Development of nodular regenerative hyperplasia (NRH) with portal hypertension following the administration of oxaliplatin for the recurrence of colon cancer.

Nodular regenerative hyperplasia (NRH) is associated with autoimmune and hematologic diseases and may lead to portal hypertension. We herein report a case of NRH diagnosed based on a liver biopsy. A 63-year-old woman developed esophageal varices and splenomegaly.

The effect of inflammatory cytokines in alcoholic liver disease.

Alcohol is the most common cause of liver disease in the world. Chronic alcohol consumption leads to hepatocellular injury and liver inflammation. Inflammatory cytokines, such as TNF-α and IFN-γ, induce liver injury in the rat model of alcoholic liver disease (ALD).

Branched-chain amino acids suppress the cumulative recurrence of hepatocellular carcinoma under conditions of insulin-resistance.

Branched-chain amino acids (BCAAs) reportedly inhibit the incidence of hepatocellular carcinoma (HCC) in patients with liver cirrhosis and obesity that is frequently associated with insulin resistance (IR). We previously reported that BCAAs exert a chemopreventive effect against HCC under IR conditions in rats. The aim of the present study was to examine the effect of BCAAs on the cumulative recurrence of HCC under IR conditions in the clinical practice.

A case of severe acalculous cholecystitis associated with sorafenib treatment for advanced hepatocellular carcinoma.

Sorafenib, a multikinase inhibitor, is the first and only drug, which improves significantly the overall survival in patients with advanced hepatocellular carcinoma (HCC). However, many patients experience diverse side effects, some of them severe and unexpected. To date, acute acalculous cholecystitis has not been documented in association with a HCC patient treated with sorafenib.

ADAMTS13 activity may predict the cumulative survival of patients with liver cirrhosis in comparison with the Child-Turcotte-Pugh score and the Model for End-Stage Liver Disease score.

Aim:   Decreased plasma ADAMTS13 activity (ADAMTS13:AC) results in accumulation of unusually large von Willebrand factor multimers and platelet thrombi formation. Our aim was to evaluate whether ADAMTS13:AC is a prognostic marker in patients with liver cirrhosis.

Methods:   Plasma ADAMTS13:AC and its related parameters were examined in 108 cirrhotic patients.

Combination of branched-chain amino acid and angiotensin-converting enzyme inhibitor improves liver fibrosis progression in patients with cirrhosis.

An effective therapeutic strategy for suppressing liver fibrosis should improve the overall prognosis of patients with chronic liver diseases. Although enormous efforts are ongoing to develop anti-fibrotic agents, no drugs have yet been approved as anti-fibrotic agents for humans. Insulin resistance (IR) is reportedly involved in the progression of liver fibrosis.

Combination of branched-chain amino acids and angiotensin-converting enzyme inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: a randomized control trial.

Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Since neovascularization plays an important role in hepatocarcinogenesis and IR, an angiostatic therapy may be considered as one of the promising approaches for chemoprevention against HCC. The aim of the current study was to examine the combination effect of a clinically used branched-chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I), both reportedly possess anti-angiogenic and IR-improving activities, on the cumulative recurrence after curative therapy.

Salvage living donor liver transplantation after percutaneous transluminal angioplasty for recurrent Budd-Chiari syndrome: a case report.

Introduction: Budd-Chiari syndrome is a very rare pathological entity that ultimately leads to liver failure. Several therapeutic modalities, including percutaneous transluminal angioplasty, have been attempted to save the life of patients with Budd-Chiari syndrome. Few reports have described a salvage living donor liver transplantation performed after percutaneous transluminal angioplasty in a patient with acute Budd-Chiari syndrome.

Soluble VEGF receptor-2 may be a predictive marker of anti-angiogenic therapy with clinically available safe agents.

The identification of biomarkers of anti-angiogenic therapy that predict clinical benefit is of vital importance. We previously reported that a combination treatment with clinically available safe agents, specifically angiotensin-converting enzyme inhibitor (ACE-I) and vitamin K (VK), inhibited the cumulative recurrence of hepatocellular carcinoma (HCC) via suppression of the vascular endothelial growth factor (VEGF). The present study aimed to identify non-invasive biological markers that predict the clinically beneficial effect of this combination regimen.

Immunotherapy for nonalcoholic steatohepatitis using the multiple cytokine production modulator Y-40138.

Aim: To investigate the possible use of the multiple cytokine production modulator, Y-40138, as a novel immunotherapy in the rat nonalcoholic steatohepatitis (NASH) model.

Methods: We allocated 6-wk-old male F344 rats to choline-supplemented, L-amino acid-defined (CSAA) diet (control group), CSAA diet + Y-40138 (control + Y-40138 group), choline-deficient, L-amino acid-defined (CDAA) diet (NASH group), or CDAA diet + Y-40138 (NASH + Y-40138 group). In each group, we measured the plasma alanine aminotransferase (ALT) levels, and the plasma and liver levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-10 (IL-10).

Crosstalk between angiogenesis, cytokeratin-18, and insulin resistance in the progression of non-alcoholic steatohepatitis.

Aim: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH).

Methods: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18-immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively.

Potential role of ADAMTS13 in the progression of alcoholic hepatitis.

Alcoholic hepatitis (AH) is a potentially life-threatening complication of alcohol abuse. The severe form of AH, severe alcoholic hepatitis (SAH), is characterized by multiorgan failure (MOF) with manifestations of acute hepatic failure and is associated with high morbidity and mortality. However, the pathogenesis of SAH in addition to AH remains to be elucidated.

Combination of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates cumulative recurrence of hepatocellular carcinoma.

Background/aims: No chemopreventive agent has been approved against hepatocellular carcinoma (HCC) yet. Since neovascularization plays a pivotal role in HCC, an angiostatic agent is considered as one of the promising approaches. The aim of this study was to elucidate the combined effect of the clinically used vitamin K(2) (VK) and angiotensin-converting enzyme inhibitor (ACE-I) on cumulative recurrence after curative treatment on a total of 87 patients, especially in consideration of neovascularization.

Development of hepatocellular carcinoma in a patient 13 years after sustained virological response to interferon against chronic hepatitis C: a case report.

Background: Although several recent reports have shown that hepatocellular carcinoma (HCC) developed in patients with chronic hepatitis C (CH-C) even after having a sustained virological response (SVR) to interferon (IFN) therapy, it is not common for HCC to develop more than 10 years after SVR.

Case Presentation: A 73-year-old Japanese man with CH-C who achieved SVR to IFN therapy 13 years ago was admitted into our hospital because of huge multiple liver tumors along with marked elevation of the tumor markers. Several diagnostic modalities strongly suggested HCC, and we performed histopathological examination.

Potential role of enhanced cytokinemia and plasma inhibitor on the decreased activity of plasma ADAMTS13 in patients with alcoholic hepatitis: relationship to endotoxemia.

Background: Deficiency of ADAMTS13 (adisintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13) results in an increase in unusually large von Willebrand factor multimer (UL-VWFM) of the plasma and finally causes microcirculatory disturbance. Our previous study demonstrated that the imbalance of increased UL-VWFM over decreased ADAMTS13 activity may contribute to the development of multiorgan failure in patients with alcoholic hepatitis (AH). The aim of this study was to explore the potential mechanism to reduce the activity of plasma ADAMTS13.

Plasma ADAMTS13 activity parallels the APACHE II score, reflecting an early prognostic indicator for patients with severe acute pancreatitis.

Objective: Severe acute pancreatitis (SAP) frequently progresses to pancreatitis-associated multiorgan failure (MOF) with high mortality. Decreased plasma ADAMTS13 activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimers (UL-VWFM) and the formation of platelet thrombi, ultimately leading to MOF. The purpose of the study was to investigate the potential role of ADAMTS13:AC in the severity of SAP.

Expression of Toll-like receptor 4 in various organs in rats with D-galactosamine-induced acute hepatic failure.

Background And Aims: Activation of the pro-inflammatory cytokine cascade, including tumor necrosis factor alpha (TNF-alpha) is considered to play an important role in the pathophysiology and clinical outcome of severe liver injury. Kupffer cells, resident macrophages of the liver, have a transmembrane protein Toll-like receptor 4 (TLR4), which recognizes endotoxin (lipopolysaccharide; LPS) or LPS-CD14 complex and mediates macrophage activation and pro-inflammatory cytokine release. D-Galactosamine (GalN), a hepatocyte-specific inhibitor of RNA synthesis, is known to sensitize animals to the lethal effects of LPS and TNF-alpha.

[A case of intrahepatic splenosis].

When a 32-year-old man was 18 a traffic accident caused splenic rupture, for which he underwent splenectomy, complicated postoperatively by hepatitis. As part of routine follow-up with his family doctor for chronic hepatitis C, a hepatic tumor was detected on plain abdominal computed tomography (CT), and he was admitted to our hospital for further investigation and treatment. Based on the results of abdominal dynamic CT, abdominal magnetic resonance imaging(MRI), abdominal angiography, CT during hepatic arteriography (CTHA) and CT during arterial portography (CTAP), we performed a laparotomy for suspected hepatocellular carcinoma.

Eosinophilic cholecystitis along with pericarditis caused by Ascaris lumbricoides: a case report.

Although the etiology of eosinophilic cholecystitis is still obscure, the postulated causes include allergies, parasites, hypereosinophilic syndrome, and eosinophilic gastroenteritis. It is sometimes accompanied by several complications, but a simultaneous onset with pericarditis is very rare. A 28-year-old woman complained of acute right hypocondrial pain and dyspnea associated with systemic eruption.

Combined treatment of vitamin K2 and angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a patient with liver cirrhosis.

Although it is well known that the hepatocellular carcinoma (HCC) is an ominous complication in patients with liver cirrhosis, there has been no approved drug to prevent the development of HCC to date. We previously reported that the combined treatment of vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) significantly suppressed the experimental hepatocarcinogenesis. A 66-year-old Japanese woman with hepatitis C virus (HCV)-related liver cirrhosis developed a dysplastic nodule in the liver detected by enhanced computed tomography along with elevation of the tumor markers, namely, alpha-fetoprotein (AFP) and lectin-reactive demarcation (AFP-L3), suggesting the presence of latent HCC.

Increased von Willebrand factor over decreased ADAMTS13 activity may contribute to the development of liver disturbance and multiorgan failure in patients with alcoholic hepatitis.

Background: Severe alcoholic hepatitis (SAH) in addition to alcoholic hepatitis (AH) is a life-threatening complication of alcohol abuse, and its pathogenesis remains unclear. The deficiency of ADAMTS13 results in an increase of the plasma unusually large von Willebrand factor multimer (UL-VWFM) and finally causes microcirculatory disturbance and multiorgan failure. We investigated the relationship of ADAMTS13 and von Willebrand factor antigen (VWF:Ag) with the clinical features of AH and SAH.

Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C.

Aim: To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-I) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC).

Methods: Perindopril (an ACE-I; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed.

Results: ACE-I decreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects.

Immune thrombocytopenic purpura associated with pulmonary tuberculosis.

A 22-year-old woman was admitted into our hospital because of generalized purpura and abnormalities in her chest X-ray. Isolated thrombocytopenia and elevated platelet-associated IgG levels were detected, while the bone marrow examination was normal. Mycobacterium tuberculosis was detected in the bronchoalveolar lavage fluid, and consequently she was diagnosed as having active tuberculosis.

Glucocorticoid therapy ameliorated hypoglycemia in insulin-like growth factor-II-producing solitary fibrous tumor.

A 54-year-old man with a past history of multi-operation for solitary fibrous tumor was hospitalized for hypoglycemia. Computed tomography demonstrated multiple tumors in the liver but not in the pancreas. His serum insulin-like growth factor (IGF)-II level was normal, but immunoblot analysis and immunohistochemistry revealed a high molecular weight form of IGF-II in the serum and tumor.