Positive Response to Tolvaptan Treatment Would Be a Good Prognostic Factor for Cirrhotic Patients with Ascites.

AIMS: Ascites is one of the major complications in advanced cirrhotic patients. Tolvaptan is a non-peptide orally available arginine vasopressin V2 receptor antagonist. We investigated and found that tolvaptan therapy improved the prognosis and predictive factor of cirrhotic patients with ascites. METHODS: Overall, 99 patients with newly diagnosed ascites with cirrhosis were enrolled. No patients had intrahepatic malignancy. The patients were divided into 2 groups based on tolvaptan therapy: 86 patients treated with tolvaptan (tolvaptan-group) and 13 patients treated without tolvaptan (non-tolvaptan-group). Tolvaptan-responder was defined as body weight loss of ≥1.5 kg/week after administering tolvaptan. RESULTS: Tolvaptan therapy was effective in 61.6% of cirrhotic patients. There was a significant difference in the overall survival (OS) between the tolvaptan-responder-group and the other groups (p < 0.001). Male (HR 5.05; p = 0.01), tolvaptan responder (HR 0.21; p = 0.02), and dosage of furosemide < 40 mg/day (HR 0.17; p = 0.01) were factors that were independently associated with the OS. The multivariate analysis revealed that C-reactive protein < 0.9 mg/dL (HR 0.07; p = 0.001), and furosemide dosage < 40 mg/day (HR 0.09; p = 0.003) were independently associated with the tolvaptan response. CONCLUSION: Therapeutic response to tolvaptan was associated with longer survival in cirrhosis patients complicated with ascites. These preliminary findings warrant validation and further exploration.

Slow walking speed overlapped with low handgrip strength in chronic liver disease patients with hepatocellular carcinoma.

AIM: Walking speed and grip strength are parameters of muscle function; however, evaluating walking speed is not always available in clinical practice. We aimed to investigate the impact of walking speed on the evaluation of muscle dysfunction in chronic liver disease (CLD) patients with hepatocellular carcinoma (HCC). METHODS: We enrolled 107 consecutive CLD patients with HCC in this study (age 76 years [range 60-92 years]; female/male 39/68; body mass index 22.9 [range 20.0-25.3]; chronic hepatitis/liver cirrhosis 25/82). Muscle dysfunction was evaluated using the Asian Working Group for Sarcopenia criteria (grip strength or walking speed) and the Japan Society of Hepatology criteria (grip strength). A correlation between walking speed and skeletal muscle index was evaluated. Independent factors for slow walking speed were evaluated using a logistic regression analysis. RESULTS: There was no significant correlation between walking speed and skeletal muscle index (r = 0.14, P = 0.16). For both the Asian Working Group for Sarcopenia and Japan Society of Hepatology criteria, 33.6% of all patients were classified as having muscle dysfunction. All patients with slow walking speed (4.7% of all patients) also showed low handgrip strength. The logistic regression analysis identified grip strength as an independent factor for slow walking speed (OR 0.65; 95% CI 0.432-0.838; P = 0.008). CONCLUSIONS: No difference was seen in the prevalence of muscle dysfunction between the Asian Working Group for Sarcopenia and Japan Society of Hepatology criteria in CLD patients with HCC. Furthermore, all patients with slow walking speed also showed low handgrip strength. Thus, for the evaluation of muscle dysfunction, grip strength might be a suitable proxy for walking speed in CLD patients with HCC.

Efficacy of noninvasive positive pressure ventilation in elderly patients with acute hypercapnic respiratory failure.

BACKGROUND: There have been no reports on the efficacy of noninvasive positive pressure ventilation (NPPV) in elderly patients. OBJECTIVES: The purpose of this study was to clarify the efficacy and identify the predictors of a successful outcome of NPPV in patients over the age of 75 years with acute hypercapnic respiratory failure (AHRF). METHODS: We retrospectively evaluated the data of 42 patients (21 men) with AHRF who were treated at our unit. The patients were divided into survivor and nonsurvivor groups, and the clinical parameters measured prior to the initiation of NPPV were compared between the 2 groups. RESULTS: The mean age of the patients was 83.0 ± 6.3 years. The etiology of the respiratory failure was acute exacerbation of chronic obstructive pulmonary disease in 19 patients, acute cardiogenic pulmonary edema in 18 patients, idiopathic pulmonary fibrosis in 3 patients, sequelae of tuberculosis in 1 patient, and asthma in 1 patient. Of the 42 patients, 33 (78.6%) survived. All patients with a Glasgow Coma Scale (GCS) score ≥9 and/or an APACHE II score <29 survived after the initiation of NPPV. CONCLUSION: An APACHE II score <29 and a GCS score ≥9 were predictors of a successful outcome of NPPV in elderly people.

Estimation of protein intake using urinary urea nitrogen in patients with liver cirrhosis.

OBJECTIVE: Evaluation of protein intake of patients with liver cirrhosis (LC) would facilitate optimal nutritional support. However, this has never been done based on urinary urea nitrogen (UUN). The aim of this study was to determine the usefulness of the estimated protein intake (EPI) based on UUN in patients with LC. MATERIAL AND METHODS: Eighty-two patients with LC were enrolled in this study. The actual protein intake (API) was defined as the dietary protein intake (1.0 g/kg/day) plus supplementation of any enteral diets containing branched-chain amino acids (BCAA). We calculated EPI from UUN using the formula [(UUN (g/day) + 0.031 x body-weight (kg)) x0.625]. We examined the correlation between EPI and API and the EPI/API ratio (EAR), and the correction based on the results. RESULTS: A significant positive correlation was found between API and EPI (r=0.72, p<0.001). The EAR in all patients was 0.82+/-0.13. EPI x 1.2 was the correction needed to adjust EAR to 1. The corrected EPI was correlated with API (r=0.704, p<0.001). The corrected EAR of all 82 patients was 0.99+/-0.16. CONCLUSIONS: EPI calculated from UUN is a useful tool for optimal nutritional support in LC patients, and our correction greatly improves EPI accuracy.

Portal vein thrombosis in a patient with hepatitis C virus-related cirrhosis complicated with antiphospholipid syndrome.

We report a rare case of portal vein thrombosis (PVT) associated with antiphospholipid syndrome (APS) and hepatitis C virus-related cirrhosis. A 59-year-old woman with hepatitis C virus (HCV) infection was admitted because of coma. The blood test showed a typically cirrhosis pattern including an elevated serum ammonia level. Abdominal computed tomography showed liver cirrhosis and thrombus in the right branch of the portal vein. To elucidate the cause of PVT, antiphospholipid antibodies were examined. Both IgG anti-cardiolipin antibody (ELISA) and IgG anti-cardiolipin-beta2 -glycoprotein I complex antibody (ELISA) were positive. When PVT is detected in a patient with cirrhosis, it might be necessary to examine antiphospholipid antibodies to clarify the cause of PVT.

Adjuvant chemotherapy with tegafur/uracil administration after transcatheter arterial chemoembolization for advanced hepatocellular carcinoma.

Although transcatheter arterial chemoembolization (TACE) is considered to be an effective treatment for advanced hepatocellular carcinoma (HCC), it is difficult to achieve complete necrosis by TACE alone due to incomplete embolization and tumor angiogenesis. Recent studies have shown that tegafur/uracil (UFT) inhibits tumor angiogenesis in several cancer types. Therefore, this study was conducted to test the efficacy and toxicity of the UFT administration after TACE in advanced HCC. Thirty patients with HCC who had been treated with TACE alone more than three times and had a recurrence within 6 months were enrolled. All of the patients were treated with TACE and 28 patients were randomly assigned to the UFT (UFT 300 mg/day, three days after TACE, n=14) and control groups (n=14). The primary end point was the time to treatment failure (TTF) and the secondary end points were mainly the response rate and toxicity. Administration and observation were continued up to 6 months after TACE unless local recurrence was detected or serious adverse events developed. The median TTF in the control group was 87 days, whereas in the UFT group it was 127 days, thus significantly prolonged as compared to the control group (P=0.0016). Moreover, the overall response rate (35.7%) in the UFT group was significantly higher than that in the control group (0%). As for toxicity, only 4 patients in the UFT group developed grade 1-2 toxicities such as ascites. Serious complications by TACE were not observed in either group. Notably, there were no increases in the serum VEGF levels in the UFT group whereas those in the control group increased significantly. In conclusion, UFT administration after TACE was an effective treatment and showed no severe adverse events. This regimen may have an adjuvant role and antiangiogenic function in advanced HCC.

Poor sensitivity of symptoms in early detection of COPD.

The prevalence of chronic obstructive pulmonary disease (COPD) has been increasing. However, COPD is often underdiagnosed. The objective of this study was to determine how many outpatients had persistent airflow limitation and could be diagnosed as COPD by post-bronchodilator spirometry. We also evaluated whether the newly diagnosed patients had any symptoms. All outpatients with liver or general diseases over 40 years old who regularly visited to our hospital were tested for pulmonary function by spirometry. Patients with airflow limitation by the first screening spirometry had further examinations including post-bronchodilator spirometry and chest radiograph by pulmonary specialists. A total of 288 patients accepted a first spirometry. The most common chronic diseases of these patients were chronic hepatitis (33.7%), fatty liver (26.4%), liver cirrhosis (8.3%), diabetes (3.5%) and hypertension (3.1%). Approximately half of the patients had a smoking history. 44 of 288 patients (15.3%) showed airflow limitation by pre-bronchodilator spirometry. Of these, 8 patients did not show airflow limitation by a repeat pre-bronchodilator spirometry nor did 5 patients by post-bronchodilator spirometry. The rest were diagnosed as COPD (80.6%), asthma (16.1%) and bronchiectasis (3.2%). The prevalence of COPD was 8.7%. Approximately half of the patients (13/25, 52.0%) diagnosed as COPD had never complained of any respiratory symptoms. Because symptoms such as dyspnea on exertion, cough and sputum are less sensitive for the diagnosis of COPD, the propagation of spirometry in a general practice/setting should be recommended for establishing the diagnosis rate of COPD rather than relying on the presence of respiratory symptoms.

Hepatic encephalopathy with status epileptics: a case report.

A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephalopathy with status epilepticus. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy. The status epilepticus was resolved after antiepileptic therapy (phenytoin sodium) and treatment for hepatic encephalopathy (Branched chain amino acids). The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephalopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephalopathy.

Combination hepatic arterial infusion therapy is effective for ocular melanoma metastasis to the liver.

Regional treatments including chemotherapy have been applied to patients with malignant melanoma metastasis to the liver in clinical trials, but with limited efficacy. To improve efficacy, combination therapy may be beneficial. We had a case of multiple liver metastasis from right ocular malignant melanoma. The primary melanoma was surgically resected, and combination hepatic arterial infusion (HAI) therapy using dacarbazine, nimustine, vincristine (DAV), and cisplatin was applied to the metastatic focus. After HAI, marked regression of the liver metastatic focus was observed. Unfortunately, the patient passed away due to involvement of thrombotic thrombocytopenic purpura 9 months after the initial consultation, however, aggravation of the liver metastatic focus was not observed. Combination HAI therapy may have a potent therapeutic effect on malignant melanoma metastasis to the liver, and our regimen using DAV and CDDP may be beneficial to the improvement of prognosis without serious side effects.

Rapid intrahepatic tumor seeding after percutaneous ethanol injection therapy for hepatocellular carcinoma.

A 73-year-old man with hepatocellular carcinoma (HCC) had been treated repeatedly with transcatheter arterial embolization (TAE) and percutaneous ethanol injection therapy (PEIT) since 2000. HCC recurrence near the intrahepatic left portal vein was treated by PEIT in 2004. The patient complained of fatigue and upper abdominal pain 28 days later. Abdominocentesis and abdominal computed tomography demonstrated rupture of the recurrent HCC and multiple intrahepatic recurrences. We successfully performed emergency TAE, but the patient died of liver failure. Rapid seeding of multiple intrahepatic tumors after PEIT is a rare event, but such a possibility must be kept in mind.

Estimation of protein intake using urinary urea nitrogen in patients with early-stage liver cirrhosis.

PURPOSE: Evaluation of protein intake of patients with liver cirrhosis (LC) would facilitate optimal nutritional support. However, it has never been done on the basis of urinary urea nitrogen (UUN). The aim of this study, therefore, is to determine the usefulness of the estimated protein intake (EPI) based on UUN in patients with LC. METHODS: A total of 42 patients with early-stage LC were enrolled in this study. The actual protein intake (API) was defined as the dietary protein intake (1.0 g/kg/d) plus supplementation of any enteral diets containing branched-chain amino acids (BCAA). We calculated EPI from UUN using the formula [UUN (g/d) + 0.031 x body weight (kg)] x 0.625. We examined the correlation between EPI and API, the EPI/API ratio (EAR), and the correction based on the results. RESULTS: A significant positive correlation was found between API and EPI (r = 0.703, p < 0.001). The EAR in all patients was 0.84 +/- 0.11. EPI times 1.2 was the correction needed to adjust EAR to 1. The corrected EPI was correlated with API (r = 0.704, p < 0.001). The corrected EAR of all 42 patients was 1.01 +/- 0.13. CONCLUSION: In conclusion, for patients with early-stage LC, an EPI calculated from UUN may be a useful tool for optimal nutritional support. The corrected EPI would be very useful for improved monitoring of early-stage LC.

A case of polymyositis with a significantly high level of KL-6 associated with pancreatic cancer.

A 53-year-old man was diagnosed with polymyositis (PM) in 1997 and treated with prednisolone. The subjective symptoms of pneumonitis were poor. However, the KL-6 values were elevated to 2230 IU/l in March 2001. Abdominal computer tomography findings revealed a pancreatic-tail tumor and multiple liver nodules, diagnosed as primary pancreatic adenocarcinoma with multiple liver metastasis. The stage of the pancreatic cancer was IV, and curative surgery of the tumor was not indicated. Chemotherapy and radiotherapy were administered for the liver metastasis. However, these therapies were ineffective against the tumors. The patient died on 12 September 2001. If a high level of KL-6 is found without the increasing activity of lung disease containing interstitial pneumonia in PM patients, examination for the internal malignancies including pancreatic cancer should be performed, although cases of PM with a significantly high level of KL-6 associated with pancreatic cancer are rare.

A case of systemic lupus erythematosus expressing intractable thrombocytopenia remedied effectively by intermittent and continuous administrations of a small amount of immune globulin.

We describe a case where intermittent and continuous administrations of a small amount of immune globulin were effective in the treatment of refractory chronic immune thrombocytopenic purpura by systemic lupus erythematosus (SLE). Steroid pulse therapy and cyclophosphamide pulse therapy were considered for thrombopenia. However, the patient had compressed fracture of the lumbar vertebrae due to osteoporosis and right external malleolus ulcer with complications of infection. Therefore, high-dose intravenous immune globulin (IVIG) therapy (400 mg/kg daily for 5 consecutive days) was administered. Then, as a maintenance therapy, a small amount of 400 mg/kg for 1 day (400 mg/kg monthly) was given in an intermittent and continuous manner, which resulted in improvement of thrombocytopenia and reduction of the amount of steroid administered.

Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation.

Hyperthermia (HT), in combination with other conventional therapeutic modalities, has become a promising approach in cancer therapy. In addition to heat-induced apoptosis, an augmented immunological effect is considered to be a benefit of hyperthermic treatment over chemo- or radiotherapy. Here, we investigated the effect of regional HT targeting the liver on immune cells, especially T cells and antigen-presenting cells, which are important in recognizing and eliminating tumor cells and pathogens such as viruses. In healthy volunteers exposed to such regional HT, both CD4(+) and CD8(+) T cells that express an activation marker CD69 increased transiently at 1 h post-treatment, with a subsequent decrease to base levels at 6 h after the treatment. At 24 h post-treatment, the percentage of CD69-positive cells significantly increased again but only among CD8(+) T cells. IFN-gamma production from PHA-stimulated peripheral blood mononuclear cells was gradually and significantly increased in the 2 days following the heating procedure, peaking at 36 h post-treatment. Furthermore, we found marked increases in plasma levels of IL-1beta and IL-6 starting at 24 h post-treatment. With regard to the number of each leukocyte subpopulation, a transient and dramatic decrease in the number of a subset of monocytes, CD14(+) CD16(-) cells, was observed at 1 h after the hyperthermic treatment, suggesting that the regional HT aimed at the liver may have influenced the extravasation of blood monocytes. No significant changes in T-cell activities or monocyte counts were observed in the volunteers exposed to heating of the lungs or the legs. These results suggest that heating of the liver may efficiently induce cellular immune responses to liver cancers.