Efficacy and Safety of Lenvatinib for Patients With Advanced Hepatocellular Carcinoma: A Retrospective, Real-world Study Conducted in Japan.

AIM: We evaluated real-world efficacy and toxicity of lenvatinib in 142 patients with advanced hepatocellular carcinoma (HCC) at six tertiary referral centres. PATIENTS AND METHODS: The patients with advanced HCC treated with lenvatinib were grouped into two categories based on REFLECT criteria for analysis of efficacy and safety. The primary endpoint was progression-free survival (PFS). RESULTS: The objective response rate (ORR) at week 12 of therapy was 41.5%, with a median PFS of 176 days. Child-Pugh score of 5 points, the presence of extrahepatic metastasis and adverse effects grade 2 or higher were considered independent factors associated with both better PFS and ORR. The ORR for patients who fulfilled the REFLECT inclusion criteria was significantly higher than that for those who did not. However, no significant differences in PFS were observed between the two groups. The incidence rate of adverse effects grade 3 or higher was 40.1%, which was similar for the two groups. CONCLUSION: Lenvatinib is safe and effective for patients, whether or not they satisfy REFLECT criteria. The result warrants replication in a larger study.

Effect of L-carnitine on health-related quality of life in patients with liver cirrhosis.

L-carnitine (4-N-trimethylammonium-3-hydroxybutyric acid) is the physiologically active form of carnitine and is a natural compound that has been shown to exhibit antioxidant activity. L-carnitine is used as a supplementary treatment in patients with cirrhosis with hepatic encephalopathy, hyperammonemia or muscle cramps. In the present study, the effect of L-carnitine supplementation on health-related quality of life in 30 patients with cirrhosis was prospectively examined. L-carnitine (1,800 mg/day) was administered orally for 6 months. To assess the effects of L-carnitine on chronic fatigue, patients filled out a self-report questionnaire regarding their physical and mental health. The levels of total and free carnitine, and acylcarnitine were found to be significantly higher 1, 3 and 6 months after therapy initiation compared with before treatment. Serum albumin levels were significantly increased 3 and 6 months after initiation of therapy. L-carnitine supplementation significantly increased the BAP/d-ROM ratio, a marker of antioxidant status in patients with cirrhosis. Changes in serum carnitine concentrations were positively correlated with changes in serum albumin levels (R2=0.369; P=0.012), but not with changes in serum ammonia levels (R2= 0.005; P=0.78). Total and mental health scores improved significantly, and physical scores improved marginally 3 and 6 months after initiation of L-carnitine. These findings may be attributed to the enhanced serum albumin levels and oxidative stress rather than the reduced serum ammonia levels. Based on these results, it is suggested that L-carnitine can potentially alleviate chronic fatigue, along with the increased BAP/d-ROM ratio, which were involved in increased oxidative stress in patients with cirrhosis. The specific mechanisms by which L-carnitine ameliorates chronic fatigue is not fully understood and requires further investigation.

Severe Aplastic Anemia following Parvovirus B19-Associated Acute Hepatitis.

Human parvovirus (HPV) B19 is linked to a variety of clinical manifestations, such as erythema infectiosum, nonimmune hydrops fetalis, and transient aplastic anemia. Although a few cases have shown HPVB19 infection as a possible causative agent for hepatitis-associated aplastic anemia (HAAA) in immunocompetent patients, most reported cases of HAAA following transient hepatitis did not have delayed remission. Here we report a rare case of severe aplastic anemia following acute hepatitis with prolonged jaundice due to HPVB19 infection in a previously healthy young male. Clinical laboratory examination assessed marked liver injury and jaundice as well as peripheral pancytopenia, and bone marrow biopsy revealed severe hypoplasia and fatty replacement. HPVB19 infection was diagnosed by enzyme immunoassay with high titer of anti-HPVB19 immunoglobulin M antibodies. Immunosuppressive therapy was initiated 2 months after the onset of acute hepatitis when liver injury and jaundice were improved. Cyclosporine provided partial remission after 2 months of medication without bone marrow transplantation. Our case suggests that HPVB19 should be considered as a hepatotropic virus and a cause of acquired aplastic anemia, including HAAA.

Assessing the efficacy of famotidine and rebamipide in the treatment of gastric mucosal lesions in patients receiving long-term NSAID therapy (FORCE--famotidine or rebamipide in comparison by endoscopy).

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection are major causes of gastric mucosal lesions. In Japan, histamine-2 receptor antagonists are frequently prescribed, but the literature regarding their efficacy is limited. In this study, we compare the effects of famotidine and rebamipide on NSAID-associated gastric mucosal lesions using upper gastrointestinal endoscopy. METHODS: This study examined 112 patients taking NSAIDs for either gastric hemorrhage or erosion. Before treatment, the patients were assessed by endoscopy. Using blind randomization, patients were divided into two groups: group F (famotidine, 20 mg/day) and group R (rebamipide, 300 mg/day). Efficacy was examined 4 weeks later using endoscopy. RESULTS: After treatment, the Lanza score decreased significantly in group F (P < 0.001) but not in group R (P = 0.478). The change in the Lanza score in group F was significantly greater (P = 0.002) than that in group R. CONCLUSIONS: Famotidine was superior to rebamipide in treating NSAID-associated mucosal lesions.

Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study with special reference to the cause of liver disturbance.

BACKGROUND: Liver disturbance in rheumatoid diseases results not only from liver disease associated with the rheumatoid diseases themselves but also from various other causes. This study aimed to elucidate the clinical features of liver disturbance in rheumatoid diseases, focusing on the cause of this disturbance. METHODS: A clinicopathological study was performed in 306 patients (106 with systemic lupus erythematosus, 71 with Sjögren's syndrome, 59 with rheumatoid arthritis, 27 with scleroderma, 30 with polymyositis, and 13 with polyarteritis nodosa). RESULTS: Liver disturbance occurred in 43% of these patients and resulted from various causes. Its degree and duration varied from one cause to another. Liver disease associated with rheumatoid diseases was the leading cause of the liver disturbance in these patients and was characterized by mild and transient liver disturbance (maximum alanine aminotransferase [ALT] level during the study period, 68 +/- 8 IU/ml; maximum alkaline phosphatase [ALP] level, 410 +/- 31 IU/ml; duration of liver disturbance, 6 +/- 2 months). Most patients with this type of liver disease showed minimal change in liver histology, although two-thirds of those evaluated by the international scoring system for autoimmune hepatitis (AIH) were classified as "probable" or "definite". Eight of 14 patients with histologically proven chronic hepatitis or cirrhosis were infected with hepatotropic virus (7 with hepatitis C virus [HCV] and 1 with hepatitis B virus [HBV]). Five of 9 patients in whom the hepatic lesion progressed had hepatotropic virus infection (4 with HCV and 1 with HBV), and the other 4 patients suffered from autoimmune liver diseases. CONCLUSIONS: Liver disease associated with rheumatoid diseases was the leading cause of liver disturbance in these patients and was characterized by mild and transient liver disturbance, whereas progressive liver diseases were often associated with hepatotropic virus, mainly HCV, or autoimmune liver diseases. Liver histology is indispensable for differentiating AIH from liver disease associated with rheumatoid diseases.