熊去氧胆酸对Ⅰ型自身免疫性肝炎的疗效观察

观察熊去氧胆酸 (UDCA)对Ⅰ型自身免疫性肝炎的疗效。随机选取 4 2例Ⅰ型自身免疫性肝炎分为三组 ,分别采用UDCA(A组 ) ,皮质类固醇激素 UDCA (B组 )和单纯皮质类固醇激素 (C组 )治疗八周 ,观察患者症状、肝功能及免疫学指标的变化。B组和C组均能较好地改善症状和A组比较有显著差异性 (P <0 0 5 ) ,TBil、ALT、γ -GT以及IgGB组和C组均较A组明显改善 (P <0 0 5 ) ,B、C组间比较有显著差异 (P <0 0 5 ) ;B组产生副作用与C组比较差异显著 (P <0 0 5 )。UDCA与皮质类固醇激素合用能有较好疗效 ,可以减少其使用量及副作用     

A case of severe recurrent hepatitis with common variable immunodeficiency.

Severe hepatitis with an indistinct etiology manifested in a 16-year-old boy who had no particular history. The histological features of the liver and clinical course of the patient were similar to those of patients with autoimmune hepatitis characterized by interface hepatitis and severe lobular inflammation of the liver and recurrent exacerbations of hepatitis. We administered intravenous glycyrrhizin preparation daily or three times a week combined with the oral administration of ursodeoxycholic acid daily throughout the term after the initial onset of disease for the control of disease activity. The normalization of the concentration of alanine aminotransferase in serum was achieved in response to the therapy during the course. The serum concentration of immunoglobulins of the patient gradually decreased from the onset of the disease to an unacceptable level without globulin preparation during the following period of 17 months. Immunological tests revealed impairment of immunoglobulin production bythe B cell population of the patient, which led to the diagnosis of the patient as common variable immunodeficiency (CVID). The patient, with improved liver histology after 27 months from the onset of disease, benefited from the current combination therapy without severe infection through the avoidance of overimmunosuppression. CVID is defined as a heterogeneous syndrome characterized by various degrees of hypogammaglobulinemia without any specific predisposing causes, frequently associated with autoimmunity. Diagnostic criteria and therapeutic options of persistent hepatitis with CVID are to be established, as discussed in the current report.     

Flutamide-induced cyanosis refractory to methylene blue therapy

Flutamide, an anti-androgen used in prostate cancer therapy, is also a derivative of aniline. Mild, usually asymptomatic, methaemoglobinaemia has been reported. We report a patient receiving flutamide therapy who developed cyanosis, dyspnoea and anaemia, initially attributed to marked methaemoglobinaemia by the CO-Oximeter method. An unsuccessful trial of methylene blue therapy led to the finding of marked sulphaemoglobinaemia. Sulphaemoglobinaemia has not previously been reported with flutamide use. Recognition of this association is important, given the refractoriness of sulphaemoglobinaemia to methylene blue therapy.     

Acute hepatitis induced by HMG-CoA reductase inhibitor,lovastatin

Summary The HMG-CoA reductase inhibitor, lovastatin, is known to induce asymptomatic liver dysfunction in a few patients. We report the case of an adult who suffered from clinical hepatitis three months after the onset of lovastatin administration. Manifestations included asthenia, jaundice, and increased aminotransferase and alkaline phosphatase activities. Histologic examination showed centrilobular necrosis, centrilobular cholestasis, and infiltrates with mononuclear and polymorphonuclear cells, including eosinophils. Withdrawal of lovastatin was followed by complete normalization of liver tests within two months.     

Interferon and ursodeoxycholic acid combined therapy in chronic viral C hepatitis: controlled randomized trial in 203 patients

AIMS: This prospective randomized trial was carried out in order to determine whether the long-term administration of ursodeoxycholic acid after discontinuation of interferon had any beneficial effect on the clinical course of hepatitis C virus infection. METHODS: Enrolled in the study were 203 patients with chronic active hepatitis C. They were all given: interferon alpha-2a (3 MU subcutaneously thrice a week) and ursodeoxycholic acid (10 mg/kg/day) for 9 months. At month 9, biochemical responders only were randomized into ursodeoxycholic acid treatment or placebo for 12 additional months (double blind study). RESULTS: At the end of interferon therapy, 71 patients (37%) were virological responders and 107 (56%) patients were biochemical responders and were randomized: 54 into the ursodeoxycholic acid group and 53 into the placebo group. Sustained response was evaluated 12 months after withdrawal of interferon. Sustained biochemical and virological responses were, respectively, 30% and 22% in the ursodeoxycholic acid group and 46% and 32% in the placebo group, which did not significantly differ. Histological evolution of fibrosis and necrotic inflammatory activity were similar in the two groups. CONCLUSION: Continuation of ursodeoxycholic acid therapy after withdrawal of interferon in patients with end-of-treatment response did not result in any significant improvement either in the maintenance of response to interferon or in liver histology.     

Cholestatic hepatitis with severe systemic reactions induced by trimethoprim-sulfamethoxazole

Trimethoprim-Sulfomethoxazole (TMP-SMX) related hepatotoxicity and associated severe systemic reaction are not frequent and documented only in case reports. We report a case of a 30-year-old man, who underwent a 15-day therapy with TMP-SMX for urinary tract infection and two weeks later developed acute cholestatic hepatitis, fever and a skin rash followed by severe systemic reaction. He was admitted in Intensive Care unit and with supportive therapy and prednisolone administration, he showed subsequent improvement over a period of few days. He had fully recovered months later. All tests for other causes of liver disease were negative and his liver biopsy showed evidence of drug-induced hepatic injury.     

Effect of ursodeoxycholic acid on autoimmune-associated chronic hepatitis C

BACKGROUND: Hypergammaglobulinaemia and various auto-antibodies which are commonly seen in autoimmune hepatitis are also found in patients with chronic hepatitis C. We recently reported that ursodeoxycholic acid (UDCA) improved liver function tests and immunoserological markers in patients with type I autoimmune hepatitis. The aim of this study was to prospectively evaluate the efficacy of UDCA on autoimmune-associated chronic hepatitis C. METHODS: Immunoglobulin G (IgG), anti-nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) were determined in 95 patients with chronic hepatitis C. All patients were positive for hepatitis C virus RNA. Autoimmune-associated chronic hepatitis C (C-AIH) was defined by elevated serum IgG level (> or = 2.0 g/dL) and high titres of ANA and/or ASMA (> or = 1 : 160). Nine (9%) of 95 patients were diagnosed as C-AIH. All the C-AIH patients and 30 of the remaining 86 chronic hepatitis C patients without autoimmune features (CHC) were treated with UDCA (600 mg/day) for 1 year. RESULTS: Autoimmune-associated chronic hepatitis C patients included one man and eight women and their AIH scores, as defined by the International Autoimmune Hepatitis Group, were significantly higher than the CHC patients. Before UDCA therapy, there were no significant differences in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and y-glutamyl transpeptidase (gamma-GTP) levels between C-AIH and CHC patients. However, after 1 year UDCA therapy, AST, ALT and gamma-GTP were significantly lower in C-AIH patients (P< 0.05) than in CHC patients. In C-AIH, ANA titres in seven of nine patients and ASMA titres in five of seven patients were reduced after 1 year UDCA treatment. CONCLUSIONS: These results suggest that UDCA is a useful therapeutic agent for autoimmune-associated chronic hepatitis C.     

Cholestatic hepatitis following flutamide

Summary Previous reports have indicated that administration of flutamide—a nonsteroidal antiandrogen drug—may induce hepatic toxicity. However, cholestatic hepatitis following flutamide is a rare event. This case report describes a 72-year-old male with metastatic adenocarcinoma of the prostate who underwent bilateral orchiectomy and treatment with flutamide. After seven weeks he developed jaundice and elevated AST and ALT levels. A liver biopsy showed cholestatic hepatitis without signs of biliary obstruction. The patient's clinical symptoms and elevated bilirubin resolved after the flutamide was discontinued. Monitoring of serum liver enzyme tests is advocated during flutamide administration to identify drug-induced liver injury.     

Post-infantile giant cell hepatitis in patients with primary sclerosing cholangitis and autoimmune hepatitis

Abstract: In post-infancy, multinucleated giant cell hepatitis is rare. Various conditions and diseases associated with post-infantile giant cell hepatitis have been described, but the pathogenesis remains unknown. In this paper we review the case reports of four patients (3 male, 1 female; aged 22 to 32 years) with primary sclerosing cholangitis and autoimmune hepatitis. The follow-up ranges from five to seven years. All patients showed cholestasis and repeated elevation of hepatic transaminases. Patients with viral infections, metabolic disorders and toxic influences were excluded. Histopathology of liver tissue in all four patients revealed giant cell formation with up to 20 nuclei in 20–70% of all hepatocytes. Post-infantile giant cell hepatitis was defined histopathologically. The clinical course of all four patients markedly improved after immunosuppressive treatment. Further improvement was observed with the addition of ursodeoxycholic acid. Follow-up liver biopsies during treatment showed reduced inflammation and a decreased number of giant cells. One patient, who initially was admitted to the hospital with liver cirrhosis died five years later due to a sepsis. The clinical course of the other three patients remained stable during the observation period, and no progression of liver fibrosis was recorded as long as immunosuppressive treatment was continued. Cholestasis and autoimmunity seem to be two important mechanisms triggering hepatic giant cell formation in post-infancy. In the reported cases long-lasting cholestasis in primary sclerosing cholangitis together with features of autoimmune hepatitis seem to have triggered the formation of syncytial hepatic giant cells.     

Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis

Ursodeoxycholic acid (UDCA) has been shown to have beneficial effects on patients with primary biliary cirrhosis, suggesting that UDCA has immunomodulating effects. We investigated the effect of UDCA in patients with autoimmune hepatitis (AIH) which is characterized by immunological abnormalities. Eight patients with type 1 AIH were treated with 600 mg of UDCA per day for 2 years. Based on the criteria of the International Autoimmune Hepatitis Group, five patients were diagnosed as definite and three as probable type 1 AIH. Liver function tests were performed every 4 weeks, before and during UDCA therapy and the serum levels of anti-nuclear antibodies (ANA), smooth muscle antibodies (SMA), immunoglobulin G and gamma globulin were determined every 3 months. The levels of serum aspartate aminotransferase and alanine aminotransferase significantly decreased from 154 ± 24 IU/L and 170 ± 17 IU/L before UDCA therapy to 31 ± 3 IU/L and 25 ± 5 IU/L ( P < 0.001) after 1 year of treatment and 28 ± 2 IU/L and 23 ± 4 IU/L ( P < 0.001) after 2 years of treatment. After 2 years of treatment, the levels of serum immunoglobulin G and gamma globulin significantly decreased ( P < 0.05) and ANA titres (5/8 patients) were reduced and SMA (3/5. patients) became negative. Furthermore, hepatic histopathological changes of four patients were assessed after 1 year of treatment, and an improvement of intrahepatic inflammation, but not fibrosis, was observed. In conclusion, these results suggest that UDCA has a beneficial therapeutic effect in patients with type 1 autoimmune hepatitis.     

Effect of ursodeoxycholic acid on serum liver enzymes and bile acid metabolism in chronic active hepatitis C virus infection

Aim:  Many reports have revealed ursodeoxycholic acid (UDCA) to be effective against chronic hepatitis C virus (HCV). However, some cases resist this therapy and the mechanism of action remains unclear. In this study, UDCA was administered to patients with chronic HCV and the correlation between the bile acids of the biliary bile and serum and the drug efficacy was investigated.
Methods:  Fifteen patients were given 600 mg/day of UDCA for more than 24 weeks. The serum bile acid concentrations and biliary and serum bile acid were collected before and after 24 weeks of UDCA treatment, and composition determined by high-performance liquid chromatography.
Results:  The treatment was effective in nine cases (ALT decreased to less than twice the normal values 80 IU/L) and ineffective in six cases. There was no significant difference in the serum bile acid concentrations before and after UDCA treatment between the values of both cases. After UDCA treatment, the serum percentage of UDCA (effective, 62.5 ± 2.0; ineffective, 53.5 ± 2.5, ( P  = 0.02)) and the percentage of chenodeoxycholic acid (CDCA) showed no remarkable changes. In the biliary bile the percentage of CDCA (effective, 30.9 ± 2.0; ineffective, 20.0 ± 3.0, ( P  = 0.007)) and the percentage of UDCA showed no remarkable changes.
Conclusion:  In the effective cases, the percentage of UDCA in the serum and the percentage of CDCA in biliary bile were significantly higher than in the ineffective cases. This indicates that, when effective, CDCA decreases in hepatocytes and this reduction contributes to hepatoprotection.     

药物诱发自身免疫性肝炎的研究进展

随着药物(或中草药、保健品)的滥用和“被用”,药物性肝损害不断增加.某些药物本身或代谢产物可与蛋白结合形成半抗原,刺激机体发生免疫反应,和(或)由于宿主的遗传易感性、女性、高龄等因素,导致药物诱发自身免疫性肝炎( drug-induced autoimmune hepatitis,DIAIH)的发生.DIAIH的临床症...     

熊去氧胆酸治疗药物性肝病62例疗效观察

目的 观察熊去氧胆酸治疗药物性肝病的临床疗效.方法 将我院130例药物性肝病随机分为对照组(68例)和治疗组(62例),对照组给予甘草酸二铵、还原型谷胱甘肽、多烯磷酯酰胆碱,治疗组在对照组的基础上,加用熊去氧胆酸12～15 mg·kg-1 ·d-1,口服分三次,两组疗程均为4周.监测治疗前,2周、4周肝功能变化和观察临床疗效.结果 治疗组在肝功能改善方面明显优于对照组(P＜0.01),治疗组和对照组临床疗效比较,差异有统计学意义(P＜0.01).结论 熊去氧胆酸治疗药物性肝病确有较好疗效.     

Efficacy of ursodeoxycholic acid in the treatment of patients with chronic hepatitis C

A case-control study was conducted to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with chronic hepatitis C. Patients who failed to have sustained responses to interferon (IFN) therapy, refused to take IFN or were unsuitable for IFN treatment were enrolled into this study. The treatment group had 15 patients and they received UDCA 600 mg orally per day for 6 months. Another 15 patients with matched sex, age and initial serum alanine aminotransferase (ALT) levels were chosen as the control group. Three parameters (i.e. serum ALT levels, serum hepatitis C virus (HCV) RNA and serum cytokines) were measured before and after UDCA treatment. After the treatment period, the mean serum ALT levels in both groups were not significantly different (153.8 ± 111.0 U/L vs 112.1 ± 53.8 U/L, P > 0.05) and mean serum ALT level in the UDCA-treated group did not decrease after the treatment (pre-treatment vs post-treatment value: 139.1 ± 73.1 U/L vs 153.8 ± 111.0 U/L, P > 0.05). In addition, all of the patients with positive HCV RNA before treatment still had active HCV viraemia after the UDCA treatment. Also, the serum levels of interleukin-6 (IL-6) and the tumour necrosis factor-α (TNF-α) were not significantly different between the two groups before and after the treatment period. In conclusion, a regimen of UDCA as prescribed in the present study did not show obvious benefits in the treatment of Chinese patients with chronic hepatitis C.     

Autoimmune cholangitis with features of autoimmune hepatitis: successful treatment with immunosuppressive agents and ursodeoxycholic acid

We report a 42-year-old Chinese female with elevated serum levels of liver aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol and immunoglobulin M. Serum antimitochondrial antibody was negative, but antinuclear antibody was strongly positive. Liver histology showed features of both autoimmune cholangitis and autoimmune hepatitis. Combination therapy with immunosuppressive (prednisone and azathioprine) and choleuretic agents (ursodeoxycholic acid) was given. Serum aminotransferases and biliary enzymes showed much improvement after treatment. A follow-up liver biopsy showed improvement of both hepatic necroinflammation and bile duct damage. Biliary enzymes rose after withdrawal of the immunosuppressive agents and declined again with reinstitution of prednisone. This case demonstrates that a combination of immunosuppressive agents and ursodeoxycholic acid may effectively treat patients with features of both autoimmune cholangitis and autoimmune hepatitis.     

Fatal hepatitis and renal failure during treatment with nimesulide

A healthy 70-year-old woman who took nimesulide for 5 days, presented 2 weeks later with jaundice for which no other cause was found. Laboratory evidence of coagulopathy, hypoalbuminaemia and hypoglycaemia were present on admission, and liver biopsy showed massive necrosis of hepatocytes and severe inflammatory infiltrate. Despite supportive and corticosteroid treatment, her jaundice deepened and progressive acute renal failure developed, characterized by a 'prerenal' profile changing into irreversible acute tubular necrosis pattern, coma, occult Gram-negative sepsis and death. Although rare, nimesulide-associated hepatotoxicity and nephrotoxicity may occur and should be recognized as early as possible, to ensure immediate drug withdrawal and treatment.