One-Step Method in Creation of Artificial Ascites.

Background: The study aims to improve the success rate and the rapidity in creating artificial ascites before starting the treatment for subcapsular hepatocellular carcinomas. Methods: Two hundred and forty-six consecutive hepatocellular carcinoma patients who required the instillation of artificial ascites for better visualization or prevention from organ injury were recruited between November 2011 and September 2017. Initially, 95 patients were using the Seldinger technique, while the remaining 151 patients were using the one-step method. The proportions of patients who had undergone surgery, transarterial chemoembolization, or radiofrequency ablation therapy before performing artificial ascites infusion were 11.6% (11/95), 3% (3/95), and 37% (35/95) in the Seldinger group, and 15.9% (24/151), 15.2% (23/151), and 52.3% (79/151), respectively, in the one-step group. Results: The complete success rate, partial success rate, and failure rate in creating artificial ascites using the Seldinger technique and the one-step method were 76.8% (73/95), 11.6% (11/95), 11.6% (11/95) and 88.1% (133/151), 7.9% (12/151), 4% (6/151), respectively. The complete success rate was significantly higher in the one-step method group (P < 0.05) than that of the Seldinger group. The mean time required from starting the procedure to successful intraperitoneal instillation of glucose water was 145.79 ± 133.37 s in the one-step method, which was statistically shorter than that of 238.68 ± 95.58 s in the Seldinger group (P < 0.05). Conclusion: The one-step method has a higher success rate than the Seldinger method in creating artificial ascites and is faster, especially in treatment-experienced patients.

Long term outcomes of colon polyps with high grade dysplasia following endoscopic resection.

BACKGROUND: The risk of recurrent colonic adenoma associated with high-grade dysplasia (HGD) colon polyps at baseline colonoscopy remains unclear. We conducted a clinical cohort study with patients who underwent polypectomy during screen colonoscopy to assess recurrent colonic adenoma risk factors. METHODS: 11,565 patients at our facility underwent screen colonoscopy between September 1998 and August 2007. Data from patients with HGD colon polyps who had undergone follow-up colonoscopy were included for analysis. RESULTS: Data from 211 patients was included. Rates of metachronous adenoma and advanced adenoma at follow-up were 58% and 20%, respectively. Mean follow-up period was 5.5 ± 1.8 (3-12) years. Univariate logistic regression analysis revealed that an adenoma count of ≥ 3 at baseline colonoscopy was strongly associated with overall recurrence, multiple recurrence, advanced recurrence, proximal recurrence, and distal adenoma recurrence with odds ratios of 4.32 (2.06-9.04 95% CI), 3.47 (1.67-7.22 95% CI), 2.55 (1.11-5.89 95% CI), 2.46 (1.16-5.22 95% CI), 2.89 (1.44-5.78 95% CI), respectively. Multivariate analysis revealed gender (male) [P = 0.010; OR 3.09(1.32-7.25 95% CI)] and adenoma count ≥ 3 [P = 0.002; OR 3.08(1.52-6.24 95% CI)] at index colonoscopy to be significantly associated with recurrence of advanced adenoma. CONCLUSION: Recurrence of colonic adenoma at time of follow-up colonoscopy is common in patients who undergo polypectomy for HGD colon adenomas during baseline colonoscopy. Risk of further developing advanced adenomas is associated with gender and the number of colon adenomas present.

Carbon dioxide insufflation during colonoscopy can significantly decrease post-interventional abdominal discomfort in deeply sedated patients: A prospective, randomized, double-blinded, controlled trial.

BACKGROUND AND AIM: CO2 has been reported to be absorbed from the bowel more rapidly than air, resulting in a discomfort reduction after colonoscopy. Its role in deeply sedated patients is limited. This study was designed to investigate the efficacy and safety of CO2 insufflation during colonoscopy in patients deeply sedated with propofol. METHODS: A total of 125 continuous patients were randomly assigned to receive either CO2 (n = 63) or air (n = 62) insufflation during propofol-sedated colonoscopy. Postcolonoscopy abdominal pain, distention, and satisfaction were assessed at 1, 3, and 24 h after the procedure, and the proportions of pain-free and distention-free patients were compared. Residual bowel gas in the colon and small bowel was evaluated at 1 h after colonoscopy. End-tidal CO2 and O2 saturation was measured for safety analysis. RESULTS: There was a significant difference between the two groups regarding the postcolonoscopy abdominal pain, distention, and subjective satisfaction at 1 h (P < 0.001) and 3 h (P < 0.01) after the procedure. Patients' pain and distention at 1 and 3 h after the procedure were significantly lower in the CO2 group (P < 0.01). Residual bowel gas in the colon and small bowel was significantly less in the CO2 group (P < 0.001). There was no significant difference in end-tidal CO2 levels between two groups before, during, and after the procedure. CONCLUSIONS: Compared with air, CO2 insufflation during colonoscopy reduced postcolonoscopy abdominal discomfort and improved patients' satisfaction. It was safe to use CO2 insufflation in deeply sedated colonoscopy.

Treatment-emergent depression and anxiety between peginterferon alpha-2a versus alpha-2b plus ribavirin for chronic hepatitis C.

BACKGROUND: This study investigates differences in depression and anxiety between patients with chronic hepatitis C who are treated with peginterferon alpha-2a (PegIFN-α-2a) plus ribavirin and those who are treated with peginterferon alpha-2b (PegIFN-α-2b) plus ribavirin. METHODS: In this 24 week, non-randomized, observational, prospective study, 55 patients with chronic hepatitis C were treated with PegIFN-α-2a plus ribavirin (Group 1), and 26 patients were treated with PegIFN-α-2b plus ribavirin (Group 2). All patients underwent assessment using the Hospital Anxiety and Depression Scale (HADS) at the baseline and at weeks 4, 12 and 24. Patients with depression scores (HADS-D) ≥ 8 and anxiety scores (HADS-A) ≥ 8 were defined as having depression and anxiety, respectively. The factors that were associated with depression and anxiety during the 24 week antiviral treatment were determined. RESULTS: During the 24 week antiviral treatment, the proportion of patients with depression significantly increased over time in both groups (Group 1: p = 0.048; Group 2: p = 0.044). The proportion of patients with anxiety did not significantly change during the follow-up period in either group. Incidences of depression or anxiety did not differ significantly between Group 1 and Group 2. A history of alcohol use disorder was an independent predictor of depression at week 12 (p < 0.001) and week 24 (p < 0.001), and a poor virological response to treatment was associated with depression at week 24 (p = 0.029). Patients who had more physical comorbidities were more likely to suffer from anxiety at week 12 (p = 0.038). CONCLUSIONS: This study did not identify significant differences in depression or anxiety between in patients with chronic hepatitis C who underwent a 24 week antiviral treatment regimen with PegIFN-α-2a plus ribavirin and those who underwent a regiment with PegIFN-α-2b plus ribavirin. Future research with larger samples and a randomized, controlled design are required to verify the findings in this study. TRIAL REGISTRATION: This clinical study has been registered at ClinicalTrials.gov. (Trial registration: NCT02943330 ).

Transient Elastography for Spleen Stiffness Measurement in Patients With Cirrhosis: Role in Degree of Thrombocytopenia.

OBJECTIVES: The purpose of our study was to evaluate the relationship between spleen stiffness measured by transient elastography and the degree of thrombocytopenia in patients with liver cirrhosis. METHODS: A total of 67 patients with liver cirrhosis were prospectively enrolled in the study. All patients underwent single-day hematologic and biochemical tests, sonography, and transient elastography of the liver and spleen. Thrombocytopenia was categorized as mild (platelet count, 75,000-150,000/µL), moderate (50,000-75,000/µL), and severe (<50,000/µL). RESULTS: The degree of thrombocytopenia was significantly correlated with spleen stiffness (P = .001) and spleen size (P = .002) but not with liver stiffness (P = .086). In patients without splenomegaly, spleen stiffness values were significantly higher in patients with thrombocytopenia than in those without thrombocytopenia (P = .035). In patients with splenomegaly, spleen stiffness values were significantly higher in patients with moderate to severe thrombocytopenia than in those with a normal platelet count or mild thrombocytopenia (P = .007). Compared to liver stiffness, spleen stiffness showed a better and statistically significant correlation with platelet count and spleen size in patients with cirrhosis. CONCLUSIONS: The degree of thrombocytopenia was directly correlated with spleen stiffness, irrespective of the presence of splenomegaly. The clinical phenomenon of unexpected thrombocytopenia may be explained by a subtle or irreversible change in spleen stiffness.

Pretreatment platelet count early predicts extrahepatic metastasis of human hepatoma.

BACKGROUND & AIMS: Thrombocytosis is associated with metastasis in many human cancers. Most hepatocellular carcinomas (HCC) develop in cirrhotic livers, which are characterized by thrombocytopenia. We aimed to elucidate the pretreatment platelet count in prediction of extrahepatic metastasis of HCC during the follow-up. METHODS: Three cohorts containing 1660, 480 and 965 HCC patients enrolled from three hospitals were used for discovery and validation respectively. Pretreatment clinical factors associated with extrahepatic metastasis during follow-up up to 5 years were identified using multivariate Cox regression model. RESULTS: In early-stage HCC (BCLC stage 0-A), pretreatment platelet count (hazard ratio [HR], 1.04 per 10,000/µl; 95% CI, 1.01-1.07; P = 0.010) and serum alpha-foetoprotein (AFP) >100 ng/ml (HR, 1.70; 95% CI, 1.04-2.78; P = 0.033) were the only two independent factors associated with extrahepatic metastasis. Receiver operating characteristic evidenced that pretreatment platelet count predicted metastasis better than AFP did. Survival tree analysis identified platelet counts <118,000/µl (HR, 0.49; 95% CI, 0.38-0.63; P < 0.001) or >212,000/µl (HR, 2.12; 95% CI, 1.67-2.70; P < 0.001) to categorize patients into low and high risk of metastasis subgroups, which were verified using both validation cohorts. CONCLUSIONS: Pretreatment platelet count is a reliable marker to predict extrahepatic metastasis of early-stage HCC following curative treatment. Cirrhotic thrombocytopenia contributes to relatively low metastasis incidence of HCC than many other cancers. High platelet count identifies a subgroup of HCC patients at high risk of metastasis, who might benefit from adjuvant therapies following initial curative treatment.

The Charlson Comorbidity Index is an Independent Prognostic Factor for Treatment-Naïve Hepatocellular Carcinoma Patients with Extrahepatic Metastases.

BACKGROUND/AIMS: This study aimed to investigate the association between comorbidity, anti-cancer treatment, and overall survival in patients with hepatocellular carcinoma (HCC) with extrahepatic metastases. METHODOLOGY: We retrospectively analyzed data from 57 patients diagnosed as having treatment-naïve stage IV HCC with extrahepatic metastases between 2007 and 2010. Comorbidity was assessed using two scoring systems, the Charlson comorbidity index (CCI) and the Kaplan-Feinstein index. Associations between comorbidity, demographic variables, treatment modality, and overall survival were analyzed. RESULTS: Univariate analysis showed that a CCI of ≥ 2 (P = 0.017), an Okuda score of II/III (P = 0.026), and the use of anti-cancer therapy (P = 0.039) was associated with overall survival. Fewer patients with a CCI of ≥ 2 received treatment (P < 0.001), and anti-cancer treatment of any modality did not show a survival benefit in these patients (P = 0.174). The multivariate analysis showed that a CCI of ≥ 2 was the only independent prognostic factor for overall survival (P = 0.043). CONCLUSIONS: The pre-treatment comorbidity status played an important role in overall survival because of its association with the administration of anti-cancer therapy. Therefore, comprehensive evaluation of comorbidities before treatment is recommended for HCC patients with extrahepatic metastases.

Discontinuing Hepatitis Activity Reduced Hepatocellular Carcinoma Recurrence after Primary Curative Therapy.

BACKGROUND: Hepatocellular carcinoma (HCC) tends to recur after curative treatment. This study aimed to identify the clinical factors associated with HCC recurrence after initial curative therapy. METHODS: We retrospectively included patients with early stage HCC Barcelona Clinic Liver Cancer (BCLC) stages 0 and A who received curative surgical resection or local ablation at three different Chang Gung Memorial Hospitals in Taiwan (527 patients from Linkou, 150 patients from Keelung, and 127 patients from Chiayi) from 2000 to 2009. Pretreatment clinical data were subjected to univariate and multivariate logistic analyses to identify the risk factors for HCC recurrence within five years after the primary curative treatment. Recurrence and survival rates were assessed using Kaplan-Meier curves and log-rank tests. RESULTS: Patients with a history of nucleoside analog or peg-interferon treatment for hepatitis B or hepatitis C infection had lower HCC recurrence rates than did those without such treatment. By contrast, alcohol drinking habits (p = 0.0049, hazard ratio (HR): 1.508, 95%CI: 1.133-2.009), a platelet count of < 14 × 104/µL (p = 0.003, HR: 1.533, 95%CI: 1.155-2.035), and a serum alanine aminotransferase level > 40 U/L (p = 0.0450, HR: 1.305, 95%CI: 1.006-1.694) were independent risk factors for HCC recurrence. The five-year HCC recurrence rates did not differ between patients who received either local radiofrequency ablation or surgical resection at BCLC stages 0 and A. CONCLUSIONS: Factors contributing to persistent hepatitis activity and advanced fibrosis precipitate tumor recurrence. Active intervention to discontinue liver injury or hepatitis could reduce HCC recurrence.

Waist-to-height ratio for the prediction of gallstone disease among different obesity indicators.

Background: Factors of metabolic syndrome such as obesity are well-known risk factors for gallstone disease (GSD). There are different indicators of obesity, including weight, body mass index, waist circumference, and waist-to-height ratio. The predictive ability of different obesity indicators for GSD remains unclear. Objective: To explore the most efficient predictor of GSD among the different anthropometric indicators of obesity. Methods: This population-based cross-sectional study included 2263 participants who completed a questionnaire detailing their demographics, medical history, and lifestyle between 2014 and 2017 in Taiwan. Blood samples were collected and physical examinations, including anthropometric measurements, were performed. Gallstone disease was ascertained using ultrasonography. Multivariate analyses were performed to identify independent risk factors for GSD. Results: The overall prevalence of GSD was 8.8%. According to the multivariate analysis, individuals with a waist-to-height ratio ≥0.5 (odds ratio|odds ratios (OR) = 1.65, 95% confidence interval (CI) = 1.10-2.48, p = 0.017) had an increased risk of GSD. Diabetes was the main risk factor for GSD in men (OR = 2.06, 95% CI = 1.17-3.65, p = 0.013). Among women, waist-to-height ratio >0.5 (OR = 1.76, 95% CI = 1.03-3.02, p = 0.040) and current hormone drug use (OR = 2.73, 95% CI = 1.09-6.84, p = 0.033) were significant risk factors for gallstones. Conclusion: GSD was independently associated with central obesity and exogenous hormone intake in women. Among the anthropometric indicators used to assess central obesity, waist-to-height ratio was the most accurate predictor of GSD.

Liver angiosarcoma, a rare liver malignancy, presented with intraabdominal bleeding due to rupture--a case report.

Liver angiosarcoma is a rare disease, however it still ranks as the third of most common primary liver maligancies. The prognosis of liver angiosarcoma is very poor with almost all patients with this kind of disease die within 2 years after diagnosis. No specific symptoms and signs are closely associated with this disease. Here, we report a case presenting shock status at first due to rupture of liver angiosarcoma- induced internal bleeding. After emergent transarterial embolization (TAE), she received partial hepatectomy two weeks later. 4 months after operation, she is still with a good performance status without obvious recurrence or metastasis identified.

Predictors of changes in hemoglobin levels in patients with chronic hepatitis C treated with ribavirin plus pegylated interferon-α.

BACKGROUND: Combination therapy with pegylated interferon (pegIFN)-α and ribavirin (RBV) for chronic hepatitis C virus (HCV) infection is associated with reduction in hemoglobin (Hb) concentrations and anemia. The aim of this study was to evaluate the magnitude and frequency of change in Hb and determine the predictive risk factors for Hb decrease during this therapy. METHODS: We enrolled 308 patients with chronic HCV infection who were receiving weekly subcutaneous pegIFN injection in combination with body weight-based oral RBV for 24 weeks. Clinical and virological characteristics were used for studying the predictors of decrease in Hb. RESULTS: The majority (95%) of patients showed reduction in Hb concentration of at least 1 g/dL during pegIFN and RBV combination therapy. The mean and median maximal decrease in Hb level of the study patients was 3.9 g/dL (range -0.3 to 8.2 g/dL; interquartile range 2.8-5.0 g/dL). Of all patients, 49.4% showed a reduction in Hb level of more than 4 g/dL; a higher number of male patients than female patients showed an Hb decrease of >4 g/dL. Multivariate analysis of our data showed that older age, high baseline Hb concentration, high HCV RNA viral load, low estimated glomerular filtration rate (eGFR), and low platelet count were independent predictors of significant decline in Hb levels. CONCLUSIONS: Patients with low eGFR before antiviral therapy may have an increased risk of RBV-related anemia and should be closely monitored. Clinician should consider the potential risk of significant reduction in Hb level according to eGFR while deciding the RBV dose.

Therapeutic effects of pegylated interferon plus ribavirin in chronic hepatitis C patients with occult hepatitis B virus dual infection.

BACKGROUND AND AIM: Occult hepatitis B virus (HBV) infection is defined by the detectable serum HBV-DNA in HBV surface antigen-negative patients. This retrospective study aims to evaluate the therapeutic effects of combined pegylated interferon (PEG-IFN) plus ribavirin (RBV) in patients with concurrent occult HBV/hepatitis C virus (HCV) dual infection. METHODS: In total, 126 consecutive chronic hepatitis C (CHC) patients who received combined PEG-IFN and RBV therapy were included. Patients were divided into the occult HBV/HCV dual infection group or the HCV-monoinfected group according to whether or not they had the detectable serum HBV-DNA. The biochemical and virological responses to combined therapy were compared between these two groups. Serum HCV-RNA and HBV-DNA were checked before treatment, at the end of treatment as well as at 6- and 12-months' follow up in the occult HBV/HCV group. RESULT: Six patients were seropositive for HBV-DNA and were included in the occult HBV/HCV dual infection group. There were no statistical differences in the biochemical and virological responses to combined therapy between these two groups. Undetectable serum HBV-DNA was noted at the end of the treatment and the 6- and 12-months' follow up in patients with occult HBV/HCV dual infection. CONCLUSION: Occult HBV infection in CHC patients is rare. The biochemical and virological responses to combined PEG-IFN and RBV therapy might be similar in CHC patients with or without occult HBV infection. The serum HBV-DNA level was low in patients with occult HBV/HCV dual infection who responded to combined therapy.

Nomogram predicting extrahepatic metastasis of hepatocellular carcinoma based on commonly available clinical data.

BACKGROUND AND AIM: Extrahepatic metastasis (EHM) of hepatocellular carcinoma (HCC) leads to a worse prognosis. We aimed to develop a nomogram based on noninvasive pretreatment clinical data to predict EHM of HCC sooner. METHODS: Three cohorts containing 1820, 479, and 988 HCC patients were enrolled from three hospitals in different regions in Taiwan and served as the training and validation cohorts. Pretreatment clinical data were analyzed by Cox regression modeling for independent risk factors of EHM. RESULTS: Platelet count ≥ 200 × 103/µL, serum alfa-fetoprotein ≥ 100 ng/dL, tumor size ≥ 3 cm, tumor number > 1, and macrovascular invasion were independent risk factors for EHM and were used to develop a nomogram. This nomogram had concordance indices of 0.733 (95% confidence interval [CI]: 0.688-0.778) and 0.739 (95% CI: 0.692-0.787) for the prediction of EHM during a 5-year follow-up duration in the training and validation cohorts, respectively. A nomogram score > 61 implied a high risk of EHM (hazard ratio [HR] = 3.83; 95% CI: 2.77-5.31, P < 0.001). CONCLUSION: We have developed a nomogram that could accurately predict EHM of HCC and be readily available for formulating individualized treatment for all individual HCC patients to improve therapeutic efficacy.

Spontaneous rupture of the liver in a patient with chronic hepatitis B and D.

Spontaneous rupture of the liver is a rare condition with serious consequences, if not recognized and treated in time. It has been reported as a complication of several disorders, including benign or malignant liver tumors, connective tissue disease, infiltrating liver disease, preeclampsia, and post anticoagulant therapy. We report a case of spontaneous rupture of liver in a non-cirrhotic, chronic hepatitis B and D patient presenting with acute hemoperitoneum and shock. The subcapsular hematoma and rupture of liver were documented by image studies. The patients' condition gradually stabilized after fluid resuscitation. The reported case and literature review suggest that spontaneous rupture of liver must be considered in a differential diagnosis of acute hemoperitoneum. A high index of suspicion and early diagnosis with imaging are critically important.

A comparative study on Helicobacter pylori infection in peptic ulcer disease patients with or without previous eradication therapy.

BACKGROUND/AIMS: Although H. pyloric eradication therapy is indicated for peptic ulcer patients, the prevalence of H. pylori infection may be different between patients with active or chronic (scarred) peptic ulcers. This study aimed to compare the prevalence of H. pylori infection in active and chronic peptic ulcer patients with or without previous H. pyloric eradication therapy. METHODOLOGY: Both non-invasive (13C or 14C urea breath test) and invasive methods (rapid urease test and histology) were used to detect H. pylori. From Dec. 2002 to Jan. 2003, 153 patients with 63% male were enrolled in this study. Fifty-six patients who previously received H. pyloric eradication therapy were enrolled as treated patients, and 97 patients who did not receive therapy were enrolled as untreated patients. RESULTS: H. pylori infection rate was still high in untreated patients even when duodenal ulcer had been scarred (96% in active duodenal ulcer and 63% in scarred duodenal ulcer). In treated patients, H. pyloric infected rates were very low when peptic ulcers were scarred (0% in scarred gastric ulcer, 4% in scarred duodenal ulcer and 0% in both scarred ulcers). CONCLUSIONS: H. pyloric eradication therapy is indicated for untreated patients even when endoscopic examination revealed chronic scarred duodenal ulcer.

Body mass index above 24 is beneficial for the 6-month survival rate in hepatocellular carcinoma patients with extrahepatic metastases.

BACKGROUND AND OBJECTIVES: To investigate the effect of overweight status on the 6-month survival rate in patients with extrahepatic hepatocellular carcinoma (HCC). METHODS AND STUDY DESIGN: We retrospectively analyzed the records of 51 patients with hepatocellular carcinoma and extrahepatic metastases between 2007 and 2010 before treatment. The associations among overweight status (body mass index [BMI] >24 kg/m2), demographic variables, and survival outcome were analyzed by univariate and multivariate analysis. RESULTS: BMI>24 kg/m2 was significantly associated with the 6-month survival rate (p=0.042). Gender (p=0.149), Child Pugh classification (p=0.149), Okuda staging (p=0.093), and albumin concentration >3.5 mg/dL (p=0.082) showed marginal survival benefits in univariate analysis. Multivariate analysis confirmed that BMI >24 kg/m2 was an independent prognostic factor for the 6-month survival rate (p=0.03). CONCLUSIONS: BMI >24 kg/m2 was associated with an improved 6-month survival rate in patients with extrahepatic metastatic hepatocellular carcinoma.

Gallbladder polyp as a manifestation of hemobilia caused by arterial-portal fistula after percutaneous liver biopsy: a case report.

Outpatient percutaneous liver biopsy is a common practice in the differential diagnosis and treatment of chronic liver disease. The major complication and mortality rate were about 2-4% and 0.01-0.33% respectively. Arterio-portal fistula as a complication of percutaneous liver biopsy was infrequently seen and normally asymptomatic. Hemobilia, which accounted for about 3% of overall major percutaneous liver biopsy complications, resulted rarely from arterio-portal fistula We report a hemobilia case of 68 years old woman who was admitted for abdominal pain after liver biopsy. The initial ultrasonography revealed a gallbladder polypoid tumor and common bile duct (CBD) dilatation. Blood clot was extracted as endoscopic retrograde cholangiopancreatography (ERCP) showed hemobilia. The patient was shortly readmitted because of recurrence of symptoms. A celiac angiography showed an intrahepatic arterio-portal fistula. After superselective embolization of the feeding artery, the patient was discharged uneventfully. Most cases of hemobilia caused by percutaneous liver biopsy resolved spontaneously. Selective angiography embolization or surgical intervention is reserved for patients who failed to respond to conservative treatment.

Ribavirin monotherapy increases sustained response rate in relapsers of end treatment virologic responders.

AIM: To assess the efficacy of ribavirin monotherapy in patients with biochemical relapse after combination therapy. METHODS: Twenty-four weeks of ribavirin monotherapy was given to biochemical relapsers of end treatment biochemical responders within 6 mo after combination therapy, including non-responders with HCV-RNA level < or =0.2 Meq/mL and end treatment virologic responders (ETVRs) with or without reappearance of HCV-RNA. RESULTS: Sixty-two chronic HCV-infected patients completed 24 wk of interferon-alpha plus ribavirin combination therapy. Fifty patients (80%) achieved end treatment biochemical response including 16 non-responders and 34 of 36 ETVRs. Twenty-six patients (41.9%) were non-responders. Ribavirin monotherapy was given to 20 biochemical relapsers including 12 non-responders with HCV-RNA levels < or =0.2 Meq/mL, four of eight HCV-RNA reappearing ETVRs, and four HCV-RNA negative ETVRs. After 24 wk of ribavirin monotherapy, one of 12 non-responders, two of four HCV-RNA reappearing ETVRs and all four RNA-negative biochemical relapsers of ETVRs showed sustained virologic response. Two of 12 monotherapy treated non-responders showed persistent normalization of liver function test. In total, 50% (31/62) of patients achieved sustained virologic response. CONCLUSION: Resumption of ribavirin monotherapy in ETVRs at signs of viral rebound and recurrent biochemical abnormalities rather than continuation of monotherapy appears to be the key to success of ribavirin monotherapy after interferon-related combination therapy.

Hepatocellular carcinoma cells express 25(OH)D-1α-hydroxylase and are able to convert 25(OH)D to 1α,25(OH)2D, leading to the 25(OH)D-induced growth inhibition.

Hepatocellular carcinoma (HCC) is the most diagnosed liver cancer without effective treatments available for advanced HCC. Vitamin D is getting popular due to its anti-cancer characteristics. However, the clinical application of 1α,25(OH)2D, the active form of vitamin, is hampered by its hypercalcemia side effect. 1α,25(OH)2D is converted from 25(OH)D, the index of serum vitamin D status, by CYP27B1, which is originally found in kidneys but recently detected in non-renal tissues. 25(OH)D has been shown to repress some cancers expressing CYP27B1 due to the local conversion of 25(OH)D to 1α,25(OH)2D, which works in a intra-, auto-, or paracrine manner and thus minimizes the risk of hypercalcemia. In this study, we found CYP27B1 expression in human hepatocyte, HCC, and HepG2 cells. As we treated HepG2 cells with 25(OH)D, the 1α,25(OH)2D target gene CYP24A1 expression was increased and was further upregulated as CYP27B1 transfection or downregulated as CYP27B1 knockdown. Other 1α,25(OH)2D target genes in HepG2 cells, p21 and p27 were also stimulated by 25(OH)D after CYP27B1 transfection. Further, 25(OH)D could inhibit HepG2 cells growth, which was potentiated by CYP27B1 transfection. Collectively, we showed for the first time that HCC expressed CYP27B1 and was able to covert 25(OH)D to 1α,25(OH)2D in vitro, thus responsive to 25(OH)D treatment. Our data justifies the application of 25(OH)D and CYP27B1 gene transfection therapy in further HCC treatment studies.