Efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for hepatitis C in Korea: a Phase 3b study

Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

Three-Dimensional Analysis of Mouse Habenula Subnuclei Reveals Reduced Volume and Gene Expression in the Lipopolysaccharide-mediated Depression Model

The habenula (Hb) is small but important brain structure, anatomically and functionally links the forebrain with the midbrain to modulate various neuropsychiatric functions associated with drug addiction and emotion-associated dysfunctions. Several reports suggested that the dysfunction of Hb-related functions affected the Hb structurally and functionally. However, the technical limitation has awaited the solid conclusion of whether Hb change due to depression is likely to occur in certain subnuclei of the Hb. To probe this possibility, we developed 3-dimensional reconstruction methods for the high-resolution volumetric analysis of Hb and the mRNA levels at the given volume in normal or lipopolysaccharide (LPS)-mediated mouse model of depression. Notably, we discovered that the volume reduction was prominent in medial Hb but not in lateral Hb after LPS treatments. On the other hand, the RNA expression levels of known Hb regional markers such as Tac1 (dorsal part of medial Hb), ChAT (ventral part of medial Hb), and Tacr1 (medial and lateral Hb) were all decreased in all Hb subnuclei in LPS-injected mice. Accordingly, accurate volumetry with marker labeling was not feasible. Collectively, these established 3D analyses of mouse Hb successfully and precisely determine the volume-based changes of small brain structure, which should be applicable in a wider range of mouse models or pathological specimens.

Predictable Factors of Histologic Discrepancy of Gastric Cancer between the Endoscopic Forceps Biopsy and Endoscopic Treatment Specimen / 대한소화기학회지

BACKGROUND/AIMS: Recently, variable gastrointestinal track tumors including early stage malignancies are treated by endoscopic procedure. However, the discrepancy of histologic diagnosis may sometimes exist between the pretreatment forceps biopsy results and those of post treatment specimen. So the prediction of malignant lesion is important in the aspect of treatment selection. In this study, we investigated the predictable factors of the histologic discrepancy through the clinical, endoscopic features of the lesion diagnosed as adenocarcinoma in the post-endoscopic treatment specimen after the adenoma was diagnosed by the endoscopic forceps biopsy. METHODS: From March 2005 to April 2009, 129 gastric tumor lesions (129 patients) which were not diagnosed as malignancy and treated with endoscopic procedure were enrolled retrospectively. We compared the pretreatment endoscopic forceps biopsy results and post-treatment specimen biopsy results, then, analyzed the tumor characteristics. RESULTS: Twenty-one cases (16.3%) were diagnosed as malignancy after endoscopic treatment. Especially, discrepancy occurred more frequently in depressed lesions than in flat or elevated lesions (41.7% vs. 13.7%, p=0.012), and in lesions diagnosed as high grade adenomas than low or moderate grade adenomas (33.3% vs. 11.1%. p=0.004). CONCLUSIONS: In cases of depressed type lesions in the pretreatment endoscopy or those diagnosed as high grade adenoma in the pretreatment forceps biopsy, we should consider combined malignant lesion. Therefore, treatment modalities ensuring accurate diagnosis and potentially curative resection, should be carefully selected and performed in cases which have these features.

A Case of Portal Vein Thrombosis by Protein C and S Deficiency Completely Recanalized by Anticoagulation Therapy / 전남의대학술지

Portal vein thrombosis (PVT) is a rare form of venous thrombosis that affects the hepatic portal vein flow, which can lead to portal hypertension. Treatment of PVT includes anticoagulants, thrombolysis, insertion of shunts, bypass surgery, and liver transplantation. Single anticoagulation therapy is not regarded as a curative treatment but can be associated with a reduction in new thrombotic episodes. We experienced a case of acute total occlusion of PVT provoked by protein C and S deficiency syndrome. PVT was completely recanalized with oral anticoagulant therapy following low molecular weight heparin therapy.

A Case of Portal Vein Thrombosis by Protein C and S Deficiency Completely Recanalized by Anticoagulation Therapy / 전남의대학술지

Portal vein thrombosis (PVT) is a rare form of venous thrombosis that affects the hepatic portal vein flow, which can lead to portal hypertension. Treatment of PVT includes anticoagulants, thrombolysis, insertion of shunts, bypass surgery, and liver transplantation. Single anticoagulation therapy is not regarded as a curative treatment but can be associated with a reduction in new thrombotic episodes. We experienced a case of acute total occlusion of PVT provoked by protein C and S deficiency syndrome. PVT was completely recanalized with oral anticoagulant therapy following low molecular weight heparin therapy.

A Case of Ampullary Adenomyoma Associated with Dilatations of Pancreatic and Biliary Ducts / 대한소화기내시경학회지

Adenomyoma is a nonneoplastic lesion that can be found anywhere in the gastrointestinal tract, but it's rarely found in the ampulla of Vater. To the best of our knowledge, it is a benign lesion, but most cases are misdiagnosed as carcinoma or adenoma by a preoperative endoscopic or radiologic procedure, and this leads to unnecessarily extensive surgical resection. We report here on a case of ampulla of Vater adenomyoma that resulted in biliary and pancreatic duct dilatation. The tumor was diagnosed by endoscopic papillectomy.

Does a single dose of intravenous nicardipine or nimodipine affect the bispectral index following rapid sequence intubation? / 대한마취과학회지

BACKGROUND: Theoretically, L-type calcium channel blockers could modulate anesthetic effects. Nicardipine does not affect the bispectral index (BIS), but nimodipine, which can penetrate the blood-brain barrier, has not been studied. The aim of this study was to evaluate whether a single dose of intravenous nicardipine or nimodipine could affect BIS following rapid sequence intubation. METHODS: This study was done in a double-blind, randomized fashion. Anesthesia was induced with fentanyl 2 microgram/kg, thiopental sodium 5 mg/kg, and 100% oxygen. After loss of consciousness, patients received rocuronium 1.0 mg/kg and either a bolus of 20 microgram/kg nicardipine, nimodipine, or a comparable volume of normal saline (n = 20). Intubation was performed 1 min after study drug administration. BIS, mean blood pressure (MBP), and heart rate (HR) were measured before anesthetic induction, after loss of consciousness, before intubation, during intubation, and 1, 2 and 5 min after intubation. RESULTS: BIS dropped rapidly after induction but increased to 60 before intubation in all groups irrespective of study drug. In nimodipine, the increase in BIS during intubation was not significant compared to pre-intubation, in contrast to the other two groups, but there was no difference in BIS during intubation. HR significantly increased, but MBP just rose to pre-induction values after intubation in nicardipine and nimodipine groups. BIS, MBP, and HR following intubation increased in control group. CONCLUSIONS: A single dose of intravenous nicardipine or nimodipine could attenuate blood pressure increases but not affect BIS increases in rapid sequence intubation.

Polyarteritis Nodosa Localized in Small Intestine: A Case Report / 대한소화기내시경학회지

Polyarteritis nodosa is a systemic necrotizing vasculitis that affects mainly small and medium-sized arteries that involve multiple organs. In addition to the systemic involvement of classical vasculitis, localized vasculitis involves blood vessels within a confined vascular distribution or single organ without clinical evidence of generalized inflammation. Localized vasculitis of the gastrointestinal tract is a rare entity. In particular, a limited involvement of the small bowel is an unusual manifestation of polyarteritis nodosa. In this report, we describe a case of biopsy-proven polyarteritis nodosa presenting as small bowel bleeding without other systemic manifestations.

Accidental malpositioning of 9Fr central venous catheter in the right subclavian vein via right internal jugular vein: A case report

Central venous catheters can provide important hemodynamic information in patients with cardiopulmonary disease and access for medicine, fluid, and blood administration during surgery. The placement of central venous catheters is associated with a complication rate of 0.4% to 20%, including pneumothorax, arterial puncture, infection and cardiac tamponade. In addition, malposition of central venous catheter is another complication of central venous catheterization. We report a case of malpositioning of central venous catheter which is located in the right subclavian vein via internal jugular vein in a liver transplant recipient. The malpositioning was confirmed by portable X-ray after several field attempts to advance Swan-Ganz catheter and achieve normal sequences of pressure waves.

Two-stage liver transplantation in a surgically complicated liver failure patient after hepatic tumor resection: A case report / 대한마취과학회지

Two-stage liver transplantation, involving a total hepatectomy with a temporary portocaval shunt followed by liver transplantation, requires intensive perioperative care, especially during the prolonged anhepatic period. The pathophysiology and management of this prolonged anhepatic state is not fully elucidated and the proper management during this period is a great challenge to clinicians in the intensive care unit and anesthesiologists. We report a case and management of a total hepatectomy with a temporary portocaval shunt followed by living-donor liver transplantation in a patient with a surgically complicated liver failure after a hepatic tumor resection.

Prognostic value of serum osteopontin in hepatocellular carcinoma patients treated with transarterial chemoembolization / 대한간학회지

BACKGROUND/AIMS: Osteopontin (OPN) is overexpressed in hepatocellular carcinoma (HCC) with postoperative recurrence or extrahepatic metastasis. However, its prognostic value in patients treated with transarterial chemoembolization (TACE) is unclear. We investigated the utility of serum OPN levels and changes therein as prognostic markers in HCC patients who have received TACE. METHODS: Forty-six patients with HCC were enrolled. Serum OPN levels were measured before and 4 weeks after TACE. Serum biochemistry and computed tomography (CT) scans were analyzed. We evaluated baseline serum OPN levels and subsequent changes therein in relation to tumor responses and cumulative survival rates following TACE. A decreasing pattern was defined as a decrease after TACE of more than 10% relative to baseline levels. A "responder" was defined as a patient who exhibited a tumor necrosis rate of higher than 50% on the follow-up CT scan. RESULTS: Higher initial serum OPN levels were associated with a large tumor, portal vein invasion, and an advanced tumor stage. Patients who had lower initial serum OPN levels and those who exhibited decreasing patterns after TACE tended to have more favorable tumor responses (P=0.043 and 0.055, respectively) and exhibited better cumulative survival rates (P=0.036 and 0.030, respectively). However, the initial serum OPN level and subsequent changes in serum OPN levels were not independent predictors for survival on multivariate analysis. CONCLUSIONS: Serum OPN levels were significantly higher in patients with advanced HCC. In addition, HCC patients with low pretreatment serum OPN levels and those for whom serum OPN declined following TACE exhibited better tumor responses and survived for longer.

A Case of Vanishing Bile Duct Syndrome Associated with Hypersensitivity to Allopurinol / 대한간학회지

Allopurinol is frequently used for the treatment of hyperuricemia and gout. Sometimes, a life-threatening reaction develops, as is illustrated by the following case report. We describe a 60-year-old male patient who was treated with allopurinol because of asymptomatic hyperuricemia, and he was presented with fever, skin rash, eosinophilia, worsening renal function and vanishing bile duct syndrome. In this report, we discussed vanishing bile duct syndrome as a serious side effect of allopurinol, and we briefly reviewed the etiology, prevention, and treatment modalities for vanishing bile duct syndrome.

Phase II Study to Topotecan and Cisplatin in Advanced Hepatocellular Carcinoma

BACKGROUND: Hepatocellular carcinoma remains a highly chemoresistant neoplasm and is a common malignancy with poor prognosis in Korea. We performed a phase II study to evaluate the efficacy and toxicities of topotecan and cisplatin combination chemotherapy for advanced hepatocellular carcinoma. METHODS: Between November 1999 and May 2001, ten patients with histologically proven hepatocellular carcinoma were enrolled in this study. The median age was 54 (range: 53~74) years and all were male. Six patients demonstrated stage IV, 1 stage IIIC, 2 stage IIIB and 1 stage IIIA. Six patients showed a ECOG performance status of 1. The treatment regimen consisted of topotecan 1.25 mg/m2 and cisplatin 20 mg/m2 for 5 days. The treatment was repeated every 4 weeks. Toxicities were evaluated according to WHO toxicity criteria. RESULTS: All ten patients were evaluable for response and toxicity. There was only one patient who achieved partial response. The overall response rate was 10% (95% C.I.) and the response duration was 46 weeks. The median survival of all patients was 21 (range: 17~54+) weeks. During a total of 24 cycles, neutropenia of WHO grade 3 and 4 occurred in 33%, thrombocytopenia in 33% and anemia in 21%. In non-hematologic toxicity, diarrhea and hepatoxicity of grade 3 occurred in 1 and 2 patients, respectively. But there was no treatment-related death. CONCLUSION: When used in this dose and schedule, topotecan and cisplatin combination chemotherapy does not seem to be effective for patients with advanced hepatocellular carcinoma.

Efficacy and safety of lamivudine therapy in patients with liver cirrhosis associated with chronic hepatitis B / 대한내과학회지

BACKGROUND: Lamivudine has been reported to be effective and safe in the treatment of chronic hepatitis B. However, in patients with advanced liver cirrhosis (LC) who have less hepatic reserve function and so higher chances of serious complications, its outcomes remained to be clarified. We evaluated the effectiveness and safety of lamivudine in patients with LC caused by hepatitis B. METHODS: Twenty four patients with HBV-associated LC who had clinical evidence of hepatic dysfunction (Child-Pugh Class A:B:C = 13:7:4) as well as 76 patients with biopsy-proven chronic hepatitis B (CH) as controls were administered with 150 mg of lamivudine orally everyday for at least more than 6 months. Serum HBeAg and HBV-DNA (liquid phase hybridization assay) as well as CBC, prothrombin time and biochemistry were tested sequentially during the follow-up period. RESULTS: All patients in both groups became negative for HBV-DNA in their sera during the treatment. Five out of 24 LC (21%) and 33 (43%) of 76 CH patients were relapsed within the follow-up periods of median 19 and 22 months, respectively (p=0.42). HBeAg seroconversion was observed in 7 of 19 LC (37%) and 25 of 69 CH (36%) patients with positive HBeAg (p=0.52). The hemoglobin, white blood cell and platelet counts were not changed significantly in both groups during the follow-up periods. The prothrombin time, serum cholesterol and bilirubin levels were also not changed significantly during the treatment. All of 76 CH patients had not presented any fatal complication during the follow-up periods. In contrast, 3 out of 4 LC patients in Child-Pugh class C died of serious complications (1 out of 5 relapsers, 2 of 19 persistent responders, p=NS; 1 died of sepsis, 2 of variceal bleeding). CONCLUSION: Lamivudine therapy may be as effective in patients with LC as in those with CH in terms of the clearance of serum HBV-DNA and the seroconversion of HBeAg. Our data also suggest that the lamivudine therapy is as safe even in decompensated LC as in CH.

A Case of Acute Staphylococcal aureus Esophagitis in Immunocompromised Patients / 감염

Bacterial esophagitis is an uncommon disease and has not been well characterized. Bacterial infection of the esophagus is usually presented as a superimposed infection upon a preexisting viral or fungal esophagitis and most patients are immunocompromised hosts. A 67-year-old man was admitted for retrosternal pain and hematemesis, who had a past history of long-standing diabetes mellitus and end stage renal disease, also had a history of steroid medication. Extensive esophageal ulcerations of the mucosa were visualized by endoscopy. Staphylococcus aureus grew in blood culture. After the 2 weeks of antibiotics treatment, he was successfully recovered without any sequelae. Due to its rarity, this case is herein reported with a review of the corresponding literature.

Expression of Transforming Growth Factor beta-1 in Chronic Hepatitis and Hepatocellular Carcinoma Associated with Hepatitis C Virus Infection

BACKGROUND: Transforming growth factor beta-1 (TGF beta 1) has been suggested to play a role in the development, growth or progression of hepatocellular carcinoma (HCC). Genotype and serum titer of HCV also affect the occurrence of HCC in chronic hepatitis C. In this study, we were to evaluate the effects of genotype or serum titer of HCV on the expression of TGF beta 1. We also intended to examine the correlation between the up-regulation of TGF beta 1 and the association with HCC in patients with chronic hepatitis C. METHODS: We studied 19 patients with chronic hepatitis C and 18 with HCC associated with HCV infection. HCV genotype was determined by line probe reverse hybridization assay and the amount of HCV-RNA was quantitated by branched DNA signal amplification assay. Serum TGF beta 1 level was measured by enzyme linked immunosorbent assay. RESULTS: HCV genotypes of patients with HCC were similar to those without it. Serum HCV-RNA titer was higher in genotype 1b than in non-1b (p < 0.05). Serum TGF beta 1 levels were higher in HCC than in chronic hepatitis (p < 0.05). However, there was no significant difference in the serum TGF beta 1 level between genotype 1b and non-1b. Also, it was not correlated with the serum HCV-RNA titer or alanine aminotransferase levels. CONCLUSION: TGF beta 1 seems to be overexpressed in HCC compared to that of chronic hepatitis C: it was not affected by serum ALT levels, genotype or serum HCV titer. It is suggested that TGF beta 1 may be associated with the malignant transformation of hepatocyte or the progression of HCV-associated HCC.

Prevalence and Clinical Significance of Autoantibodies in Patients with Chronic Hepatitis C / 대한간학회지

BACKGROUND/AIMS: Chronic hepatitis C virus (HCV) infection is often associated with extrahepatic autoimmune disease, and autoantibodies such as anti-nuclear antibody (ANA) or anti-smooth muscle antibody (ASA). The presence of autoantibodies may make discrimination between chronic hepatitis C with autoimmune features and type 1 autoimmune hepatitis difficult. We studied the prevalence of autoantibodies in patients with chronic HCV infection and their clinical significance. MATERIALS AND METHODS: ANA, ASA, anti-mitochondrial antibody (AMA), anti-microsomal antibody (AmA), rheumatoid factor (RF), anti-cardiolipin antibody (aCL) and lupus anti-coagulant (LA) were tested in 116 patients (80 chronic hepatitis C, 36 liver cirrhosis). Genotypes of HCV were determined in 25 patients by INNO LiPA. RESULTS: The overall prevalence of autoantibody was 65.5%. The most common autoantibody was aCL (34.5%), followed by ANA (25%), RF (18%), LA (15.5%), ASA (6.9%), anti-microsomal antibody (6%) and AMA (1%). The positive rate of either ANA or ASA was 30.2%, but both were positive in 1.7% only. There was no difference in the demographic features, biochemistry, HCV genotypes and disease status between autoantibody-positive and autoantibody-negative patients. CONCLUSIONS: Autoantibodies were commonly found in patients with chronic HCV infection. But, the presence of autoantibodies may be a non-specific finding in chronic hepatitis C infection without clinical significance.

Ischemic Bile Duct Injury as A Serious Complication Following Transarterial Chemoembolization / 대한간학회지

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) has been reported to be one of the useful palliative treatments in patients with unresectable hepatocelluar carcinoma. However, Bile duct injuries following TACE have been reported occasionally. In this study, we intended to clarify the incidence, pathogenic mechanisms and clinical implications of bile duct injuries following TACE. METHODS: A total of 950 consecutive patients with hepatocellular carcinoma (HCC) were subjected. 807 patients were treated with TACE. The remaining 143 were treated with transarterial chemoinfusion (TACI) of cisplatin. RESULTS: None of 143 HCC patients treated with TACI revealed to have any ischemic biliary injury radiologically. In contrast, out of 807 with TACE, 17 (2%) appeared to have biliary complications. Twelve out of 17 (71%) had bilomas at subcapsular area, three out of 17 (18%) had focal strictures at common hepatic duct or common bile duct with marked dilatation of intrahepatic bile ducts and two out of 17 (11%) had diffuse mild dilatation of intrahepatic bile ducts. Interestingly, two (17%) out of 12 bilomas were found at the lobe which was not embolized with Gelfoam. The median sessions of TACE to the occurrences of focal strictures tended to be longer compared with those of bilomas (median: 6 vs. 2.5; p=0.08). All three patients with focal strictures and four (33%) out of 12 patients with bilomas were associated with serious bacterial infections at presentation. CONCLUSIONS: Biloma seems to be caused by lipiodol rather than Gelfoam; focal strictures of large bile ducts by Gelfoam. It is suggested that adjustments of the amounts of lipiodol or Gelfoam and the sites or embolization may be required to reduce the ischemic biliary injuries following TACE.

Correlation of p53 Mutations and Microvascular Invasions of Hepatocellular Carcinoma: A Possible Factor of Poor Prognosis Following Surgical Resection / 대한간학회지

BACKGROUND/AIMS: p53 mutations have been reported to be a poor prognostic indicator in patients with HCC treated by surgical resection because of the association with frequent recurrence and shorter survival periods. Although poor differentiation of tumor has been considered to be associated with p53 mutation more frequently, the exact causes of unfavorable prognosis have not been clarified. METHODS: To evaluate the relationship of p53 mutation and details of histological features, we examined 20 HCCs and surrounding liver tissues from the patients treated with surgical resection using direct sequencing of p53 gene at exons 5, 6, 7 and 8, and analyzed histopathologic features. We also analyzed the clinical, biochemical and radiological characteristics including the recurrences of tumor and survival periods in HCC patients with p53 mutant comparing to those with wild type p53 gene. RESULTS: p53 mutants were found in 9 (45%) out of 20 resected HCC tissues, none from any surrounding tissues. p53 mutations were all point substitutions of a base; 5 in exon 8, 4 in exon 5 and 1 in exon 7. Between patients with mutants and those with wild type of p53 gene, there were no differences in age, sex, serum ALT, albumin, bilirubin and AFP levels, and HBV-ositivity. HCCs with p53 mutants tended to be larger in size (14% in 5 cm; p=0.03) and multinodular in type (3/9 vs 0/11; p=0.07). p53 mutants tended to be found in poorly differentiated HCCs comparing to wild types. Even though there was no evidence of vascular or biliary invasion radiologically in all, 5 of 9 p53 mutant (+) (56%) and none of 11 p53-utant (- cases showed vascular invasions microscopically (p<0.01). However, there was no correlation between p53 mutations in tumor tissues and formation of capsules, biliary invasions or association with cirrhosis. During follow-p periods (median: 22;2 -8 mos) recurrences of HCC had been found in 6 of 9 patients with mutants (67%) in contrast to only 2 of 11 with wild types (18%)(p=0.07). Extrahepatic metastases were also common in patients with p53 mutant than those without it (56% vs 9%; p=0.05). Consequently, the 1 year cancer free survival rate of HCC patients with p53 mutant was significantly lower than that with wild type (44% vs 82%; p=0.02). CONCLUSIONS: Thus, it is suggested that p53 mutations tend to be commonly associated with microvascular invasions as well as poor differentiation microscopically, which may result in micrometastasis and frequent recurrences, and consequently shorter survival periods in HCC patents undergoing surgical resection.

Tumor Necrosis Factor-a and Interleukin- in Ascitic Fluid and Plasma in Spontaneous Bacterial Peritonitis / 대한간학회지

BACKGROUND/AIMS: Spontaneous bacterial peritonitis (SBP) is a major problem associated with liver cirrhosis which has high mortality. Increased production of inflammatory mediators, such as tumor necrosis factor-a (TNF-a) and interleukin- (IL-) may be associated with development of renal impairment, one of the most important prognostic parameters in SBP. The aim of this study is to investigate the changes of these cytokines in ascitic fluid and plasma in patients with SBP and the relationship between these cytokines and development of renal impairment. METHODS: Forty patients with liver cirrhosis and ascites were studied 21 with SBP and 19 with sterile ascites. TNF-a and IL- levels in ascitic fluid and plasma were determined by ELISA at the time of diagnosis in both groups and 48 hours after antibiotics treatment in SBP patients. RESULTS: TNF-and IL- levels in ascitic fluid and plasma were significantly higher in patients with SBP than those without SBP (ascitic fluid TNF-a: 2.5+/-0.5 vs. 1.6+/-0.2; plasma TNF-a: 2.3+/-0.5 vs. 1.5+/-0.2; ascitic fluid IL-: 3.8+/-0.5 vs. 3.0+/-0.4; plasma IL-: 3.4+/-0.5 vs. 2.3+/-0.3, log pg/mL)(p<0.001). In patients with SBP, levels of TNF-a and IL- in ascitic fluid and plasma decreased 48 hours after antibiotics treatment. Eleven patients with SBP (11/21, 52%) developed renal impairment. Patients with renal impairment had significantly higher ascitic fluid and plasma TNF-a levels than those without renal impairment (median 2.5 vs. 2.1 for ascitic fluid, p=0.006; median 2.4 vs. 2.0, log pg/mL for plasma, p=0.04). Although four out of eleven (36%) patients who developed renal impairment died during hospitalization, all the patients without renal impairment survived (p=0.09). CONCLUSION: Our results suggest that the levels of TNF-a and IL- in ascitic fluid and plasma are increased in SBP and elevated levels of TNF-a in ascitic fluid and plasma may be associated with development of renal impairment, thus indicating poor prognosis in patients with SBP.