Response-Guided Therapy With Cefotaxime, Ceftriaxone, or Ciprofloxacin for Spontaneous Bacterial Peritonitis: A Randomized Trial: A Validation Study of 2021 AASLD Practice Guidance for SBP.

INTRODUCTION: For the treatment of spontaneous bacterial peritonitis (SBP), cefotaxime, ceftriaxone, and ciprofloxacin were used as first-line agents. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs can be initially recommended. This study aimed to compare the current efficacy of the 3 antibiotics, namely cefotaxime, ceftriaxone, and ciprofloxacin, for the treatment of SBP in patients with cirrhosis with ascites, when guided by therapeutic responses. METHODS: This study was a multicenter, prospective, randomized controlled trial. The inclusion criteria were 16- to 75-year-old patients with liver cirrhosis with ascites, having polymorphonuclear cell count of >250/mm 3 . We performed a follow-up paracentesis at 48 hours to decide continuing or changing the assigned antibiotics and then assessed the resolution rates at 120 and 168 hours of treatment. RESULTS: A total of 261 patients with cirrhosis who developed SBP were enrolled. Most of the patients were diagnosed as those with SBP within 48 hours of admission. The resolution rates at 120 hours, which is the primary endpoint, were 67.8%, 77.0%, and 73.6% in the cefotaxime, ceftriaxone, and ciprofloxacin groups, respectively ( P = 0.388), by intension-to-treat analysis. The 1-month mortality was similar among the groups ( P = 0.770). The model for end-stage liver disease score and the SBP resolution were significant factors for survival. CONCLUSION: The efficacy of empirical antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, against SBP was not significantly different. In addition, these antibiotics administered based on response-guided therapy were still efficacious as initial treatment for SBP, especially in those with community-acquired infections.

Comparison of Sorafenib versus Hepatic Arterial Infusion Chemotherapy-Based Treatment for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis.

BACKGROUND/AIMS: Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. METHODS: Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). RESULTS: Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). CONCLUSIONS: HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.

Daily Norfloxacin vs. Weekly Ciprofloxacin to Prevent Spontaneous Bacterial Peritonitis: A Randomized Controlled Trial.

OBJECTIVES: For the prevention of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites, norfloxacin 400 mg per day is recommended as a standard regimen. This study aims to investigate whether ciprofloxacin once weekly administration is not inferior to norfloxacin once daily administration for the prevention of SBP. METHODS: This is an investigator-initiated open-label randomized controlled trial conducted at seven tertiary hospitals in South Korea. Liver cirrhosis patients with ascites were screened, and enrolled in this randomized controlled trial if ascitic protein ≤1.5 g/dL or the presence of history of SBP. Ascitic polymorphonucleated cell count needed to be <250/mm3. Patients were randomly assigned into norfloxacin daily or ciprofloxacin weekly group, and followed-up for 12 months. Primary endpoint was the prevention of SBP. RESULTS: One hundred twenty-four patients met enrollment criteria and were assigned into each group by 1:1 ratio (62:62). Seven patients in the norfloxacin group and five patients in the ciprofloxacin group were lost to follow-up. SBP developed in four patients (4/55) and in three patients (3/57) in each group, respectively (7.3% vs. 5.3%, P = 0.712). The transplant-free survival rates at 1 year were comparable between the groups (72.7% vs. 73.7%, P = 0.970). Incidence of infectious complication, hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding rates were not significantly different (all P = ns). The factors related to survival were models representing underlying liver function. CONCLUSION: Once weekly ciprofloxacin was as effective as daily norfloxacin for the prevention of SBP in cirrhotic patients with ascites.

An Explorative Analysis for the Role of Serum miR-10b-3p Levels in Predicting Response to Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

The prognostic role of aberrant serum miRNA expression for predicting response to sorafenib treatment in advanced hepatocellular carcinoma (HCC) patients has not been well characterized. We aimed to identify specific serum miRNAs that are associated with positive radiologic responses or improved survival in sorafenib-treated HCC patients. miR-18a, miR-21, miR-139-5p, miR-221, miR-224, and miR-10b-3p, were selected for analysis. Serum samples from 24 patients with advanced stage HCC and 25 patients with liver cirrhosis (LC) were analyzed. All of the miRNAs except miR-21 were found to be upregulated in serum samples from HCC patients. None of the miRNAs assayed differed significantly in terms of expression between the responder and non-responder groups among HCC patients. However, miR-10b-3p levels were significantly higher in the subgroup of HCC patients with worse overall survival (fold change = 5.8, P = 0.008). Serum miRNA-10b-3p was upregulated in the presence of macrovascular invasion (MVI), and those with higher serum miRNA-10b-3p had significantly shorter survival during treatment (P = 0.042). Although no single serum miRNA was predictive of response to sorafenib treatment, analysis of serum miR-10b-3p levels may be valuable for diagnosis of HCC and prediction of survival of sorafenib-treated patients.

[A Case of Tenofovir-associated Fanconi Syndrome in Patient with Chronic Hepatitis B].

Tenofovir disoproxil fumarate (TDF) is one of the most widely used treatment options for human immunodeficiency virus (HIV) and HBV infections. Despite its efficacy and safety, some cases of nephrotoxicity have been reported in the treatment of HIV patients. Even more recently, very few cases of Fanconi syndrome associated with tenofovir therapy in HBV monoinfection have been reported. Herein, we report a case of a 47-year-old male with an HBV monoinfection, who developed Fanconi syndrome and a secondary osteomalacia with multiple bone pain. After TDF withdrawal and supplementation of calcitriol, his renal function was reverted. Although the overall risk of TDF-associated nephrotoxicity is very low, both glomerular and tubular function should be monitored in patients undergoing TDF treatment.

Systemic cytotoxic chemotherapy of patients with advanced hepatocellular carcinoma in the era of sorafenib nonavailability.

GOALS: The goal of the study was to compare the efficacy and safety of sorafenib with those of systemic cytotoxic chemotherapy. BACKGROUND: Sorafenib treatment has shown to improve the survival in patients with advanced hepatocellular carcinoma (HCC) when compared with placebo. However, whether sorafenib controls advanced-stage HCC better than systemic cytotoxic chemotherapy has not been elucidated. STUDY: We retrospectively reviewed the medical records of 220 patients with measurable advanced HCC who had not received systemic treatment previously between January 2007 and April 2012. Among these patients, 78 had been treated with sorafenib. Another 14 patients who were treated with a 4-weekly regimen of adriamycin, cisplatin, and capecitabine were included as the historical control group for comparison. The median overall survival, the progression-free survival, response rates, and safety profiles were evaluated. RESULTS: Baseline characteristics were similar between the treatment groups. The median overall survival was 7.2 months [95% confidence interval (CI), 5.6-8.8] in the sorafenib group and 11.2 months (95% CI, 8.1-14.2) in the cytotoxic chemotherapy group (P=0.10). The median progression-free survival was 3.2 months (95% CI, 2.2-4.3) in the sorafenib group and 5.9 months (95% CI, 3.6-8.2) in the cytotoxic chemotherapy group (P=0.07). The deterioration of liver function and neutropenia were the most frequent serious adverse events in the sorafenib and the systemic chemotherapy group. CONCLUSIONS: Although a direct head-to-head comparison could not be done, there were some patients who showed a good response to systemic cytotoxic chemotherapy. Further assessment is necessary to study the role of chemotherapy in patients who are intolerant or intractable to sorafenib.

[Current status of molecular targeted therapies in hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in Korea. Curative treatment is only possible when the disease is diagnosed at the early stage. The prognosis of patients with HCC is even dismal in advanced stages. No systemic cytotoxic chemotherapy has proven to be beneficial in overall survival. Recently, the understanding of the molecular pathogenesis led to the development of new therapies. With the evidence of dysregulation of critical genes associated with cellular proliferation, growth factor signaling, cell cycling, apoptosis, and angiogenesis in HCC, a number of molecular target agents are under clinical trials. Sorafenib is the first systemic anticancer drug which has proven to gain survival benefit in the global as well as Asia-Pacific trials. However, the survival gain is still modest, and further efforts to improve outcomes in patients with HCC are necessary by developing novel drugs or combining other forms of therapies. This article will review signaling pathways in HCC and introduce molecular target agents under investigation currently.