Ascitic microbiota alteration is associated with portal vein tumor thrombosis occurrence and prognosis in hepatocellular carcinoma.

Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.IMPORTANCEFirst, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC.

Disseminated phaeohyphomycosis with hepatic artery and portal vein thrombosis caused by Pleurostomophora richardsiae in a liver transplant recipient: A case report.

Pleurostomophora richardsiae is a dematiaceous mold that causes subcutaneous cystic phaeohyphomycosis. Few cases of invasive P richardsiae infection have been reported. Hepatic artery thrombosis following organ transplantation caused by a fungal organism is also very rare. We present here a 57-year-old man with refractory ascites and liver failure following liver transplantation for treatment of hepatocellular carcinoma. Abdominal computed tomography demonstrated total occlusion of hepatic artery and blood clot in the portal vein and inferior vena cava. P richardsiae was isolated from blood culture and the blood clot in his liver. The patient was treated successfully with a 4-week course of amphotericin B deoxycholate and liver retransplantation.

Bacterial DNA translocation contributes to systemic inflammation and to minor changes in the clinical outcome of liver transplantation.

Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.

Unique microbial-derived volatile organic compounds in portal venous circulation in murine non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease is now the leading liver disease in North America. The progression of non-alcoholic fatty liver disease to the inflammatory condition, non-alcoholic steatohepatitis is complex and currently not well understood. Intestinal microbial dysbiosis has been implicated in the development of non-alcoholic fatty liver disease and progression of non-alcoholic steatohepatitis. Volatile organic compounds are byproducts of microbial metabolism in the gut that may enter portal circulation and have hepatotoxic effects contributing to the pathogenesis of non-alcoholic steatohepatitis. To test this hypothesis, we measured volatile organic compounds in cecal luminal contents and portal venous blood in a mouse model of non-alcoholic steatohepatitis. METHODS: Gas chromatography-mass spectrometry analysis was conducted on cecal content and portal vein blood for volatile organic compound detection from mice fed a methionine and choline deficient diet, which induces non-alcoholic steatohepatitis. The colonic microbiome was studied by 16S rRNA gene amplification using the Illumina MiSeq platform. RESULTS: Sixty-eight volatile organic compounds were detected in cecal luminal content, a subset of which was also present in portal venous blood. Importantly, differences in portal venous volatile organic compounds were associated with diet-induced steatohepatitis establishing a biochemical link between gut microbiota-derived volatile organic compounds and increased susceptibility to non-alcoholic steatohepatitis. CONCLUSION: Our model creates a novel tool to further study the role of gut-derived volatile organic compounds in the pathogenesis of non-alcoholic steatohepatitis.

[Pylephlebitis: a rare but possible complication of intra-abdominal infections]. / Pileflebitis: una extraña pero posible complicación de las infecciones intraabdominales.

BACKGROUND: Pylephlebitis or septic thrombophlebitis of the portal venous system is a rare but serious complication of intra-abdominal infections which drain into the portal venous system. Its diagnosis is based on clinical suspicion and imaging tests, mainly a computed tomography scan, given the lack of specificity of the signs and symptoms. Spread of septic emboli is the major cause of morbidity and mortality. The aim of the study was to analyse patients diagnosed in our hospital. MATERIAL AND METHODS: Retrospective descriptive study of patients diagnosed with pylephlebitis in our hospital. CLINICAL CASES: Four patients were included, 3 men and one woman. In 3 cases it was acute cholecystitis that led to the diagnosis of pylephlebitis at the same time as the intra-abdominal infection. Emergency surgery was performed in one case, whilst the other 2 were treated conservatively. Blood cultures were performed in all cases, and empirical antibiotic treatment was used. In the only case of acute appendicitis, diagnosis of pylephlebitis was achieved during the study of postoperative fever, with empirical antibiotic treatment also being started. The haematologist was requested to start the required anticoagulation therapy in all cases. CONCLUSIONS: Pylephlebitis is a rare complication of intra-abdominal infections that may make lead to a worse outcome. A high level of suspicion is required as well as imaging tests to make an early diagnosis and appropriate treatment.

Intermittent Pringle maneuver is unlikely to induce bacterial translocation to the portal vein: a study using bacterium-specific ribosomal RNA-targeted reverse transcription-polymerase chain reaction.

BACKGROUND: The occurrence of bacterial translocation (BT) to the mesenteric lymph nodes following the Pringle maneuver is well established; however, the incidence of BT to the portal circulation remains unclear. METHODS: Portal blood of patients with suspected hilar malignancy who underwent major hepatobiliary resection with cholangiojejunostomy was sampled three times during surgery: immediately after laparotomy (PV-1); before liver transection and after skeletonization of the hepatoduodenal ligament (PV-2); and after completion of the liver transection (PV-3). The samples were analyzed for microbes with a bacterium-specific ribosomal RNA-targeted reverse transcription-polymerase chain reaction method. RESULTS: Fifty patients were enrolled in the study, with a mean total Pringle time of 86 min. Microbes in the portal blood were detected in 11 (22%) of the 50 patients. The occurrence of microbes was not different among the PV-1 samples (8% = 4/50), PV-2 samples (14% = 7/50), and PV-3 samples (14% = 7/50) (P = 0.567). Obligate anaerobes were predominantly detected. The positivity of the PV-3 samples showed no correlation with the total Pringle time or with the occurrence of postoperative infectious complications. The total Pringle time did not affect the surgical outcomes, including infectious complications, liver failure, or mortality. The concentrations of aspartate aminotransferase and alanine aminotransferase on postoperative day 1 significantly correlated with the total Pringle time. CONCLUSIONS: The intermittent Pringle maneuver is unlikely to induce BT to the portal circulation and is safe, even in difficult, complicated hepatobiliary resections requiring long clamping times.

Pylephlebitis: Incidence and prognosis in a tertiary hospital / Pileflefitis: incidencia y prognosis en un hospital terciario

OBJECTIVES: Septic thrombophlebitis of the portal vein or its branches, most often secondary to intra-abdominal infection is known as pylephlebitis. The frequency and the prognosis of this complication are unknown. The aim of this study was to determine the global and relative incidence of the most frequent intra-abdominal infections and the real prognosis of this disease. Methods An observational retrospective study was conducted in a tertiary care hospital (University Hospital of Salamanca, Spain) from January 1999 to December 2008.ResultsA total of 7796 patients with intra-abdominal infection were evaluated, of whom 13 (0.6%) had been diagnosed with pylephlebitis. Diverticulitis was the most frequent underlying process, followed by biliary infection. Early mortality was 23%. Survivors had no recurrences, but one of them developed portal cavernomatosis. Conclusions Pylephlebitis is a rare complication of intra-abdominal infection, with a high early mortality, but with a good prognosis for survivors

OBJETIVOS: La tromboflebitis séptica de la vena porta o de sus ramas se conoce como pileflebitis. En la mayoría de ocasiones es secundaria a infecciones intraabdominales. La frecuencia y el pronóstico deesta complicación infecciosa no son conocidas. El objetivo de este estudio es describir la incidenciaglobal, relativa y el pronóstico real de esta enfermedad respecto a las infecciones intraabdominales más frecuentes. MÉTODOS: Estudio observacional retrospectivo en un hospital de tercer nivel (Hospital Universitario de Salamanca) desde enero de 1999 a diciembre de 2008.RESULTADOS: Se evaluó a 7.796 pacientes con infecciones intraabdominales. Trece (0,6%) fueron diagnosticados de pileflebitis. La diverticulitis fue el proceso subyacente más frecuente, seguida de la infección biliar. La mortalidad precoz fue del 23%. Los pacientes que sobrevivieron no presentaron recurrencias, pero uno de ellos desarrolló una cavernomatosis portal. CONCLUSIONES: La pileflebitis es una complicación poco frecuente de las infecciones intraabdominales. Presenta una elevada mortalidad precoz, pero tiene un buen pronóstico vital para los pacientes que sobreviven

[Esophageal varices and dyspnea. A clinicopathological conference report]. / Ruokatorven laskimolaajentumat ja hengenahdistus.

A young man who had moved from India to Finland was extensively examined for abdominal complaints. The findings included large esophageal varices, open portal vein and enlarged lymph nodes. The large spleen was excised. The diagnosis did not become clear from laboratory investigations. After ten years the patient was repeatedly examined to reveal the cause of esophageal varices and abdominal complaints. Autoimmune pancreatitis and cholangitis were suspected after 23 years from the initial symptoms. In the end, the most plausible explanation for the patient's mixed disease was tuberculosis. Sarcoidosis was another disease that came into question.

Influence of fish to soybean oil ratio on hepatic mononuclear cell function and survival after intraportal bacterial challenge in parenterally fed mice.

BACKGROUND: Parenteral nutrition (PN) is indispensable for meeting the caloric and substrate needs of patients who cannot receive adequate amounts of enteral nutrition. However, PN decreases hepatic mononuclear cell (MNC) numbers and impairs their functions. We examined the effects of various ratios of ω-3 to ω-6 polyunsaturated fatty acids on hepatic MNC number and function in a murine model. We focused on serum liver enzymes, lipid metabolism, cytokine production, histopathology, and the outcomes of an intraportal bacterial challenge. MATERIAL AND METHODS: In experiment 1, male Institute of Cancer Research mice were randomized to CHOW, 67%, 33%, 16%, 8%, 4%, and 0% fish oil (FO)-PN groups. After receiving their respective diets for 5 days, 1.0 × 10(7) Pseudomonas aeruginosa were delivered by intraportal injection. Survival was observed ≤ 7 days after injection. Liver histologies after intraportal bacterial challenge were examined in the CHOW, 33%, 8%, and 0% FO-PN groups. In experiment 2, the mice were divided into 4 groups: CHOW, 33%, 8%, and 0% FO-PN. After the mice had been fed for 5 days, MNC were isolated. Hepatic MNC were counted and cytokine productions (tumor necrosis factor [TNF]-α and interleukin [IL]-10) by MNC in response to lipopolysaccharide (LPS) were measured. Blood samples were analyzed for lipid metabolism and hepatobiliary biochemical parameters. Liver histologies were also examined. RESULTS: In experiment 1, survival times were significantly shorter in the 4% and 0% FO-PN groups than in the CHOW group. Survival rates at 168 hours were 100%, 64%, 86%, 73%, 67%, 11%, and 13% in the CHOW, 67%, 33%, 16%, 8%, 4%, and 0% FO-PN groups, respectively. At 72 hours after intraportal bacterial challenge, the 0% FO-PN group showed severe tissue damage, whereas such damage was reduced in the 8% and 33% FO-PN groups. In experiment 2, the CHOW, 33%, 8%, and 0% FO-PN groups showed LPS dose-dependent increases in TNF-α levels. IL-10 levels were also LPS dose-dependently increased in the CHOW and 33% FO-PN groups. However, no marked changes were observed in response to LPS stimulation in either the 8% or the 0% FO-PN group. There were no differences in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, or total bilirubin among these 4 groups. In the 0% FO-PN group, serum total cholesterol levels were greater than those in the 8% and 33% FO-PN groups. Without bacterial challenge, livers from the 0% FO-PN group showed steatosis, but these changes were attenuated in the 8% and 33% FO-PN groups. CONCLUSION: The 30-40% ratio of FO to soybean oil with 20% of total calories supplied by lipid seems to be the best PN for preservation of hepatic MNC number and function.

Recent trend of pylephlebitis in Taiwan: Klebsiella pneumoniae liver abscess as an emerging etiology.

BACKGROUND AND AIMS: Pylephlebitis (septic thrombophlebitis of the portal venous system) is a rare complication of intra-abdominal infection. We aimed to investigate the recent trend of its etiology, clinical manifestation, and prognosis. METHODS: We retrospectively studied the etiology, clinical manifestation, and outcome by reviewing the medical records of all imaging-confirmed pylephlebitis cases diagnosed during the period 2002-2011 in a university hospital in Taiwan. To identify the risk factors for pylephlebitis, we randomly selected 160 patients with intra-abdominal infections but without pylephlebitis as the comparison group. RESULTS: We identified 35 cases of pylephlebitis. Most patients were men [29/35 (83 %)]. The median age of the patients was 57 years (range 35-90 years). Unspecified abdominal pain (18/35) and fever (10/35) were the most common clinical manifestations. Klebsiella pneumoniae liver abscess (7/35) and cholangitis (7/35) were the most common etiologies. Liver abscess was a risk factor for pylephlebitis (13/35 vs. 27/160, P = 0.01). With antibiotic therapy, there was no in-hospital mortality, but pylephlebitis was still associated with an excess hospital stay (22.2 ± 17.6 vs. 9.8 ± 7.1 days, P < 0.001). CONCLUSIONS: Our study results suggested a different pattern of pylephlebitis from previous Western literature. K. pneumoniae liver abscess (7/35) is an emerging etiology of pylephlebitis in Taiwan.

No difference in portal and hepatic venous bacterial DNA in patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt insertion.

BACKGROUND: Bacterial translocation (BT) with immune activation may lead to hemodynamical alterations and poor outcomes in patients with cirrhosis. AIMS: We investigated bacterial DNA (bDNA), a marker of BT, and its relation to portal pressure and markers of inflammation in the portal and hepatic veins in patients with cirrhosis undergoing TIPS insertion. METHODS: We analysed plasma for bDNA and markers of inflammation in 28 patients [median portal pressure gradient 15 (11-19) mmHg] during TIPS treatment for refractory ascites (n = 19) or acute variceal bleeding (n = 9). Advanced cirrhosis was present in the majority [Child-Pugh class (A/B/C): 1/14/13], and most often caused by alcohol (n = 21). RESULTS: bDNA was detectable in one or both samples in 16 of 28 patients (57%). bDNA was present in 39% of the samples from the portal vein vs 43% of the samples in the hepatic vein (P = 0.126). Antibiotics had no effect on bDNA or markers of inflammation. Markers of inflammation did not differ between the hepatic and portal veins with the exceptions of soluble urokinase plasminogen activating receptor (suPAR) and vascular endothelial growth factor (VEGF), both higher in the hepatic vein (P = 0.031 and 0.003 respectively). CONCLUSIONS: No transhepatic gradient of bDNA was evident, suggesting that no major hepatic elimination of bDNA occurs in advanced liver disease. bDNA, in contrast to previous reports was largely unrelated to a panel of markers of inflammation and without relation to portal pressure.

Septic thrombophlebitis of the portal venous system: clinical and imaging findings in thirty-three patients.

AIM: Our purpose was to review the clinical and imaging findings in a series of patients with septic thrombophlebitis of the portal venous system in order to define criteria that might allow more confident and timely diagnosis. MATERIALS AND METHODS: This is a retrospective case series. The clinical and imaging features were analyzed in 33 subjects with septic thrombophlebitis of the portal venous system. RESULTS: All 33 patients with septic thrombophlebitis of the portal venous system had pre-disposing infectious or inflammatory processes. Contrast-enhanced CT studies of patients with septic thrombophlebitis typically demonstrate an infectious gastrointestinal source (82%), thrombosis (70%), and/or gas (21%) of the portal system or its branches, and intrahepatic abnormalities such as a transient hepatic attenuation difference (THAD) (42%) or abscess (61%). CONCLUSIONS: Septic thrombophlebitis of the portal system is often associated with an infectious source in the gastrointestinal tract and sepsis. Contrast-enhanced CT demonstrates an infectious gastrointestinal source, thrombosis or gas within the portal system or its branches, and intrahepatic abnormalities such as abscess in most cases. We report a THAD in several of our patients, an observation that was not made in prior reports of septic thrombophlebitis.

Pylephlebitis: an overview of non-cirrhotic cases and factors related to outcome.

Pylephlebitis is a condition with significant morbidity and mortality. We review herein 100 relevant case reports published since 1971. Eighty-one patients were reported with acute pylephlebitis, while the remaining patients had chronic pylephlebitis. The most common predisposing infections leading to pylephlebitis were diverticulitis and appendicitis. Cultures from blood or other tissues were positive in 77%. The infection was polymicrobial in half of the patients and the most common isolates were Bacteroides spp, Escherichia coli and Streptococcus spp. Thrombosis was extended to the superior mesenteric vein (SMV), splenic vein, and intrahepatic branches of the portal vein (PV) in 42%, 12%, and 39%, respectively. Antibiotics were administered in all and anticoagulation in 35 cases. Patients who received anticoagulation had a favourable outcome compared to those who received antibiotics alone (complete recanalization 25.7% vs 14.8% (p > 0.05), no recanalization 5.7% vs 22.2% (p < 0.05), and death 5.7% vs 22.2% (p < 0.01)). Cases with complete recanalization had prompt diagnosis and management and two-thirds were recently published. Nineteen patients died; the majority of these (73.7%) died over the period 1971-1990. In conclusion, pylephlebitis remains an entity with high morbidity and mortality, but modern imaging modalities have facilitated an earlier diagnosis and have improved the prognosis. Anticoagulation has a rather beneficial effect on patients with pylephlebitis.

Abscess of the round ligament of the liver associated with acute obstructive cholangitis and septic thrombosis.

A man with abscess of the round ligament of the liver associated with acute obstructive suppurative cholangitis and portal thrombosis is reported. A 63-year-old man was admitted with epigastralgia and high fever. Blood tests showed elevation of hepato-biliary enzymes and coagulopathy consistent with acute obstructive suppurative cholangitis and disseminated intravascular coagulation. Computed tomography revealed a small abscess of the round ligament of the liver and left portal thrombosis. After endoscopic biliary stenting, antibiotics and thrombolytic therapy, the high fever, disseminated intravascular coagulation and portal thrombosis rapidly improved, and the round ligament abscess was also later resolved.

Aeromonas hydrophila bacteraemia and portal pyaemia.

The Aeromonas species uncommonly cause disease in humans. We report portal pyaemia secondary to Aeromonas hydrophila bacteraemia occurring in a 71-year-old Chinese man with no history of hepatobiliary disease or malignancy. He presented with fever, rigors and abdominal bloating for four days and was subsequently found to have Aeromonas hydrophila bacteraemia, portal vein thrombosis and a psoas abscess. He was treated with ciprofloxacin and had a good recovery. Aeromonas hydrophila infection is an uncommon cause of intestinal and extraintestinal infection in man, but must be suspected in immunocompromised hosts and in those exposed to brackish or salt water.