Hepatitis A and hepatitis E virus co-infection with right pleural effusion, ascites and acute acalculous cholecystitis. A case report.

Hepatitis A and hepatitis E are the leading causes of acute viral hepatitis in developing countries due to our poor sanitary conditions, both spread by fecal-oral route or through contaminated water and food. Being both self-limiting diseases, they are usually benign but may present with atypical clinical findings. A 32 year-old female with right pleural effusion, ascites and acalculous cholecystitis during the course of HAV and HEV co-infection is reported. Clinical improvement was observed with conservative management. As far as we know, this is the first case described of a patient with these three complications in the background of a hepatitis A virus and hepatitis E virus co-infection.

Acute Epstein-Barr infection presenting as cholecystitis with ascites.

A young female patient presented with features of ascites and cholecystitis. She was subsequently diagnosed with an acute Epstein-Barr virus infection. This is a rare presentation of a common infection. The patient was managed conservatively and the illness resolved within 6 weeks.

Hepatitis A and hepatitis E virus co-infection with right pleural effusion, ascites and acute acalculous cholecystitis. A case report / Coinfección por el virus de la hepatitis A y la hepatitis E con derrame pleural derecho, ascitis y colecistitis acalculosa aguda. Reporte de caso

ABSTRACT Hepatitis A and hepatitis E are the leading causes of acute viral hepatitis in developing countries due to our poor sanitary conditions, both spread by fecal-oral route or through contaminated water and food. Being both self-limiting diseases, they are usually benign but may present with atypical clinical findings. A 32 year-old female with right pleural effusion, ascites and acalculous cholecystitis during the course of HAV and HEV co-infection is reported. Clinical improvement was observed with conservative management. As far as we know, this is the first case described of a patient with these three complications in the background of a hepatitis A virus and hepatitis E virus co-infection.

RESUMEN Hepatits A y hepatitis E son las principales causas de hepatitis viral en países en desarrollo debido a las limitadas condiciones sanitarias. Son condiciones usualmente benignas y autolimitadas, pero pueden presentarse de forma atípica. Se reporta una paciente de 32 años con efusión pleural derecha, colecistitis acalculosa y ascitis en el curso de una co-infección por el virus de Hepatitis A y hepatitis E. Hasta donde tenemos conocimiento, este es el primer caso de una paciente con estas tres complicaciones como resultado de una infección por el virus de hepatitis A y hepatitis E.

Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B.

Hepatitis E virus (HEV) infection is a major cause of morbidity in endemic areas. Its consequences among chronic hepatitis B (CHB) patients have been under-reported. The aim of this study was to assess the impact of superinfective HEV infection (acute and past) on virological and clinical features of patients with CHB infection. Clinical, biochemical, virological and immunological data of 153 CHB patients including 98 with hepatitis B virus (HBV) monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan, China. An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients. HBV-HEV superinfection patients showed significantly higher rate of complications (ascites, hepato-renal syndrome & encephalopathy) (all with P=0.04), cirrhosis (P<0.001) and acute-on-chronic liver failure (P<0.001) than HBV monoinfection patients. They also displayed elevated ALTs (P<0.001) and total serum bilirubin (P<0.001) with diminished albumin (P<0.001) and HBV viral load (P<0.001). Cytokines assay revealed increased expression of IL-6 (P=0.02), IL-10 (P=0.009) and TNF-α (P=0.003) in HBV-HEV superinfection patients compared to HBV monoinfection patients. Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation, which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis. HEV was also associated with repressed HBV replication, but the underlying mechanism requires further investigation.

Baseline Factors Associated With Improvements in Decompensated Cirrhosis After Direct-Acting Antiviral Therapy for Hepatitis C Virus Infection.

BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce Model for End-Stage Liver Disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus. However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials on the effects of sofosbuvir-based therapy in patients with hepatitis C virus-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C). In these trials, patients were given 12 or 24 weeks of treatment with ledipasvir, sofosbuvir, and ribavirin or velpatasvir, sofosbuvir, and/or ribavirin, or 48 weeks of treatment with sofosbuvir and ribavirin. We collected demographic, clinical, treatment response, and laboratory data from patients and tested their associations with patient outcomes at 36 weeks. The primary outcome was factors associated with reduction of CPT score to class A. RESULTS: The presence of ascites or encephalopathy, serum level of albumin <3.5 g/dL or alanine aminotransferase <60 U/L, and body mass index >25 kg/m2 were associated with an increased risk of not achieving a reduction in CPT to class A, independent of sustained viral response to therapy. Serum level of albumin <2.8 g/dL and abnormal level of bilirubin were associated with an increased risk of liver transplantation or death. We developed a scoring system based on 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated significantly with patient outcomes, which we called the "BE3A score." For patients with scores of 4-5, the hazard ratio for reduction of CPT score to class A was 52.3 (95% confidence interval, 15.2-179.7). CONCLUSIONS: We identified 5 baseline factors (body mass index, encephalopathy, ascites, and serum levels of alanine aminotransferase and albumin) associated with a reduction of CPT score to class A in patients with hepatitis C virus-associated decompensated cirrhosis receiving DAA therapy. We developed a predictive score using these factors, called the BE3A score, which can be used as a shared decision-making tool, quantifying the potential benefits of DAA therapy for patients with decompensated cirrhosis.

The pathogenicity and biological features of Santee-Cooper Ranaviruses isolated from Chinese perch and snakehead fish.

Ranavirus has become a noticeable threat to both farmed and natural populations of fish and amphibians. Herein, we reported that 3 strains of novel viruses, designated as ScRIV-GM-20150902, CmRIV-XT-20150917 and ScRIV-ZS-20151201, were isolated from diseased Chinese perch and snakehead fish in China. Efficient propagation of these isolates were determined in Chinese perch brain (CPB) cell line by the means of cytopathic effect observation, PCR amplification and electron microscopy observation. And their viral titers in CPB cells reached 108.13 TCID50 ml-1, 107.71 TCID50 ml-1 and 107.94 TCID50 ml-1, respectively. While the challenge experiment results showed that 3 isolates resulted in 100% mortality of Chinese perch after virus infection. Electron microscopy analysis showed that two kinds of viral inclusion bodies (intracytoplasmic and intranuclear inclusion body) were observed in infected CPB cells. Sequence alignment and phylogenetic analysis of major capsid protein gene sequences of isolates revealed that these isolates belonged to the species Santee-Cooper Ranavirus.

A Tumor-targeting Adenovirus with High Gene-transduction Efficiency for Primary Pancreatic Cancer and Ascites Cells.

BACKGROUND: Optimizing targeting strategies for vectors in order to enhance antitumor activity and secure patient safety is important for cancer gene therapy. We previously identified two pancreatic cancer-targeting ligands (PFWSGAV: PFW and SYENFSA: SYE) by screening an adenovirus library in vivo and in vitro, respectively. MATERIALS AND METHODS: To examine clinical usefulness, we assessed gene-transduction efficiency using surgically-resected pancreatic cancer specimens and ascites cells. RESULTS: For surgical specimens, vectors displaying PFW and SYE improved transduction efficiency by 4.4- and 4.3-fold, respectively. The SYE-displaying vector was >2-fold more efficient for all seven cases, whereas the PFW-displaying vector increased efficiency in two out of four cases. For ascites samples, both vectors increased gene-transduction efficiency of epithelial cell adhesion molecule (EpCAM)-positive ascites cells by >2-fold in two out of five cases. CONCLUSION: Both vectors enhanced adenovirus infectivity of pancreatic cancer cells and have potential for gene therapy of pancreatic cancer; therefore they should be further evaluated in clinical studies.

Mean arterial pressure drop is an independent risk factor of death in patients with HBV-related cirrhosis ascites.

BACKGROUND/AIMS: In patients with cirrhosis ascites, mean arterial pressure (MAP) is a credible sign of circulatory dysfunction. There are no studies on the relationship between MAP and long-term prognosis in hepatitis B virus (HBV)-related liver cirrhosis ascites. Therefore, we assessed the association between MAP and prognosis in patients with liver cirrhosis ascites. MATERIALS AND METHODS: In total, 110 patients of HBV-related liver cirrhosis ascites were prospectively followed for 5 years. After their admission, the patients underwent laboratory tests and MAP measurements. Multivariate analysis was conducted using backward stepwise Cox proportional hazards regression. Receiver operator characteristic (ROC) curves were used to confirm the best cutoff value of several baseline parameters, including MAP, for predicting death in patients with liver cirrhosis ascites. RESULTS: In a follow-up period of 5 years, 60 (54.5%) patients survived. MAP (OR 1.176, 95% CI 1.045 to 1.326, p=0.003) was an independent risk factor of death, together with Child-Pugh score (OR 1.204, 95% CI 1.068 to 1.357, p=0.002) and model for end-stage liver disease score (OR 1.297, 95% CI 1.198 to 1.405, p=0.000). The area under the ROC curve of MAP was 0.819 at baseline (95% CI 0.741 to 0.897, p=0.000). A baseline MAP value of ≤83.5 mmHg was an independent risk factor of death. CONCLUSION: A decrease in MAP was a valuable predictor of death in patients with HBV-related liver cirrhosis ascites. MAP may be used for determining the prognosis and exploring new treatment measures directed at optimizing the treatment of liver cirrhosis ascites.

Vesicular stomatitis virus is a potent agent for the treatment of malignant ascites.

Cancer cells in ascites are usually exposed to a hypoxia tumor microenvironment and utilize enhanced glycolysis which produces energy and metabolizes nutrients to support proliferation. Vesicular stomatitis virus (VSV) is an oncolytic virus that relies on the host cellular metabolism for replication. We tested the efficacy of VSV on peritoneal carcinomatosis and assessed VSV replication in cancer cells from ascites. BALB/c female mice bearing peritoneal H22 or MethA cells received an i.p. administration of 1x108 PFU VSV or 1x108 PFU equivalent of UV-inactivated VSV on day 10, 12 and 14 after incubation. Administration of VSV resulted in a significant inhibition of ascites formation and prolonged survival of the treated mice. The replication of VSV was obviously enhanced in the cancer cells from the ascites. Considering the central carbon metabolic pathways, cancer cells in the malignant ascites provided more exogenous glucose, glutamine and pyruvate after VSV infection due to its unregulated glycolytic activity and glutamine metabolism. Pharmacologically, inhibition of the glycolytic pathway and glutamine metabolism reduced VSV replication, and this inhibited replication was rescued by the addition of multiple tricarboxylic acid (TCA) cycle intermediates. Our results demonstrated that metabolic adaptive processes in peritoneal carcinoma, such as high glycolytic activity and glutamine metabolism, favor VSV replication. These results suggest the clinical potency of VSV in the treatment of malignant ascites and provide new insights into the further exploration of the potential application of VSV in the treatment of hypoxia ascites cancer cells.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis.

Human cytomegalovirus (CMV) is a herpesvirus, which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However, CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis, portal hypertension-related ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation, and suggests that testing for CMV should be carried out, even in patients with normal immune status, presenting with severe liver damage or cholestasis.

Vascular invasion in hepatitis B virus-related hepatocellular carcinoma with underlying cirrhosis: possible associations with ascites and hepatitis B viral factors?

Vascular invasion is one of the most important prognostic factors for patients with hepatocellular carcinoma (HCC). The objective of the current, retrospective study was to determine the associations of ascites and hepatitis B viral factors (HBeAg and anti-HBe status and HBV DNA levels), as well as tumor-related factors (size, tumor number, grade, and location) with micro- or macroscopic vascular invasion in patients with HCC that developed as a result of hepatitis B virus (HBV)-related cirrhosis. A total of 336 consecutive patients were included. Potential factors associated with micro- or macroscopic vascular invasion were analyzed by logistic regression. Ascites were more commonly detected in patients with micro- or macroscopic vascular invasion, and the presence of ascites was independently associated with vascular invasion. Among patients with mild-to-moderate or severe ascites, the odds ratio for macroscopic vascular invasion was 4.83 (95 % confidence interval [CI] 2.29-10.16) and 11.87 (95 % CI 4.53-31.07), respectively. Similarly, the presence of ascites was associated with microscopic vascular invasion (OR 5.00; 95 % CI 1.23-20.31). In contrast, hepatitis B viral factors were not significantly associated with vascular invasion. The presence of ascites was associated with vascular invasion in patients with HBV-related cirrhotic HCC. Thus, patients with ascites, vascular invasion should be considered and more frequent surveillance should be performed after curative treatment.

Levels of murine, but not human, CXCL13 are greatly elevated in NOD-SCID mice bearing the AIDS-associated Burkitt lymphoma cell line, 2F7.

Currently, few rodent models of AIDS-associated non-Hodgkin's lymphoma (AIDS-NHL) exist. In these studies, a novel mouse/human xenograft model of AIDS-associated Burkitt lymphoma (AIDS-BL) was created by injecting cells of the human AIDS-BL cell line, 2F7, intraperitoneally into NOD-SCID mice. Mice developed tumors in the peritoneal cavity, with metastases to the spleen, thymus, and mesenteric lymph nodes. Expression of the chemokine receptor, CXCR5, was greatly elevated in vivo on BL tumor cells in this model, as shown by flow cytometry. CXCL13 is the ligand for CXCR5, and serum and ascites levels of murine, but not human, CXCL13 showed a striking elevation in tumor-bearing mice, with levels as high as 200,000 pg/ml in ascites, as measured by ELISA. As shown by immunohistochemistry, murine CXCL13 was associated with macrophage-like tumor-infiltrating cells that appeared to be histiocytes. Blocking CXCR5 on 2F7 cells with neutralizing antibodies prior to injection into the mice substantially delayed tumor formation. The marked elevations in tumor cell CXCR5 expression and in murine CXCL13 levels seen in the model may potentially identify an important link between tumor-interacting histiocytes and tumor cells in AIDS-BL. These results also identify CXCL13 as a potential biomarker for this disease, which is consistent with previous studies showing that serum levels of CXCL13 were elevated in human subjects who developed AIDS-lymphoma. This mouse model may be useful for future studies on the interactions of the innate immune system and AIDS-BL tumor cells, as well as for the assessment of potential tumor biomarkers for this disease.

A phase I clinical trial of Ad5/3-Δ24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer.

OBJECTIVE: The conditionally replicative adenovirus Ad5/3-Δ24 has a type-3 knob incorporated into the type-5 fiber that facilitates enhanced ovarian cancer infectivity. Preclinical studies have shown that Ad5/3-Δ24 achieves significant oncolysis and anti-tumor activity in ovarian cancer models. The purpose of this study was to evaluate in a phase I trial the feasibility and safety of intraperitoneal (IP) Ad5/3-Δ24 in recurrent ovarian cancer patients. METHODS: Eligible patients were treated with IP Ad5/3-Δ24 for 3 consecutive days in one of three dose cohorts ranging 1 × 10(10)-1 × 10(12)vp. Toxicity was assessed utilizing CTC grading and efficacy with RECIST. Ascites, serum, and other samples were obtained to evaluate gene transfer, generation of wildtype virus, viral shedding, and antibody response. RESULTS: Nine of 10 patients completed treatment per protocol. A total of 15 vector-related adverse events were experienced in 5 patients. These events included fever or chills, nausea, fatigue, and myalgia. All were grades 1-2 in nature, transient, and medically managed. Of the 8 treated patients evaluable for response, six patients had stable disease and 2 patients had progressive disease. Three patients had decreased CA-125 from pretreatment levels one month after treatment. Ancillary biologic studies indicated Ad5/3-Δ24 replication in patients in the higher dose cohorts. All patients experienced an anti-adenoviral neutralizing antibody effect. CONCLUSIONS: This study suggests the feasibility and safety of a serotype chimeric infectivity-enhanced CRAd, Ad5/3-Δ24, as a potential therapeutic option for recurrent ovarian cancer patients.

Detection of ascitic feline coronavirus RNA from cats with clinically suspected feline infectious peritonitis.

Ascitic feline coronavirus (FCoV) RNA was examined in 854 cats with suspected feline infectious peritonitis (FIP) by RT-PCR. The positivity was significantly higher in purebreds (62.2%) than in crossbreds (34.8%) (P<0.0001). Among purebreds, the positivities in the Norwegian forest cat (92.3%) and Scottish fold (77.6%) were significantly higher than the average of purebreds (P=0.0274 and 0.0251, respectively). The positivity was significantly higher in males (51.5%) than in females (35.7%) (P<0.0001), whereas no gender difference has generally been noted in FCoV antibody prevalence, indicating that FIP more frequently develops in males among FCoV-infected cats. Genotyping was performed for 377 gene-positive specimens. Type I (83.3%) was far more predominantly detected than type II (10.6%) (P<0.0001), similar to previous serological and genetic surveys.

[A neonate with subumbilical swellings]. / Een neonaat met subumbilicale zwellingen.

A neonate presented with hypoplasia of the abdominal wall muscles after fetal ascites due to anemia caused by an intra-uterine infection with parvovirus B19. Because this is an extremely rare complication, pathogenesis and prognosis are currently unclear.

Serum leptin level and its association with fatigue in patients with chronic hepatitis C virus infection.

BACKGROUND AND STUDY AIM: Fatigue is one of the most common presenting symptoms of chronic hepatitis C virus (HCV) infection. Its pathogenesis has been poorly investigated. Serum leptin levels are increased in cirrhosis and are suggested to have a role in the mediation of fatigue. This study was designed to assess possible association of serum leptin levels with fatigue and severity of liver disease in Egyptian patients with chronic hepatitis C infection. PATIENTS AND METHODS: Seventy patients and 20 control subjects participated in the study. They were subjected to clinical and laboratory assessment, the determination of serum leptin level by ELISA and the assessment of fatigue using the multidimensional assessment of fatigue (MAF) scale. Respondents are asked to reflect on fatigue patterns for the past week. The MAF is a revision of the Piper Fatigue Scale. RESULTS: Fatigue was present in all patients (100%) and 13 subjects of the control group (65%). There was a highly significant statistical difference between cases and controls regarding the presence and severity of fatigue. Serum leptin level was significantly higher in cases (24.9±28) in comparison to the control subjects (14.8±8). Serum leptin was not related to severity of liver disease as assessed by the Child Pugh classification. Serum leptin levels were directly correlated to the severity of fatigue (p<0.01) in patients but not in the control subjects. CONCLUSION: Fatigue is highly prevalent in Egyptian patients with chronic HCV infection. Leptin might play a role in the mediation of fatigue in those patients drawing attention to biological basis of one of the most common symptoms facing clinician dealing with this problem.

The natural history of hepatitis B virus cirrhosis after the first hepatic decompensation in Tunisia.

AIM: To define the natural long term course of viral B cirrhosis after the onset of hepatic decompensation and to determine the predictive factors of death. METHODS: Retrospective longitudinal study including 77 cases of viral B cirrhosis among 192 consecutive patients with cirrhosis, hospitalized between 1997 and 2005 for the first hepatic decompensation. All those patients were followed- up until death or until December 2006. The probability of survival after the first hepatic decompensation was calculated using the Kaplan Meier method. The predictive factors of death were determined through univariate and multivariate analyses with the Cox regression model. RESULTS: Fifty four men and 23 women with an average age of 54±14.9 years were hospitalized for the first decompensation of the viral B cirrhosis. The 77 patients had been under observation for an average period of 24.2 ±21.1 months. During that time 64% among them died. The probability of survival after decompensation was 47% in 2 years and 22 % in 5 years. During follow- up, ascites was the most frequent decompensation (85%) followed by hepatic encephalopathy (38 %), variceal hemorrhage (34 %), jaundice (30%), hepato renal syndrome (27%), hepatocellular carcinoma (21%), and spontaneous bacterial peritonitis (14%). At univariate analysis four factors were predictive of death: Child Pugh C score (p=0.009), hepatocellular carcinoma (p=0.01), rate of serum gammaglobulin superior to18g / l (p=0.008) and prothrombin time inferior to 50 % (p=0.02). According to the multivariate analysis only the rate of serum gammaglobulin superior to 18g /l was an independent predictive factor of mortality (p=0,001) with IC (95 %) [1.623 - 5.88]. CONCLUSION: In Tunisia, the prognosis of viral B cirrhosis after the first decompensation is bad, because a patient on 5 only was able to survive beyond 5 years. Ascites is the most frequent decompensation. Only the rate of serum gammaglobulin superior to 18g / l is an independent predictive factor of mortality.

Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients.

Decompensated liver cirrhosis (LC), a life-threatening complication of chronic liver disease, is one of the major indications for liver transplantation. Recently, mesenchymal stem cell (MSC) transfusion has been shown to lead to the regression of liver fibrosis in mice and humans. This study examined the safety and efficacy of umbilical cord-derived MSC (UC-MSC) in patients with decompensated LC. A total of 45 chronic hepatitis B patients with decompensated LC, including 30 patients receiving UC-MSC transfusion, and 15 patients receiving saline as the control, were recruited; clinical parameters were detected during a 1-year follow-up period. No significant side-effects and complications were observed in either group. There was a significant reduction in the volume of ascites in patients treated with UC-MSC transfusion compared with controls (P < 0.05). UC-MSC therapy also significantly improved liver function, as indicated by the increase of serum albumin levels, decrease in total serum bilirubin levels, and decrease in the sodium model for end-stage liver disease scores. UC-MSC transfusion is clinically safe and could improve liver function and reduce ascites in patients with decompensated LC. UC-MSC transfusion, therefore, might present a novel therapeutic approach for patients with decompensated LC.