Adjusting the starting dose of telaprevir according to renal function decreases adverse effects and affects the sustained virological response rate.

BACKGROUND: Telaprevir (TVR) plays a major role in renal damage and anemia associated with TVR/pegylated interferon/ribavirin therapy for chronic hepatitis C. Adjusting the TVR starting dose may reduce these adverse effects. We aimed to determine whether adjusting the starting dose according to renal function reduces TVR-associated renal damage and anemia and affects the sustained virological response (SVR). PATIENTS AND METHODS: Our study included 112 patients infected with hepatitis C genotype 1 treated with pegylated interferon/ribavirin/TVR triple therapy. The TVR starting dose adjusted according to renal function was calculated as TVR/unadjusted estimated glomerular filtration rate (eGFR) ratio=TVR/(eGFR×body surface area/1.73). RESULTS: A TVR/unadjusted eGFR ratio of 32 or greater was a predictor of renal impairment and anemia in multivariate analysis (odds ratio 12.09, P<0.001, and OR 4.14, P<0.001, respectively). Patients with a TVR/unadjusted eGFR ratio of 32 or greater developed significant renal impairment and anemia (P<0.001 and P=0.002, respectively). SVR was significantly reduced in patients with a TVR/unadjusted eGFR ratio less than 23 versus 23 or greater (66.7 and 87.2%, respectively, P=0.045). SVR tended to increase stepwise [<23.0 (66.7%), ≥23 to <32 (84.8%), and ≥32 (89.6%), respectively]. The TVR/unadjusted eGFR ratio was correlated significantly with the serum TVR concentration (r=0.541, P<0.001). CONCLUSION: Adjusting the TVR starting dose according to the TVR/unadjusted eGFR ratio decreased adverse effects and affected the SVR rate. The TVR starting dose should be adjusted by a TVR/unadjusted eGFR ratio of 23 or greater to less than 32 to safely achieve SVR.

Late-evening snack with branched-chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma.

AIM: This prospective study was designed to examine whether consumption of a branched-chain amino acid (BCAA)-enriched nutrient mixture as a late-evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: An equal number (10) of 30 LC patients who had undergone RFA for HCC was randomly assigned to a standard diet group (control) group, a morning BCAA (M-BCAA) administration group, or a LES with BCAA (LES-BCAA) administration group. Liver function testing was performed and Child-Pugh scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12 weeks post-RFA. RESULTS: Compared to the control and M-BCAA groups, the LES-BCAA group experienced a rapid and significant improvement in albumin and total serum bilirubin levels and in CPS that began during the initial post-RFA period. These results indicate that LES with BCAA supplementation significantly improved the CPS of the LES-BCAA group at 4 and 12 weeks post-RFA. Although no patients experienced serious adverse effects, two patients who had been diagnosed with diabetes mellitus before undergoing RFA required blood sugar management to improve glycemic control and one subject withdrew due to supplement-induced vomiting. CONCLUSION: LES with BCAA supplementation significantly and rapidly improves liver functioning and CPS in LC patients who have undergone RFA for HCC. Control of blood sugar levels is necessary when calorie-containing BCAA is administrated to LC patients with impaired glucose tolerance.

Clinical features of Wilson disease: Analysis of 10 cases.

AIM: The diagnosis of Wilson disease is based on the results of several clinical and biochemical tests. This study aimed to clarify the clinical features and spectrum of Wilson disease, including severe Wilson disease. METHODS: Between 1985 and 2009, 10 patients with clinical, biochemical or histological evidence of Wilson disease were either diagnosed or had a previously established diagnosis confirmed at Fukuoka University Hospital. Severe Wilson disease was defined by a serum prothrombin time ratio of more than 1.5 or serum prothrombin activity of less than 50%. The 10 Wilson disease patients were divided into two groups, one containing three non-severe patients and the other containing seven severe patients, and the biochemical features of the patients in these two groups were compared. RESULTS: The mean age at diagnosis was 21.5 ± 11.7 years (range, 7-39). Decreased serum ceruloplasmin, enhanced 24-h urinary copper excretion, presence of Kayser-Fleischer rings and histological signs of chronic liver damage were confirmed in 100%, 100%, 66.7% and 100% of patients, respectively. Severe Wilson disease patients had higher levels of serum ceruloplasmin and serum copper (P < 0.05, P < 0.05, respectively) than non-severe patients. CONCLUSION: In severe Wilson disease patients, the serum ceruloplasmin and serum copper levels were higher than those in non-severe Wilson disease patients.

Reduced expression of low-density lipoprotein receptor in hepatocellular carcinoma with paraneoplastic hypercholesterolemia.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic hypercholesterolemia. In familial hypercholesterolemia, genetic mutation of the low-density lipoprotein (LDL) receptor gene has been recognized as being a pathogenesis of the disease. We investigate the expression of a LDL receptor protein and gene abnormalities of a LDL receptor in HCC cells in cases with paraneoplastic hypercholesterolemia. METHODS: Eleven patients with HCC associated with paraneoplastic hypercholesterolemia and seven patients with HCC who did not have hypercholesterolemia were studied. Paraffin-embedded tissues were obtained at operative resection, autopsy, or biopsy. Immunohistochemistry was performed using a monoclonal antibody against human LDL receptors. Confocal laser-scanning microscopy was used to observe the FITC-labeled LDL receptor. DNA samples were extracted from paraffin-embedded tissues. Since a LDL receptor gene is located on chromosome 19p13.2, a microsatellite marker, D19S413, was used to analyze the chromosomes. RESULTS: Immunoreactive LDL receptors were observed all over the surface of non-tumorous hepatocytes. However, expression of the LDL receptor was significantly decreased in all HCC cells derived from the 11 patients with hypercholesterolemia. In contrast, the expression was retained in the HCC cells of all patients without hypercholesterolemia. In two patients with hypercholesterolemia, DNA analysis revealed a loss of heterozygosity on chromosome 19p13.2. CONCLUSION: We demonstrated reduced expression of the LDL receptor in HCC cases with paraneoplastic hypercholesterolemia. LDL receptor genes with genomic disorders may cause decreased expression of the LDL receptor protein, leading to feed-back failure of the cholesterol regulation system, as seen in familial hypercholesterolemia. This is the first report considering the mechanism behind the development of paraneoplastic hypercholesterolemia in HCC.

Postoperative recurrence in hepatocellular carcinoma: Comparison between percutaneous ethanol injection and radiofrequency ablation.

AIM: Recently percutaneous ethanol injection (PEI) turned into percutaneous radiofrequency ablation (PRFA), and it has become widely used for the treatment of hepatocellular carcinoma (HCC). The present study was to compare the incidence in postoperative HCC recurrence between these two therapeutic approaches. METHODS: One hundred and sixty-eight first-time HCC in patient cases were chosen for PEI (n=94) and PRFA (n=74). The localized recurrence rate based on the operator's experience in percutaneous treatment for HCC (on <5 years versus >/=5 years experience) was examined. RESULTS: The PRFA group demonstrated a significantly lower localized recurrence rate within 2 years than the PEI group (8% and 22%, respectively, P<0.01). The local recurrence rate of HCC within 2 years after PEI was significantly lower in those for whom the operator's experience was more than 5 years compared to those for whom it was less than 5 years (12% versus 24%, respectively, P<0.05). In contrast, after PRFA there was no significant difference between these two groups of <5 years and of >/=5 years experience (8% versus 8%, respectively, P=0.98). CONCLUSION: The present study demonstrated that PRFA resulted in a lower rate of local recurrence in comparison to conventional PEI, regardless of the operator's experience.

Altered expression of alkaline phosphatase (ALP) in the liver of primary biliary cirrhosis (PBC) patients.

Serum alkaline phosphatase (ALP) is a representative marker of cholestasis, in diseases such as primary biliary cirrhosis (PBC). However, the hepatic localization of ALP in patients with cholestatic liver diseases has not been fully clarified. Accordingly, we studied the expression of ALP in the liver of PBC, chronic hepatitis C and controls. By immunohistochemistry, in the liver tissue of controls and chronic hepatitis C patients, ALP was found to be localized in the canalicular membrane of hepatocytes and the apical area of the cytoplasm of bile duct epithelial cells. In PBC, ALP was localized in both the canalicular and baso-lateral membranes of hepatocytes and in the whole cytoplasm of the remaining bile duct epithelial cells. The expression of ALP in liver tissues evaluated by Western blotting was increased to 3.6-fold in PBC compared with that in the controls and chronic hepatitis C patients, while the expression of mRNA of ALP evaluated by RT-PCR was increased to 7.0-fold in PBC compared with that in the controls and chronic hepatitis C patients. The present study is the first study to reveal altered localization and increased expression of ALP which may result in the elevation of serum ALP in PBC.

Rapid-onset primary biliary cirrhosis resembling drug-induced liver injury.

A 54-year-old woman was admitted to our hospital because of acute liver injury. Since she had a history of having used a diet product, drug-induced liver injury (DILI) was initially considered. However, the patient was subsequently diagnosed as suffering from primary biliary cirrhosis (PBC) based on the findings of liver histology and serum anti-mitochondrial antibody positivity. Overlap syndrome between PBC and autoimmune hepatitis (AIH) was also suspected, however, serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase became normal three months later, after treatment with combination therapy comprising ursodeoxycholic acid plus bezafibrate. We therefore concluded that the liver disease in this patient was actually PBC, but that it resembled overlap syndrome or DILI. In cases of PBC, a rapid onset, as frequently seen in the case of DILI, viral hepatitis or AIH, is not common. We herein report a rare case of PBC which resembled DILI.

Nonalcoholic steatohepatitis associated with psoriasis vulgaris.

A 24-year-old man was admitted to our hospital because of liver dysfunction. He had been diagnosed as having psoriasis vulgaris at 18 years of age. Physical examination demonstrated obesity, general erythema, and hepatomegaly. Laboratory data revealed elevated serum levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and glucose. A histological examination of the liver revealed macrovesicular fatty change and infiltration of inflammatory cells, including lymphocytes and polymorphonuclear cells, within the liver lobules. Pericentral fibrosis and pericellular fibrosis were also recognized. He was diagnosed as having nonalcoholic steatohepatitis (NASH), based on the fact that he had no habit of drinking alcohol, as well as psoriasis vulgaris and diabetes mellitus. We herein report a very rare case of NASH associated with psoriasis vulgaris.

Hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV tests but positive liver tissue HCV RNA.

A 70-year-old woman was admitted to our hospital because of a liver tumor. Laboratory data revealed mild liver dysfunction. Neither serum anti-HCV antibody nor HCV-RNA was detected. Computed tomography revealed a tumor lesion measuring 2 cm in diameter within the liver. Histological examination of the tumor revealed moderately differentiated hepatocellular carcinoma while the non-tumorous liver tissue demonstrated liver cirrhosis. By the RT-PCR method, HCV-RNA was detected from the non-tumorous liver tissue. We herein report a very rare case of hepatocellular carcinoma in a patient with liver cirrhosis associated with negative serum HCV findings, but positive finding for liver tissue HCV RNA.