to investigate the association between G vs A transitions in the promoter region of the tumour necrosis factor (TNF) alpha at positions -308 (TNF308.2) and -238 (TNF238.2) and clinical features of chronic hepatitis C (CHC). These two promoter TNF-alpha variants were determined in 250 biopsy-proven CHC patients by polymerase chain reaction amplification, followed by the Restriction Fragment Length Polymorphism (RFLP) method. The distribution of -308 and -238 TNF-alpha promoter genotypes were TNF308.1/TNF308.1: 187 (74.8%), TNF308.1/TNF308.2: 57 (22.8%) and TNF308.2/TNF308.2: 6 (2.4%), respectively, and TNF238.1/TNF238.1: 247 (98.8%) and TNF238.1/TNF238.2: 3 (1.2%). The frequencies of the TNF308.2 and TNF238.2 promoter alleles were 13.8% and 0.6%. Increased TNF308.2 allele copy numbers were significantly associated with increased frequency of lower pretreatment hepatitis C virus (HCV) RNA levels (<800 000 IU/mL; P = 0.031) and severe fibrosis stage (F3-F4; P = 0.006) and higher mean fibrosis score (P = 0.007). The higher cytokine production (with one or two TNF308.2 alleles) was correlated significantly with lower pretreatment HCV RNA levels with a lower mean HCV RNA level (P = 0.024) and increased frequency of lower pretreatment HCV RNA levels (<800 000 IU/mL; P = 0.017). Stepwise logistic regression showed that higher fibrosis score and low HCV RNA levels were independently related to the TNF308.2 allele [odds ratio (95% CI): 1.385 (1.127-1.702) and 0.698 (0.488-0.990)]. We conclude that inheritance of the TNF-alpha promoter genotype at the position -308 appears to be associated with variability in severity of fibrosis and viral load in chronic HCV infection.

Serum adiponectin levels in cholesterol and pigment cholelithiasis.

BACKGROUND: Altered adiponectin levels are associated with metabolic abnormalities. The aim of this study was to explore the role of adiponectin in cholelithiasis. METHODS: A radioimmunoassay was used to determine serum adiponectin levels in 58 patients with cholesterol gallstones and 47 with pigment gallstones, and 101 healthy controls. The chemical composition of extracted gallstones was determined by Fourier transform infrared spectroscopy. RESULTS: The mean(s.d.) adiponectin level was decreased in patients with cholesterol gallstones (7.6(4.1) microg/ml; P < 0.001) but raised in patients with pigment gallstones (17.9(9.0) microg/ml; P < 0.001) in comparison with healthy controls (11.7(6.5) microg/ml). Decreased adiponectin levels (odds ratio (OR) 0.85 (95 per cent confidence interval (c.i.) 0.76 to 0.96); P = 0.008) and female sex (OR 6.06 (95 per cent c.i. 2.10 to 17.46); P = 0.001) were associated with cholesterol gallstone formation. Increased adiponectin levels (OR 1.11 (95 per cent c.i. 1.01 to 1.22); P = 0.025) and increased age (OR 1.06 (95 per cent c.i. 1.01 to 1.12); P = 0.029) were associated with pigment gallstone formation. Raised serum aspartate aminotransferase concentration was a risk factor for both cholesterol (OR 1.16 (95 per cent c.i. 1.03 to 1.30); P = 0.013) and pigment (OR 1.23 (95 per cent c.i. 1.10 to 1.38); P < 0.001) gallstones. CONCLUSION: Gallstone formation is associated with altered serum adiponectin levels. Serum adiponectin might serve as a novel marker for cholesterol and pigment cholelithiasis.

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan.

Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy-proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferon alpha-2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n = 76) or 3 MU of interferon alpha-2b t.i.w. plus ribavirin (IFN group, n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but no difference was found in genotype non-1 patients (PEG vs IFN: 68.4%vs 86.8%, P = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG-IFNalpha2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNalpha2b ribavirin.

Serum insulin-like growth factor-II as a serologic marker of small hepatocellular carcinoma.

OBJECTIVE: Alpha-fetoprotein (AFP) is not a useful tumor marker for diagnosis of small hepatocellular carcinoma (HCC). There is over-expression of insulin-like growth factor (IGF)-II in HCC tissue. This study investigates the diagnostic application of IGF-II in small HCC. MATERIAL AND METHODS: Serum levels of IGF-II and AFP were determined in 41 patients with small cirrhotic HCC (< or = 3 cm), 41 sex- and age-matched patients with cirrhosis alone (LC), and 41 healthy adults. The optimal cut-off values for diagnosing HCC were determined with receiver operating characteristics (ROC) curve. RESULTS: Both IGF-II and AFP levels in HCC were higher than those in LC patients or controls (each p = 0.0001). The IGF-II levels in LC patients were lower than those in controls (p = 0.001). In HCC patients, multivariate analysis indicated that that both IGF-II (odds ratio, 4.54; 95% confidence interval, 2.15-9.55; p = 0.0001) and AFP (odds ratio, 1.05; 95% confidence interval, 1.01-1.08; p = 0.003) were found to be associated with an increased risk of presence of HCC. The optimal cut-off values of IGF-II (4.1 mg/g prealbumin) and AFP (50 ng/ml) were determined with ROC curves. The sensitivity, specificity, and diagnostic accuracy values for IGF-II were 63%, 90%, and 70%, respectively. Those for AFP were 44%, 95%, and 70%, respectively. Determination of both markers in parallel significantly increase the diagnostic accuracy (88%) and sensitivity (80%), with a high specificity (90%). CONCLUSIONS: Serum IGF-II level can be used as an independent serologic marker or a complementary tumor marker to AFP for diagnosis of small HCC.

Serum insulin-like growth factor-II and alpha-fetoprotein as tumor markers of hepatocellular carcinoma.

To evaluate the diagnostic application of serum insulin-like growth factor-II (IGF-II) and alpha-fetoprotein (AFP) levels in hepatocellular carcinoma (HCC), IGF-II and AFP were determined in 100 cirrhotic patients with HCC, 100 sex- and age-matched patients with cirrhosis alone and 50 healthy controls. The results indicated that IGF-II and AFP levels in patients with HCC were higher than in those with cirrhosis alone (p = 0.0001). There is an inverse correlation between IGF-II and (log)AFP (r = -0.410, p = 0.0001) in patients with HCC. Multivariate analysis indicated that IGF-II and AFP were closely associated, in a dose-related fashion, with the presence of HCC. Receiver operating characteristic curves were used to determine the optimal cutoff values of IGF-II (4.5 mg/g prealbumin) and AFP (100 ng/ml), respectively. Both IGF-II and AFP show a high specificity and positive likelihood ratio. The sensitivity was 42.0% for IGF-II and 73.0% for AFP. Determination of both markers in parallel significantly increased the diagnostic accuracy (96.5%) and sensitivity (97.9%), with a high specificity (95.1%) and positive likelihood ratio (19.9). In conclusion, IGF-II and AFP may be used as complementary tumor markers to discriminate HCC from cirrhosis.

The prevalence of TT virus and GB virus C/hepatitis G virus infection in individuals with raised liver enzymes but without HBV or HCV infection in Taiwan.

The prevalence of TT virus (TTV) and GB virus-C/hepatitis G virus (GBV-C/HGV) infection and the association with raised liver function tests in 546 Taiwanese with negative HBsAg, anti-HCV and HCV RNA was elucidated. They were tested for serum alanine aminotransferase (ALT), GBV-C/HGV RNA, anti-envelope protein 2 antibody (anti-E2) and TTV DNA. Direct sequencing and phylogenetic analyses were performed on 58 isolates for TTV genotype determination. The prevalence of TTV DNA, GBV-C/HGV RNA, anti-E2 and over all GBV-C/HGV exposure was 24.9, 3.4, 8.2 and 11.1%, respectively. Using uni- and multi-variate analyses, male gender and TTV viremia were associated significantly with raised ALT values. Sixty-nine percent of TTV isolates were deduced to be TTV genotype 1 and they had significantly lower mean age than genotype non-1 isolates. In the population, raised ALT may be related to male gender and be attributable to TTV infection but not to GBV-C/HGV among individuals with no evidence of current HBV and HCV infection. TTV genotype 1 is the most prevalent genotype and associated with younger age.

Changing prevalence of hepatitis C virus genotypes: molecular epidemiology and clinical implications in the hepatitis C virus hyperendemic areas and a tertiary referral center in Taiwan.

To determine the hepatitis C virus (HCV) genotype distribution in Taiwan and to clarify the relationship between genotype and the pathogenesis of HCV infection, 1,164 subjects positive for serum HCV antibodies and HCV RNA from three HCV hyperendemic areas (Masago, Tzukuan, and Taoyuan) and a tertiary referral center in Taiwan were studied during 1995-1997. HCV genotypes and viral loads were determined using Okamoto's method and branched DNA assay, respectively. Genotype 1b was the most prevalent in Tzukuan (61.9%), Taoyuan (76.9%), and the referral center (47.0%). By contrast, genotype 2a was the major HCV type in Masago (63.5%). Prevalence of genotype 1b positively and that of genotype 2a negatively correlated to age, regardless of study populations (P < 0.01). Based on multivariate analysis, the significant factors associated with the presence of cirrhosis, with or without hepatocellular carcinoma, in chronic hepatitis C patients were genotype 1b and age. In conclusion, these results underline that independent HCV outbreaks continue in HCV hyperendemic areas in Taiwan, concomitant with a changing relative prevalence of HCV genotypes in relation to age. Both the correlation of genotype 1b with age (cohort effect) and intrinsic properties of HCV genotypes are probably responsible for the association between genotype and the pathogenesis of HCV infection.

The molecular epidemiology and clinical significance of TT virus (TTV) infection in healthy blood donors from southern Taiwan.

To evaluate the molecular epidemiology and clinical significance of th

Influence of hepatitis C virus on the profiles of patients with chronic hepatitis B virus infection.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common causes of chronic liver disease, cirrhosis and hepatocellular carcinoma. The influence of HCV infection on the clinicopathological and virological profiles of chronic HBV infection was investigated. METHODS: A total of 100 chronic HBV carriers with histopathological diagnoses by liver biopsy were studied. Hepatitis B e antigen (HBeAg) and anti-HCV antibody were tested. Serum HCV-RNA was detected by using a nested reverse transcription-PCR assay. A branched DNA (bDNA) assay was used to detect HBV-DNA and quantitate the serum levels. RESULTS: Eighteen (18%) of 100 patients were positive for anti-HCV and HCV-RNA. Patients with concurrent HCV and HBV infection were significantly older than those without HCV infection (P < 0.05). The positive rates of HBeAg and HBV-DNA as well as the serum levels of HBV-DNA in patients with concurrent HCV and HBV infection were significantly lower than those without concurrent HCV and HBV infection (P < 0.01, P < 0.05, and P < 0.001, respectively). By using multivariate analysis, the factors of seroconversion of HBeAg and decreasing level of HBV-DNA were significantly correlated to concurrent HCV and HBV infection in chronic HBV carriers. The factors of increasing age and concurrent HCV and HBV infection were significantly correlated to seroconversion of HBeAg. CONCLUSIONS: The concurrent HCV and HBV infection in chronic HBV carriers might result in a suppression of HBV replication that presented with a lower level of serum HBV-DNA and HBeAg seroconversion. Nevertheless, neither more obvious increase in biochemical parameters nor histopathological progression to more advanced liver diseases was observed.

Hepatitis C virus infection among teenagers in an endemic township in Taiwan: epidemiological and clinical follow-up studies.

The aim of the study was to elucidate the epidemiological features of Hepatitis C virus (HCV) infection among teenagers in an endemic area by conducting a mass screening study. We also investigated the clinical outcome of the anti-HCV-positive subjects by conducting subsequent short-term and long-term follow-up studies. All 2837 students of two junior middle schools in Tzukuan, aged 13-16 years, were invited to be screened for anti-HCV, HBsAg, AST and ALT in October 1995. A total of 2726 (96%) students responded. Anti-HCV, HCV RNA and aminotransferase levels were evaluated among anti-HCV-positive students 1 month and 30 months later, respectively. A total of 38 (1.4%; M/F = 22/16) participants were anti-HCV-positive. The anti-HCV-positive students had higher rates of exposures to transfusion, anti-HCV-positive families and surgery. The prevalence (2.8%) of the 7 maritime villages was markedly higher than that (0.7%) of the other 8 villages (P < 0.001). Subsequent follow-up studies demonstrated that there might be 5 cases of acute or recent HCV infection, and 6 cases who had recovered from chronic HCV infection.

Percutaneous ethanol injection of the supplying artery to hepatocellular carcinoma that is not amenable to conventional treatment.

The purpose of this study was to evaluate the clinical usefulness of ultrasound-guided percutaneous ethanol injection of the supplying artery (PEISA) to the tumour in the palliative management of hepatocellular carcinoma (HCC) that is not amenable to conventional treatments. A total of 23 cases of HCC, measuring from 3.1 cm to larger than 15 cm (median 5.4 cm) in 17 cirrhotic patients, were treated by PEISA. PEISA was used to control rapid growth of the tumour in seven patients and to reduce abdominal discomfort caused by rapid expansion of the tumour in 10 patients. Tumours with arterial Doppler signals persisting after PEISA underwent repeated treatment. The follow-up period ranged from 2-48 months. PEISA was achieved in 69 out of 76 attempts (90.8%). The amount of ethanol injected on each occasion ranged from 2.5-33 ml. Follow-up colour Doppler scanning showed complete elimination of tumour Doppler signals in 22 out of 23 lesions (95.7%). Following treatment, one tumour disappeared, 13 tumours shrank and nine tumours were unchanged in size. All patients with abdominal discomfort had relief after treatment. The common complications of PEISA were local pain and fever. In conclusion, PEISA is effective at treating painful HCC unsuitable for conventional treatment.

Role of serum C-reactive protein as a marker of hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND: The usefulness of C-reactive protein (CRP) as a tumour marker in patients with hepatocellular carcinoma (HCC) is controversial. The purpose of this study was to determine whether CRP estimation could be used to identify patients with HCC among those with cirrhosis. METHODS: Serum levels of CRP and alpha-fetoprotein (AFP) were investigated in 122 previously untreated patients with cirrhosis and HCC. Another 76 patients with cirrhosis alone were also investigated as controls. RESULTS: Of the subjects tested, 47.5% of patients with HCC and 39.5% of controls had elevated CRP values (> 6 microg/mL). Although using elevated CRP and/or AFP (> 20 ng/mL) as a criterion showed a significant difference between controls and patients with multiple nodular, massive, or diffuse type HCC (all P < 0.005), the clinical application of this criterion was limited because of low specificity (58%) and accuracy (all < 73%). By using receiver-operating characteristic curves no valuable threshold value of CRP was found to discriminate various types of HCC, except for distinguishing the diffuse type from controls. The CRP value of 12 microg/mL could be used as the cut-off value to differentiate diffuse-type HCC from controls (sensitivity 82.4%, specificity 82%, accuracy 82.1%, P<0.005). CONCLUSIONS: Serum CRP is not a good marker for HCC. However, very high values of CRP in patients with cirrhosis may suggest the presence of a diffuse-type HCC.