Differential impact of adherence to pegylated interferon and ribavirin in the treatment of genotype 1 high viral titer chronic hepatitis C.

To clarify the impact of adherence, we treated 122 genotype 1 high viral titer chronic hepatitis C patients with pegylated interferon (peg-IFN) and ribavirin for 48 weeks at nine referral hospitals, and evaluated the prognostic factors with a focus on the adherence to the treatment. This study included 68 (55.7%) treatment-naïve patients and 54 (44.3%) patients who did not respond to the previous treatment. Multivariate analysis revealed adherence to peg-IFN and ribavirin as the only significant predictor. Sustained virological response (SVR) rate was 72.2%, 19.0%, and 27.3% in patients given ≥80%, 60%-80%, and <60% dose peg-IFN, respectively, and was 68.6%, 41.2%, and 5.3% in those given ≥80%, 60%-80%, and <60% dose ribavirin, respectively. SVR rate sharply fell when exposure to peg-IFN was below 80% whereas it decreased in a stepwise manner as for ribavirin. Therefore, ≥80% of peg-IFN and as much as possible dose of ribavirin are desired to achieve SVR in the treatment of genotype 1 high viral titer chronic hepatitis C.

Non-response to previous interferon therapy and cirrhosis are risk factors for predicting breakthrough during lamivudine therapy in patients with chronic hepatitis B.

AIMS: Lamivudine is a potent oral anti-viral medicine for the treatment of hepatitis B virus (HBV) infection. However, one of the major problems is the breakthrough (BT) followed by flare-up of hepatitis. We examined the influences of clinical background, progression of liver fibrosis, presence or absence of HBeAg and previous interferon (IFN) therapy on the occurrence of breakthrough. SUBJECTS AND METHODS: This study comprised 51 patients with HBV related chronic hepatitis (CH) or cirrhosis (LC) who were treated with lamivudine for the mean period of 33.8 ± 13.1 months (range 3-63 months). Thirty-six patients were CH, 25 were HBeAg- positive, and 25 had a previous history of IFN therapy. Patients were divided into two groups according to the occurrence of BT, either BT(+) or BT(-). Age, gender, alanine aminotransferase (ALT) and HBV titer before treatment, normalization of ALT (≤ 40 IU/L) and flare-up of hepatitis (ALT > 80 IU/L) rates, degree of hepatic fibrosis (CH/LC), presence or absence of HBeAg (HBeAg(+)/(-), and previous IFN therapy (IFN(+)/(-) were analyzed using Cox's proportional hazards analysis. RESULTS: Twenty-five patients showed BT. Background data were not different between the patients with and without BT. Flare-up of hepatitis occurred more frequently in BT. Rates of BT were markedly higher in LC (P = 0.025) and IFN(+) (P = 0.036), but HBeAg was not associated with BT. In multivariate analysis, progression of liver fibrosis (P = 0.006) and previous IFN therapy were independent risk factors for BT (P = 0.023). CONCLUSIONS: BT significantly occurred in patients with LC and the history of previous IFN therapy. Multivariate analysis showed that progression of hepatic fibrosis and previous interferon therapy are independent risk factors for BT.

Study of energy metabolism of skeletal muscles in alcoholic liver disease--expired gas analysis during exercise.

BACKGROUND: The effects of chronic alcohol intake on skeletal muscle are clinically observed as muscle cramps with decrease in the amount of muscle. It was clarified by expired gas analysis that acute alcohol load affects disturbed energy metabolism of skeletal muscle. We studied abnormal energy metabolism of skeletal muscles in alcoholic liver diseases using expired gas analysis. METHODS: Subjects of the study were five inpatients with alcoholic liver disease (fatty liver: one case, hepatic fibrosis: one case, liver cirrhosis: three case). Expired gas analysis during exercise was performed using AEROMONITOR. Minute ventilation, oxygen consumption and carbon dioxide output were monitored, and anaerobic threshold (AT) and respiratory compensation point (RCP) were calculated. RESULTS: The anaerobic threshold, which is the limit of the aerobic exercise, was significantly reduced in patients with alcoholic disease (p < 0.01). The respiratory compensation point, which is the limit of the metabolic compensation of intracellular lactic acidosis, was decreased (p < 0.01). CONCLUSIONS: The results of expired gas analysis during exercise indicate that the aerobic energy metabolism of skeletal muscle had been disturbed in alcoholic liver disease. The reduced RCP suggests that the lactate metabolism in skeletal muscle is also disturbed in alcoholic liver disease. Expired gas analysis during exercise allows determination of the amount of exercise required to treat liver diseases through analysis of AT.

Hemophagocytic syndrome in ileum-origin B-cell lymphoma.

A 56 year-old-man was admitted due to upper abdominal tumor and was diagnosed as having stage IVb diffuse B-cell malignant lymphoma that originally developed in the terminal ileum. The first and the second administrations of CHOP (cyclophosphamide, 750 mg/m(2); adriamycin, 50 mg/m(2); vincristine, 1.4 mg/m(2); and prednisolone, 100 mg/day) therapy were effective; however, the third course of therapy was postponed because of an episode of massive hematochezia. After this episode, lymph nodes began to enlarge and progressive pancytopenia occurred. Bone marrow smear showed the proliferation of reactive histiocytic cells which phagocytized red blood cells, white blood cells, and platelets. B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) was diagnosed. This case is extremely rare because: (1) LAHS occurred in an ileum-origin B-cell lymphoma, and (2) LAHS developed during an interval after chemotherapy.

Influence of acute alcohol load on metabolism of skeletal muscles--expired gas analysis during exercise.

BACKGROUND: The chronic intake of alcohol affects the function of skeletal muscles. To elucidate the influence of acute alcoholic load on muscular metabolism during exercise, we analyzed expired gases to measure the volume of consumed oxygen and the volume of exhaled CO2. METHODS: Healthy volunteers were enrolled for the study. For the exercise test, they were asked to rest for 5 min, warm up on an aerobike at 20 W for 2 min, and then gradually increase the load by 2 W every 6 sec. On another day, they were asked to drink 0.5 to 0.6 g/kg ethanol in 30 min, rest for 30 min, and then do the test. The expired gas analysis was used to measure changes in the anaerobic threshold and the respiratory compensation point. The blood concentrations of lactate, ethanol, and acetate also were measured. RESULTS: The anaerobic threshold showed no significant change in the case of exercise without alcoholic load. The respiratory compensation point decreased significantly in the case of alcoholic load (p < 0.001), and the interval from the anaerobic threshold to the respiratory compensation point decreased (p < 0.02). The blood concentration of lactate increased, after alcoholic load, to a level significantly higher than the level measured before the alcoholic load (p < 0.001). It showed a marked increase immediately after exercise stress (p < 0.001). The blood concentration of acetate tended to decrease after exercise load, but no significant change was noted. CONCLUSIONS: The anaerobic threshold, which is the limit of the aerobic glycolytic system (i.e., the so-called aerobic exercise limit) was not influenced by exercise under an acute alcoholic load. However, after the production of lactate started, the respiratory compensation point, which is the limit of the metabolic compensatory action, appeared earlier. This suggested that the intake of alcohol would influence the energy metabolism of skeletal muscles by a mechanism in which the disturbed metabolism of lactate in skeletal muscles was mainly involved.