Zinc Administration and Improved Serum Markers of Hepatic Fibrosis in Patients with Autoimmune Hepatitis.

AIM: The aim of the present study is to investigate the effect of long-term zinc supplementation, which is important for the activation of various enzymes that contribute to antioxidant and antifibrotic activities, on the improvement of serum fibrotic markers in patients with autoimmune hepatitis (AIH). METHODS: A total of 38 patients with AIH under regular treatment at our hospital who provided their consent for being treated with polaprezinc (75 mg twice daily) were included and classified into 2 groups: the patients with zinc elevation (n = 27) and the patients without zinc elevation (n = 11). Serum biomarker of fibrosis, protein expression levels of matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) were evaluated. RESULTS: A significant difference was found between the variability of serum procollagen type Ⅲ and collagen type Ⅳ-7S between the 2 groups before and after zinc administration for more than 24 months (p = 0.043 and p = 0.049). In the patients with zinc elevation, no significant changes were found in collagenase (MMP-1 and MMP-13) before and after zinc administration, whereas a significant increase in the expression of gelatinase (MMP-2 and MMP-9) was found after administration (p = 0.021 and p = 0.005). As for the relative ratio of MMPs to TIMPs, only MMP-9 to TIMP-1 showed a significant increase (p = 0.004). CONCLUSIONS: Long-term treatment with polaprezinc has been demonstrated to safely improve serum fibrosis indices through increases in MMP-2/-9 and MMP-9/TIMP-1 and is expected to be well combined with direct antifibrotic therapies such as molecularly targeted agents.

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.

Efficacy of L-carnitine on ribavirin-induced hemolytic anemia in patients with hepatitis C virus infection.

BACKGROUND/AIMS: L-carnitine not only alleviates hyperammonemia and reduces muscle cramps in patients with liver cirrhosis, but also improves anemia in patients with chronic hepatitis and renal dysfunction. This study prospectively evaluated the preventative efficacy of L-carnitine supplementation against hemolytic anemia during antiviral treatment using ribavirin in patients with hepatitis C virus (HCV)-related chronic liver disease. METHODS: A total of 41 patients with chronic hepatitis were consecutively enrolled in this study. Group A (n=22) received sofosbuvir plus ribavirin for 3 months, whereas group B (n=19) was treated with sofosbuvir, ribavirin, and L-carnitine. Hemoglobin concentration changes, the effects of antiviral treatment, and the health status of patients were analyzed using short form-8 questionnaires. RESULTS: A significantly smaller decrease in hemoglobin concentration was observed in group B compared to group A at every time point. Moreover, the prescribed dose intensity of ribavirin in group B was higher than that of group A, resulting in a higher ratio of sustained virological response (SVR) 24 in group B compared with group A. The physical function of patients in group B was also significantly improved compared to group A at the end of antiviral treatment. CONCLUSION: L-carnitine supplementation alleviates ribavirin-induced hemolytic anemia in patients with HCV and helps relieve the physical burden of treatment with ribavirin-containing regimens. These advantages significantly increase the likelihood of achieving SVR.

Pneumatosis cystoides intestinalis following alpha-glucosidase inhibitor treatment: a case report and review of the literature.

A 69-year-old man was diagnosed as having myasthenia gravis (MG) in September 2004, and treated with thymectomy and prednisolone. He was then diagnosed as having steroid-induced diabetes mellitus, and received sulfonylurea (SU) therapy in May 2005. An alpha-glucosidase inhibitor (alphaGI) was added in March 2006, resulting in good glycemic control. He experienced symptoms of abdominal distention, increased flatus, and constipation in October 2007, and was admitted into our hospital in late November with hematochezia. Plain abdominal radiography revealed small linear radiolucent clusters in the wall of the colon. Computed tomography (CT) showed intramural air in the sigmoid colon. Colonoscopy revealed multiple smooth surfaced hemispherical protrusions in the sigmoid colon. The diagnosis of pneumatosis cystoides intestinalis (PCI) was made on the basis of these findings. As the alphaGI voglibose was suspected as the cause of this patient's PCI, treatment was conservative, ceasing voglibose, with fasting and fluid supplementation. The patient progressed well, and was discharged 2 wk later. Recently, several reports of PCI associated with alphaGI therapy have been published, predominantly in Japan where alphaGIs are commonly used. If the use of alphaGIs becomes more widespread, we can expect more reports of this condition on a global scale. The possibility of PCI should be considered in diabetic patients complaining of gastrointestinal symptoms, and the gastrointestinal tract should be thoroughly investigated in these patients.