Hormone-replacement Therapy for Hepatopulmonary Syndrome and NASH Associated with Hypopituitarism.

The patient was a 23-year-old man who was diagnosed with severe hypoxemia and liver dysfunction after suffering from sudden difficulty breathing. At 2 years of age, he had been diagnosed with hypopituitarism, and had received hormone-replacement until he was 18 years of age. Echocardiography using micro bubbles and pulmonary scintigraphy indicated intrapulmonary shunt and a liver biopsy showed steatohepatitis. He was diagnosed with hepatopulmonary syndrome associated with nonalcoholic steatohepatitis. Hormone-replacement therapy was re-started. After 5 months, a second liver biopsy revealed the amelioration of nonalcoholic steatohepatitis, which improved his respiratory condition. This case suggested that early effective therapy for chronic liver diseases might improve the pathological and clinical conditions of hepatopulmonary syndrome.

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan.

Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy. Methods This was a single-center retrospective study. A total of 95 Japanese cirrhotic patients (60 men, median age 63 years) were enrolled and received tolvaptan orally after hospitalization for ascites treatment. The serum Na level was monitored during the period of tolvaptan treatment. The laboratory data and survival rates of patients who achieved serum Na levels of <135 and ≥135 mEq/L after 1 week were compared. Results Patients showed serum Na levels of 136 (121-145) mEq/L, and 42.1% had a serum Na level of <135 mEq/L. Among patients with an initial serum Na level <135 mEq/L, 60.0% achieved a normal level after 1 week, and the survival rate was significantly higher in patients with a normalized serum Na level (p<0.01). The pretreatment brain natriuretic peptide (BNP) level was predictive of achieving a serum Na level of ≥135 mEq/L (odds ratio: 0.87, 95% confidence interval: 0.316-0.987, p<0.05). Conclusion Normalization of the Na level after one week was associated with a favorable outcome of tolvaptan therapy, and Na correction improved the prognosis.

Four cases of type 1 diabetes mellitus showing sharp serum transaminase increases and hepatomegaly due to glycogenic hepatopathy.

Poorly controlled diabetes mellitus (DM) patients sometimes show serum transaminase elevations due to steatohepatitis. However, we experienced four cases with type 1 DM with sharp elevations in serum transaminases that could not be explained by steatohepatitis alone and showed bright liver. They were diagnosed with glycogenic hepatopathy (GH) clinicopathologically. The four patients had a median age of 22.5 years (range, 19-29 years) and 12.5 (4-15)-year histories of type 1 DM and showed marked increases in serum transaminases (aspartate aminotransferase, 698 U/L [469-2763 U/L]; alanine transaminase, 255 U/L [216-956 U/L]). Diabetes mellitus control was poor and hemoglobin A1c was 12.7% (11-16.5%). Three cases had a past history of diabetic ketoacidosis. Hepatomegaly and hyperdense liver were seen on computed tomography scans. Magnetic resonance imaging showed low intensity in T2-weighted images. The pathological findings revealed pale and swollen hepatocytes and glycogenated nuclei. The architecture of the liver was preserved, and steatosis and fibrosis were mild. The cytoplasm of hepatocytes stained densely positive with periodic acid-Schiff, and the positive staining disappeared after diastase digestion, suggesting glycogen deposition. No other cause of hepatitis was evident, and the diagnosis was GH. Elevated transaminases improved within 1 month with good glycemic control. Transaminase elevations were observed several times in three cases with poor glycemic control. Glycogenic hepatopathy is rare, but extremely high serum elevations of transaminases are important to identify clinically. Despite showing a good clinical course in general, GH sometimes recurs and requires strict glycemic control. Clinicians should be aware of and recognize GH when dealing with uncontrolled DM patients.

Response to tolvaptan and its effect on prognosis in cirrhotic patients with ascites.

AIM: The vasopressin V2 receptor antagonist tolvaptan has been used for the treatment of cirrhotic patients with ascites; however, no predictor of efficacy and prognosis has been developed. We evaluated candidate predictors of response to tolvaptan treatment. METHODS: This was a single-center retrospective study. Overall, 97 Japanese cirrhotic patients (60 men, median age 63 years), who were hospitalized for ascites treatment including oral tolvaptan coupled with conventional diuretics, were enrolled. The efficacy of tolvaptan was defined as a urination increase of ≥500 mL or a urine volume ≥2000 mL/day on the day following treatment. The prognosis of tolvaptan treatment was evaluated by the post-treatment survival time by Kaplan-Meier analysis. RESULTS: Tolvaptan therapy was effective in 67% of cirrhotic patients. Patients showed -1.5 (-17.2 to +6.2) kg change in body weight and 40% achieved ≥2.0 kg reduction in body weight after 1 week of treatment. Platelet counts, urine sodium (Na) level, and urine Na/potassium (Na/K) ratio were higher, and the blood urea nitrogen (BUN)/creatinine (Cr) ratio was lower, in cases showing a response to tolvaptan. The combination of a BUN/Cr ratio ≥17.5 and urine Na/K ratio <3.09 was predictive of being non-responsive to tolvaptan, and the response rate in these patients was only 39% (P < 0.01). The mean post-treatment survival duration was significantly longer in patients who responded to tolvaptan therapy. CONCLUSIONS: Urinary BUN and Na excretion were predictive of a response to tolvaptan, and tolvaptan treatment may improve the prognosis of cirrhotic patients.

Successful Treatment of Ascites using a Denver® Peritoneovenous Shunt in a Patient with Paroxysmal Nocturnal Hemoglobinuria and Budd-Chiari syndrome.

A 56-year-old man was diagnosed with aplastic anemia and paroxysmal nocturnal hemoglobinuria at 43 years of age and treatment with cyclosporin A was started. Liver cirrhosis, ascites, and thrombus in the hepatic veins were found at 56 years of age and Budd-Chiari syndrome (BCS) was diagnosed according to angiography findings. He was treated with diuretics and paracentesis was performed several times, but with limited efficacy. A Denver® peritoneovenous shunt (PVS) was inserted into the right jugular vein; his ascites and renal function improved immediately and his general condition has remained good for 12 months since starting the above treatment regimen. A PVS is a treatment option for ascites due to BCS.

Safety and efficacy of long-term tolvaptan therapy for decompensated liver cirrhosis.

AIM: Recently, the short-term efficacy of the vasopressin V2 receptor antagonist tolvaptan for the treatment of ascites in cirrhosis was reported. However, the long-term effects remain unknown. Here, we report the clinical features of decompensated cirrhosis treated using long-term tolvaptan therapy, and evaluate its safety and efficacy. METHODS: Fifty-five cirrhotic patients hospitalized due to ascites, despite receiving appropriate diuretic treatment, were treated with tolvaptan. We excluded 35 patients due to liver transplant (20.0%), death (28.6%), poor general status (14.3%), improved ascites (5.7%) or other reasons (31.4%). In 20 cases treated with tolvaptan for 6 months, total body water (TBW) and extracellular fluids (ECW) were measured using bioelectric impedance analysis (BIA) with an InBody720. RESULTS: The median age of the 20 patients was 64 years (range, 48-90), and 60% were male. The etiology of cirrhosis included hepatitis C (45%), alcohol-induced (20%) and other (35%). The percentage of patients with Child-Pugh class A, B and C was 0%, 40% and 60%, respectively. Biochemical findings revealed that serum creatinine levels and estimated glomerular filtration rate were not affected during 6 months of treatment with tolvaptan, and there was no renal disturbance. The median serum sodium levels were increased from 138 to 139 mEq/L, but serious adverse events related to renal and liver function were not observed. Data also revealed that long-term treatment reduced the BIA-estimated ECW/TBW ratio. CONCLUSION: Long-term tolvaptan treatment was a safe and effective treatment for decompensated cirrhosis.

Spontaneous clearance of HCV accompanying hepatitis after liver transplantation.

Re-infection by the hepatitis C virus (HCV) occurs rapidly after liver transplantation (LT), and spontaneous clearance of HCV is rare under immunosuppressive conditions. Here, we report on two patients who underwent LT to treat liver cirrhosis and hepatocellular carcinoma. The immunosuppressants prescribed were short-term corticosteroids, tacrolimus, and mycophenolate mofetil. A 50-year-old woman underwent LT, with her brother as the donor. She acquired HCV of serological type 1 after LT; the HCV RNA level was 6.0 logIU/mL. Corticosteroids were discontinued within 24 days, with a total dose of 669 mg (adjusted) prednisolone (PSL). The serum alanine aminotransferase (ALT) level increased to 700 U/L by day 55 post-LT. Surprisingly, HCV RNA was not detected on day 87. A 52-year-old man underwent LT, with his sister as the donor. He became rapidly re-infected with HCV of serological type 2; the HCV RNA level was 6.9 logIU/mL. Corticosteroids were given for 24 days, with a total dose of 827 mg (adjusted) PSL. The serum ALT level increased continuously and his HCV cleared 115 days after LT. Both donor and recipient had the major IL28B genotype. HCV was eliminated spontaneously, even under immunosuppressive conditions, after PSL discontinuation without interferon treatment. Minimal use of immunosuppressants and the presence of hepatitis may have contributed to HCV clearance. However, it is important to evaluate additional relevant cases.

Primary hyperoxaluria complicated with liver cirrhosis: A case report.

Primary hyperoxaluria (PH) is a rare, autosomal recessive disorder characterized by overproduction of oxalate caused by a deficiency in a hepatic enzyme. The excess oxalate combines with calcium in the kidneys to form deposits of calcium oxalate, which can lead to nephrocalcinosis and renal failure. PH type 1 (PH1), the most common form of this disease, is caused by a deficiency of the liver-specific enzyme alanine/glyoxylate aminotransferase (AGT). Liver transplantation is performed as a definitive therapy for PH to correct the enzyme defect. Usually, liver depositions are limited and liver function is normal without fibrosis. Here, we report an adult case of liver cirrhosis caused by PH1. A 28-year-old woman was admitted to our hospital under suspicion of PH1 and the presence of nephrocalcinosis. The patient had suffered from kidney stone recurrences from 17 years of age, and was initiated on hemodialysis due to renal failure at the age of 27 years. The serum level of oxalic acid was high, whereas the AGT level in the liver tissue was decreased. Thus, the patient was definitively diagnosed with PH1. Although she had normal liver function, surface nodularity and splenomegaly were detected by computed tomography, suggesting liver cirrhosis. The native liver showed micronodular cirrhosis and portal fibrosis. Several arterioles were filled with rhomboid and polyhedral refractile oxalate crystals and various portal tracts showed these crystals. Our case suggests that long-term oxalosis can lead to liver cirrhosis; thus, PH should be considered one of the causes of liver cirrhosis.

Investigation of ornithine carbamoyltransferase as a biomarker of liver cirrhosis.

OBJECTIVE: Ornithine carbamoyltransferase (OCT) is a liver-specific mitochondrial matrix enzyme and potential biomarker of liver fibrosis. This study investigated the OCT levels in patients with chronic liver disease with or without cirrhosis in order to assess the usefulness of OCT as a biomarker of cirrhosis. METHODS: The subjects included 440 Japanese patients with chronic liver disease and 80 control subjects. The patients were divided into two groups, those with and without cirrhosis, both of which were further stratified into high-OCT and low-OCT subgroups. RESULTS: In the non-cirrhosis group, the patients with non-alcoholic steatohepatitis (NASH), alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis (PSC) comprised the high-OCT subgroup, while the patients with hepatitis B, hepatitis C and autoimmune hepatitis formed the low-OCT subgroup. There were significant differences in the OCT levels, OCT/aspartate aminotransferase ratios and OCT/alanine transaminase (ALT) ratios between these two subgroups (p<0.001). The same findings were observed in the cirrhosis group. The OCT levels were markedly higher in the cirrhosis group than in the non-cirrhosis group, particularly among the patients with PSC (p<0.001). The most useful biomarker for predicting cirrhosis was the OCT/ALT ratio in the patients with hepatitis C and NASH and the OCT level in patients with PSC. CONCLUSION: The OCT level differs among patients with different chronic liver diseases. The role of OCT should be further evaluated in order to improve our understanding of the pathogenesis of these diseases. The OCT level is a useful surrogate marker of cirrhosis, particularly in PSC patients.

Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease.

BACKGROUND: Biomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. METHODS: (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups. RESULTS: 1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3ß ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC. CONCLUSION: Several metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.

Roles of gender, obesity, and lifestyle-related diseases in alcoholic liver disease: Obesity does not influence the severity of alcoholic liver disease.

AIM: To elucidate gender differences and the influence of obesity and/or metabolic syndrome-related fatty liver on alcoholic liver disease (ALD), we analyzed characteristic features of ALD. METHODS: We investigated 266 ALD patients (224 males and 42 females) without hepatocellular carcinoma stratified by gender and the presence of cirrhosis. Male and female patients matched for age and total ethanol intake were also analyzed. A diagnosis of ALD was based on alcohol intake (>70 g daily for more than 5 years), clinical features, and exclusion of other liver diseases. The prevalence of obesity, lifestyle-related diseases, and psychological disorders were assessed. RESULTS: The prevalence of psychological disorders showed a significant gender difference among all ALD patients (12% in males versus 43% in females, P < 0.001), as well as in patients matched for age and total ethanol intake. There were 156 cirrhotic patients. Absence of dyslipidemia, presence of diabetes, and high total ethanol intake were selected as independent predictors of cirrhosis in males by multivariate analysis after excluding laboratory data of liver function tests. The prevalence of obesity was significantly lower in cirrhotic male patients than in non-cirrhotic male patients (34% vs. 20%, P = 0.023). Among females, there were no significant predictors of cirrhosis on multivariate analysis after eliminating liver function tests. The prevalence of obesity and diabetes was similar in non-cirrhotic and cirrhotic female patients. The prevalence of psychological disorders was 47% in cirrhotic females with ALD. CONCLUSIONS: Obesity was not common in cirrhotic ALD. Psychological disorders seem to be important for female ALD.

Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos(t)ide analogs in patients with chronic hepatitis B.

AIM: The factors associated with hepatitis recurrence after discontinuation of nucleos(t)ide analogs (NAs) in patients with chronic hepatitis B were analyzed to predict the risk of relapse more accurately. METHODS: A total of 126 patients who discontinued NA therapy were recruited retrospectively. The clinical conditions of a successful discontinuation were set as alanine aminotransferase (ALT) below 30 IU/L and serum hepatitis B virus (HBV) DNA below 4.0 log copies/mL. RESULTS: Relapse of hepatitis B were judged to occur when maximal serum ALT became higher than 79 IU/L or when maximal serum HBV DNA surpassed 5.7 log copies/mL following NA discontinuation since these values corresponded with mean values of ALT (30 IU/L) and HBV DNA (4.0 log copies/mL), respectively. At least 90% of patients with either detectable hepatitis B e antigen or serum HBV DNA higher than 3.0 log copies/mL at the time of NA discontinuation relapsed within one year. In the remaining patients, higher levels of both hepatitis B surface and core-related antigens at the time of discontinuation, as well as a shorter course of NA treatment, were significantly associated with relapse by multivariate analysis. CONCLUSIONS: It appears that negative results for hepatitis B e antigen and serum HBV DNA lower than 3.0 log copies/mL are essential for successful NA discontinuation, which may be attained by a longer treatment period. Levels of hepatitis B surface and core-related antigens are also significant factors independently associated with relapse of hepatitis.

Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C.

BACKGROUND: This study was performed to clarify the outcomes and recurrence of hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) in comparison with the data for HCC caused by hepatitis C virus (HCV) infection. METHODS: Data for 34 NASH patients with HCC (NASH-HCC) were analyzed prospectively, and data for 56 age- and sex-matched patients with HCC due to HCV chronic liver disease (HCV-HCC) were collected retrospectively. After the initial treatment for HCC, patients were followed regularly at least every 4 months by performing clinical examinations, serum liver function tests, monitoring alpha-fetoprotein and des-gamma-carboxy prothrombin, and utilizing various imaging modalities. RESULTS: The five-year survival rate was 55.2% and the cumulative recurrence of HCC at 5 years was 69.8% in treated cases of NASH-HCC. The NASH-HCC and HCV-HCC groups showed similar survival and recurrence rates. Of the 16 NASH-HCC patients curatively treated, recurrence was detected more than 2 years after the initial treatment in 9. Three patients showed intrahepatic recurrences away from the initial HCC, and 3 patients showed a change in tumor marker production after treatment of the initial HCC. The size of the HCC and the stage of fibrosis were significant risk factors for HCC recurrence in NASH-HCC. CONCLUSIONS: HCC recurrence was very high in NASH, and the HCC may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important for NASH patients with HCC, even after curative treatment. This study confirmed that NASH-HCC has a similar course to that of HCV-HCC.

Clinical significance of serum ornithine carbamoyltransferase in patients with non-alcoholic steatohepatitis.

AIM: Ornithine carbamoyltransferase (OCT) is reported to be a liver-specific marker for the evaluation of hapatocellular damage. In this study, we investigated its clinical significance in non-alcoholic steatohepatitis (NASH). METHODS: Serum OCT levels were measured by the ELISA (enzyme-linked immunosorbent assay) method. One hundred and twenty patients with NASH (18 liver cirrhosis induced by NASH and 9 NASH combined with hepatocellular carcinoma) were measured. RESULTS: The serum levels of OCT and the ratios of OCT : alanine amino transferase (ALT) and OCT : aspartate amino transferase (AST) were increased in parallel with the progression of NASH. Especially, OCT and both ratios were markedly increased in hepatocellular carcinoma. As for the relationship between fibrosis grade and OCT, the serum OCT levels and the ratio of OCT : ALT levels were increased in parallel with liver fibrosis. In NASH patients with ALT within normal range, about 30% showed elevation of OCT. CONCLUSION: Serum OCT levels and the ratios of OCT : ALT and OCT : AST increase in parallel with the progression of NASH. It was suggested that OCT is a useful marker in the progression of NASH.

Influence of adiponectin gene polymorphisms in Japanese patients with non-alcoholic fatty liver disease.

PURPOSE: Single nucleotide polymorphisms (SNPs) of the adiponectin gene have been reported to be associated with insulin resistance and the prevalence of type-2 diabetes. We investigated the SNPs of adiponectin in non-alcoholic fatty liver disease (NAFLD) patients. METHODS: One hundred nineteen patients histologically diagnosed as having NAFLD and 115 control subjects were examined. Adiponectin SNP sites were investigated at +45 of exon 2 and at +276 of intron 2; these sites have been thought to be associated with diabetes or insulin resistance. RESULTS: Regarding the +276 SNP, the frequency of G/G tended to be higher in NAFLD patients than in controls, but not significantly. Among females only, however, the G/G frequency was significantly higher in NAFLD patients. As for the +45 SNP, in the severe fibrosis group, the frequency of G/G homozygotes was significantly higher than that in the mild fibrosis group, and G/G homozygotes of the +45 SNP proved by multivariate analysis to be an independent factor in severe fibrosis. In NAFLD patients with adiponectin +45 G/G, homeostasis model assessment-insulin resistance was significantly higher than in NAFLD patients without adiponectin +45 G/G. CONCLUSION: Adiponectin SNPs were found to be associated with the progression of liver fibrosis and insulin resistance, suggesting that adiponectin SNPs might play roles in the occurrence and progression of NAFLD.

Imaging of nonalcoholic steatohepatitis: advantages and pitfalls of ultrasonography and computed tomography.

OBJECTIVE: The present study was performed to clarify the ability of ultrasonography (US) and computed tomography (CT) to detect steatosis and advanced fibrosis in nonalcoholic steatohepatitis (NASH) patients, and to assess the influence of steatosis, fibrosis, and obesity on the radiological detection of steatosis and advanced fibrosis. METHODS: One hundred and eighteen biopsy proven NASH patients underwent US and CT within 6 months before or after biopsy. The ability of US and CT to detect histological steatosis and advanced fibrosis was assessed. To evaluate whether fibrosis and obesity interfered with the detection of moderate to severe histological steatosis by US and CT, we analyzed 88 NASH patients with moderate to severe steatosis. To evaluate interference with the detection of advanced fibrosis by steatosis and obesity, we analyzed 59 NASH patients with advanced fibrosis. RESULTS: The sensitivity of US for detecting moderate to severe histological steatosis in patients with mild histological fibrosis was 100%, but this was reduced to 77.8% in patients with advanced histological fibrosis (p=0.001). The sensitivity of CT was 69.8% in patients with mild histological fibrosis and 48.9% in those with advanced histological fibrosis (p=0.047). The sensitivity of US and CT for moderate to severe histological steatosis was similar in each body mass index group. The sensitivity for detecting advanced fibrosis was markedly decreased by severe steatosis and obesity in the case of both US and CT. CONCLUSION: If we are aware of these disadvantages of US and CT, it is useful for diagnosing steatosis and fibrosis in NAFLD patients.

Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis.

BACKGROUND: There have been few reports on hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) and the natural history of NASH. Accordingly, we assessed the clinical features of HCC in NASH, the risk factors for HCC, and natural history of NASH with advanced fibrosis. PATIENTS AND METHODS: There were 34 NASH patients with HCC and 348 NASH patients without HCC. To clarify the clinical features of NASH patients with HCC and to determine the risk factors for HCC, we compared NASH patients with HCC with those without HCC. Univariate and multivariate logistic regression models were used for statistical analysis. A prospective cohort study of the outcomes of 137 NASH with advanced fibrosis was started in 1990. The impact of baseline risk factors on the development of HCC and survival was evaluated by Cox regression analysis. RESULTS: In total, 88% of patients with HCC had advanced fibrosis, with a median age of 70 years. Older age, low level of AST, low grade of histological activity, and advanced stage of fibrosis were risk factors for HCC. A prospective cohort study showed that the 5-year cumulative incidence of HCC was 7.6%, and the 5-year survival rate was 82.8%. HCC was the leading cause of death. CONCLUSIONS: The present study confirmed that older age and advanced fibrosis were important risk factors for HCC, and that HCC was the major cause of mortality in NASH patients with advanced fibrosis. Regular screening for HCC is thus extremely important for NASH patients with advanced fibrosis.

Long-term follow up of esophageal varices after balloon-occluded retrograde transvenous obliteration for gastric varices.

AIM: Because the procedure of balloon-occluded retrograde transvenous obliteration (B-RTO) causes extensive thrombosis of the major shunt that connects the spleen and gastric/renal venous systems, an increase in portal pressure is unavoidable. The aim of the present study was to assess the long-term outcome of B-RTO, including changes in esophageal varices. METHODS: B-RTO was conducted in 22 patients with gastric varices, who were divided according to the severity of esophageal varices at baseline; there were no esophageal varices (n = 7), F(1) varices (n = 11), and F(2) varices (n = 4). The outcome measures included the development/worsening of esophageal varices after B-RTO and survival rates. RESULTS: The cumulative bleeding-free probability for all 22 patients at 3 years after B-RTO was 100%. The overall 3-year survival was 94.4%. Seven patients who had no esophageal varices prior to B-RTO did not develop any after the procedure. Seven (63.6%) of the 11 patients with stage F(1) esophageal varices prior to B-RTO showed no changes in the varices after B-RTO, while two patients progressed to F(2) varices and two developed F(3) varices. The cumulative treatment-free probability of the esophageal varices at 24 months after B-RTO was 100% for patients without esophageal varices at baseline, 80.8% for patients with pre-existing F(1) varices, and 75% for those with pre-existing F(2) varices. CONCLUSION: Although the B-RTO procedure is considered useful for the treatment of gastric varices, changes in hemodynamics due to obliteration of this major shunt must be taken into account and observed closely.

[A case of Turner syndrome complicated with Crohn's disease, erythema nodosum and Hashimoto disease].

A 26-year-old woman, who had had Turner syndrome from age 10 years old, had diarrhea, fever, joint pain, and erythema in the lower left leg. She was given a diagnosis of Crohn's disease, erythema nodosum, and Hashimoto disease. Systemic steroid therapy was very effective for both intestinal and skin lesions. It has been reported that half of inflammatory bowel disease patients with Turner syndrome have 46XiX (q) type chromosome abnormality, and this case also has this type of abnormality.

Transcatheter arterial embolization for the treatment of liver metastases in a patient with malignant pheochromocytoma.

A 63-year-old male patient was admitted for the treatment of malignant pheochromocytoma with multiple liver metastases. Plasma and urinary levels of catecholamines were elevated. Transcatheter arterial embolization (TAE) with concomitant administration of mitomycin C and gelatin sponge was performed for the treatment of liver metastases. Dose of alpha-1 blocker before TAE was increased to prevent hypertensive crisis during and after TAE. The hepatic metastatic lesion of CT findings was decreased after TAE. Although blood pressure showed a transient hypertension (180/100 mmHg) after every TAE, it returned rapidly to normal. The patient experienced transient abdominal pain, nausea, and loss of appetite after every TAE; however, those symptoms were readily controlled by conventional medications. Slight elevation of liver transaminases was recognized but returned to normal range within 3 weeks. No other major side effects were seen with TAE. While plasma and urinary level of catecholamines were unchanged, plasma chromogranin A (CgA) level was significantly decreased. These results suggest that TAE is a useful treatment for hepatic metastases. Plasma CgA level is a useful marker in the treatment of malignant pheochromocytoma.