Immunoserological and histological differences between autoimmune hepatitis with acute presentation and chronic autoimmune hepatitis.

AIM: The histological features of clinically chronic autoimmune hepatitis (AIH) have been well established, with interface hepatitis and plasma cell infiltration as hallmark lesions, however, the immunoserological and histological features of recent-onset and acute AIH remain undefined. The goal of this study was to define the immunoserological and histological differences between AIH with acute presentation and chronic AIH. METHODS: Thirty-two consecutive patients with well-characterized AIH who had undergone a liver biopsy were identified at our institution. These patients were divided into two groups. Sixteen patients whose liver dysfunction had persisted for at least 12 months were defined as chronic AIH (C-AIH) patients, and 16 patients whose liver dysfunction had been within normal limits for >12 months previously, and had only recently been found to have abnormal function for the first time, were defined as AIH with acute presentation (AIH-a) patients. Various biological and histological characteristics were compared between these two patient groups. RESULTS: No significant differences were found between the groups for age, body mass index, serum levels of total bilirubin, transaminase, alkaline phosphatase, prothrombin activity, immunoglobulin, titers of antinuclear antibody, or diagnostic scores between the groups. Histologically, there was no significant difference in the degree of interface hepatitis, plasma cell infiltration, or centrilobular necrosis between AIH-a and C-AIH patients. However, histological active findings such as activity, lobular inflammation, rosette formation, spotty necrosis, seroid-laden macrophages, and single cell necrosis were significantly more frequent in AIH-a patients, whereas portal fibrosis was significantly more frequent in C-AIH patients. Only one case among the 16 AIH-a patients was confirmed as acute AIH, showing massive centrilobular necrosis with a mild degree of portal inflammation and interface hepatitis. All patients with AIH-a and C-AIH responded well to corticosteroid or ursodeoxycholic acid treatment. CONCLUSIONS: Patients with AIH-a could not be distinguished from C-AIH patients clinically or immunoserologically. Based on the histopathological findings of the liver, almost all cases of AIH-a might be exacerbations of non-symptomatic pre-existing C-AIH.

[A case of drug-induced liver injury caused by Keishi-karyukotsu-boreito and Shin-i-seihaito].

A 43-year-old woman was admitted to our hospital due to liver dysfunction. She had a history of liver injury induced by the herbal medicine Keishi-karyukotsu-boreito, which occurred at the age of 35 years. On the present occasion, she had taken the herbal medicine Shin-i-seihaito to treat her sinusitis for one month. We diagnosed liver injury caused by Shin-i-seihaito, and her liver dysfunction normalized after discontinuation of Shin-i-seihaito. This is the first reported case of drug-induced liver injury caused by the herbal medicines Keishi-karyukotsu-boreito and Shin-i-seihaito.

Effectiveness of fenofibrate in comparison to bezafibrate for patients with asymptomatic primary biliary cirrhosis.

BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) is currently the only available pharmacological treatment for asymptomatic primary biliary cirrhosis (aPBC). Fibrates may be useful for treating aPBC patients who exhibit incomplete responses to UDCA. The mechanism of action of such fibrates involves the regulation of the expression of various kinds of lipids and proteins through the activation of peroxisome proliferator-activated receptor-alpha (PPAR-alpha ), which increases the phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids. Among these fibrates, the binding activity of fenofibrate to PPAR-alpha is stronger than that of bezafibrate. Because the majority of PBC patients exhibit a slow progression of their disease, and since the administration of UDCA plus fibrate may further delay the liver deterioration, cardiovascular risk factors, such as dyslipidemia may thus have a bigger impact on the long-term survival of PBC patients. The aim of this study was to evaluate the effects of fenofibrate in patients with aPBC who are refractory to UDCA and to simultaneously compare the effectiveness of fenofibrate with that of bezafibrate. METHODS: This study included 14 patients with aPBC treated with fenofibrate (80 mg/day) plus UDCA (fenofibrate group) for 48 weeks and seven patients with aPBC treated with bezafibrate (400 mg/day) plus UDCA (bezafibrate group) for 48 weeks. The data for the aPBC patients in both groups were analyzed to compare the effects of fenofibrate and bezafibrate. RESULTS: In the patients in the fenofibrate group, the serum alkaline phosphatase (ALP), gamma-glutamyl transpeptitase (gamma GTP) and serum IgM levels decreased from 522.5 +/- 181.4 to 236.8 +/- 47.8 IU/l, 197.1 +/- 98.4 to 47.2 +/- 37.5 IU/l and 337.6 +/- 160.6 to 174.5 +/- 101.1 mg/dl (p < 0.0001), respectively. In the patients in the bezafibrate group, the serum levels of ALP, gamma GTP and IgM decreased from 595.9 +/- 247.8 to 238.0 +/- 80.4 IU/l, 188.3 +/- 85.6 to 46.3 +/- 31.9 IU/l and 304.7 +/- 165.2 to 155.1 +/- 45.4 mg/dl (p < 0.0001), respectively. The serum levels of triglycerides (TG) and low-density lipoprotein cholesterol (LDL) significantly decreased in both groups and the LDL levels significantly decreased in the patients in the fenofibrate group compared to those in the bezafibrate group (p = 0.0357). In addition, the serum uric acid levels of the patients in the fenofibrate group decreased significantly (from 4.7 +/- 1.4 to 3.6 +/- 0.9 mg/dl, p < 0.0001), while those in the patients in the bezafibrate group did not change from 4.1 +/- 0.6 to 4.1 +/- 0.4 mg/dl. CONCLUSION: Combination therapies with fenofibrate plus UDCA and bezafibrate plus UDCA induce significant biochemical improvements in patients with aPBC. However, the ability of fenofibrate to reduce the LDL and uric acid levels in aPBC patients is superior to that of bezafibrate. As a result, the use of fenofibrate might translate into a decreased risk of developing cardiovascular events and renal failure in patients with aPBC.

The incidence and risk factors for the development of hepatocellular carcinoma after peginterferon plus ribavirin therapy for chronic hepatitis C.

BACKGROUND/AIMS: Although the incidence of hepatocellular carcinoma (HCC) has been shown to be reduced after pegylated glycol-interferon plus ribavirin (Peg-IFN/RBV) therapy in patients with chronic hepatitis C, the risk factors for the development of HCC are not fully understood. The aim of this study was to clarify the incidence and the risk factors for the development of HCC after Peg-IFN/RBV therapy in patients with chronic hepatitis C. METHODOLOGY: A total of 474 patients with chronic hepatitis C who received Peg-IFN/RBV therapy between December 2004 and August 2010 were enrolled and followed in a multicenter trial. The patients were assessed for HCC by either ultrasound or computed tomography every 6 months. The incidence and risk factors for the development of HCC were identified. RESULTS: Of the 474 patients, 23 developed HCC during a median follow-up of 4 years and 8 months (range 1-6 years and 3 months) after completion of Peg-IFN/RBV therapy. According to a univariate analysis, higher age, low platelet counts, a low level of serum albumin, a high level of alpha-fetoprotein (AFP) and a sustained viral response (SVR) to Peg-IFN/RBV therapy were independent factors associated with the occurrence of HCC. The multivariate analysis using the Cox proportional hazard model revealed the risk factors for HCC were the platelet count, AFP level and the outcome of Peg-IFN/RBV therapy. CONCLUSIONS: To reduce the incidence of HCC in chronic hepatitis C, attainment of a sustained response rate is an essential issue. For patients with low platelet counts and/or a high AFP level, strict surveillance should be continued even after eradication of HCV because the risk of HCC was found to be higher for these patients.

Clinico-roentogenologic findings in hepatocellular carcinoma fed by the right inferior phrenic artery at the initial chemoembolization.

BACKGROUND/AIMS: The purpose of this study was to investigate factors that may predict the development of the right inferior phrenic artery (RIPA) as a feeding artery in hepatocellular carcinoma (HCC) at the initial (first session) chemoembolization. METHODOLOGY: From January 1997 to June 2002, 538 patients with HCC were treated with a first session of transcatheter arterial chemoembolization (TACE). Twenty-six of these patients underwent TACE via both the Hepatic artery (HA) and RIPA at the initial TACE. We retrospectively analyzed the Child-Pugh's classification, macroscopic tumor type, location and size of the tumor, past history of intervention, complications and outcome in these 26 patients with HCC fed by the RIPA. RESULTS: The incidence of HCC fed by both the HA and RIPA at the initial TACE was 4.8% (26/538 patients). No hepatic arterial occlusion or attenuation was found in any of these 26 patients. All of the tumors abutted the diaphragm and were located at the surface of the liver. All of the tumors that were larger than 5 cm in diameter protruded from the surface of the liver. Seven of the 9 patients with HCC smaller than 5 cm in diameter had a defect in the liver capsule induced by previous intervention for the treatment of a different tumor, such as hepatic resection or percutaneous ablation therapy. There were no serious complications after TACE. CONCLUSION: The RIPA can be an extrahepatic feeding artery for HCC even at the initial TACE. A high incidence of HCC fed by the RIPA was recognized in cases in which a large tumor protruded from the surface of the liver, and when the liver capsule was damaged due to previous intervention such as hepatic resection or in ruptured HCC even at the initial TACE.

Hepatic hydrothorax occurring rapidly after manual abdominal compression.

Hepatic hydrothorax is a relatively infrequent but potentially serious complication of liver cirrhosis that often causes respiratory dysfunction. Several hypotheses for the development of hepatic hydrothorax have been suggested to explain a transdiaphragmatic shift of ascitic fluid through small defects between the peritoneal cavity and the pleural space. However, the rapid development of hydrothorax within several hours is seldom encountered. In addition, the causal factors for rapid passage of ascitic fluid into the pleural cavity are unknown. This report describes a patient with liver cirrhosis who suffered rapid development of a hydrothorax after manual compression of the abdomen.

[A case of hepatocellular carcinoma with tumor thrombi in the first branch of the portal vein and hepatic vein trunks treated by transcatheter hepatic arterial chemoembolization and hepatic arterial infusion chemotherapy--two years and six months follow-up].

The patient was a 73-year-old man. In March 2002, abdominal computed tomography revealed hepatocellular carcinoma (HCC) with tumor thrombi in the first branch of the portal vein (Vp3) and two hepatic vein trunks (Vv2). He had no hepatitis virus. Serum AFP and PIVKA-II levels were as high as 6,919 ng/ml and 91,700 mAU/ ml, respectively. He was treated by transcatheter hepatic arterial chemoembolization (TACE) 3 times. On post 1st TACE week 8, he received hepatic arterial infusion chemotherapy (low-dose cisplatin and 5-FU) for Vp3 Vv2 HCC. The patient is still alive with no recurrence after two years and six months since the initial TACE treatment.

Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T(2-3)N(any) M(0) squamous cell carcinoma of the esophagus.

PURPOSE: To compare the treatment results between radical surgery and definitive chemoradiotherapy for resectable squamous cell carcinoma of the esophagus and to identify useful clinicopathologic and biologic markers to select better treatment. METHODS AND MATERIALS: Between August 1992 and April 1999, 98 consecutive patients were selected for this study; 53 were treated with chemoradiotherapy and 45 with surgery. The patients in the chemoradiotherapy group received 5-fluorouracil combined with cisplatin plus 60 Gy of radiation, and those in the surgery group received an esophagectomy with radical node dissection. Biologic markers were investigated immunohistochemically using pretreatment biopsy specimens. RESULTS: The baseline clinical TNM stage was more advanced in the chemoradiotherapy group than in the surgery group. With a median follow-up period of 43 months, the 5-year survival rate was 46% in the chemoradiotherapy and 51% in the surgery group, without statistical significance (p = 0.47, log-rank test). Cox regression analysis for prognosis revealed that epidermal growth factor receptor positivity, high microvessel density, and cyclin D1 positivity yielded a low value for relative risk (0.66, 0.54, and 0.62, respectively), which favored chemoradiotherapy over surgery, without statistical significance. CONCLUSION: This nonrandomized study showed a trend for the chemoradiotherapy in the treatment of esophageal carcinoma, but the results need to be confirmed by additional study.