Chi-Yi Chen

Spontaneous rupture of hepatocellular carcinoma : a review of 141 Taiwanese cases and comparison with nonrupture cases

We reviewed the records and statistics of 560 patients hospitalized with hepatocellular carcinoma (HCC) over a 5-year period. One hundred and forty-one patients (26%) had spontaneous rupture of their HCCs. Different characteristics of the rupture (R) and nonrupture (NR) groups were compared; there were statistically significant differences (p < 0.05) in the size of the tumor (R, 9.83 +/- 4.36 cm, and NR, 7.67 +/- 4.01 cm; p < 0.0001), and the minimal thickness of peritumor liver parenchyma (R, 0.03 +/- 0.20 cm, and NR, 0.30 +/- 0.70 cm; p < 0.001), the presence of the ¿hump sign¿ (R, 87.8%, and NR, 45.7%; p < 0.0001), and the minimal thickness of peritumor liver parenchyma (R, 0.03 +/- 0.20 cm, and NR, 0.30 +/- 0.70 cm; p < 0.001). The percentage of left-lobe tumors was significantly higher in the rupture group than in the nonrupture group (p < 0.05). In addition, the Child-Pughs score and serum transaminase levels were higher, and the prothrombin times more prolonged, in the rupture group. Factors that were not statistically significant included sex, age, etiology of cirrhosis, platelet count, portal vein thrombosis, and the presence of a varix. Multivariate logistic regression analysis indicated that the tumor size, the presence of a hump sign, and the Pughs score correlated the best with HCC rupture (p < 0.05). Ninety-four patients from the rupture group died during hospitalization. The mortality rate was 66.7%. We conclude that (a) spontaneous rupture of HCC is a likely sequel of progressive expansion of tumor that finally protrudes outside the liver surface and hemorrhages, (b) left-lobe tumor presents a higher risk of rupture, and (c) portal hypertension does not play a major role in the pathogenesis of tumor rupture.

Low dose erythropoietin-beta improves anemia and maintains ribavirin dose in chronic hepatitis C patients receiving combination therapy with ribavirin plus pegylated interferon Alfa-2b.

Aim:  Anemia during combination therapy with pegylated interferon alfa‐2b plus ribavirin (RBV) for chronic hepatitis C virus (HCV) patients usually leads to RBV dose reduction or discontinuation. This study evaluated the effect of erythropoietin‐beta (EPO‐β) to maintain RBV dose and hemoglobin (Hb) level in chronic HCV patients treated with antiviral combination therapy.

Efficacy of Ledipasvir and Sofosbuvir Treatment of HCV Infection in Patients Coinfected With HBV

BACKGROUND & AIMS There have been reports of reactivation of hepatitis B virus (HBV) infection during treatment of hepatitis C virus (HCV) infection with direct-acting antiviral agents. We performed a prospective study of risks and outcomes of HCV infection treatment with ledipasvir and sofosbuvir in patients with HBV infection. METHODS We performed a phase 3b, multicenter, open-label study in Taiwan of 111 patients with HCV infection (61% HCV genotype 1, 39% HCV genotype 2 infection; 62% women, 16% with compensated cirrhosis) along with HBV infection. All but 1 were positive for the hepatitis B surface antigen (HBsAg); 1 patient who was HBsAg-positive at screening was found to be HBsAg-negative at baseline. Overall, 33% of participants had received prior treatment for HCV and 5% had previously been treated for HBV; no patient was on HBV therapy at the start of the study. All patients received a fixed-dose combination of 90 mg of the HCV NS5A inhibitor ledipasvir with 400 mg of the NS5B nucleotide analogue inhibitor sofosbuvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of therapy. RESULTS All 111 patients (100%) achieved a sustained virologic response. Of the 37 patients with baseline HBV DNA below 20 IU/mL, 31 (84%) had at least 1 episode of quantifiable HBV DNA through posttreatment week 12. Of the 74 patients with baseline HBV DNA levels of 20 IU/mL or more, 39 (53%) had increases of HBV DNA greater than 1 log10 IU/mL through posttreatment week 12. Overall, 5 patients had increased levels of HBV DNA concomitant with a level of alanine aminotransferase >2 times the upper limit of normal through posttreatment week 12. Of these, 3 patients started HBV treatment. In addition, 1 patient with HBV reactivation since week 8 and concomitant alanine aminotransferase elevation >2 times upper limit of normal at posttreatment week 48 started treatment at posttreatment week 53. This patient had clinical signs and symptoms associated with HBV reactivation. The most common adverse events were headache, upper respiratory infection, and fatigue. CONCLUSIONS In a prospective study, the combination of ledipasvir and sofosbuvir for 12 weeks produced a sustained virologic response in 100% of patients with HCV infection who were coinfected with HBV. Most patients had an increase in level of HBV DNA not associated with signs or symptoms. ClinicalTrials.gov no: NCT02613871.

Endoscopic variceal ligation versus conservative treatment for patients with hepatocellular carcinoma and bleeding esophageal varices

BACKGROUND Endoscopic variceal ligation (EVL) is currently a favored treatment for control of bleeding from esophageal varices. However, little is known about the treatment of bleeding varices in hepatocellular carcinoma. METHODS EVL was performed in 16 patients with bleeding esophageal varices due to concomitant hepatocellular carcinoma. Treatment results were compared with those of another 23 patients who were conservatively treated. RESULTS Comparing the two groups, ligation significantly reduced the risk of fatal bleeding (44% vs 70%; P < 0.05). Significantly fewer patients in the ligation group died at the time of the index hemorrhage (11% vs 52%; P < 0.05). Rebleeding occurred in 44% of the ligation group and 73% in the control group (P > 0.05). The mean days of survival were 40 +/- 20 (range, 7 to 103) in the ligation group and 20 +/- 30 (range, 1 to 136) in the control group (P = 0.08). In the absence of portal vein thrombosis, ligation significantly reduced the rebleeding rate (17% vs 50%, P < 0.05) and the mortality rate (0% vs 100%, P < 0.05). CONCLUSION EVL is a good choice for palliation in patients with esophageal variceal bleeding and hepatocellular carcinoma. Aggressive use of EVL may be tried in those patients without portal venous thrombosis.

Clinical comparison of high-dose interferon-α2b with or without ribavirin for treatment of interferon-relapsed chronic hepatitis C

BACKGROUND Interferon a with ribavirin combination therapy is effective but still unsatisfactory in the treatment of patients with interferon-relapsed chronic hepatitis C. AIMS To compare, in a randomized, double blind, placebo-controlled study, high-dose interferon-alpha2b with or without ribavirin in the treatment for interferon-relapsers. PATIENTS A total of 52 patients with interferon-relapsed chronic hepatitis C were randomly assigned to receive 24-week treatment with interferon-alpha2b (6 MU three times per week) combined with either ribavirin (1,000 to 1,200 mg per day) or a matched placebo and then followed for an additional 24 weeks. METHODS Hepatitis C virus RNA was detected by reverse-transcription polymerase chain reaction. For determining viral concentration, the commercial bDNA Quantiplex hepatitis C virus-RNA 2.0 assay was used. Genotyping was performed by reverse hybridization assay RESULTS At the end of treatment, no detectable hepatitis C virus RNA levels were observed in 92% (24/26) of patients on interferon alpha2b/ribavirin and 81% (21/26) of patients on interferon alpha2b/placebo. At the end of the follow-up, a higher sustained virological response rate was seen in patients treated with interferon alpha2b/ribavirin than those treated with interferon alpha2b/placebo (69% vs 23%, p < 0.001). Patients with either initially high levels of viral concentration or with genotype 1 responded poorly. Patients who received interferon-alpha2b/ribavirin treatment and in whom no hepatitis C virus RNA was detected at 4th week after treatment had 90% chance to achieve sustained virological response. CONCLUSIONS High-dose interferon-alpha2b plus ribavirin treatment is highly effective in interferon-relapsed patients.

IDDF2018-ABS-0106 Tenofovir alafenamide (taf) compared with tenofovir disoproxil fumarate (tdf) in patients with chronic hbv: week 96 efficacy and safety results in chinese patients enrolled in 2 global phase 3 studies

Background TAF, a novel prodrug of tenofovir, has demonstrated efficacy noninferior to that of TDF at Week 48 in patients with chronic HBV (CHB) with significantly reduced bone and renal effects. Here we evaluated the efficacy and safety of TAF vs TDF in the subset of patients of Chinese ethnicity enrolled in two overseas studies. Methods In 2 Phase 3 studies, HBeAg-negative (Study 108) and HBeAg-positive (Study 110) CHB patients were randomised 2:1 to TAF 25 mg QD or TDF 300 mg QD and treated for 96 weeks. In this analysis, the efficacy (HBV DNA). Results Of 1298 patients randomised and treated, 471 (36%) were of Chinese ethnicity; 156 (TAF 97; TDF 59) and 315 (TAF 207; TDF 108) patients were HBeAg-negative and HBeAg-positive, respectively. For the TAF and TDF groups within each study, baseline characteristics of the study populations were generally similar. Key efficacy results at Weeks 48 and 96 are presented in the Table (table 1). In both HBeAg-negative and HBeAg-positive patients of Chinese ethnicity, the antiviral efficacy of TAF was similar to that of TDF and results were comparable to those in the overall overseas population. Numerically higher percentages of patients treated with TAF achieved normalisation of serum ALT values and anti-HBe seroconversion at Weeks 48 and 96. The safety of TAF and TDF, including changes in renal and bone parameters, were similar to results previously reported in the overall overseas population. Conclusions In CHB patients of Chinese ethnicity, TAF 25 mg showed similar antiviral efficacy to TDF 300 mg, with less change in bone and renal parameters. Results in this subgroup were comparable to those in the overall population.Abstract IDDF2018-ABS-0106 Table 1 Efficacy Results at Week 48 and 96 HBeAg-negative Patients (Study 108) HBeAg-positive Patients (Study 110) n/N (%) TAF (n= 97) TDF (n= 59) TAF (n= 207) TDF (n= 108) Week 48 HBV DNA<29 IU/mL 90 (93%) 55 (93%) 143 (69%) 76 (70%) ALT normalisation (AASLD criteria)a 46/94 (49%) 18/59 (31%) 100/207 (48%) 39/108 (36%) HBeAg loss NAb NA 28/204 (14%) 11/103 (11%) HBeAg seroconversion NA NA 23/204 (11%) 8/103 (8%) Week 96 HBV DNA<29 IU/mL 88 (91%) 57 (97%) 161 (78%) 86 (80%) ALT normalisation (AASLD criteria)a 46/94 (49%) 24/59 (41%) 119/207 (57%) 46/108 (43%) HBeAg loss NAb NA 55/204 (27%) 17/103 (17%) HBeAg seroconversion NA NA 47/204 (23%) 13/103 (13%) All results are reported as missing=failure; aUpper limit of normal (ULN) 30 U/L males, 19 U/L females; bNA, not applicable.

Comorbidities, concomitant medications and potential drug-drug interactions with interferon-free direct-acting antiviral agents in hepatitis C patients in Taiwan

While direct‐acting antivirals have been approved for treating hepatitis C, the guidelines highlight the importance of considering potential drug‐drug interactions between DAAs and concomitant medications.