Influences of CYP2C19 polymorphism on recurrence of reflux esophagitis during proton pump inhibitor maintenance therapy.

BACKGROUND/AIMS: Patients with erosive gastroesophageal reflux disease (GERD) have rapid recurrence after treatment withdrawal. The aim is to study the influences of CYP2C19 polymorphism on recurrence of GERD during proton pump inhibitor maintenance therapy. METHODOLOGY: Ninety-nine patients with initial healing of GERD (judged by endoscopy) after 8 wk of treatment with PPIs were enrolled into maintenance therapy for 6 mo with rabeprazole (10 mg/day), omeprazole (20 mg/day) or lansoprazole (15 mg/day). The recurrence of GERD symptoms in the maintenance therapy was assessed by a QUEST questionnaire. RESULTS: The recurrence rate of GERD symptoms in the group of CYP2C19 homozygous extensive metabolizers (38.5%) was significantly greater than those in groups of heterozygous extensive metabolizers (10.9%) and poor metabolizers (5.6%). The recurrence rates in patients treated with omeprazole (25%) and lansoprazole (30.8%) were significantly greater than that with rabeprazole (4.4%). The gender, age and H. pylori did not significantly affect the rate. CONCLUSIONS: The CYP2C19 genotypes affected the recurrence rate of GERD symptoms during PPI maintenance therapy. The reason for the low recurrence rate with 10 mg/day rabeprazole possibly is due to its sufficient acid suppression independent of CYP2C19 genotypes in Japanese patients.

Changes in the Th1/Th2 ratio during a 24-week course of an interferon alpha-2b plus ribavirin combination therapy for patients with chronic hepatitis C.

BACKGROUND AND AIM: It has been reported that immunological factors, such as the T-helper cell (Th)1/Th2 ratio, play a part in the mechanisms for the antihepatitis C virus (HCV) effect of the interferon (IFN) alpha-2b plus ribavirin combination therapy. By using flow cytometry, we examined this ratio during a 24-week course of combination therapy for patients with chronic hepatitis C. METHODS: We recruited 21 patients with chronic hepatitis C (16 males, five females, genotype 1b, 17 patients; genotype 2a or 2b, four patients) who had been treated by combination therapy. Flow cytometry was used to examine the Th1/Th2 ratio before and at the 4th and 24th week of therapy. Patients who were HCV-RNA negative 24 weeks after the treatment was completed were defined to show sustained virological response (SVR). RESULTS: Among the 21 patients, 10 showed SVR, the overall SVR rate being 47.6%. Patients were classified into an 'increase group' (Th1/Th2 ratio at 4 or 24 weeks of therapy being higher than those before therapy) and a 'decrease group' (the ratio being lower than before therapy). After 24 weeks of therapy, the SVR rate was 66.7% for the Th2 'increase group' and 14.3% for the Th2 'decrease group'. The former showed a significantly higher SVR rate (P = 0.0361). CONCLUSIONS: The significant changes in the Th2 level correlated with the therapeutic effect during the IFN alpha-2b plus ribavirin combination therapy. The increase of the Th2 level during therapy could be a predictor for achieving SVR.

Stent-graft to treat intrahepatic portosystemic venous shunt causing encephalopathy.

Spontaneous intrahepatic portosystemic venous shunts (IPSVS) are rare, and angiographic intervention to treat IPSVS has been limited. To our knowledge, we present the first case of an IPSVS between the right portal vein and inferior vena cava accompanied by intractable encephalopathy that was successfully obliterated using a stent-graft deployed in the inferior vena cava to disconnect the portal and systemic venous circulation. Our patient, a 58-year-old woman, has shown no evidence of recurrent portosystemic venous shunt or encephalopathy for 30 months. We believe this intervention to be a useful alternative therapy for this type of shunt.

Type C chronic hepatitis with the discovery of a small hepatocellular carcinoma 7 years after successful interferon therapy.

The patient, a 61-year-old man, had sustained injuries in a traffic accident at the age of 26, for which he received a blood transfusion. Since 1988 (age, 49 years), abnormal hepatic function had been detected, and, because of the presence of hepatitis C virus antibodies, he was diagnosed as having type C chronic hepatitis. Based on a liver biopsy that was conducted in July 1992 (age, 53), a histological diagnosis of chronic active hepatitis (F(1)/A(2)) was made. Over a period of 6 months, starting in 1992, the patient was treated with interferon (IFNalpha-2a; total dosage, 720 MU). At the end of this regimen, the alanine aminotransferase level was normalized and serum hepatitis C virus-ribonucleic acid was negative. This condition was maintained until August 1996 (age, 57), after which the patient stopped reporting to our hospital. In June 2000 (age, 61) when he was hospitalized for an adhesive ileus, a small hepatocellular carcinoma (a solitary lesion measuring 18 mm in diameter) at S(8) was found, and it was extirpated by a segmental excision in July. The case is introduced to call attention to the need for longterm follow-up observation, even after effective IFN therapy.

Tuberculous liver abscess not associated with lung involvement.

Hepatic tuberculosis is one of the uncommon forms of extrapulmonary tuberculosis. We report a 78-year-old woman who developed tuberculous liver abscesses with splenic abscess not associated with pulmonary foci. Ultrasonography and computed tomography of the abdomen showed the low-density lesions in the liver and spleen. Histopathology of specimens obtained by percutaneous needle biopsy revealed coagulation necrosis and epithelioid cells but not tumor cells, suggesting tuberculosis infection in the liver and spleen. Systemic chemotherapy with anti-tuberculous agents led to the improvement of the lesions in the liver as well as spleen. Although tuberculous liver abscess is a very rare case, it should be included in the differential diagnosis of unknown hepatic mass lesions.

Acquired factor V inhibitor responsive to corticosteroids in a patient with double cancers.

A 70-year-old woman suffering from HCV-related liver cirrhosis was admitted for abnormal bleeding. Laboratory findings included PT at 46.6 sec, APTT at >212 sec, factor V activity of <3%, and factor V inhibitor of 2 BU. Having experienced a persistent bleeding tendency for one month, the patient was started on prednisolone (0.8 mg/kg/day). Within a few days, the inhibitor became undetectable and clinical bleeding disappeared. Although clinical improvement was achieved, she died 6 months after the initial bleeding episode from the progression of a lung cancer. An autopsy revealed squamous cell carcinoma of the lung and hepatocellular carcinoma.

Treatment effects and predictors of a 24-week course of interferon alpha-2b plus ribavirin combination therapy for patients with chronic hepatitis C.

BACKGROUND AND AIMS: In chronic hepatitis C patients with genotype 1b and a high viral load, the sustained virological response (SVR) rate remained as low as 2-3% with conventional interferon (IFN) monotherapy, but improved to more than 20% with IFN alpha-2b plus ribavirin combination therapy. This study examined the therapeutic effects and predictors of this combination therapy. METHODS: Subjects were 105 patients with chronic hepatitis C (73 males, 32 females) with a median age of 53 years (range 19-70 years). Seventy-two patients had genotype lb and 33 patients had genotype 2 (2a or 2b). Six million units (MU) or 10 MU of IFN alpha-2b was administered by intramuscular injection six times a week for the first 2 weeks, and the same amount of IFN was administered three times a week for the following 22 weeks. During the IFN administration period, 600-800 mg of oral ribavirin was administered daily. Patients who were hepatitis C virus (HCV)-RNA negative 24 weeks after the completion of administration were defined as SVR. RESULTS: The overall SVR rate was 39%; 22.2% for the genotype 1b group and 75.8% for the genotype 2 group, and the difference between the groups was significant (P < 0.0001). Multivariate logistic regression analysis indicated that the factors that contributed to SVR include genotype 2, age (younger than 53 years), and an increase in Th2 measured by flow cytometry before and 4 weeks after start of treatment. CONCLUSIONS: The overall SVR rate of IFN alpha-2b plus ribavirin combination therapy for 24 weeks was 39%, and contributing factors for SVR rate include genotype 2, age younger than 53 years and elevated Th2.

Improvement of thrombocytopenia with disappearance of HCV RNA in patients treated by interferon-alpha therapy: possible etiology of HCV-associated immune thrombocytopenia.

We evaluated the relationship between the severity of thrombocytopenia and the serum hepatitis C virus (HCV) RNA level to investigate the mechanism of thrombocytopenia in patients with HCV infection. Patients who had chronic hepatitis without splenomegaly were divided into two groups according to the platelet count, which were 18 patients with a platelet count < or =150 x 10(9)/L and 22 patients with a platelet count >150 x 10(9)/L. HCV RNA, platelet-associated immunoglobulin G (PAIgG), rheumatoid factor (RF), and other immunological parameters were measured and correlations were investigated. Patients in the low platelet group had higher levels of PAIgG, Th1 cells, thrombopoietin (TPO), and RF than those in the normal platelet group (textitP < 0.05). Twenty-two patients completed 6 months of IFN therapy and were followed for more than 1 yr afterwards. Twelve patients who responded to IFN therapy with clearance of HCV showed an increase of the platelet count, whereas the 10 patients who did not respond to IFN showed a decrease of the platelet count. The improvement of thrombocytopenia after interferon therapy suggests a contribution of HCV infection to this condition.