Liver Stiffness Measurement Is Useful to Predict Early Recurrence of Hepatocellular Carcinoma after Sustained Virological Responses by Direct Antiviral Agents in Patients with Hepatitis C

Background: Recently, increases in the risk of Hepatocellular carcinoma (HCC) recurrence in patients with hepatitis C virus (HCV) due to the administration of direct antivirals agents (DAA) have been reported. Methods: One hundred and nineteen patients who were treated with DAA and achieved sustained viral response (SVR) were prospectively followed-up for over two years by transient elastography with liver stiffness measurements (LSM). Fourteen out of 119 patients (12%) had a history of being treated for HCC by radiofrequency ablation or resection and achieved complete responses after previous HCC treatments before the initiation of DAA. HCC was diagnosed by contrast-enhanced computed tomography (CT) or enhanced magnetic resonance imaging (MR). CT or MR was performed before the DAA treatment and every 6 months after during the follow-up. LSM was performed at the initiation of DAA (LSM0), at 24 weeks after the start of DAA (LSM24), at 48 weeks after that (LSM48) and at 2 years after that (LSM2y). Results: LSM0, LSM24, LSM48 and LSM2y of 105 patients without HCC were 7.5 (3.027.0), 6.0 (2.5 - 31.6), 4.6 (2.6?- 25.2) and 4.4 (3.1 - 29.9) kPa, respectively, showing significant improvements. Three out of 105 patients (2.9%) subsequently developed HCC and their LSM showed improvements. Eight out of fourteen patients (57%) with a history of HCC treatments subsequently developed HCC recurrence. LSM0 in the eight patients with recurrence increasing from 12.1 to 27.0 kPa, LSM24 from 9.9 to 26.6 kPa and LSM48 from 9.6 to 18.0 kPa. On the other hand, the six other patients without recurrence had LSM values that were less than 12.0 kPa at last. Based on the ROC analysis, LSM0 15.4, LSM24 12.8 and LSM48 9.6 kPa were identified as cut-off values. Conclusion: HCV patients previously treated for HCC with high LSM values before and after DAA have an elevated risk of HCC recurrence, particularly LSM24 >12.8 kPa and LSM48 >9.6 kPa.

Predictive Factors Differ between Hepatocellular Carcinoma Occurrence and Recurrence after Sustained Virological Responses by Direct-Acting Antivirals in Patients with Hepatitis C

Background: Interferon-free direct-acting antivirals (DAA) have markedly increased the sustained virological response (SVR) rate among patients with hepatitis C. Although DAA inhibit the development of hepatocellular carcinoma (HCC), predictive factors remain unclear. The aims of the present study were to investigate predictive factors for HCC occurrence and recurrence after SVR by DAA in prospectively followed patients with hepatitis C (HCV). Methods: One hundred and eighty-three HCV-infected patients treated with DAA and achieving SVR were prospectively followed up for more than one year. Among these patients, 166 had no history of HCC before DAA therapy, while 17 had a history of being treated for HCC by radiofrequency ablation or resection before the initiation of DAA. Liver stiffness (LS) measurements were conducted using transient elastography, and LS was assessed at the initiation of DAA (LS0), 24 weeks after the initiation of DAA (LS24), 48 weeks after (LS48), and every year after that. Results: HCC occurred in 7 out of 166 patients without a history of HCC (4.2%), and recurred in 9 out of 17 with a history of HCC (52.9%). Patients with a history of HCC were significantly older, mainly males, had higher alpha-fetoprotein (AFP) levels before DAA and at SVR24, higher Fib-4 levels, and higher LS0, 24, and 48 than those without a history of HCC. Age (p = 0.013) and AFP at SVR24 (p = 0.036) correlated with occurrence. LS48 (p = 0.043) correlated with recurrence. Conclusions: Predictive factors differed between HCC occurrence and recurrence after SVR by DAA in HCV patients. High recurrence rates were due to fibrosis in the liver being more advanced in patients with than in those without a history of HCC. Age and AFP at SVR24 were identified as predictive factors of HCC occurrence and LS48 of HCC recurrence.

The Evaluation of Tolvaptan Therapy and Long-Term Prognosis in Hepatocellular Carcinoma with Refractory Ascites

We investigated Tolvaptan efficacy and long-term prognosis with focus on nutrition in 20 patients with refractory hepatic ascites in hepatocellular carcinoma (HCC). Bloating improved in 55% of patients, as determined using a Japanese version of the Support Team Assessment Schedule. Nutritional status improved with Tolvaptan treatment, based on the Controlling Nutritional Status score and Onodera’s prognostic nutritional index. Long-term prognosis was better in responders than in non-responders (mean survival time: 308 days vs. 97 days, p = 0.031). Tolvaptan was even effective in many patients with HCC, with additional improvement in long-term prognosis expected with improvement in the nutritional status.

The Effect of Loop Diuretics on Sarcopenia and Long-Term Prognosis in Patients with Refractory Hepatic Ascites Treated with Tolvaptan

We investigated sarcopenia, focusing on the dose of loop diuretics used in 70 patients with refractory hepatic ascites treated with tolvaptan. Bloating improved in 68.5% of patients, as determined using the Japanese version of the Support Team Assessment Schedule. The psoas muscle index (PMI) was used to define sarcopenia. A statistically significant difference was observed in the PMI between patients receiving low-dose (3.6 ± 1.2 cm2/m2) and high-dose furosemide (3.1 ± 1.2 cm2/m2) before tolvaptan treatment (P = 0.048). The PMI increased from 3.2 ± 1.1 cm2/m2 to 3.5 ± 1.3 cm2/m2 (P = 0.002) in responders, but decreased from 3.4 ± 1.2 cm2/m2 to 3.0 ± 1.0 cm2/m2 (P = 0.106) in non-responders before and after tolvaptan treatment, respectively. The long-term prognosis improved in responders compared with non-responders (mean survival time: 646 days vs. 228 days, P < 0.001). Early introduction of tolvaptan treatment is necessary to prevent the progression of sarcopenia.